Mini-laparoscopic Sentinel Node Detection in Endometrial Cancer: Further Reducing Invasiveness for Patients with Early-Stage Disease.
Lymphatic mapping and sentinel lymph node (SLN) biopsy have been proposed as a safer and less morbid approach than full lymphadenectomy for patients with early endometrial cancer (EC), through either cervical or corporeal dye injection.1 (-) 4 The advantage of mini-laparoscopy is a further reduction in the overall surgical trauma for the patient. This video aims to show the feasibility of SLN biopsy using a 3-mm mini-laparoscopic approach. A 56-year-old woman with grade 2 endometrioid EC underwent mini-laparoscopic pelvic SLN detection plus extrafascial total hysterectomy and bilateral salpingo-oophorectomy (TLH-BSO). A two-sided superficial and deep cervical injection of indocyanine green (2 mL diluted to 1.25 mg/mL) was used for inoculation before the procedure. A 5.8-mm 0° optical camera with a near-infrared high-intensity light source for detection of fluorescence imaging was inserted through the umbilicus. Two ancillary 3-mm trocars were inserted suprapubically. The procedure was accomplished using only 3-mm instruments. Neither intraoperative complications nor conversion to conventional laparoscopy or open surgery occurred. The operative time was 60 min, and the estimated blood loss was 50 mL. SLN was detected bilaterally, and removal of the two identified nodes was achieved through meticulous dissection and preservation of the surrounding structures followed by TLH-BSO. No postoperative complications were registered, and the patient was discharged 24 h after surgery. An SLN ultrastaging exam was negative, and the final pathology showed a International Federation of Gynaecology and Obstetrics (FIGO) stage 1A G2 EC with a 2/21-mm myometrial invasion. Mini-laparoscopic SLN detection plus TLH-BSO is a feasible procedure that guarantees minimal surgical trauma to selected patients with early EC.


Midwives' perceptions and experiences of routine enquiry for domestic violence.
To examine midwives' perceptions and experiences of routine enquiry for domestic violence. Focus groups and semi-structured interviews. The study was conducted in the maternity services of Guy's and St Thomas' NHS Hospital Trust, an inner London teaching hospital. Twenty-eight midwives were interviewed. One hundred and sixteen out of 145 (80%) midwives were trained to screen routinely pregnant women for domestic violence at booking, at 34 weeks of gestation and postpartum. Twenty midwives attended one of four focus groups and eight semi-structured interviews were conducted. Interviews were transcribed and analysed using content analysis. Midwives' views of routine enquiry for domestic violence. Midwives felt that domestic violence was an important issue to be addressed. However, practical and personal difficulties were encountered during the study. These included: time constraints, lack of confidential time, safety issues, staff shortages, low staff morale and midwives' personal experiences of domestic violence. The study produced a raised awareness about domestic violence within the maternity unit. There was considerable support for the idea of a specialist domestic violence midwife. Routine enquiry for domestic violence cannot be implemented effectively without ensuring that in-depth training, resources, staff support and policies to ensure that screening can be conducted safely and confidentially are in place.


Veratrum alkaloids in sneezing-powder a potential danger.
Sneezing-powders containing pulverized root of veratrum album (white hellebore) have recently been marketed in the Scandinavian countries. The powder, imported from the Federal Republic of Germany, has caused severe intoxications.


Autologous stem cell transplantation with PCR-negative graft would be associated with a favorable outcome in core-binding factor acute myeloid leukemia.
Although core-binding factor acute myeloid leukemia (CBF-AML) is generally considered to be a low-risk form of AML, the survival rate is still 50% to 60%. To evaluate the effectiveness of autologous stem cell transplantation (ASCT) with a PCR-negative graft we analyzed a series of consecutive CBF-AML patients. Between 1997 and 2006, 18 patients aged<60 years were referred under a diagnosis of CBF-AML. Peripheral blood stem cells (PBSC) were collected after a second or further course of postremission therapy. When >2.0x10(6)/kg CD34-positive cells with minimal residual disease (MRD) undetectable by nested polymerase chain reaction (PCR) had been collected, ASCT was performed with busulfan, etoposide, and cytarabine combined with granulocyte colony-stimulating factor. Event-free survival (EFS) and complications of ASCT were then assessed. Fourteen of the 18 patients received ASCT. The median observation period was 4.4 years. The 5-year EFS was 93% for ASCT patients, despite the presence of adverse factors. In 8 of 10 patients who had detectable MRD in the bone marrow before ASCT, MRD became undetectable after ASCT. Neutrophils recovered promptly within 2 weeks, but platelets recovered relatively slowly. Half of the patients suffered from varicella zoster virus infection. Although 1 case of myelodysplastic syndrome occurred, there was no case of relapse. ASCT with a PCR-negative graft was associated with excellent EFS. For patients with CBF-AML, especially with adverse factors or remnant MRD in the bone marrow, this strategy is the treatment of choice.


Mitochondrial cytopathies.
Defects of the mitochondrial respiratory chain and mutations of mitochondrial DNA have now been associated with a wide range of human diseases. The precise pathogenetic mechanisms by which these biochemical abnormalities induce tissue dysfunction are not understood. The identification of a mutation in the proline anticodon and in the 12S RNA genes of mitochondrial DNA are interesting new additions to the catalogue of pathogenetic mutations of this genome. The recent demonstration of nuclear complementation of mitochondrial DNA depletion provides the opportunity to identify nuclear genes involved in mitochondrial DNA replication. The possible role for mitochondrial deficiencies in certain neurodegenerative diseases and in the ageing process have given additional momentum to research in this area. Treatment for the mitochondrial 'cytopathies' remains disappointing and improvement in this area awaits a better understanding of their aetiology.


A time-saving-modified Giemsa stain is a better diagnostic method of Helicobacter pylori infection compared with the rapid urease test.
Despite having chronic gastritis, most people infected by Helicobacter pylori (H. pylori) are asymptomatic and have no specific clinical signs and symptoms. H. pylori infection can be diagnosed by several detection methods. Giemsa stain and rapid urease test (CLO test) are the most performed tests of H. pylori infection at first-line clinical examination because of their simplicity and reliability. However, the sensitivity of CLO test is significantly reduced in patients with atrophic gastritis and intestinal metaplasia, and the weaknesses of Giemsa stain are higher cost and time-consuming. The Giemsa stain was modified in several staining solutions and procedures based on the simplified Giemsa technique described by Gray, Wyatt, & Rathbone (1986). The modified Giemsa stain is examined its efficacy and compared with the CLO test using 233 H. pylori-infected patients with gastric disease. The modified Giemsa stain is comparable to the traditional one. Statistical analysis indicated that the modified Giemsa stain obtains greater accuracy in H. pylori-infected patients with gastritis and ulcer than the CLO test (48.1% vs. 43.7%). Moreover, considering the prognosis of different symptoms of gastric diseases, the modified Giemsa stain has a more accurate prognosis than combination symptoms (P = 1.8E-05 vs. P = 5.49E-05). The modified Giemsa stain is confirmed to be better than CLO test using 233 H. pylori-infected patients with gastric disease. The modified Giemsa stain is more simplified and time-saving than traditional Giemsa stain, which is comparable to the traditional one and is confirmed to be better than CLO test using 233 H. pylori-infected patients with gastric disease. In clinical examination, this modified Giemsa stain can be applied to routine examination and provides quick and accurate diagnosis and prognosis to H. pylori-infected patients with gastric diseases.


The three most common variations of the left renal vein: a review and meta-analysis.
The authors describe three anatomic variations, circumaortic, retroaortic left renal vein, and retropelvic tributary of the renal vein, in Japanese cadavers. The incidences and the clinical significances of these variations are discussed with a detailed review of the literature. The median incidences of circumaortic left renal vein (CLRV) were 7.0% in cadavers examined and 1.8% in clinical subjects examined. The detection of CLRV in CT/MDCT or angiography was relatively difficult compared with that by cadaver dissection. The median incidences of retroaortic left renal vein (RLRV) were 1.7% in cadavers examined and 2.2% in clinical subjects examined. The detection of RLRV was lower in operations, and relatively easy by ultrasonography. The incidence of retropelvic tributary of the renal vein ranged from 30.0 to 46.4%, which is very frequent. Moreover, the incidences of communicating veins between the left renal vein and retroperitoneal veins ranged from 30.0 to 84.2% in cadaver dissections and from 34.0 to 75.8% in clinical reports.


Glaucoma and expulsive hemorrhage mechanisms in the Sturge-Weber syndrome.
An eye from an adult with Sturge-Weber syndrome and glaucoma is described histologically following enucleation for massive choroidal hemorrhage. The specimen is noted to contain hemangiomas of the episclera and choroid as well as a partial angle cleavage abnormality. Histologic evidence reviewed herein supports the concept that infantile glaucoma associated with this syndrome may be associated with marked filtration angle cleavage deformities. Some Sturge-Weber patients who develop unilateral glaucoma later as juveniles or adults appear to have milder expressions of angle cleavage abnormality or a forme fruste of this angle disorder. Any surgical procedure for this glaucoma preferably should be one which minimizes or eliminates operative hypotony, thus avoiding a possible expulsive hemorrhage.


Isoelectrophoretogram of gazelle hemoglobin--a suggested tool for proving hunting offenses.
Hunting gazelle is an offense according to Israeli law. When comparative isoelectric focusing was performed on bloodstains made from gazelle, goat, sheep, and cow blood, the pattern obtained from gazelle hemoglobin differed from those of the other animals tested. The use of this difference in hemoglobin pattern is suggested as a means to identify gazelle blood in hunting offense cases.


Serum vascular endothelial growth factor as a possible marker for early ectopic pregnancy.
This study evaluated serum vascular endothelial growth factor (VEGF) concentrations in women with normal intrauterine pregnancy (IUP), arrested IUP and ectopic pregnancy (EP). This was a prospective, case-control study evaluating serum VEGF concentrations among 45 early pregnant women who subsequently were found to have an EP, a normal IUP or an arrested IUP (15 women in each group). Patients were stratified according to serum VEGF concentrations above and below 200 pg/ml. There was a significant difference in VEGF concentrations among women with EP, arrested IUP and normal IUP (306.1 +/- 26.5, 169.7 +/- 16.6 and 27.0 +/- 4.4 pg/ml respectively, P < 0.001). With a cut-off concentration of 200 pg/ml, serum VEGF could distinguish normal IUP from EP with a sensitivity of 88%, a specificity of 100% and a positive predictive value of 100%. Between EP and arrested IUP, the sensitivity was 87.5%, specificity 75% and positive predictive value of 77.8%. VEGF is a potential marker for EP. Its concentrations in women with EP are higher than in those with normal and arrested IUP.


Organs at risk radiation dose constraints.
Dose constraints are essential for performing dosimetry, especially for intensity modulation and for radiotherapy under stereotaxic conditions. We present the update of the recommendations of the French society of oncological radiotherapy for the use of these doses in classical current practice but also for reirradiation.


Ultra-large chemical libraries for the discovery of high-affinity peptide binders.
High-diversity genetically-encoded combinatorial libraries (108-1013 members) are a rich source of peptide-based binding molecules, identified by affinity selection. Synthetic libraries can access broader chemical space, but typically examine only ~ 106 compounds by screening. Here we show that in-solution affinity selection can be interfaced with nano-liquid chromatography-tandem mass spectrometry peptide sequencing to identify binders from fully randomized synthetic libraries of 108 members-a 100-fold gain in diversity over standard practice. To validate this approach, we show that binders to a monoclonal antibody are identified in proportion to library diversity, as diversity is increased from 106-108. These results are then applied to the discovery of p53-like binders to MDM2, and to a family of 3-19 nM-affinity, α/β-peptide-based binders to 14-3-3. An X-ray structure of one of these binders in complex with 14-3-3σ is determined, illustrating the role of β-amino acids in facilitating a key binding contact.


A peptidomimetic inhibitor suppresses the inducibility of β1-adrenergic autoantibody-mediated cardiac arrhythmias in the rabbit.
Previous studies demonstrated that burst pacing and subthreshold infusion of acetylcholine in β1-adrenergic receptor (β1AR)-immunized rabbits induced sustained sinus tachycardia. The aim of this study was to examine the anti-arrhythmogenic effect of a newly designed retro-inverso (RI) peptidomimetic inhibitor that specifically targets the β1AR antibodies in the rabbit. Six New Zealand white rabbits were immunized with a β1AR second extracellular loop peptide to produce sympathomimetic β1AR antibodies. A catheter-based electrophysiological study was performed on anesthetized rabbits before and after immunization and subsequent treatment with the RI peptide inhibitor. Each rabbit served as its own control. No sustained arrhythmias were induced at preimmune baseline. At 6 weeks after immunization, there was a marked increase in induced sustained tachyarrhythmias, predominantly sinus tachycardia, which was largely suppressed by the RI peptide. The atrial effective refractory period was shortened significantly in immunized rabbits compared to their preimmune state. The RI peptide reversed and prolonged this shortening. β1AR antibody levels were negatively correlated with the atrial effective refractory period. Postimmune sera-induced β1AR activation in transfected cells in vitro was also blocked by the RI peptide. β1AR-activating autoantibodies are associated with reduction of the atrial effective refractory period and facilitate arrhythmia induction in this model. The RI peptide reversal may have important therapeutic implications in subjects who harbor these autoantibodies.


Hepatitis B viruses: reverse transcription a different way.
Hepatitis B virus (HBV), the causative agent of B-type hepatitis in humans, is the type member of the Hepadnaviridae, hepatotropic DNA viruses that replicate via reverse transcription. Beyond long-established differences to retroviruses in gene expression and overall replication strategy newer work has uncovered additional distinctions in the mechanism of reverse transcription per se. These include protein-priming by the unique extra terminal protein domain of the reverse transcriptase (RT) utilizing an RNA hairpin for de novo initiation of first strand DNA synthesis, and the strict dependence of this process on cellular chaperones. Recent in vitro reconstitution systems enabled first biochemical insights into this multifactorial reaction, complemented by high resolution structural information on the RNA, though not yet the protein, level. Genetic approaches have revealed long-distance interactions in the nucleic acid templates as an important factor enabling the puzzling template switches required to produce the relaxed circular (RC) DNA found in infectious virions. Finally, the failure of even potent HBV RT inhibitors to eliminate nuclear covalently closed circular (ccc) DNA, the functional equivalent of integrated proviral DNA, has spurred a renewed interest in the mechanism of cccDNA generation. These new developments are in the focus of this review.


Teaching Psychopathology in a Galaxy Far, Far Away: The Light Side of the Force.
Star Wars films are among the top box office hits of all time. The films have been popular internationally for almost 40 years. As such, both trainees and attending psychiatrists are likely to be aware of them. This article highlights a vast array of psychopathology in Star Wars films which can be useful in teaching, even when the characters are considered the "good guys". Included are as follows: histrionic, obsessive-compulsive, and dependent personality traits, perinatal psychiatric disorders, prodromal schizophrenia, pseudo-dementia, frontal lobe lesions, pathological gambling, and even malingering. As such, Star Wars has tremendous potential to teach psychiatric trainees about mental health issues.


Role of Non-Perfusion Factors in Mildly Symptomatic Large Vessel Occlusion Stroke.
Uncertainty regarding reperfusion of mildly-symptomatic (minor) large vessel occlusion (LVO)-strokes exists. Recently, benefits from reperfusion were suggested. However, there is still no strong data to support this. Furthermore, a proportion of those patients don't improve even after non-hemorrhagic reperfusion. Our study evaluated whether or not non-perfusion factors account for such persistent deconditioning. Patients with identified minor LVO-strokes (NIHSS ≤ 8) from our stroke alert registry between January-2016 and May-2018 were included. Variables/ predictors of outcome were tested using univariate/multivariate logistic and linear regression analyses. Three month-modified ranking scale (mRS) was used to differentiate between favorable (mRS = 0-2) and unfavorable outcomes (mRS = 3-6). Eighty-one patients were included. Significant differences between the two outcome groups regarding admission-NIHSS and discharge-NIHSS existed (OR = 0.47, 0.49 / p = 0.0005, <0.0001 respectively).The two groups had matching perfusion measures. In the poor outcome group, discharge-NIHSS was unchanged from the admission-NIHSS while in the good outcome group, discharge-NIHSS significantly improved. Admission and discharge NIHSS are independent predictors of outcome in patients with minor-LVO strokes. Unchanged discharge-NIHSS predicts worse outcomes while improved discharge-NIHSS predicts good outcomes. Unchanged NIHSS in the poor outcome group was independent of the perfusion parameters. In literature, complement activation and pro-inflammatory responses to ischemia might account for the progression of stroke symptoms in major-strokes. Our study concludes similar phenomena might be present in minor-strokes. Therefore, discharge-NIHSS may be useful as a clinical marker for future therapies.


HSPA5 promoter polymorphisms and risk of Parkinson's disease in Taiwan.
Endoplasmic reticulum (ER) stress induced by misfolded proteins has been implicated in Parkinson's disease (PD) pathogenesis. A malfunction of unfolded protein response (UPR) to ER stress can result in PD as well as other neurodegenerative diseases. Heat shock 70 kDa protein 5 (HSPA5) is one of the UPR chaperones reactive to ER stress to block the apoptotic process. HSPA5 promoter polymorphisms -415 G/A (rs391957), -370 C/T (rs17840761) and -180 del/G (rs3216733) and their derived haplotypes may affect promoter activity of the gene. This study examines whether these HSPA5 promoter polymorphisms are associated with the risk of Taiwanese PD and the age of disease onset using a case-control study. Polymorphisms -415 G/A and -180 del/G were completely linked in our population (D'=1.00, Delta(2)=1.00). The genotype or allele frequency distribution of each HSPA5 polymorphism was not significantly different between the controls (n=341) and the PD patients (n=393). Neither the linked -415 G/A and -180 del/G nor -370 C/T polymorphism influences PD onset age. Our data suggest that the HSPA5 -415 G/A, -370 C/T, and -180 del/G polymorphisms are unlikely to play a major role in risk of developing PD in Taiwan.


'Hunt the thimble': a study of the radiology of ingested foreign bodies.
The role of radiology in the management of patients with a history of ingested foreign bodies is reviewed in a retrospective study over a 2-year period in a Children's Hospital. If radiography was confined to those children who have a clinical history suggestive of foreign body impaction in the oesophagus, a foreign body aspiration or having swallowed a button battery, the work load and unnecessary radiation arising from this practice could be halved. This study demonstrates another misuse of radiological services.


Prevention of kainic acid seizures-induced changes in levels of nitric oxide and high-energy phosphates by 7-nitroindazole in rat brain regions.
Previous studies using the spin trapping agent N-tert-butyl-alpha-phenylnitrone (PBN) and the antioxidant vitamin E established the involvement of free radicals in kainic acid (KA)-induced neurotoxicity. In the present study, we examined the effects of the neuronal nitric oxide synthase (nNOS) inhibitor 7-nitroindazole (7-NI) to establish a possible role of nitric oxide (NO) in the neurotoxicity caused by KA-induced status epilepticus (SE). A single injection of KA (15 mg/kg, s.c.) induced seizures within 40-45 min, progressing to full seizure activity lasting about 3 h. Following microwave (head-focused) irradiation, perchloric acid extracts of rat brain regions (cortex, amygdala, and hippocampus) were analyzed for citrulline (determinant of NO) and high-energy phosphates (HEP) and their metabolites using high-performance liquid chromatograph (HPLC). KA-induced seizures produced a maximum increase in NO (3- to 6-fold) and a decrease in HEP (ATP 45-51% and phosphocreatine 45-58%) 2 h after KA injection in brain regions tested. 7-NI (50 mg/kg, i.p.) when given alone, reduced citrulline/NO levels (10-24%), while repeat administration of 7-NI (60 min apart) reduced NO levels by 32-49%. Neither application of 7-NI produced changes in HEP levels or toxicity. Pretreatment with 7-NI 30 min before KA injection, delayed the onset of seizures by 15-20 min, and significantly prevented an increase in NO and a decrease in HEP. Repeat administration of 7-NI, i.e. 30 min before and 30 min after KA injection, further increased protection by the delayed onset of seizures, attenuating the increase in NO and the decrease in HEP. Neurotoxicity of seizures involves activation of nNOS and of energy consumption in affected neurons. This increased energy consumption, coupled with decreased energy production caused by NO-induced mitochondrial dysfunction, may be a contributing factor to neuronal injury in KA toxicity.


Motivation as an Axiological Factor in Learning Chinese.
Motivation and a positive attitude play a decisive role in learning any foreign language. This study aims to investigate the motivation behind learning Chinese language in Central Asia and Russia and to identify the main problems related to mastering this language in those countries. The study draws on an anonymous questionnaire survey involving students and multiple oral interviews with Chinese language learners and teachers. The information was collected and analyzed manually by the researchers. The resulting statistical data was generated in Microsoft Excel and then presented as charts and tables. Through a student survey and teacher interviews, the study identified the long-term and short-term motivators for learning Chinese language, namely study (5%), cultural interest (7%), friendship (15%), cross-border communication (20%), travel intentions (25%), and greater employment opportunities (28%). The most common reason for learning the language was a desire to work in China (28%), and the least popular one was to study there (5%). Teachers defined motivation as a major challenge in teaching Chinese language (79%). According to teachers, learners with low motivation and unmotivated individuals are hardly responding to what happens in the classroom. The results of the study may be used as a platform for further research in education, teaching, psychology and linguistics.


Plasma kinetics of free and esterified cholesterol in familial hypercholesterolemia: effects of simvastatin.
The objective of this study was to evaluate the kinetics of both free and esterified forms of cholesterol contained in a emulsion that binds to LDL receptors (LDE) in subjects with heterozygous familial hypercholesterolemia (FH), and the same subjects under the effects of high-dose simvastatin treatment, as compared with a control normolipidemic group (NL). Twenty-one FH patients (44.0 +/- 13.0 yr, 12 females, LDL cholesterol levels 6.93 +/- 1.60 mmol/L) and 22 normolipidemic patients (44.0 +/- 15.0, 10 females, LDL cholesterol levels 3.15 +/- 0.62 mmol/L) were injected intravenously with 14C-cholesteryl ester and 3H-cholesterol. FH patients were also evaluated after 2 mon of 40 or 80 mg/d simvastatin treatment, and plasma samples were collected over 24 h to determine the residence time (RT, in h) of both LDE labels, expressed as the median (25%; 75%). The RT of both 14C-cholesteryl ester and 3H-cholesterol were greater in FH than in NL [FH: 36.0 (20.5; 1191.0), NL: 17.0 (12.0-62.5), P = 0.015; and FH: 52.0 (30.0; 1515.0); NL 20.5 (14.0-30.0) P < 0.0001]. Treatment reduced LDL cholesterol by 36% (P < 0.0001), RT of 14C-cholesteryl ester by 49% (P = 0.0029 vs. baseline), and 3H-cholesterol RT by 44% (P = 0.019 vs. baseline). After treatment, the RT values of 14C-cholesteryl ester in the FH group approached the NL values (P = 0.58), but the RT of 3H-cholesterol was still greater than those for the NL group (P = 0.01). The removal of LDE cholesteryl esters and free cholesterol was delayed in FH patients. Treatment with a high dose of simvastatin normalized the removal of cholesterol esters but not the removal of free cholesterol.


Tutor-Student Partnership in Practice OSCE to Enhance Medical Education.
Training of examiners is essential to ensure the quality of objective structured clinical examination (OSCE). We aimed to study a perceived effectiveness of tutor-student partnership in a practice OSCE module by novice OSCE tutors and medical students. We implemented a practice OSCE at a medical faculty in France with novice tutors and third year medical students as partners. Each tutor (n = 44) served as a partner for the group of 5 students in the conception of the scenario and as an evaluator of the tutored station. Students (n = 303) were involved in the conception of a case and the roles of a physician, evaluator and a simulated patient. Data were obtained through self-assessment questionnaires. Descriptive statistics were used to analyze items of the questionnaires. Free-form answers were coded and analyzed thematically. A total of 36 tutors (82%) and 185 students (61%) responded to the questionnaires. The intervention was well perceived. Thirty-two percent of the tutors reported some difficulties in the assessment of student performance and were disposed to receive further training. Fifty-five percent of the students considered the participation in the OSCE case development appropriate to their level of knowledge, and 70% perceived it as beneficial allowing them to set their learning goals. This initiative provides a relevant method beneficial to OSCE tutors, medical students, and the faculty. Tutors learn how to assess student performance according to expected achievement levels. It allows students to be engaged as partners in co-creation of learning and teaching. The online version contains supplementary material available at 10.1007/s40670-021-01421-9.


[Stereotactic Body Radiation Therapy for less than 3cm (stage I) and 5cm (stage II) inoperable lung tumors: 10 years experience of Montpellier Cancer Institute].
Search for predictive factors on survival and local control for less than 3 centimeters (cm) (stage I) and 5cm (stage II) inoperable lung tumors treated by Stereotactic Body Radiation Therapy (SBRT) in a retrospective monocentric study from Montpellier Cancer Institute (ICM) PATIENTS AND METHOD: Every patients treated at ICM for a stage I or II inoperable lung tumors from 2009 to 2019 were analyzed. One hundred and seventy nine lesions were treated in 176 patients, with a major part (82,7%) in operated due to chronic obstructive pulmonary disease. Median overall survival for all patients was 71,7 months with a 35 months follow-up and the 2 years loco-regional free survival was 94,0 months. Better associated outcomes were stage I (median overall survival 71,7 versus 29,0 months P=0,004 ; HR=2,37 P=0,005), BED≥150Gy (median time-to-progression not reached versus 76,7 months P=0,025), small size of Planning Target Volume (PTV) (HR=0,42 P=0,032 when PTV<15,6 cc). 7,3% of all patients developed radiation pneumonitis. SBRT is associated with an excellent overall survival and a high rate of local control for less than 3cm (stage I) and 5cm (stage II) lung tumors but a low rate of toxicities. For these patients with many comorbidities, BED over 150Gy seems to be associated with a better loco-regional free survival, while cause of death is often other than lung cancer.


Proton pump inhibitors use and dementia risk: a meta-analysis of cohort studies.
The aim of this study was to explore the relationship between proton pump inhibitors use and the risk of dementia. A comprehensive literature search was conducted in English and Chinese databases from origination to December 2018. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with a random-effects model. Subgroup analyses and sensitivity analyses were also conducted. Cochran's Q test and the I2 statistic were used to evaluate the heterogeneity. Publication bias was assessed by Begg's test and Egger's test. Six studies were included, which contained a total of 166,146 participants. The overall result demonstrated a significant increase in dementia risk with proton pump inhibitors use (HR = 1.29, 95% CI = 1.12-1.49). In subgroup analyses, a significant association was detected between proton pump inhibitors use and the risk of dementia in Europe (HR = 1.46, 95% CI = 1.23-1.73) and among participants aged ≥ 65 years (HR = 1.39, 95% CI = 1.17-1.65). For the factor follow-up time ≥ 5 years, the pooled HR was 1.28 (95% CI = 1.12-1.46), demonstrating a 1.28-fold increase in the risk of dementia among proton pump inhibitors users. In the case of regional impact, participants from Europe showed an overall pooled HR estimate of 1.46 (95% CI = 1.23-1.73). There was no evidence of publication bias. The overall result of this meta-analysis supports the hypothesis that proton pump inhibitors increase the risk of dementia. Furthermore, high-quality cohort studies are needed to confirm these findings.


Anti-human-TIGIT agonistic antibody ameliorates autoimmune diseases by inhibiting Tfh and Tph cells and enhancing Treg cells.
T cells play important roles in autoimmune diseases, but it remains unclear how to optimally manipulate them. We focused on the T cell immunoreceptor with Ig and ITIM domains (TIGIT), a coinhibitory molecule that regulates and is expressed in T cells. In autoimmune diseases, the association between TIGIT-expressing cells and pathogenesis and the function of human-TIGIT (hu-TIGIT) signalling modification have not been fully elucidated. Here we generated anti-hu-TIGIT agonistic monoclonal antibodies (mAbs) and generated hu-TIGIT knock-in mice to accurately evaluate the efficacy of mAb function. Our mAb suppressed the activation of CD4+ T cells, especially follicular helper T and peripheral helper T cells that highly expressed TIGIT, and enhanced the suppressive function of naïve regulatory T cells. These results indicate that our mAb has advantages in restoring the imbalance of T cells that are activated in autoimmune diseases and suggest potential clinical applications for anti-hu-TIGIT agonistic mAbs as therapeutic agents.


Modulation of auditory-evoked potentials recorded in the inferior colliculus by GABAergic mechanisms in the basolateral and central nuclei of the amygdala in high- and low-anxiety rats.
The central nucleus of the inferior colliculus (CIC) is an important relay station for acoustic information that has an aversive connotation. γ-Aminobutyric acid (GABA) mechanisms exert tonic inhibitory control over the neural substrates of aversion in the midbrain tectum. Recent evidence obtained in this laboratory showed that low- (LA) and high-anxiety (HA) rats selected in the elevated plus maze (EPM) exhibit low and high auditory-evoked potential (AEP) amplitudes, respectively, recorded in the CIC when subjected to loud click noises. The present study investigated the eventual top-down regulation exerted by GABA mechanisms in the basolateral (BLA) and central (CeA) nuclei of the amygdala on aversive information processing at the level of the CIC. The GABA inhibitors bicuculline (10 ng/0.2 μl) and semicarbazide (7 μg/0.2 μl) and GABA agonist muscimol (1 nmol/0.2 μl) were locally infused into the CeA and BLA in rats subjected to an AEP recording procedure that used electrodes implanted in the CIC. Freezing behavior induced by these intra-amygdala injections was also measured. The results confirmed that the processing of aversive acoustic information depends on anxiety levels in LA and HA rats. Freezing behavior and the increased AEPs induced by intra-CeA injections of bicuculline and semicarbazide were more pronounced in HA than in LA animals. Intra-CeA injections of muscimol did not change either the basal levels of freezing or AEP amplitudes in LA and HA rats. However, freezing and the enhanced AEPs were of small magnitude following intra-BLA injections of bicuculline and semicarbazide. An unexpected magnitude of freezing and enhanced AEPs was observed following muscimol infusions into the BLA in HA rats. GABA mechanisms in the CeA appear to play a regulatory role in aversive states, and inactivation of the BLA with muscimol produced pro-aversive effects, suggesting that inactivation of the BLA removed the descending inhibitory control of the neural substrates of aversion in the CIC exerted by the BLA. Because the latter effects were observed only in HA rats, a dysfunctional BLA may underlie the differences between trait and state anxiety.


Derivation and characterization of lentoid bodies and retinal pigment epithelial cells from monkey embryonic stem cells in vitro.
For cell replacement therapies of retinal diseases, the most-needed cells are retinal pigment epithelial cells and photoreceptor cells; lens cells are needed for replacement of the cataract. Stromal cell-derived inducing activity induces the differentiation of mouse embryonic stem (ES) cells into neural cells, including midbrain tyrosine hydroxylase-positive dopaminergic neurons, and ocular cells; the method also works with primate ES cells. We describe the methods to induce retinal pigment epithelial and lens cells from monkey ES cells using stromal cell-derived inducing activity and show the characteristics of those cells in vitro and in vivo.


Relationship between chamber mechanical properties and mean pressure-mean flow diagram of the left ventricle.
We undertook a theoretical analysis of the source resistance of the left ventricle represented in a mean pressure-mean flow (P-Q) diagram, using the chamber properties established in terms of the pressure-volume relationship. This analysis showed that P-Q pairs of points should lie above the linear function proposed by Elzinga and Westerhof. A third-order polynomial function would theoretically explain better than a linear relation or a parabolic fit the curved shape of experimentally obtained P-Q relationships. The analysis resolves the discrepancy between Elzinga and Westerhof's theoretical concept of linear source resistance and the actual nonlinear P-Q relationship.


Health literacy characteristics of over-the-counter rapid antigen COVID-19 test materials.
The United States Food & Drug Administration's emergency authorized use, in December 2020, of over-the-counter (OTC) rapid antigen COVID-19 tests was a pandemic control milestone. To assess health literacy-related characteristics of OTC rapid antigen COVID-19 test materials. Between September-December 2021, we identified eleven (n = 11) OTC rapid antigen COVID-19 tests available for purchase in the US. We assessed readability (Flesch Reading Ease and Fernández-Huerta), formatting and layout features of English- and Spanish-language step-by-step OTC rapid antigen COVID-19 test package insert instructions. Video-based step-by-step OTC rapid antigen COVID-19 test instructions were evaluated for understandability and actionability (Patient Education Materials Assessment Tool for Audiovisual Materials [PEMAT-A/V]), overall quality (Global Quality Scale [GQS]) and cultural diversity and inclusiveness. Descriptive analyses were performed using IBM® Statistical Package for the Social Sciences. Nine (81.8%) OTC rapid antigen COVID-19 tests included English-language (≈8th-9th reading grade level) step-by-step instructions, while 4 included Spanish-language (≈10th-12th reading grade level) instructions. On average, instructions were printed on a tabloid sized piece of paper, with text size ranging from 4 to 12 point and including nearly 20 illustrations. English-language step-by-step OTC rapid antigen COVID-19 test video-based instructions (n = 6) ranged from 1:04 to 5:41 min with PEMAT-A/V scores ranging from 80% to 100%. As indicated by GQS scores, English-language videos were of high quality (5 videos scored 5/5; 1 video scored 4/5). One COVID-19 test product manufacturing website included Spanish-language video-based instructions (time = 4:59 min; PEMAT-A/V = 100%; GQS = 5). OTC COVID-19 test step-by-step instructions-both package inserts and video-based-included features shown to foster patient understanding and facilitate proper use. Moving forward, greater attention needs to be placed on expanding both Spanish-language and video-based OTC COVID-19 test material availability to improve accessibility across diverse populations.


[SMN1 Gene Point Mutations in Type I-IV Proximal Spinal Muscular Atrophy Patients with a Single Copy of SMN1].
Type I-IV proximal spinal muscular atrophy (SMA) is one of the most common autosomal-recessive diseas- es, which are characterized in the majority of cases by a severely disabling course. Proximal SMA results from mutations in the telomeric copy of SMN-SMN1 gene. Major SMN1 gene mutation types are deletions in the exons 7 and/or 8, which were revealed to be in the homozygous state in 95% of patients. Deletions in the in- dicated exons of SMN1 gene were revealed in a compound-heterozygous state in combination with intragenic point mutations in the remainder 5% of proximal SMA cases. In the present study, we conducted an analysis of point mutations in eight patients with type I-III proximal SMA phenotype, which had a deletion in 7-8- exons of SMN1 gene in the heterozygous state. We revealed seven different mutations, two of which (c.824G > C (p.Gly275A1a) and c.825-2A > T) are described here for the first time. In addition, mutation c.824G > C (p.Gly275A1a) was observed twice in the examined sample. In seven cases a heterozygous carrier of point mutations was one of the parents of the affected children (in six cases, the father; in one case, the mother). Only one mutation, c.43C > T (p.Gln15X), emerged de novo in a genital cell of the child's father.


Stereotactic Laser Ablation of Glioblastoma.
The previous decade has seen an expansion in the use of laser interstitial thermal therapy (LITT) for a variety of pathologies. LITT has been used to treat both newly diagnosed and recurrent glioblastoma (GBM), especially in deep-seated, difficult-to-access lesions where open resection is otherwise infeasible or in patients who would not tolerate craniotomy. This review aims to describe the current state of the technology and operative technique, as well as summarize the outcomes data and future research regarding LITT as a treatment of GBM.


Audit of the informed consent process as a part of a clinical research quality assurance program.
Audits of the informed consent process are a key element of a clinical research quality assurance program. A systematic approach to such audits has not been described in the literature. In this paper we describe two components of the audit. The first is the audit of the informed consent document to verify adherence with federal regulations. The second component is comprised of the audit of the informed consent conference, with emphasis on a real time review of the appropriate communication of the key elements of the informed consent. Quality measures may include preparation of an informed consent history log, notes to accompany the informed consent, the use of an informed consent feedback tool, and the use of institutional surveys to assess comprehension of the informed consent process.


Deep learning and wing interferential patterns identify Anopheles species and discriminate amongst Gambiae complex species.
We present a new and innovative identification method based on deep learning of the wing interferential patterns carried by mosquitoes of the Anopheles genus to classify and assign 20 Anopheles species, including 13 malaria vectors. We provide additional evidence that this approach can identify Anopheles spp. with an accuracy of up to 100% for ten out of 20 species. Although, this accuracy was moderate (> 65%) or weak (50%) for three and seven species. The accuracy of the process to discriminate cryptic or sibling species is also assessed on three species belonging to the Gambiae complex. Strikingly, An. gambiae, An. arabiensis and An. coluzzii, morphologically indistinguishable species belonging to the Gambiae complex, were distinguished with 100%, 100%, and 88% accuracy respectively. Therefore, this tool would help entomological surveys of malaria vectors and vector control implementation. In the future, we anticipate our method can be applied to other arthropod vector-borne diseases.


A Mobile Phone Application Enabling Visually Impaired Users to Find and Read Product Barcodes.
While there are many barcode readers available for identifying products in a supermarket or at home on mobile phones (e.g., Red Laser iPhone app), such readers are inaccessible to blind or visually impaired persons because of their reliance on visual feedback from the user to center the barcode in the camera's field of view. We describe a mobile phone application that guides a visually impaired user to the barcode on a package in real-time using the phone's built-in video camera. Once the barcode is located by the system, the user is prompted with audio signals to bring the camera closer to the barcode until it can be resolved by the camera, which is then decoded and the corresponding product information read aloud using text-to-speech. Experiments with a blind volunteer demonstrate proof of concept of our system, which allowed the volunteer to locate barcodes which were then translated to product information that was announced to the user. We successfully tested a series of common products, as well as user-generated barcodes labeling household items that may not come with barcodes.


The gut microbiota composition has no predictive value for the endotoxin-induced immune response or development of endotoxin tolerance in humans invivo.
It is largely unknown whether the gut microbiome regulates immune responses in humans. We determined relationships between the microbiota composition and immunological phenotypes in 108 healthy volunteers, using 16S sequencing, an ex vivo monocyte challenge model, and an in vivo challenge model of systemic inflammation induced by lipopolysaccharide (LPS). Significant associations were observed between the microbiota composition and ex vivo monocytic cytokine responses induced by several stimuli, most notably IL-10 production induced by Pam3Cys, Pseudomonas aeruginosa and Candida albicans, although the explained variance was rather low (0.3-4.8%). Furthermore, a number of pairwise correlations between Blautia, Bacteroides and Prevotella genera and cytokine production induced by these stimuli were identified. LPS administration induced a profound transient in vivo inflammatory response. A second LPS challenge one week after the first resulted in a severely blunted response, reflecting endotoxin tolerance. However, no significant relationships between microbiota composition and in vivo parameters of inflammation or tolerance were found (explained variance ranging from 0.4 to 1.5%, ns). The gut microbiota composition explains a limited degree of variance in ex vivo monocytic cytokine responses to several pathogenic stimuli, but no relationships with the LPS-induced in vivo immune response or tolerance was observed.


Ultrasound velocity through the phalanges in normal and osteoporotic patients.
Quantitative ultrasound (US) measurements have been shown to be a new technique assessing bone status. This study aimed to assess a new US instrument, the DBM Sonic 1200(R) (IGEA) which permits the measurement of the speed of sound in the proximal phalanges (SOSp) of the hand. The results obtained were compared with DXA (SOPHOS) and US measurements at the calcaneus (Achilles(R) LUNAR). The in vivo precision expressed by coefficient of variation was 0.91%. Ultrasound measurements of phalanges were significantly correlated with BMD in the entire group of 90 subjects: osteoporotic patients (n = 47) and controls (n = 43) (r = 0.44, femoral neck and 0.45, lumbar spine, P < 0.01). A significant correlation was also found in the control group (r = 0.33, lumbar spine and 0.38, femoral neck, P < 0.05) but not in the osteoporotic group (r = 0.3, lumbar spine and 0.17, femoral neck, P > 0.05). Mean values for 31 postmenopausal, osteoporotic women and age-matched controls showed a significant decrease in US measurements at the phalanges (P < 0.05) and the calcaneus (P < 0.01) as well as bone mineral density (BMD) at the spine and femoral neck (P < 0.01) in the osteoporotic group. A decision threshold for a sensitivity of 80% for osteoporotic fractures resulted in a specificity value of only 37% for SOSp, between 53 to 65% for calcaneus US measurements and 45 to 56% for BMD. The Z score, the odds ratio, the ROC curves, and areas under the curves plotted for the subgroup of 31 fractures and their healthy controls showed poorer values for SOSp than BMD and calcaneus US measurements. In conclusion, US measurements of phalanges seem to be less efficient than calcaneus US and BMD measurements to distinguish osteoporotic from healthy women. Other studies and also prospective studies are required to assess the interest in fracture risk assessment.


Isolation, structural elucidation, and insights into the anti-inflammatory effects of triterpene saponins from the leaves of Stauntonia hexaphylla.
Using various chromatographic techniques, 23 triterpene saponins (1-23) were isolated from an ethanol extract of Stauntonia hexaphylla, including two new compounds (12 and 15). Their chemical structures were established by comprehensive spectroscopic methods such as 1D- and 2D-NMR, and HR-ESI-MS, and chemical reactions. The anti-inflammatory activities of the isolated saponins were determined using the nitric oxide (NO) assay. Compound 13 exhibited the greatest inhibitory effect (IC50 = 0.59 μM). In addition to NO, compound 13 suppressed the secretion of PGE2, IL-1β, and IL-6, but not TNF-α, and inhibited the protein expression of iNOS and COX-2 in LPS-activated RAW264.7 cells. The chemical derivatives of the isolated compounds were studied using structure-activity relationships. The results suggested that compound 13 isolated from S. hexaphylla might be useful for treating inflammation. This is the first comprehensive study of saponins from the leaves of S. hexaphylla based on anti-inflammatory extract screening guidelines.


Large intestine as content of congenital inguinal hernia: A case report of intestinal obstruction.
Hernias containing appendix, caecum and transverse colon are uncommon in contrast with usual inguinal hernias containing small intestine. The patient usually presents with inguinoscrotal swelling. We present a case of a 2 months old male child presented with inguinoscrotal swelling, vomiting with abdominal distention. On Ultrasonography (USG) of the scrotum, protrusion of the abdominal cavity contents through the right inguinal canal into the scrotum of approximately 3.4 cm × 0.7 cm was found which indicates right inguinal hernia. On the opening of the hernia sac during surgical management, the appendix, caecum and transverse colon were lying inside the hernia sac. Open Herniotomy was performed and the abdomen was closed in layers. Postoperative period of the patient was uneventful. Congenital inguinal hernia in the child occurs mostly due to persistent processus vaginalis. History and clinical examination reveals the appearance of lump in the inguinal region or scrotum. Preoperative Ultrasonography can be used to supplement the physical examination and increase the accuracy of its diagnosis. Although the laparoscopic approach is increasingly used nowadays, open hernia repair is preferred in young children. Appendix, caecum and transverse colon are unusual contents of an inguinal hernia. Open herniotomy combined with relieving of the intestinal obstruction is the treatment of choice in young children.


Impact of a person-centred community rehabilitation service on outcomes for individuals with a neurological condition.
To evaluate the impact of a person-centred, community rehabilitation service on outcomes for people with a neurological condition, in the first year of service. A prospective, observational, pre-post study was conducted with 206 people who had a neurological condition and attended the rehabilitation service to restore function (e.g., Stroke); maximize recovery in an ongoing situation (e.g., Spina Bifida); or maximize function and independence while preparing for inevitable decline (e.g., Parkinson's Disease). Outcomes were measured via self-report questionnaires, prior to, and following three months of rehabilitation. The primary outcome was achievement of self-identified goals, measured by the Patient-Specific Functional scale. Secondary outcomes included the Lawton Instrumental Activities of Daily Living (IADL) scale, EQ-5D-5L European Quality of Life scale, and ICECAP-O - Index of Capability for Older Adults and health and medical resource use. Participants demonstrated significant goal achievement and a significant reduction in health and medical resource use. There were small positive changes in the Lawton IADL, EQ-5D-5L, and ICECAP-O however these changes were not significant. In the first year of operation, the community rehabilitation service made a significant impact on outcomes for individuals with a neurological condition. Further research is required to identify appropriate measures of activities of daily living and quality of life that reflect person-centred rehabilitation outcomes for restoring function, maximizing function, or preparing for functional decline. Implications for Rehabilitation Self-identified goals are an important guide for achievement of meaningful outcomes for individuals with a neurological condition. Person-centred outcome measures are required to evaluate the benefits of a person-centred community rehabilitation service for individuals with a neurological condition.


MEK inhibition in the treatment of advanced melanoma.
The RAS-RAF-MEK-ERK pathway is considered to be the most important signal transduction pathway in melanoma, and alterations in this pathway via various genetic mutations, such as BRAF and NRAS mutations, are known to be important drivers of melanomagenesis. As MEK is an essential intermediary kinase protein within this pathway, inhibition of MEK has been of a great interest as a molecular target therapy in melanoma. In fact, trametinib, a selective MEK inhibitor, has been shown to have a survival benefit over cytotoxic chemotherapy in patients with V600 BRAF-mutant metastatic melanoma, leading to the FDA approval for this patient population. MEK inhibitors may also be useful in treatment of advanced melanoma harboring other genetic mutations, such as NRAS and GNAQ/GNA11 mutations. Here, we review and discuss the preclinical and clinical data regarding MEK inhibitors and their role in the treatment of advanced melanoma.


Progress of ICD-10 (F) family in Japan: research, field trials and publications.
The Nagasaki Center, designated as a World Health Organization (WHO) Collaborating Center in 1979, has taken the lead in generalizing ICD-10 (F) in Japan. The progress of ICD-10 (F)-related research, trials and publications has been as follows. The field trials of ICD-10 Clinical Descriptions and Diagnostic Guidelines (CDDG) 1986 draft were carried out with 129 patients by 61 clinicians in five institutions coordinated by Tokyo Medical and Dental University and Nagasaki University in 1988. The Japanese version of ICD-10 CDDG was published by Tooru et al. in February 1993. The field trials of ICD-10 Diagnostic Criteria for Research (DCR) 1990 version were conducted with 847 patients by 169 clinicians at 28 institutions and 2299 assessments were obtained. The Japanese version of ICD-10 DCR final version was published by Nakane et al. in May 1994. The Japanese version of the Glossaries and Conversion Tables between ICD-9 and ICD-10 was published by Nakane et al. in October 1994. The field trials of ICD-10 Multiaxial Presentation were conducted with 34 psychiatrists at six institutions in 1993 and the total of 676 assessments was obtained, and the adequacy and usefulness of the text were examined.


Hypoxia enhances high-voltage-activated calcium currents in rat primary cortical neurons via calcineurin.
Hypoxia regulates neuronal ion channels, sometimes resulting in seizures. We evaluated the effects of brief sustained hypoxia (1% O(2), 4h) on voltage-gated calcium channels (VGCCs) in cultured rat primary cortical neurons. High-voltage activated (HVA) Ca(2+) currents were acquired immediately after hypoxic exposure or after 48h recovery in 95% air/5% CO(2). Maximal Ca(2+) current density increased 1.5-fold immediately after hypoxia, but reverted to baseline after 48h normoxia. This enhancement was primarily due to an increase in L-type VGCC activity, since nimodipine-insensitive residual Ca(2+) currents were unchanged. The half-maximal potentials of activation and steady-state inactivation were unchanged. The calcineurin inhibitors FK-506 (in the recording pipette) or cyclosporine A (during hypoxia) prevented the post-hypoxic increase in HVA Ca(2+) currents, while rapamycin and okadaic acid did not. L-type VGCCs were the source of Ca(2+) for calcineurin activation, as nimodipine during hypoxia prevented post-hypoxic enhancement. Hypoxia transiently potentiated L-type VGCC currents via calcineurin, suggesting a positive feedback loop to amplify neuronal calcium signaling that may contribute to seizure generation.


Contributions of Modifiable Risk Factors to Dementia Incidence: A Bayesian Network Analysis.
To determine and compare the contributions of modifiable risk factors (RFs) with the prevention of dementia in older adults. A systematic review and Bayesian network meta-analysis (NMA). The observational group was set as a reference to collect all existing RFs and compare them with each other. An exhaustive and comprehensive literature search strategy was used to identify relevant prospective cohort studies from several online databases from their inception to May 1, 2019. Participants without dementia were adults aged greater than 50 years. The required data were extracted from the eligible studies to facilitate the Bayesian NMA. Forty-three cohort studies with 277,294 participants were included in this NMA. Using the observation group as the reference, all defined RFs, except for antioxidants, were associated with lower risks of all-cause dementia [no sleep disturbances (odds ratio, OR 0.43, 95% credible interval, CrI 0.24-0.62), a high level of education (OR 0.50, 95% CrI 0.34-0.66), no history of diabetes (OR 0.57, 95% CrI 0.36-0.78), nonobese patients (OR 0.61, 95% CrI 0.39-0.83), no smoking history (OR 0.62, 95% CrI 0.45-0.79), living with family members (OR 0.67, 95% CrI 0.45-0.89), participation in physical exercise (OR 0.73, 95% CrI 0.46-0.94), abstinence from drinking (OR 0.78, 95% CrI 0.56-0.99), and no history of hypertension (OR 0.80, 95% CrI 0.65-0.96)]. The findings provide reliable support for the hypothesis that modifiable somatic and lifestyle factors are strong predictors of all-cause dementia.


Genome-wide identification and expression analysis of BrAGC genes in Brassica rapa reveal their potential roles in sexual reproduction and abiotic stress tolerance.
AGC protein kinases play important roles in regulating plant growth, immunity, and cell death. However, the function of AGC in Brassica rapa has not yet been clarified. In this study, 62 BrAGC genes were identified, and these genes were distributed on 10 chromosomes and divided into six subfamilies. Analysis of gene structure and conserved motifs showed that the activation segment of BrAGC genes was highly conserved, and genes of the same subfamily showed higher sequence and structural similarity. Collinearity analysis revealed that BrAGCs were more closely related to AtAGCs than to OsAGCs. Expression profile analysis revealed that BrAGCs were preferentially expressed in flowers and BrAGC26, BrAGC33, and BrAGC04 were preferentially expressed in the stigma; the expression of these genes was significantly upregulated after self-incompatibility pollination, and the expression of BrAGC13 and BrAGC32 was significantly upregulated after cross-pollination. In addition, several typical cis-elements involved in the stress response were identified in BrAGC promoters. The expression levels of BrAGC37 and BrAGC44 significantly varied under different types of abiotic stress. Collectively, we identified that BrAGC26, BrAGC33, and BrAGC44 have the greatest potential in regulating pollen-pistil interaction and abiotic stress tolerance, respectively. Our findings will aid future functional investigations of BrAGCs in B. rapa.


Phytic acid attenuates inflammatory responses and the levels of NF-κB and p-ERK in MPTP-induced Parkinson's disease model of mice.
Phytic acid (PA) is a naturally occurring constituent which exhibits protective action in Parkinson's disease (PD). Inflammation in the central nervous system (CNS) is strongly associated with neuronal death in PD. However, the molecular mechanism of the protective effect of PA in PD has not been fully elucidated. In this study, we tried to testify the protection of PA on neuron and inflammatory responses in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model of mice and investigated the mechanism involved in them. Motor behavior test and tyrosine hydroxylase (TH) immunohistochemistry method showed PA significantly inhibited MPTP-induced dopaminergic cell loss in the substantia nigra (SN). Moreover, using immunohistochemistry method and quantitative polymerase chain reaction (qPCR), microglial activation and inducible nitric oxide synthase (iNOS) were found to be markedly repressed by PA. Via western blot assay, expressions of nuclear factor κB (NF-κB) and phosphorylated extracellular signal-regulated kinase (p-ERK) were significantly attenuated by PA. In conclusion, it is suggested that PA has a neuroprotective effect in MPTP-induced PD model and the neuroprotection is correlated with its anti-inflammatory effect which may be associated with suppression of pathways that involved in NF-κB and p-ERK.


Transanal endoscopic video-assisted excision: application of single-port access.
Transanal endoscopic microsurgery is a safe and efficacious surgical approach for local excision of benign adenomas and early-stage rectal cancer. However, utilization of the technique has been limited due to the unavailability of high-priced specialized instrumentation at many institutions and the technically demanding training required. To avoid these obstacles, we have explored an alternative approach called Transanal Endoscopic Video-Assisted excision, which combines the merits of singleport access and local transanal excision. A disposable single-incision port is inserted into the anal canal for transanal access. The port contains 3 cannulae for introducing instrumentation into the rectal lumen, and a supplementary cannula for carbon dioxide insufflation. Pneumorectum results in rectal distention and optimizes the visual field during the procedure. Standard laparoscopic instrumentation is utilized for visualization and transanal excision of rectal pathologies. Transanal endoscopic video-assisted excision is an innovative approach to local excision of benign and malignant rectal lesions. The approach averts several of the pitfalls commonly experienced with transanal endoscopic microsurgery. Continued investigation and development of this novel modality will be important in establishing its role in minimally invasive surgery.


Spontaneous intracranial extradural haematoma associated with frontal sinusitis and orbital involvement.
Intracranial extradural hematoma is usually traumatic. Rarely, it can occur spontaneously associated with coagulative disorders (spontaneous or iatrogenic), dural vascular malformation, cranio-facial tumors and infections. In these cases, spontaneous extradural hematoma (SEH) is a serious event that needs to be recognized and managed in time to avoid fatal outcome. The authors report a case of a 12-year-old young girl with a 3-year history of right frontal sinusitis treated urgently for a right frontal extradural hematoma involving the orbit. Diagnosis and management of this case is discussed reviewing the pertinent literature.


[Morphometric findings in the microcirculatory bed of the sigmoid serosa during the fetal period in man].
During fetal life, formation and arrangement of the microcirculatory bed in the serous membrane of the sigmoid colon correspond to the growth and functioning of the latter at different stages of ontogenesis. Two periods in the development of the microcirculatory bed of the serous membrane of the sigmoid colon are revealed: the first period coincides with the first half of the fetal development when capillary growth is considerable, i.e. with the growth of metabolic part in the microcirculatory bed; the second period coincides with the second half of the fetal development when intensified growth of the sigmoid portion of the large intenstine and its transport sections in the microcirculatory bed (arterioles, precapillaries, postcapillaries, venules) are observed.


Detection of proximal colorectal cancers through analysis of faecal DNA.
Detection of mutations in faecal DNA represents a promising, non-invasive approach for detecting colorectal cancers in average-risk populations. One of the first practical applications of this technology involves the examination of microsatellite markers in sporadic cancers with mismatch-repair deficiencies. Since such cancers nearly always occur in the proximal colon, this test might be useful as an adjunct to sigmoidoscopy, which detects only distal colorectal lesions. We report here the first in-depth analysis of faecal DNA from patients with proximal cancers to determine the feasibility, sensitivity, and specificity of this approach. Using a sensitive method for microsatellite mutation detection, we found that 18 of 46 cancers had microsatellite alterations and that identical mutations could be identified in the faecal DNA of 17 of these 18 cases.


Eliciting Expressions of Emotion: An Exploratory Analysis of Alexithymia in Adults with Autism Utilising the APRQ.
This study examined alternative methods for detecting alexithymia to the Toronto Alexithymia Scale-20 (TAS-20) by comparing the emotional linguistic performance of ASD and NT samples (n = 32 in each) on the Alexithymia Provoked Responses Questionnaire (APRQ). We utilised both the LIWC and tidytext approaches to linguistic analysis. The results indicate the ASD sample used significantly fewer affective words in response to emotionally stimulating scenarios and had less emotional granularity. Affective word use was correlated with ASD symptomatology but not with TAS-20 scores, suggesting that some elements of alexithymia are not well detected by the TAS-20 alone. The APRQ, in combination with the tidytext package, offers significant potential for sophisticated exploration of emotional expression in ASD.


Release of cell surface proteoglycan from chondrocytes by interleukin-1.
A cell culture model was developed to assess factors that can protect cartilage from recombinant human interleukin-1 alpha (IL-1)-induced breakdown. IL-1 (0.01-10 ng/ml) caused a dose-dependent release of cell surface proteoglycan into the medium of bovine and rabbit articular chondrocytes. Sulfated glycosaminoglycan (S-GAG) was detected in the medium and on the cell surface by a dimethlymethylene blue assay. The redistribution of the cell surface S-GAG to the medium compartment required protein synthesis because it was inhibited by cycloheximide and was time-dependent (> 5 h). Although the release was most likely due to de novo synthesis of proteases, standard protease inhibitors failed to prevent the release even when used in combination. TGF-beta and IGF-I increased the amount of S-GAG in both the medium and cell surface compartments, but did not protect from IL-1-induced release. This method has an advantage over a cartilage model of IL-1-induced matrix release because the drug and cytokine exposure time is reduced and the variability is less.


Impact of aging on heat shock protein expression in the substantia nigra and striatum of the female rat.
Many heat shock proteins are chaperones that help refold or degrade misfolded proteins and battle apoptosis. Because of their capacity to protect against protein misfolding, they may help keep diseases of aging at bay. A few reports have examined heat shock proteins (eg. Hsp25, Hsp60, Hsp70, and heat shock cognate 70 or Hsc70) as a function of age in the striatum and nigra. In the present study, we examined the impact of aging on Hsp25, heme oxygenase 1 (HO1 or Hsp32), Hsp40, Hsp60, Hsc70, Hsc/Hsp70 interacting protein (Hip), 78 kDa glucose-regulated protein (GRP78), Hsp90, and ubiquitinated proteins in the nigra and striatum of the female rat by infrared immunoblotting. Female animals are not typically examined in aging studies, adding further to the novelty of our study. Striatal HO1 and Hsp40 were both higher in middle-aged females than in the oldest group. Hsp60 levels were also highest in middle age in the nigra, but were highest in the oldest animals in the striatum. Striatal levels of Hsc70 and the co-chaperone Hip were lower in the oldest group relative to the youngest animals. In contrast, Hsp25 rose with advancing age in both regions. Hsp25 was also colocalized with tyrosine hydroxylase in nigral neurons. Ubiquitinated proteins exhibited a trend to rise in the oldest animals in both regions, and K48 linkage-specific ubiquitin rose significantly from 4-6 to 16-19 months in the striatum. Our study reveals a complex array of age-related changes in heat shock proteins. Furthermore, the age-related rises in some proteins, such as Hsp25, may reflect endogenous adaptations to cellular stress.


Integrated sample collection and handling for drug discovery bioanalysis.
An integrated sample handling process for drug discovery bioanalysis is described. The streamlining of study design, sample collection and automatic bioanalytical sample processing is demonstrated. Specific details for the entire procedure regarding the time saved, ease of automation and integration are defined. Details of sample handling involved a sample collection map, sample collection formatting and volume, dilution schemes for high concentration samples, choice of biological fluid and evaluating the capabilities of two liquid-handling workstations. Numerous comparisons were conducted between the new approaches and the conventional sample handling approaches. The precision and accuracy obtained from the new integrated sample handling process were comparable to those obtained from a conventional approach, as were pharmacokinetic profiles and parameters. This new sampling process greatly improved the efficiency of drug discovery bioanalysis. The integration of pre-clinical protocol design, sample collection and bioanalysis processes was also achieved.


Indole-3-acetic acid antagonists of the prostaglandin D2 receptor CRTH2.
Prostaglandin D2 (PGD2) acting at the CRTH2 receptor (chemoattractant receptor-homologous molecule expressed on Th2 cells) has been linked with a variety of allergic and other inflammatory diseases. We describe a family of indole-1-sulfonyl-3-acetic acids that are potent and selective CRTH2 antagonists that possess good oral bioavailability. The compounds may serve as novel starting points for the development of treatments of inflammatory disease such as asthma, allergic rhinitis, and atopic dermatitis.


Wild-type Escherichia coli producing microcins B17, D93, J25, and L; cloning of genes for microcin L production and immunity.
For the first time, an Escherichia coli strain producing four microcins (Mcc), B17, D93, J25, and L, and showing immunity to Mcc V was isolated and characterized. Each of the gene clusters encoding the production of Mcc B17, D93, and L was cloned separately. The gene cluster for Mcc L was cloned within a 13.5-kb HindIII-SalI fragment, which includes the Mcc V immunity gene, cvi.


Effect of a polyherbal formulation cream on diabetic neuropathic pain among patients with type 2 diabetes - A pilot study.
Painful diabetic neuropathy is a common complication of diabetes and can severely limit patients' daily functions. The aim of this pilot study was to evaluate the safety and effect of using a polyherbal formulation in reducing the symptoms of diabetic neuropathic pain in comparison with placebo among patients with type 2 diabetes. A total of 50 (M:F = 33:17) consecutive type 2 diabetes patients with painful diabetic neuropathy were enrolled in this study. All these patients had either two or more symptoms of diabetic neuropathy such as pain, burning and pricking sensations and numbness in their feet. They were randomly assigned to two groups: group 1 (n = 26) patients were treated with polyherbal formulation cream and group 2 (n = 24) patients were administered placebo. The patients were followed up for six months. Changes in the symptoms of painful diabetic neuropathy of each patient were recorded at baseline, third and sixth month using the Diabetic Neuropathic Score. The mean age of the patients, duration of diabetes and glycated haemoglobin (HbA 1c ) were similar in both groups at baseline. During follow up visits, there was a decrease in the HbA 1c levels in the study and control groups. The symptoms of painful diabetic neuropathy were also similar in both groups at baseline. A significant decrease in symptoms of neuropathic pain was observed among the group of patients treated with polyherbal formulation cream (76.9 per cent) compared to the placebo-treated group (12.5 per cent) (P<0.001), at the end of the final follow up. In this pilot study polyherbal formulation cream was found to be effective as well as safe to treat painful diabetic neuropathy. However, its long term use needs to be evaluated for any further effectiveness and side effects.


Statistical mechanical analysis of Raman spectroscopic order parameter changes in pressure-induced lipid bilayer phase transitions.
The statistical mechanical cluster theory of Fisher as applied by Kanehisa and Tsong to phospholipid bilayers is modified to describe the effects of hydrostatic pressure on the state of an aqueous dispersion of the phospholipid dipalmitoyl phosphatidylcholine. A high pressure Raman scattering cell has been built to obtain the Raman spectra of aqueous dispersions of phospholipids as a function of the applied hydrostatic pressure from 0 to 100 atmospheres. Predicted thermal and pressure-induced phase transitions are compared with an experimentally obtained Raman order parameter derived from the ratio of two bands in the C-H stretching region of the Raman spectrum of the sample. The parameters of the theory are adjusted to obtain a satisfactory fit of the Raman order parameter versus temperature. The theory is then found to give an excellent prediction of the observed pressure dependence of the Raman order parameter with no changes in the adjustable parameters. The implications of the success of the theoretical fit is discussed. Particularly of interest is the rather high value of the critical temperature, Tc, for lipid bilayers which is predicted by the model.


Socioeconomic Inequalities in Novel NSCLC Treatments During the Era of Tumor Biomarker-Guided Therapy: A Population-Based Cohort Study in a Publicly Funded Health Care System.
Socioeconomic inequalities in the utilization of conventional NSCLC treatments are well documented. Nevertheless, it is not known whether these inequalities are also observed with novel anticancer therapies. This study evaluated associations between deprivation and utilization of novel anticancer therapies targeting tumor biology, the immune system, or both, within the English national publicly funded health care system. A retrospective analysis of 90,785 patients diagnosed with having a histologically confirmed stage IV NSCLC from January 1, 2012, to December 31, 2017, sourced from the English national population-based cancer registry and linked Systemic Anti-Cancer Therapy database, was undertaken. Multivariable logistic regression evaluated the likelihood of novel anticancer therapy utilization by deprivation category of area of residence at diagnosis (measured by quintiles of the income domain of the index of multiple deprivation). Multivariable analyses revealed marked treatment inequalities by deprivation. Patients residing in the most deprived areas were more than half as likely to use any novel therapy (multivariable OR [mvOR] = 0.45, 95% confidence interval [CI]: 0.41-0.49) compared with patients residing in the most affluent areas. Deprivation associations with treatment utilization were slightly stronger with targeted treatments ([most versus least deprived] mvOR = 0.39, 95% CI: 0.35-0.43) than immune checkpoint inhibitors (mvOR = 0.58, 95% CI: 0.51-0.66). There are marked socioeconomic inequalities in NSCLC novel treatment utilization, even in the English National Health Service where treatment is free at the point of delivery. These findings have important implications for equitable delivery of drugs, which have transformed outcomes in metastatic lung cancer. Further work exploring the underlying causes is now needed.


Transfer of early-cleaved embryos increases implantation rate in patients undergoing ovarian stimulation and ICSI-embryo transfer.
The hypothesis that inspection for early cleavage improves pregnancy rate by aiding selection of the best embryos for transfer was tested in this study. Inspection for early cleavage was performed randomly in women undergoing intracytoplasmic sperm injection (ICSI) cycles. No differences were observed between early cleavage-inspected and uninspected embryos. When the hypothesis that transfer of early-cleaved (EC) embryos yields a higher pregnancy rate than transfer of late-cleaved (LC) embryos was tested using early cleavage-inspected cycles, it was found that transfer of EC embryos resulted in a higher implantation rate than transfer of LC embryos. In transfers for which all embryos were EC (100% EC), transfer of fewer embryos yielded a higher implantation rate compared with LC and uninspected cycles. These results indicate that, when inspected, early cleavage increases the implantation rate in ICSI patients.


Do continuous infusions of omeprazole and ranitidine retain their effect with prolonged dosing?
Prolonged infusions of H2-antagonists are commonly used in intensive care units, although little is known about their antisecretory efficacy beyond the initial 24 hours of dosing. The aim of this study was to assess the antisecretory effects of infusions of ranitidine and omeprazole for a period of 72 hours. Twelve healthy volunteers received individually titrated 72-hour intravenous infusions of omeprazole, ranitidine, or placebo in a double-blind, crossover study. Gastric pH and dosing requirements were compared. The median percentage of time with pH > 4 (interquartile range) was 93% (88%-95%) on day 1 and 96% (94%-99%) on day 3 with omeprazole and 67% (56%-78%) and 43% (31%-51%), respectively, with ranitidine (both P < 0.001 vs. omeprazole). The mean doses (+/- SD) required on days 1 and 3 for omeprazole were 235.8 +/- 44 mg and 134.0 +/- 37 mg (P < 0.0001), and ranitidine doses were 502.5 +/- 76 mg and 541.8 +/- 25 mg, respectively (P = 0.05). Omeprazole infusions consistently maintained gastric pH above 4 over a period of 72 hours with progressively lower doses. Significant tolerance to the antisecretory effect of ranitidine infusion developed in 72 hours, which was not overcome despite individually titrated doses of more than 500 mg/24 hours. Consequently, application of pharmacodynamic results of single-day H2-blocker and proton-pump inhibitor studies to prolonged infusion trials for stress ulcer-related bleeding is inappropriate.


Disappearance of quadriparesis due to a huge cervicothoracic aneurysmal bone cyst.
A young man who had suffered from rheumatoid arthritis developed a huge cervicothoracic aneurysmal bone cyst and progressive quadriparesis. Complete recovery occurred after "incomplete therapy," which consisted of an open biopsy and a small dose of irradiation. This tumor was observed and characterized as a blood-filled cyst excavated from the bone. Because of the controversy in the literature over the benefit of surgery vs. irradiation, this report emphasizes the fact that even "partial" treatment may beneficially affect this tumor.


The response of Campylobacter jejuni and Campylobacter coli in the Sydney rock oyster (Crassostrea commercialis), during depuration and storage.
Sydney Rock Oysters, when allowed to feed in waters containing approximately 10(4) cfu of Campylobacter cells per ml, concentrated between 10(2) and 10(3) cfu of the organism per g of oyster tissue, within 1 h. When these contaminated oysters were subjected to depuration, they were effectively cleaned in 48 h. The survival of Campylobacter jejuni and Campylobacter coli was also investigated. Oysters contaminated by feeding and injection were processed as half shells and bottled oysters and were held at 3 and 10 degrees C. Half shells were also stored at -20 to -24 degrees C. At all these temperatures the organism survived for periods varying between 8 to 14 days and in oysters contaminated by feeding, the survival was substantially greater. Survival was better at 3 than at 10 degrees C in half-shelled oysters. Campylobacter survived better in bottled oysters than in half shells stored at the same temperature. In frozen half shelled oysters previously contaminated by feeding, the organisms were viable for months. In contaminated unopened oysters stored at 20 and 30 degrees C, C. jejuni and C. coli failed to multiply as expected. They survived for periods varying from 2 to 9 days.


Infected tibial pseudarthrosis. A 2-year follow up on patients treated by the Ilizarov technique.
The Ilizarov technique with a circular external fixator was used in the treatment of infected tibial nonunions. This is a report on 13 patients with a 2-year follow up after removal of the external fixation. There was no debridement of the site of nonunion performed. Union was obtained in all cases. There was no recurrence of infection at follow up. The Ilizarov technique provides the orthopedic surgeon with another alternative in the treatment of complicated tibial nonunions and their associated problems.


Efficacy of interferon for chronic hepatitis B in patients with nucleoside and nucleotide combination therapy failure.
In China, inappropriate therapies with nucleos(t)ide analogues (NA) have induced hepatitis B virus resistance, combination therapy with nucleoside and nucleotide (ComTNsNt) failure, or multi-drug resistant mutations. However, the efficacy of combination therapy with entecavir plus tenofovir for ComTNsNt failure is limited. In the current study, the regimens of interferon-α (IFN-α) therapy, switching from NAs to IFN-α, and subsequent re-treatment with IFN-α were applied to treat ComTNsNt failure. We further evaluated the efficacy of this therapy. Eleven patients with ComTNsNt failure were enrolled in this study. Nine subjects (9/11) received IFN-α switching therapy. Combination therapy with IFN-α and ComTNsNt was administered in the first 4 weeks. Then, ComTNsNt was discontinued at the end of Week 4, and IFN-α monotherapy was continued for 6 months. Two (2/11) patients discontinued ComTNsNt without receiving IFN-α treatment. All 11 patients received the first re-treatment of IFN-α when they experienced hepatitis relapses after the withdrawal of IFN-α or ComTNsNt. Six (6/11) patients received a second re-treatment of IFN-α. Follow up was conducted after IFN-α therapy in all 11 patients. Two patients (2/9) receiving IFN-α switching therapy experienced alanine aminotransferase (ALT) flare. In contrast, the two patients without IFN-α switching therapy experienced ALT flare. Multiple re-treatments with IFN-α resulted in a sustained response. Interferon-α switching therapy and IFN-α re-treatment might be applied for treatment of ComTNsNt failure. IFN-α switching therapy resulted in safe ComTNsNt cessation, and IFN-α re-treatment induced a sustained response of IFN-α in all patients. This IFN-α treatment is an optional treatment for ComTNsNt failure.


Epidermal Langerhans cells in erythrokeratodermia variabilis. Histochemical and ultrastructural investigations before and after treatment with etretinate (RO 10-9359).
The distribution of epidermal Langerhans cells (LC) in erythrokeratodermia variabilis (EKV) was investigated using enzyme-histochemical (ATPase) and immunohistochemical (anti-T6 and anti-HLA-Dr) techniques. Biopsy specimens from lesional skin of five patients were examined before and 8 weeks after treatment with etretinate (RO 10-9359). In addition, electron microscopy studies were carried out in two of these cases. The number of ATPase-positive dendritic cells in lesional epidermis appeared to be remarkably reduced in comparison with normal skin from healthy subjects. After treatment, the number of ATPase-positive dentritic cells had increased but still remained below normal values. Similar but less striking results were found for anti-T6-stained specimens. The HLA-Dr antigen appeared to be unsuitable as a marker for comparative quantitative studies because of the highly variable expression of this antigen in the control specimens. Electron microscopy studies revealed LC in the basal and suprabasal layers of the lesional epidermis. Both before and after treatment, the LC exhibited a normal ultrastructure. In view of the clinical and histologic normalization of the skin lesions during treatment, these findings suggest that the decreased number of epidermal LC may be related to the abnormal keratinization that occurs in EKV.


Regulation of calcitonin gene-related peptide expression through the COX-2/mPGES-1/PGE2 pathway in the infrapatellar fat pad in knee osteoarthritis.
The infrapatellar fat pad (IFP) is implicated in knee osteoarthritis (KOA). Calcitonin gene-related peptide (CGRP), a vasoactive neuropeptide expressed in joint tissues and synovial tissues (ST), was recently found to be associated with KOA progression and pain. CGRP is expressed in the IFPs of human KOA patients; however, its regulation has not been elucidated. IFPs and STs were harvested from 138 KOA patients during total knee replacement (TKR) and analyzed for CGRP, cycloxygenase-2 (COX-2), and microsomal prostaglandin E synthase-1 (mPGES-1) expression using real-time polymerase chain reaction (PCR). To investigate CGRP regulation by prostaglandin E2 (PGE2), adipocytes (Ad) and the stromal vascular fraction (SVF) were harvested from IFPs using collagenase. Synovial cells (SYC) were also harvested from ST and stimulated with vehicle (serum-free culture medium), PGE2, or CGRP. CGRP, COX-2, and mPGES-1 expression levels were significantly higher in IFPs than STs. PGE2 stimulation increased CGRP expression in Ad, the SVF, and SYC; however, CGRP expression was significantly higher in PGE2-stimulated SVF than PGE2-stimulated SYC. CGRP stimulation had no effect on COX-2 or mPGES-1 expression. CGRP expression in the IFP of KOA patients is regulated by the COX-2/mPGES-1/PGE2 pathway.


Hemoglobin and Its Z Score Reference Intervals in Febrile Children: A Cohort Study of 98,572 Febrile Children.
Febrile disease and age of children were associated with a variation in hemoglobin (Hb) level. Both CRP and Hb serve as laboratory markers that offer valuable insights into a patient's health, particularly in relation to inflammation and specific medical conditions. Although a direct correlation between CRP and Hb levels is not established, the relationship between these markers has garnered academic attention and investigation. This study aimed to determine updated reference ranges for Hb levels for age and investigated its correlation with CRP in febrile children under the age of 18. This is a cohort study of in Chang Gung Memorial Hospitals conducted from January 2010 to December 2019. Blood samples were collected from 98,572 febrile children who were or had been admitted in the pediatric emergency department. The parameters of individuals were presented as the mean ± standard deviation or 2.5th and 97.5th percentiles. We also determined the variation of Hb and Z score of Hb between CRP levels in febrile children. We observed that the Hb levels were the highest immediately after birth and subsequently underwent a rapid decline, reaching their lowest point at around 1-2 months of age, and followed by a steady increment in Hb levels throughout childhood and adolescence. In addition, there was a significant and wide variation in Hb levels during the infant period. It revealed a significant association between higher CRP levels and lower Hb levels or a more negative Z score of Hb across all age subgroups. Moreover, in patients with bacteremia, CRP levels were higher, Hb concentrations were lower, and Z scores of Hb were also lower compared to the non-bacteremia group. Furthermore, the bacteremia group exhibited a more substantial negative correlation between CRP levels and a Z score of Hb (r = -0.41, p < 0.001) compared to the non-bacteremia group (r = -0.115, p < 0.049). The study findings revealed that the Hb references varied depending on the age of the children and their CRP levels. In addition, we established new reference values for Hb and its Z scores and explore their relationship with CRP. It provides valuable insights into the Hb status and its potential association with inflammation in febrile pediatric patients.


Expression and DNA-binding properties of the 14K carboxyl terminal fragment of Escherichia coli DNA topoisomerase I.
DNA sequence coding for the last 121 amino acids of Escherichia coli topoisomerase I was synthesized by PCR and cloned into a plasmid under the control of the T7 promoter. Induction of T7 RNA polymerase in E. coli carrying the plasmid clone resulted in over-expression of this C-terminal domain fragment previously shown to confer higher DNA binding affinity to the enzyme. Purification to homogeneity was achieved by phosphocellulose and single-stranded DNA agaraose chromatography. Direct interaction between this 14K domain and poly(dA) was demonstrated by UV spectroscopy. Noncovalent complexes formed between this fragment and oligo(dT) 8 and oligo(dT) 16 can also be trapped by photo-crosslinking.


Influence of diuretics on brachial artery diameter and distensibility in hypertensive patients.
Blood pressure, brachial artery diameter and pulse wave velocity were determined before and after diuretic treatment in 2 groups of hypertensive patients treated either by indapamide (2.5 mg per d) or by canreonate (50 mg per d). Brachial artery diameter, measured from pulsed Doppler flowmetry, and pulse wave velocity, evaluated from mechanography, did not alter significantly despite a significant blood pressure reduction. The study indicates that, in hypertensive patients of middle age, diuretics did not change brachial artery diameter and distensibility, whether the drug caused an increase or a decrease in plasma potassium levels.


Combining albumin deficiency and acute exercise reduces hepatic lipid droplet size in mice.
Hepatic lipid droplets (LDs) are implicated in ectopic lipid accumulation. The core of LDs, triacylglycerol (TAG), is synthesized from the esterification of fatty acids to a glycerol-3-phosphate (G-3-P) backbone. Albumin transports plasma free fatty acids, and previously albumin knockout (Alb-/-) mice were shown to exhibit lower hepatic TAG levels than wildtype (WT). Exercise is a beneficial strategy to alter hepatic metabolism, but its impacts on reducing hepatic lipids are far from satisfactory. The aim of this study was to investigate the combined effect of albumin deficiency and acute exercise on hepatic LDs. Eight-week-old male Alb-/- and WT mice were divided into sedentary and exercise groups. Exercised mice performed a 30-min high-intensity exercise bout. Results showed that sedentary Alb-/- mice had smaller hepatic LDs (P < 0.0001), associated with mitochondria, while WT mice exhibited larger LDs, surrounded by glycogen granules. Following acute exercise, hepatic LDs in Alb-/- mice reduced by 40% in size, while in WT increased by 14% (P < 0.0001). The maintenance of WT hepatic LDs was associated with elevated G-3-P level (P < 0.05), potentially derived from glycogen (R = -0.32, %change in glycogen versus LD content, P < 0.05). The reduction in Alb-/- mice LDs after exercise was possibly due to their low glycogen level. In conclusion, Alb-/- mice exhibited an enhanced capacity for reducing hepatic LD size and content in response to exercise. These findings suggest that modulating albumin's functions combined with exercise could be a potential strategy to reduce ectopic lipid deposition in the liver.


WITHDRAWN: Protracted intensive care unit-stay >14 days in cardiac surgery: risk factors and long-term survival.
Ahead of Print article withdrawn by publisher.


Summits that matter.
The European Commission has made good progress in gathering support for its new programme of basic and applied research. Now Europe's industries and heads of state need to fulfill promises made two years ago.


Development and in vitro characterization of a mucoadhesive gel with Moringa oleifera extract for periodontal drug delivery.
Extensive in vitro and in vivo research has been conducted in the previous decades to analyze the effectiveness of medicinal plants in the treatment of periodontal diseases. Moringa oleifera is a highly potent medicinal plant that has anti-inflammatory and immuno-modulatory properties. In our study, we aim to design, formulate, and evaluate the antibacterial efficacy of M. oleifera extract for local drug delivery (LDD) as periodontal treatment. This study was an in vitro experimental model. M. oleifera extract was prepared using a maceration process with powdered dried leaves of M. oleifera and 70% ethanol. The minimum inhibitory concentration (MIC) of Moringa extract against Porphyromonas gingivalis was assessed using the broth dilution method. The gel was prepared with the obtained MIC of Moringa extract and a combination of polymers- Polyethylene glycol 6000, Carbopol 940, and Chitosan. Further, the formulated gel was subjected to in vitro characterization by thermodynamic stability tests, pH determination, and syringeability test. Viscosity was determined using Brookfield DV-II + Viscometer. Mucoadhesive strength was determined using a fabricated mucoadhesive strength test apparatus. M. oleifera leaves extract possesses a bactericidal effect against P. gingivalis even at a low amounts of 25 μg/ml and so is a potent botanical extract for the formulation of LDD agents for periodontal diseases. The formulation shows adequate stability, good mucoadhesiveness, and controlled drug release, on incorporating the herbal extract into the blank gel. The M. oleifera leaves extract possesses a bactericidal effect against P. gingivalis which has been suggested to be the keystone pathogen in the etiopathogenesis of periodontitis. Hence, M. oleifera leaves extract can be used to treat periodontal diseases as a LDD agent.


Lupus relapse presented as frosted branch retinal angiitis: case report.
To describe a systemic lupus erythematosus (SLE) relapse, which presented as frosted branch retinal angiitis. Clinical case report. A 16-year-old female patient had an SLE relapse that appeared as frosted branch angiitis while being treated with deflazacort and azathioprine. Complete resolution of the vasculitis was achieved with a 3-day course of pulsed intravenous methylprednisolone and oral prednisone 3 weeks later. Even with proper immunosuppressive treatment, SLE can relapse. This case presented as frosted branch retinal angiitis, which is a clinical picture that is rarely described in SLE.


AHRQ begins first phase of intervention reviews.
Key goal is to compare effectiveness of treatments appropriateness of clinical approaches. Reviews also will identify issues where scientific evidence is insufficient to inform decisions. Review and analysis will be undertaken by the Agency for Healthcare Research and Quality's Evidence-based Practice Centers.


In vitro transformation of BALB/c 3T3 cells by 1,1,2,2-tetrachloroethane.
1,1,2,2-Tetrachloroethane (1,1,2,2-TTCE) was shown to be capable of inducing in vitro transformation of BALB/c 3T3 cells (clone A-31) either in the presence or in the absence of S9 activating system using an amplification-transformation (level-II) assay by reseeding confluent cells from each treatment and allowing additional rounds of cell replication. In the absence of metabolic activation, the highest assayed dose (1000 micrograms/ml), exerting the highest toxicity, was the only transforming dose. Lower doses of 1,1,2,2-TTCE were capable of transforming BALB/c cells in the presence of S9 activating system, the dose of 500 micrograms/ml exerting the highest transforming activity. The number and size of transformed foci recognized in the level-II plates were a function of the number of cells reseeded in the amplification assay. Foci obtained in the presence of S9 activating systems were larger in size, more deeply basophilic, and exhibited denser multilayering of constituent cells than foci recognized in the absence of exogenous metabolic activation.


Identification of genes responsible for biofilm formation or virulence in Salmonella enterica serovar pullorum.
Salmonella living in biofilms are more resistant to chemical and physical stresses. However, information regarding the regulation of genes involved in biofilm formation for Salmonella enterica serovar Pullorum remains limited. In this study, eight mutants with knockout of genes ompR, rpoS, rfaG, rfbH, rhlE, metE, spiA, or steB from the Salmonella enterica serovar Pullorum strain S6702 were constructed. Phenotypic analysis revealed that all mutants were similar to the wild-type strain in growth rate. Only the ompR mutant showed a complete loss of production ofcurli and biofilm formation. The other mutants showed a modified production of curli and cellulose with less effect related to biofilm formation. The results of animal experiments indicated that the deletion of genes ompR, spiA, rfaG, or metE in wild-type strains contributed to attenuation of virulence in 1-day-old chickens. This study may bring new insights into novel vaccines or therapeutic interventions against Salmonella enterica serovar Pullorum infections.


COLORcation: A new application to phenotype exploratory behavior models of anxiety in mice.
Behavioral analyses in rodents have successfully delineated the function of many genes and signaling pathways in the brain. Behavioral testing uses highly defined experimental conditions to identify abnormalities in a given mouse strain or genotype. The open field (OF) is widely used to assess both locomotion and anxiety in rodents. In this test, the more a mouse explores and spend time in the center of the arena, the less anxious it is considered to be. However, the simplistic distinction between center and border substantially reduces the information content of the analysis and may fail to detect biologically meaningful differences. Here we describe COLORcation, a new application for improved analyses of mouse behavior in the OF. The application analyses animal exploration patterns in detailed spatial resolution (e.g. 10×10 bins) to provide a color-encoded heat map of mouse activity. In addition, COLORcation provides new parameters to track activity and locomotion of the test animals. We demonstrate the use of COLORcation in different experimental paradigms, including pharmacological and restraint-based induction of stress and anxiety. COLORcation is compatible with multiple acquisition systems, giving users the option to make the most of their raw data organized text files containing time and coordinates of animal locations as input. These analyses validate the utility of the software and establish its reliability and potential as a new tool to analyze OF data.