Vertical Ridge Augmentation Using Distraction Osteogenesis Versus Autogenous Bone Grafting: A Systematic Review and Meta-Analysis.
The aim of this systematic review was to systematically assess the papers comparing the surgical techniques of Alveolar Distraction Osteogenesis(ADO) and Autogenous Bone grafting (ABG) for Vertical Ridge Augmentation in terms of bone gain, bone resorption and incidences of complications. The review was registered on PROSPERO with the ID : CRD42021237671. A broad electronic survey was conducted in the PubMed, Scopus, Web of Science, Cochrane Library, and Virtual Health Library databases of all studies published till 08/03/2022. Four studies fulfilled the criteria to carry out a meta-analysis a in which a total of 58 patients underwent ADO and 43 patients for ABG. A total of 133 implants were placed in the ABG group and 124 in the ADO group. DerSimonian-Laird estimator of variance was used for Random effect meta-analysis. The estimates of an intervention were expressed as the odds ratio (OR) and standard mean difference (SMD) in millimeters. There was statistically significant difference in terms of bone height gain with SMD of - 0.78 (95% 0.04-1.55) in ABG. Bone resorption and complications were statistically insignificant with SMD of 0.52 (95% - 1.59 to 0.56) and OR 0.55 (95% 0.18-1.70), respectively.PROSPERO Registration ID: CRD42021237671.


Establishment and application of cricothyrotomy in vivo.
Cricothyrotomy is a procedure performed to establish an airway in critical airway events. It is performed only rarely and anesthesiologists are often unprepared when called upon to perform it. This study aimed to simulate cricothyrotomy using pig larynx and trachea models to help anesthesiologists master cricothyrotomy and improve the ability to establish cricothyrotomy quickly. The porcine larynx and trachea were dissected and covered with pigskin to simulate the structure of the anterior neck of a human patient. An animal model of cricothyrotomy was established. Forty anesthesiologists were randomly divided into four groups. Each physician performed three rounds of cricothyrotomy, and recorded the time to accomplish each successful operation. After training the cricothyrotomy procedure, a questionnaire survey was conducted for the participating residents using a Likert scale. The participants were asked to score the utility of the training course on a scale of 1 ((minimum) to 5 ((maximum). Through repeated practice, compared with the time spent in the first round of the operation (67 ± 29 s), the time spent in the second round of the operation (47 ± 21 s) and the time spent in the third round of the operation (36 ± 11 s) were significantly shortened (P < 0.05). Results of the survey after training were quite satisfied, reflecting increased the ability of proficiency in locating the cricothyroid membrane and performing a surgical cricothyrotomy. The porcine larynx and trachea model is an excellent animal model for simulating and practicing cricothyrotomy, helping anesthesiologists to master cricothyrotomy and to perform it proficiently when required.


Invasive urothelial carcinoma, lymphoma-like/plasmacytoid variant, successfully treated by radical cystectomy with adjuvant chemotherapy: a case report.
Invasive urothelial carcinoma, lymphoma-like/plasmacytoid variant, is a rare histological type of bladder cancer similar to plasma cells and is an aggressive variant of urothelial carcinoma associated with a poor prognosis. A 41-year-old Asian man was referred to our hospital due to macroscopic hematuria. Cystoscopy detected a non-papillary tumor, and a transurethral resection of the bladder tumor revealed pT1N0M0 bladder cancer. A pathological examination showed high-grade invasive urothelial carcinoma and a component of signet ring cell carcinoma. A follow-up of the transurethral resection with radical cystectomy was carried out, and a pathological examination showed infiltrating urothelial carcinoma, with partial features of the plasmacytoid variant. We added chemotherapy treatment with gemcitabine and cisplatin for two cycles. Our patient has been free from recurrence for 2 years. We herein report the case of a patient with a plasmacytoid variant of urothelial carcinoma controlled with radial cystectomy and subsequent chemotherapy.


Successful salvage therapy with inhaled zanamivir in a patient with peramivir-resistant pandemic influenza A (H1N1) 2009 virus.
We describe a patient with multiple myeloma who developed a pandemic influenza A (H1N1) 2009 virus infection during chemotherapy. The clinical condition of the patient worsened and viral shedding persisted despite 10 days of peramivir treatment; however viral shedding ceased and the patient recovered completely with inhaled zanamivir.


Interobserver and intraobserver variability in magnetic resonance imaging evaluation of patients with suspected disc herniation.
Magnetic resonance imaging (MRI) is usually the modality of choice to assess sciatica and intervertebral disc herniation. Despite remarkable progression in diagnostic imaging and surgical techniques, definite diagnosis based on imaging interpretation is still a great challenge. The aim of this study was to determine interobserver and intraobserver variability in reporting lumbar MRI between two neuroradiologists based on the new 2014 version of disc nomenclature. The study population was composed of 134 irresponsive to conservative therapy patients with clinical presentations of disc herniation and lumbar radiculopathy. MRI was taken from all the participants using a 1.5 T MRI system. Two neuroradiologists evaluated the images, separately and one of them did it twice and interpreted the scans in sagittal and axial planes. Disc bulge, disc herniation and nerve root compression were evaluated at each level. Interobserver and interaobserver agreements between two neuroradiologists, and one neuroradiologist in two times of reporting were calculated for the evaluation of bulging and herniated discs and nerve root compression by applying the Kappa statistics. Bulging disc, herniated disc, the type of disc, location of the discs, and nerve root compression diagnosis were significantly in excellent agreement (kappa>0.7, p-value<0.001) through intraobserver assessments, while interobserver assessments presented statistically significant with a fair agreement (kappa:0.4-0.7 and p-value<0.05). Remarkable intraobserver agreement was found between diagnoses of disc-related pathologies of the lumbar spine while interobserver assessments revealed only fair concordance.


Diet, nutrition, and cancer: past, present and future.
Despite the potentially important roles of diet and nutrition in cancer prevention, the evidence to support these roles is widely perceived by the public and health professionals as being inconsistent. In this Review, we present the issues and challenges in conducting and interpreting diet-cancer research, including those relating to the design of epidemiological studies, dietary data collection methods, and factors that affect the outcome of intervention trials. Approaches to improve effect estimates, such as the use of biomarkers to improve the accuracy of characterizing dietary exposures, are also discussed. Nutritional and dietary patterns are complex; therefore, the use of a reductionist approach to investigations, by focusing on specific nutrients, can produce misleading information. The effects of tumour heterogeneity and the failure to appreciate the nonlinear, U-shaped relationship between micronutrients and cancer in both observational studies and clinical trials are discussed. New technologies and investigational approaches are enabling the exploration of complex interactions between genetic, epigenetic, metabolic, and gut-microbial processes that will inform our knowledge of the diet-cancer relationship. Communicating the status of the evolving science in the context of the overall scientific evidence base, and evidence-based dietary recommendations for cancer prevention, should be emphasized in guidance for the public and for individual patients.


Mechanism of adenylate kinase. The conserved aspartates 140 and 141 are important for transition state stabilization instead of substrate-induced conformational changes.
The goal of this work is to evaluate the quantitative contribution of Asp-140 and Asp-141 to conformational changes and/or substrate stabilization in the catalysis by chicken muscle adenylate kinase (AK), by use of kinetic and structural analysis of the single alanine mutants D140A and D141A as well as the salt bridge double mutants R138M,D140A and R132M,D141A. The single mutants D140A and D141A displayed small increases in Km (6-12-fold) and moderate decreases in kcat (17-78-fold). Kinetic analysis with the slowly reacting substrate system MgATP and dAMP suggested that the decrease in kcat is not caused by a decrease in the conformational step(s) relative to the chemical step. Most of the kinetic constants of the double mutants R138M,D140A and R132M,D141A are similar to those of the single mutants R138M and R132M, respectively. Detailed analysis by two-dimensional NMR indicated no appreciable changes in the conformations of the free enzyme or the complex with MgAP5A (where AP5A is P1,P5-bis(5'-adenosyl)pentaphosphate), for both single and double mutants. These results taken together suggest that Asp-140 and Asp-141 are unimportant for substrate-induced conformational changes in AK; their roles are mainly to assist Arg-138 and Arg-132 in stabilizing the transition state. The structural results also suggest that AK is a flexible enzyme.


Cumulative Intracranial Tumor Volume Augments the Prognostic Value of Diagnosis-Specific Graded Prognostic Assessment Model for Survival in Patients with Melanoma Cerebral Metastases.
The diagnosis-specific graded prognostic assessment scale (ds-GPA) for patients with melanoma brain metastasis (BM) utilizes only 2 key prognostic variables: Karnofsky performance status and the number of intracranial metastases. We wished to determine whether inclusion of cumulative intracranial tumor volume (CITV) into the ds-GPA model for melanoma augmented its prognostic value. To determine whether or not CITV augments the ds-GPA prognostic scale for melanoma. We analyzed the survival pattern of 344 melanoma patients with BM treated with stereotactic radiosurgery (SRS) at separate institutions and validated our findings in an independent cohort of 201 patients. The prognostic value of ds-GPA for melanoma was quantitatively compared with and without the addition of CITV using the net reclassification index (NRI > 0) and integrated discrimination improvement (IDI) metrics. The incorporation of CITV into the melanoma-specific ds-GPA model enhanced its prognostic accuracy. Addition of CITV to the ds-GPA model significantly improved its prognostic value, with NRI > 0 of 0.366 (95% CI: 0.125-0.607, P = .002) and IDI of 0.024 (95% CI: 0.008-0.040, P = .004). We validated these findings that CITV improves the prognostic utility of melanoma ds-GPA in an independent cohort of 201 melanoma cohort. The prognostic value of the ds-GPA scale for melanoma BM is enhanced by the incorporation of CITV.


[Treatment of premenopausal patients with advanced or recurrent breast cancer by chemical ablation].
To evaluate the clinical efficacy and safety of luteinizing hormone releasing hormone (LH-RH) analog in premenopausal patients with advanced or recurrent breast cancer. LH-RH analog (enantone 3.75 mg/2 ml) were administered to 28 premenopausal patients with advanced recurrent breast cancer and its efficacy and side effect were observed. The response rate (complete response and partial response) was 42.9%, and after 8 weeks of treatment, the plasma estrogen in all patients decreased to the level of postmenopause. No major adverse events were observed. LH-RH analog is effective and safe for premenopausal breast cancer with low adverse reaction and its administration method is easy.


Goal synchronization of bimanual skills depends on proprioception.
The present experiments in Human subjects were designed to test whether proprioceptive feedback plays a role in optimising bimanual synchronization in a goal-oriented familiar task. Goal-synchronization is a typical feature of bimanual everyday skills. The purpose of the study was to disturb proprioceptive signalling by means of vibrating the leading left limb while subjects performed a bimanual task on a drawer manipulandum. Blindfolded subjects reached for and opened the drawer with the left hand while the right hand was reaching for grasping an object as the drawer was fully opened. Discrete events of the task were used to measure movement onset times of pulling and grasping hands and of goal arrival times. A spatial--temporal goal invariance was still present despite asymmetrical limb assignments and subjects were blindfolded. In contrast, when vibration (80 Hz) was applied to the forearm flexors of the leading pulling limb, we found that the interval between the hands at goal reaching was significantly prolonged. This suggests that synchronization is not predetermined entirely by feedforward commands and that proprioceptive feedback is necessary for updating an internal forward model and perhaps also for lower-level corrections in order to ensure covariant limb movements for optimal goal-synchronization.


Strain-induced creation and switching of anion vacancy layers in perovskite oxynitrides.
Perovskite oxides can host various anion-vacancy orders, which greatly change their properties, but the order pattern is still difficult to manipulate. Separately, lattice strain between thin film oxides and a substrate induces improved functions and novel states of matter, while little attention has been paid to changes in chemical composition. Here we combine these two aspects to achieve strain-induced creation and switching of anion-vacancy patterns in perovskite films. Epitaxial SrVO3 films are topochemically converted to anion-deficient oxynitrides by ammonia treatment, where the direction or periodicity of defect planes is altered depending on the substrate employed, unlike the known change in crystal orientation. First-principles calculations verified its biaxial strain effect. Like oxide heterostructures, the oxynitride has a superlattice of insulating and metallic blocks. Given the abundance of perovskite families, this study provides new opportunities to design superlattices by chemically modifying simple perovskite oxides with tunable anion-vacancy patterns through epitaxial lattice strain.


Varicose veins: hooks, clamps, and suction. Application of new techniques to enhance varicose vein surgery.
Surgical principles that guided varicose vein surgery for nearly 75 years have been time honored and taught to generations of surgeons. Each of these principles has been challenged successfully, and, as a result, varicose vein surgery has changed markedly. The fundamental principle of totally removing varicose clusters from the circulation remains firmly established. However, methods of accomplishing this have changed and continue to change. Hook phlebectomy and clamp phlebectomy have replaced open dissection and tributary ligation. The place of tumescent anesthesia, transilluminated-powered phlebectomy, and sclerotherapy remain unsettled. However, there now are a number of alternatives in planning patient care.


An evaluation of sealing ability of calcium hydroxide sealers.
Solid core filling material such as gutta-percha has been used to fill the root canal in conjunction with a sealer to prevent apical leakage. The purpose of this study was to compare apical seal of five different root canal sealers. Sixty roots of maxillary central incisors were cleansed and shaped and randomly assigned to one of six groups of ten roots each. The root canals were obturated with gutta-percha and one of the sealers by the lateral-vertical condensation technique. Groups I, II, III, IV, and V consisted of roots in which the canal was filled with gutta-percha along with either Roth's sealer, AH26, Sealapex, CRCS, or Nogenol sealer, respectively. Group VI was filled with gutta-percha and without sealer to serve as a control. The access opening was filled with amalgam. Each tooth was then placed in a capped vial containing 2 X 2 inch gauze pads saturated with distilled water, and the sealer was allowed to set at 37 degrees C in the humidor for 48 hours. The roots, except for the apical 2 mm, were coated with two layers of nail polish. The roots were stained with india ink, decalcified, dehydrated, and then placed in methylsalicylate to make them transparent. The leakage was measured with a filar micrometer eyepiece under a dissecting microscope. The mean apical leakage of six groups was as follows: I = 0.45 mm, II = 0.277 mm, III = 0.343 mm, IV = 0.263 mm, V = 0.336 mm, and VI = 2.310 mm. Results showed no significant difference in the apical seal produced by gutta-percha and the tested root canal sealers.(ABSTRACT TRUNCATED AT 250 WORDS)


Separation of intact and damaged hepatocytes in sucrose following non-enzymatic liver perfusion.
This study deals with isolation of rat hepatocytes by a non-enzymatic method and the separation of intact and damaged cells in sucrose medium. Low speed centrifugation in isotonic sucrose medium of a hepatocyte suspension obtained by mechanical desaggregation of liver pre-perfused with EDTA solution results in the formation of a cell pellet which contains two different layers. A darker layer contains hepatocytes with intact plasma membranes. Their respiratory activity and xenobiotic metabolism are close to those of the cells isolated by collagenase perfusion. The study of distribution of lipophilic cation tetraphenylphosphonium (TPP(+)) indicates a predominantly mitochondrial localization of TPP(+) in the intact cells following non-enzymatic and collagenase isolation. Hepatocytes in the upper layer have damaged plasma membranes. As a result they lose the potential to accumulate TPP(+), and have low rates of endogenous respiration and biotransformation activity. Addition of exogenous NADPH restores the capability to metabolize xenobiotics. Washing and incubation of these hepaticytes in an intracellular type medium results in restoration of uncoupler-stimulated oxygen consumption and generation of membrane potential in the presence of a succinate substrate. These properties are close to those of hepatocytes permeabilized by digitonin treatment. Thus, the procedure allows the simultaneous isolation of both intact and permeabilized hepatocytes with functionally active intracellular structures without the use of relatively expensive chemicals such as collagenase and Percoll.


Generalized granuloma annulare associated with essential thrombocythemia.
The only myeloproliferative neoplasm associated with generalized granuloma annulare (GA) is chronic myelogenous leukemia (CML). We present the first reported case of GA in a patient with essential thrombocythemia (ET). Future work investigating the shared pathophysiology of GA-associated CML and ET may improve our understanding of GA pathophysiology and treatment.


[Schwartz-Jampel syndrome. A case report and review of literature (author's transl)].
A new case with distinctive features of Schwartz-Jampel syndrome is reported, which makes the patient number 28 after reviewing world literature on the subject. Clinical, genetic, neurophysiological and pathological point of view is studied. The myotonic discharges which the patient presented while resting, did not diminish either with general anesthesia or with curarization, being this the pattern of a true myotonia.


Cross-talk between gammadelta T lymphocytes and immune cells in humoral response.
The role of gamma delta T cells in immunoregulation is largely unknown. In the current study we noted that gamma delta T cells play a positive role in the humoral response. These positively acting gamma delta T cells are required for the successful adoptive cell transfer of the humoral response, as well as for in vitro generation of plaque-forming cells (PFC). The presented results show that gammadelta T cells cause an increase in interleukin-10 (IL-10) production, which partly elucidates the mechanism of action of these cells. However, experiments with cell culture inserts strongly suggest that direct cell-cell contact between immune and gamma delta H-2-compatible regulatory T cells is critical to the exertion of the positive immunoregulatory function of gamma delta cells. The mechanism of cross-talk between these two cell populations is still not clear but we regard as most likely that the positively acting gamma delta T cells may interact with a complex of heat-shock protein-non-polymorphic MHC (IB) on the surface of T helper type 2 and/or B cells. This could provide, by direct cell-cell contact, the cognate recognition between gamma delta T-cell receptors and heat-shock protein-MHC that leads to positive internal signalling in the immune cells.


Highly variable drugs: observations from bioequivalence data submitted to the FDA for new generic drug applications.
It is widely believed that acceptable bioequivalence studies of drugs with high within-subject pharmacokinetic variability must enroll higher numbers of subjects than studies of drugs with lower variability. We studied the scope of this issue within US generic drug regulatory submissions. We collected data from all in vivo bioequivalence studies reviewed at FDA's Office of Generic Drugs (OGD) from 2003-2005. We used the ANOVA root mean square error (RMSE) from bioequivalence statistical analyses to estimate within-subject variability. A drug was considered highly variable if its RMSE for C (max) and/or AUC was > or =0.3. To identify factors contributing to high variability, we evaluated drug substance pharmacokinetic characteristics and drug product dissolution performance. In 2003-2005, the OGD reviewed 1,010 acceptable bioequivalence studies of 180 different drugs, of which 31% (57/180) were highly variable. Of these highly variable drugs, 51%, 10%, and 39% were either consistently, borderline, or inconsistently highly variable, respectively. We observed that most of the consistent and borderline highly variable drugs underwent extensive first pass metabolism. Drug product dissolution variability was high for about half of the inconsistently highly variable drugs. We could not identify factors causing variability for the other half. Studies of highly variable drugs generally used more subjects than studies of lower variability drugs. About 60% of the highly variable drugs we surveyed were highly variable due to drug substance pharmacokinetic characteristics. For about 20% of the highly variable drugs, it appeared that formulation performance contributed to the high variability.


Subretinal neovascularization in senile macular degeneration.
When fluorescein angiograms from 563 patients with senile macular degeneration examined at a large community hospital during a 9.5-year period were retrospectively reviewed, 200 patients were found to have a dry atrophic type of senile macular degeneration, consisting of drusen and retinal pigment epithelial changes. Of the 363 patients with exudative senile macular degeneration, 244 had subretinal neovascular membranes. Seventy-eight membranes were less than 1 disk diameter in size. Most of the large (157 of 224) and small (44 of 78) membranes showed a predilection for the fovea. Only 13 large and six small neovascular membranes were 200 microns or more from the center of the foveal avascular zone.


A case series of dermoids in the middle ear.
Dermoid is a rare disease located in the head and neck and only sporadic cases were previously reported. Surgery with different operational paths is the best solution to the disease. We aimed to analyze the clinical characteristics and outcomes of surgical approach for treating dermoid originated from the middle ear and Eustachian tube. In this retrospective case series, four cases of dermoids of the middle ear and Eustachian tube, treated by endoscopic-assisted surgical approach were reviewed and analyzed. Patients' ages ranged from 7 months to 16 years. All cases involved the middle ear, eustachian tube, and the parapharyngeal space. Postoperative follow-up ranged from 6 months to 11 years. No facial nerve paralysis was observed during or after surgeries. Treatment was efficient in the four cases, with no residual symptoms during post-operative follow-up. Dermoid of the middle ear involving the eustachian tube usually appears in children of early age. Surgical resection with assistance of endoscope has satisfying outcome for these cases.


A Model of Cadmium Uptake and Transport in Caco-2 Cells.
We created a physiologically substantiated kinetic model of cadmium transport and toxicity in intestinal cell model (Caco-2 cells). Transcriptome profiling of Caco-2 cells revealed high content of transporter DMT1 and ZIP14 and intensive expression of some calcium channels of the CACN family. The mathematical model describing three types of transporters, as well as intracellular cadmium binding with metallothionein and excretion through the basolateral membrane allowed us to construct cadmium uptake and transport curves that approximated the previously obtained experimental data. Using the proposed model, we determined toxic intracellular cadmium concentration leading to cell death and impairing the integrity of cell monolayer and described cadmium transport in this case.


Impact of COVID-19 on volume of elective and nonelective ventral hernia repair.
The significant decrease in elective surgery during the COVID-19 pandemic prompted fears that there would be an increase in emergency or urgent operations for certain disease states. The impact of COVID-19 on ventral hernia repair is unknown. This study aimed to compare volumes of elective and nonelective ventral hernia repairs performed pre-COVID-19 with those performed during the COVID-19 pandemic. An analysis of a prospective database from 8 hospitals capturing patient admissions with the International Classification of Diseases, Tenth Revision Procedure Coding System for ventral hernia repair from January 2017 through June 2021 were included. During, COVID-19 was defined as on or after March 2020. Comparing 3,558 ventral hernia repairs pre-COVID-19 with 1,228 during COVID-19, there was a significant decrease in the mean number of elective ventral hernia repairs per month during COVID-19 (pre-COVID-19: 61 ± 5 vs during COVID-19 19: 39 ± 11; P < .001), and this persisted after excluding the initial 3-month COVID-19 surge (61 ± 5 vs 42 ± 9; P < .001). There were fewer nonelective cases during the initial 3-month COVID-19 surge (32 ± 9 vs 24 ± 4; P = .031), but, excluding the initial surge, there was no difference in nonelective volume (32 ± 9 vs 33 ± 8; P = .560). During COVID-19, patients had lower rates of congestive heart failure (elective: 9.0% vs 6.6%; P = .0047; nonelective: 17.7% vs 11.6%; P < .001) and chronic obstructive pulmonary disease (elective: 13.7% vs 10.2%; P = .017; nonelective: 17.9% vs 12.0%; P < .001) and underwent fewer component separations (10.2% vs 6.4%; P ≤ .001). Intensive care unit admissions decreased for elective ventral hernia repairs (7.7% vs 5.0%; P = .016). Length of stay, cost, and readmission were similar between groups. Elective ventral hernia repair volume decreased during COVID-19 whereas nonelective ventral hernia repairs transiently decreased before returning to baseline. During COVID-19, patients appeared to be lower risk and less complex. The possible impact of the more complex patients delaying surgery is yet to be seen.


Impact of sarcopenia on chemotherapy-triggered exacerbation of interstitial lung disease in patients with non-small cell lung cancer.
While recent evidence has suggested that sarcopenia could predict chemotoxicity, its association with chemotherapy-triggered interstitial lung disease (ILD) exacerbations has yet to be investigated. Thus, the present study sought to determine whether sarcopenia could predict ILD exacerbations and overall survival (OS) in patients with ILD-complicated non-small cell lung cancer (NSCLC). From January 2010 to July 2020, 74 patients with ILD-complicated NSCLC who received chemotherapy were retrospectively investigated. After categorizing patients according to the presence or absence of sarcopenia based on the psoas muscle index, ILD exacerbation rates and OS were evaluated. Among the patients in the study, 39 were included in the sarcopenia group. Moreover, 17 (22.9%) patients developed ILD exacerbations, with the sarcopenia and nonsarcopenia groups having an exacerbation rate of 33.3% and 11.4%, respectively (p = 0.025). Multivariate analysis identified sarcopenia as an independent predictor of ILD exacerbations (p = 0.039). Furthermore, patients with sarcopenia demonstrated a significantly shorter median OS compared to those without the same (9.2 vs. 13.3 months; p = 0.029). Sarcopenia predicted chemotherapy-triggered ILD exacerbation and OS in patients with ILD-complicated NSCLC, suggesting its utility in determining treatment approaches.


Posterior reversible encephalopathy syndrome following measles vaccination.
Due to recent domestic measles outbreaks in Japan, the Japanese government has mandated measles vaccination at ages 14 and 17 since April 2008. Since then, the number of people receiving measles vaccination has increased in Japan. Measles vaccination may cause serious neurological complications including encephalopathy, although the incidence is very low. We report here an adult case of posterior reversible encephalopathy syndrome (PRES) and myeloradiculoneuropathy following measles vaccination. Brain MRI demonstrated typical findings of PRES, high intensity signals in the occipital lobes on FLAIR imaging, isointensity signals on diffusion weighted imaging, with an increase in the apparent diffusion coefficient (ADC). Vasoconstriction mainly in the posterior cerebral arteries was detected by MRA. Physicians should keep in mind the possible occurrence of PRES and myeloradiculoneuropathy following measles vaccination.


[Validation of Subjective Estimates of Female Breast Volume and Comparison with Objective Methods].
To date it remains unclear how well we are doing in subjectively judging breast volume. 2 experienced female examiners reviewed images of 88 female breasts and estimated breast volumes. The "true" breast volumes were previously objectively obtained by breast analysis tool (BAT) software. Tests were repeated, and Bland/Altman statistics were utilised. Mean breast volume was at 419±274 cc statistically significantly larger by 59, respectively, 75 cc than estimated breast volume by the 2 examiners. The comparison of the first and second repeated test of subjective estimation of breast volumes revealed a correlation coefficient R of about 0.92 (p<0.001) while the same comparison for the BAT measurements provided a close to perfect correlation coefficient of R>0.99 (p<0.001). With increasing volumes the repeated estimations became less reliable, not so the BAT measurements. Small breast volumes were estimated as too large and large breast volumes were estimated as too small by the examiners and the connection was nearly perfectly linear. The correlation coefficient R between estimations and measurements was lower at 0.86 than in the repeated tests and estimations showed some considerable deviations in individual cases. Subjective breast assessments underestimated breast volumes by around 70 cc, with some deviations. Breast volume determination was less reproducible by subjective estimation than by objective measurement with BAT software. With increasing breast volumes the error of the subjective estimations in the repeated tests as well as in comparison to the BAT data increased, not so the error of the BAT data. Small breast volumes were overestimated and large volumes underestimated with some considerable individual deviations. There was a good reliability of the objective measurements without much systematic error, however only limited validity of the subjective method.


Novel neuropeptides in the pathophysiology of heart failure: adrenomedullin and endothelin-1.
The clinical success of neurohumoral manipulation by ACE inhibitors and beta blockers in heart failure has led to new therapeutic approaches. New neurohumoral factors are now viewed as offering the potential for treatment interventions. Not only do we consider blocking the production of deleterious hormones, but also, more recently, consideration has been given to augmenting the actions of factors with potentially beneficial actions. Hopefully such manipulation of ADM and ET-1 can result in further improvement in the well-being of heart failure patients.


Coexistence of neuroblastoma and ganglioneuroma in a girl with a hemizygous deletion of chromosome 11q14.1-23.3.
Constitutional 11q interstitial deletion syndrome presents with congenital anomalies including microcephaly with craniostenosis, minor dysmorphic features, vitreoretinopathy, and renal anomalies. This syndrome is occasionally associated with neuroblastoma (NB) as a life-threatening complication, which is important for clinical care. Although the corresponding locus to NB has been predicted to exist in 11q22-23 by previous deletion studies related to NB, the causative haploinsufficient genes have not yet been identified. We herein reported for the first time the simultaneous coexistence of adrenal NB and abdominal prevertebral ganglioneuroma in a 6-year-old girl with a constitutional hemizygous 11q14.1-23.3 deletion. Of the 11 haploinsufficient genes predicted with an in silico database, we focused on NCAM1 and CADM1 as the genes accountable for NB and ganglioneuroma. The deletion range, especially the 11q22.3 involvement, needs to be determined in 11q deletion cases in order to predict susceptibility to peripheral nerve tumors involving NB and ganglioneuroma.


Interactions between amiodarone and the hERG potassium channel pore determined with mutagenesis and in silico docking.
The antiarrhythmic drug amiodarone delays cardiac repolarisation through inhibition of hERG-encoded potassium channels responsible for the rapid delayed rectifier potassium current (IKr). This study aimed to elucidate molecular determinants of amiodarone binding to the hERG channel. Whole-cell patch-clamp recordings were made at 37°C of ionic current (IhERG) carried by wild-type (WT) or mutant hERG channels expressed in HEK293 cells. Alanine mutagenesis and ligand docking were used to investigate the roles of pore cavity amino-acid residues in amiodarone binding. Amiodarone inhibited WT outward IhERG tails with a half-maximal inhibitory concentration (IC50) of ∼45nM, whilst inward IhERG tails in a high K(+) external solution ([K(+)]e) of 94mM were blocked with an IC50 of 117.8nM. Amiodarone's inhibitory action was contingent upon channel gating. Alanine-mutagenesis identified multiple residues directly or indirectly involved in amiodarone binding. The IC50 for the S6 aromatic Y652A mutation was increased to ∼20-fold that of WT IhERG, similar to the pore helical mutant S624A (∼22-fold WT control). The IC50 for F656A mutant IhERG was ∼17-fold its corresponding WT control. Computational docking using a MthK-based hERG model differentiated residues likely to interact directly with drug and those whose Ala mutation may affect drug block allosterically. The requirements for amiodarone block of aromatic residues F656 and Y652 within the hERG pore cavity are smaller than for other high affinity IhERG inhibitors, with relative importance to amiodarone binding of the residues investigated being S624A∼Y652A>F656A>V659A>G648A>T623A.


Ablation of composite resins using Er:YAG laser--comparison with enamel and dentin.
The purpose of this work is to investigate comparative ablation rate between composite resins and dental hard tissues (enamel and dentin) after Er:YAG laser irradiation to verify possible development of an ultra-conservative dentistry to with minimum effect for the teeth tissue. We have used 11 extracted or exfoliated primary anterior and posterior teeth and six extracted permanent molar teeth. Three different types of composite resin were chosen (microfiller, hybrid, and condensable) in terms of chemical and structural composition. Composite tablets and the teeth were irradiated with a Er:YAG laser at different laser beam energy level per pulse (100, 200, 300, and 400 mJ). Diameter and depth of each resulted microcavity were measured and the material removed volumes were calculated. The resulted values were plotted and fitted to allow a comparative observation of the material removed as a function of energy level per pulse. While the idea of ultra-conservative dentistry seems to apply well for enamel of primary and permanent teeth, at the present stage it does not apply well for primary or permanent dentin. For dentin, the composition and content of water makes the Er:YAG laser ablation equal or superior in rate compared with the three used resins. This work presents of a comparative study of Er:YAG laser ablation, allowing to analyze the possible selective ablation between composite resin placed and cured and dental hard tissues, with the goal to propose a new clinical technique: differential ablation for composite resin restorations using Er:YAG laser.


Long-term neurodevelopmental outcomes in children born with gastroschisis: the tiebreaker.
We evaluated 2-year neurodevelopmental outcomes in children with gastroschisis. We reviewed the records of children with gastroschisis treated between August 2001 and July 2008. Children discharged from the neonatal intensive care unit were referred to the state-sponsored Developmental Tracking Infant Progress Statewide (TIPS) program. We reviewed TIPS assessments performed before age 2 years. School districts evaluated children referred by TIPS and determined their eligibility for early intervention services. Poor outcomes were defined as scores of "failure" or "moderate/high risk" on the screening assessment or enrollment in early intervention services by 2 years. Children with gastroschisis were compared with case-matched nonsurgical, nonsyndromic children of similar gestational age and birth weight. One hundred five children were born with gastroschisis, and 46 were followed up with TIPS. There was no statistically significant difference in performance on screening assessments or in the rate of enrollment in early intervention services between the gastroschisis children and controls. Children born with gastroschisis have similar 2-year neurodevelopmental outcomes as nonsurgical, nonsyndromic neonatal intensive care unit children of similar gestational age and birth weight. Both groups of children have a higher rate of enrollment in early intervention than their healthy peers. These data suggest that neurodevelopmental outcomes in gastroschisis children are delayed secondary to prematurity rather than the presence of the surgical disease.


Role of angiotensin converting enzyme inhibitors in essential and renal hypertension. Effects of captopril and enalapril on renin-angiotensin-aldosterone, renal function and hemodynamics, salt and water excretion, and body fluid composition.
Among the many generic classes of drugs currently being used for the treatment of hypertension, few, following long-term therapy, improve or correct the underlying renal function and hemodynamic abnormalities encountered in patients with sustained hypertension. This review focuses on the renal effects of the angiotensin converting enzyme inhibitors captopril and enalapril. Each drug is discussed in terms of its short- and long-term effects on the renin-angiotensin-aldosterone system, renal function and hemodynamics, salt and water excretion, and body fluid composition. Data are presented that demonstrate that enalapril, used alone or in combination with diuretic therapy, has the unique ability to control hypertension, to improve glomerular filtration rate and effective renal plasma/renal blood flow, and to decrease renal vascular resistance, without producing adverse effects on salt and water excretion or body fluid composition. If the safety of enalapril is confirmed in long-term studies, the drug will clearly assume a prominent role as either first- or second-step (in combination with a diuretic) therapy in the treatment of hypertension.


Non-neoplastic memmary hypertrophy in the cat associated either with pregnancy or with oral progestagen therapy.
Nine cases of mammary glandular hypertrophy in the cat are described. Three cases occurred in pregnant queens aged between six and eight months and one in an aged non-pregnant queen. The other cases were in neutered animals which had been treated with megestrol acetate for periods of between 14 months and five years. The pregnant queens were spayed and their mammae returned to normal; in the other cats the affected mammary glands were removed surgically. No recurrence occurred in seven cats in which adequate follow-up information was available. The importance of differentiating this benign lesion from mammary neoplasia is discussed.


Large scale purification of B-type fumonisins using centrifugal partition chromatography (CPC).
For toxicological studies of B-type fumonisin in animals, high amounts of pure fumonisins are needed. In the past, several methods for the isolation and purification of fumonisins have been published, stating the problem of high losses of fumonisins during chromatography on solid phases. In this manuscript we describe a new approach based on liquid-liquid partition techniques using centrifugal partition chromatography in combination with ion exchange chromatography for the large-scale isolation of B-type fumonisins with good recovery rates, minimizing losses of fumonisins during the purification. A batch of cultures grown on solid media of 2 kg maize yields approximately 1 g of pure fumonisins with a purity of >98%.


Simple modification to the punch biopsy technique to minimize handling and crush artefact.
A number of techniques have been described to retrieve the tissue core after punch biopsy. We describe a simple modification to the punch-biopsy technique that minimizes instrumentation, handling and the subsequent risk of crush artefact. Our technique is simple, quick and economical and essentially involves rotation of the punch through 90 degrees then lateral extraction with a degree of upward traction, which usually leaves the tissue core deposited beside the skin defect. At this point it can be easily grasped with a square of gauze or detached if required using scissors or a scalpel blade.


Functional characterization of the CgPGS1 gene reveals a link between mitochondrial phospholipid homeostasis and drug resistance in Candida glabrata.
Cardiolipin and its precursor phosphatidylglycerol are two anionic phospholipids that are essential for the biogenesis of functional mitochondria. To assess their role in mitochondrial and cellular functions in the pathogenic yeast Candida glabrata, a functional characterization of the CgPGS1 gene encoding the phosphatidylglycerolphosphate synthase has been carried out. Transposon insertion mutation in CgPGS1 resulted in the loss of phosphatidylglycerolphosphate synthase activity and in deficiency of both phosphatidylglycerol and cardiolipin. The Cgpgs1 Delta mutant cells displayed reduced amounts of cytochrome b and cytochrome a, and had impaired growth on minimal media containing non-fermentable carbon and energy sources. They did not grow at elevated temperatures and failed to form colonies after induction of mitochondrial DNA deletions. The mutant cells also displayed a decreased susceptibility to fluconazole, ketoconazole, clotrimazole, voriconazole and posaconazole. In the Cgpgs1 Delta mutant, a quantitative real time PCR revealed enhanced mRNA levels for multidrug resistance associated genes such as CgPDR1 encoding transcriptional activator and CgCDR1, CgPDH1 and CgSNQ2 coding for drug efflux transporters. These results indicate that CgPGS1 and anionic phospholipids are required for optimal mitochondrial functions and maintenance of yeast susceptibility to azole antifungals.


Ketone bodies inhibit leucine degradation in chick skeletal muscle.
1. DL-beta-hydroxybutyrate (4 mM) increased the net rate of leucine transamination and the net rate of 2-oxoisocaproate (KIC) production in extensor digitorum communis muscles from fed chicks. 2. DL-beta-hydroxybutyrate at 1 and 4 mM inhibited leucine oxidative decarboxylation in muscles from fed chicks. 3. Acetoacetate at 1 and 4 mM inhibited leucine oxidative decarboxylation and total leucine oxidation, but increased net KIC production in muscles from fed chicks. 4. Both DL-beta-hydroxybutyrate and acetoacetate at 1 and 4 mM inhibited the net rate of leucine transamination and the rates of leucine oxidative decarboxylation and total leucine oxidation in muscles from 24-hr fasted chicks.


Vascular endothelial growth factor activation of intramembranous absorption: a critical pathway for amniotic fluid volume regulation.
The purpose of this review is to propose a critical role for vascular endothelial growth factor (VEGF) in mediating the transfer of amniotic fluid from the amniotic compartment through the fetal membranes and fetal surface of the placenta into fetal blood. Experimental findings in humans and animal models on the action of VEGF in mediating fluid transfer are reviewed and interpreted in order to postulate a proposed mechanism for VEGF regulation of amniotic fluid absorption through the fetal membranes and placenta. Recent scientific advances suggest that up-regulation of VEGF gene expression in the amnion and chorion is associated with increased transfer of amniotic fluid into fetal blood. The possible mechanisms of action for VEGF appear to involve regulation of intramembranous blood vessel proliferation and membrane transport via passive permeation as well as nonpassive transcytotic vesicular movement of fluid. Currently evolving concepts suggest that amniotic fluid volume is regulated through modulation of the rate of intramembranous absorption of amniotic fluid by both passive and nonpassive mechanisms. The permeability factor VEGF appears to be a critical regulator of amniotic fluid transport in the fetal membranes.


The first case of autochthonous subcutaneous dirofilariasis (Dirofilaria repens) in a dog from Białowieża (NE Poland) and possible threat posed to inhabitants of Białowieża Primeval Forest area.
We present the first case of dirofilariasis in a dog from Białowieża village located in the primeval European forest-Białowieża Primeval Forest (NE Poland). Molecular analysis of adult nematode specimens isolated from subcutaneous tissue confirmed the infection with Dirofilaria repens. An adult male dog has not travelled out of the Białowieża village for at least five years; therefore, we assume this is the autochthonous case of the disease. We discuss possible inter- and intra-species transmission routes of dirofilariasis on this territory, which is inhabited by diverse community of wild carnivores, domestic animals, and humans. We also discuss the likely sources of the disease in this, highly biodiverse unique European forest complex. We underline the lack of attention to this problem and its importance for veterinary, wildlife, and human health safety.


Changes in the interleukin-1 and interleukin-2 generation in duodenal ulcer patients during cimetidine treatment.
The effect of cimetidine treatment on the generation of interleukin-1 (IL-1) and interleukin-2 (IL-2) was studied in 11 duodenal ulcer patients. The results obtained were compared with those for untreated healthy subjects. The drug was administered intravenously in a dose of 200 mg four times a day for 8 days. The investigations were performed before, during and 1 wk after cimetidine therapy. IL-1 generation was determined by the ability of supernatants from 2-day cultured adherent cells stimulated by lipopolysaccharide to enhance proliferation of PHA-stimulated mice thymocytes. IL-2 generation was determined by the ability of supernatants from 2-day cultured, PHA-stimulated mononuclear cells to proliferate autologous 17-day cultured T cells. In all ulcer patients IL-1 generation diminished during cimetidine treatment (P less than 0.005). It continued to decrease in 4 subjects and increased in the other 7 ones following drug withdrawal. All the values were higher than those in healthy controls. IL-2 activity in ulcer patients was similar to that in healthy subjects and it increased significantly in all ulcer patients following the onset of the treatment (P less than 0.005) and decreased nearly to the initial values 1 wk after termination of the treatment (P less than 0.005). The present studies indicate that cimetidine, a selective histamine H2-receptor antagonist, deeply changes mechanisms of immunoregulation in patients with duodenal peptic ulcer.


In situ doping enables the multifunctionalization of templately synthesized polyaniline@cellulose nanocomposites.
Cellulose aerogels have been widely studied as promising environmentally friendly materials due to their low density, biocompatibility and degradability. However, their applications are limited due to their highly combustible nature. In this study, polyaniline (PANI) decorated bacterial cellulose (BC) composite aerogel has been synthesized with in situ polymerization of aniline monomer on the surface of BC scaffold. The PANI decorated BC composite aerogel has a very high specific area of 124.0m2/g and well-preserved nanoporous structure, while its conductivity drastically increased to 10.44S/m. Interestingly, phosphate groups were incorporated onto PANI backbones due to its unique doping/dedoping structure. The resultant composite aerogel presented excellent flame retardancy, which can be self-extinguished within 1s. Moreover, PANI@BC composite hydrogel exhibited self-motion behavior under low voltage electric field, illustrating potential electromechanical actuator application. This simple and sustainable in situ doping method opens up new opportunities for cost-efficient fabrication of multifunctional cellulose-based electronics.


Rigidly flat-foldable class of lockable origami-inspired metamaterials with topological stiff states.
Origami crease patterns have inspired the design of reconfigurable materials that can transform their shape and properties through folding. Unfortunately, most designs cannot provide load-bearing capacity, and those that can, do so in certain directions but collapse along the direction of deployment, limiting their use as structural materials. Here, we merge notions of kirigami and origami to introduce a rigidly foldable class of cellular metamaterials that can flat-fold and lock into several states that are stiff across multiple directions, including the deployment direction. Our metamaterials rigidly fold with one degree of freedom and can reconfigure into several flat-foldable and spatially-lockable folding paths due to face contact. Locking under compression yields topology and symmetry changes that impart multidirectional stiffness. Additionally, folding paths and mixed-mode configurations can be activated in situ to modulate their properties. Their load-bearing capacity, flat-foldability, and reprogrammability can be harnessed for deployable structures, reconfigurable robots, and low-volume packaging.


The nerve supply to the orbit of the Bactrian camel.
The Bactrian camel is an important domestic animal in some desert and semi-desert areas of the world, but there is no detailed description of the nervous supply to the orbit in this animal. In this study, 10 heads of adult Bactrian camels were collected and the nerves supplying the orbit were examined grossly. The results showed that the nerves supplying the orbit included the optic nerve, oculomotor nerve, trochlear nerve, abducent nerve, the branches of ophthalmic nerve and the maxillary nerve. The anatomical characteristics of the origins, courses and distributions of the nerves to the orbit in the Bactrian camel were described and compared with those of other domestic animals. These results have importance for further research on the comparative neuroanatomy, neurophysiology and the related clinical surgery of the camel.


A novel mutant PIK3R1EY451delinsD breast cancer patient resistant to HER2-targeted therapy treated with everolimus: a case report.
Resistance to HER2-targeted therapy is a critical issue in breast cancer that must be addressed immediately. PIK3R1 mutations are more common in Chinese breast cancer patients (17%, 25/147, Fudan University Shanghai Cancer Center FUSCC vs. 1.8%, 87/4602, TCGA all breast cancer studies). However, very limited information is available on the relationship between PIK3R1 mutation status and resistance to HER2-targeted therapies in patients with HER2-positive breast cancer. We present a case of a HER2-positive advanced breast cancer patient with the PIK3R1EY451delinsD mutation who developed resistance to HER2-targeted therapy and had a better response to everolimus combined with trastuzumab and carboplatin. To the best of our knowledge, this is the first study to show that the PIK3R1EY451delinsD mutation confers resistance to anti-HER2 therapy in breast cancer and that combining with everolimus treatment may overcome this resistance mechanism. We hypothesize that the PIK3R1EY451delinsD mutation is associated with the resistance to anti-HER2 therapy, and that this mutation merits further investigation as a clinical biomarker and therapeutic target.


Mandibular bone growth induced by a hydroxylapatite-coated subperiosteal implant: a case report.
History of the tripodal mandibular subperiosteal implant and the evolution of its design are discussed. Basic principles of bone physiology are reviewed especially as they relate to bone response to loading. Modeling and remodeling are controlled by a strain-related environment. Modeling can alter the shape and volume of bone. This aspect of bone growth has been reported with transosteal implants. A case report is presented in which apparent bone growth occurred following placement of a hydroxylapatite-coated subperiosteal implant. The implant was successfully revised following an acute infection around one of the permucosal sites.


[Cerebral vasculitis with aneurysms caused by varicella-zoster virus infection during AIDS: a new clinicoangiographical syndrome].
We describe three cases of cerebral angiopathy with aneurysms caused by a meningeal varicella-zoster virus infection occurring during AIDS. The clinical picture was rather stereotyped: severe immunocompromission due to HIV infection, ongoing multifocal cerebrovascular disease with territorial infarcts, lymphocytic meningitis with normal glucose content (two cases) or hypoglycorrhachia (one case), multifocal cerebral vasculopathy with narrowings and aneurysms, healing with or without neurological sequelae after intravenous aciclovir treatment. The diagnosis of varicella-zoster virus-induced angiopathy was ascertained by the positive specific PCR in the CSF in the three cases and by the results of the cerebromeningeal biopsy in one case. Although, varicella-zoster virus is already known as a cause of cerebral angiopathy both in the immunocompetent and the immunocompromised, these three cases are the first ever described of a particular angiopathy with narrowings and ectasias complicating AIDS. The infectious treatable cause and the risk of aggravation without treatment require early active oriented investigations in case of a patient with cerebrovascular disease occurring during HIV infection, including a CSF study with varicella-zoster PCR, to allow specific antiviral treatment. In our three cases, aciclovir intravenous treatment (30mg/kg per day) enabled VZ virus clearing from the CSF and stopped the course of the vasculopathy.


Outcomes of Advanced Medullary Thyroid Carcinoma in the Era of Targeted Therapy.
Medullary thyroid carcinoma (MTC) can be targeted with tyrosine kinase inhibitors (TKIs). We aimed to report the outcomes of surgically managed MTC and to evaluate the impact of TKI use on patient survival. Consecutive patients treated surgically for MTC from 1986 to 2020 were identified from a prospectively collected database and were compared on the basis of stage at operation and TKI use. The primary outcome was overall survival (OS). Among 154 patients with a median age of 52 years, 40% presented with stage I/II disease and 60% presented with advanced (stage III or IV) disease. During a median follow-up of 7.5 years, 21% received TKIs for systemic disease. Those presenting with advanced disease were more likely to receive a TKI (31% vs. 7%), present with tumor invasion of the recurrent laryngeal nerve (RLN; 12% vs. 0%) and undergo reoperation (42% vs. 23%) compared with stage I-II patients. For the 11 patients found to have invasion of the RLN, five had preoperative functional vocal cords. Five-year OS was 84% for advanced disease, and stage IV patients who received TKIs had a median survival of 21 years, versus 15 years for those who did not (p = 0.3). Surgery achieves long-term survival for patients with advanced disease, however these patients are at greater risk of requiring RLN resection due to invasion. A significant OS benefit was not seen for TKI use. For patients with local invasion, neoadjuvant TKI therapy may have a role in reducing local morbidity if confirmed to be of benefit in clinical trials.


Slow-tight binding inhibition of xylanase by an aspartic protease inhibitor: kinetic parameters and conformational changes that determine the affinity and selectivity of the bifunctional nature of the inhibitor.
The first report of slow-tight inhibition of xylanase by a bifunctional inhibitor alkalo-thermophilic Bacillus inhibitor (ATBI), from an extremophilic Bacillus sp. is described. ATBI inhibits aspartic protease (Dash, C., and Rao, M. (2001) J. Biol. Chem., 276, 2487-2493) and xylanase (Xyl I) from a Thermomonospora sp. The steady-state kinetics revealed time-dependent competitive inhibition of Xyl I by ATBI, consistent with two-step inhibition mechanism. The inhibition followed a rapid equilibrium step to form a reversible enzyme-inhibitor complex (EI), which isomerizes to the second enzyme-inhibitor complex (EI*), which dissociated at a very slow rate. The rate constants determined for the isomerization of EI to EI*, and the dissociation of EI* were 13 +/- 1 x 10(-6) s(-1) and 5 +/- 0.5 x 10(-8) s(-1), respectively. The K(i) value for the formation of EI complex was 2.5 +/- 0.5 microm, whereas the overall inhibition constant K(i)* was 7 +/- 1 nm. The conformational changes induced in Xyl I by ATBI were monitored by fluorescence spectroscopy and the rate constants derived were in agreement with the kinetic data. Thus, the conformational alterations were correlated to the isomerization of EI to EI*. ATBI binds to the active site of the enzyme and disturbs the native interaction between the histidine and lysine, as demonstrated by the abolished isoindole fluorescence of o-phthalaldehyde (OPTA)-labeled Xyl I. Our results revealed that the inactivation of Xyl I is due to the disruption of the hydrogen-bonding network between the essential histidine and other residues involved in catalysis and a model depicting the probable interaction between ATBI or OPTA with Xyl I has been proposed.


Sensory integration and activities of daily living in children with developmental coordination disorder.
The aim of our study was to evaluate sensory integration and activities of daily living in children with developmental coordination disorder 37 cases with developmental coordination disorder and 35 healthy age-matched peers were included in this study. Ayres Southern California Sensory Integration Test was used for evaluating the sensory integration and Functional Independence Measure for Children (WeeFIM) was used for evaluating the activities of daily living. Significant differences were found in the visual shape perception, position in space, and design copying (p < 0.05). According to the results of somatosensory perception tests, significant differences were found in kinesthesia, manual form perception, finger identification, figure-ground perception, localization of tactile stimuli, double tactile stimuli perception (p < 0.05). Control group was better in motor planning (p < 0.05). Comprehension, expression, social communication, problem solving, and memory skills were significant in favor of the control group (p < 0.05). Graphestesia and self-care domain was found to be correlated (r = 0,491, p = 0.002) between the groups. Special education and rehabilitation programs including sensory integration therapy and motor performance will increase independence in the activities of daily living in children with developmental coordination disorder.


Clinical characteristics and prognosis of patients admitted for heart failure: A 5-year retrospective study of African patients.
Mortality associated with heart failure (HF) remains high. There are limited clinical data on mortality among HF patients from African populations. We examined the clinical characteristics, long-term outcomes, and prognostic factors of African HF patients with preserved, mid-range or reduced left ventricular ejection fraction (LVEF). We conducted a retrospective longitudinal cohort study of individuals aged ≥18years discharged from first HF admission between January 1, 2009 and December 31, 2013 from the Cardiac Clinic, Directorate of Medicine of the Komfo Anokye Teaching Hospital, Ghana. A total of 1488 patients diagnosed of HF were included in the analysis. Of these, 345 patients (23.2%) had reduced LVEF (LVEF<40%) [HFrEF], 265(17.8%) with mid-range LVEF (40%≥LVEF<50%) [HFmEF] and 878 (59.0%) had preserved LVEF (LVEF≥50%) [HFpEF]. Kaplan-Meier curves and log-rank test demonstrated better prognosis for HFpEF compared to HFrEF and HFmEF patients. An adjusted Cox analysis showed a significantly lower risk of mortality for HFpEF (hazard ratio (HR); 0.74; 95% confidence interval (CI) 0.57-0.94) p=0.015). Multivariate analyses showed that age, higher New York Heart Association (NYHA) functional class, lower LVEF, chronic kidney disease, atrial fibrillation, anemia, diabetes mellitus and absence of statin and aldosterone antagonist treatment were independent predictors of mortality in HF. Although, prognostic factors varied across the three groups, age was a common predictor of mortality in HFpEF and HFmEF. This study identified the clinical characteristics, long-term mortality and prognostic factors of African HF patients with reduced, mid-range and preserved ejection fractions in a clinical setting.


Optimization of the beam shaping assembly in the D-D neutron generators-based BNCT using the response matrix method.
Optimization of the Beam Shaping Assembly (BSA) has been performed using the MCNP4C Monte Carlo code to shape the 2.45 MeV neutrons that are produced in the D-D neutron generator. Optimal design of the BSA has been chosen by considering in-air figures of merit (FOM) which consists of 70 cm Fluental as a moderator, 30 cm Pb as a reflector, 2mm (6)Li as a thermal neutron filter and 2mm Pb as a gamma filter. The neutron beam can be evaluated by in-phantom parameters, from which therapeutic gain can be derived. Direct evaluation of both set of FOMs (in-air and in-phantom) is very time consuming. In this paper a Response Matrix (RM) method has been suggested to reduce the computing time. This method is based on considering the neutron spectrum at the beam exit and calculating contribution of various dose components in phantom to calculate the Response Matrix. Results show good agreement between direct calculation and the RM method.


Epidemiological features of biliary atresia in Taiwan, a national study 1996-2003.
The incidence of biliary atresia (BA) varies among different countries. It is supposed to be higher in Asian countries than in Western countries; however, the incidence of BA in Taiwan has not been well investigated. The aim of this study was to analyze the epidemiological characteristics and the incidence of BA in Taiwan. National Health Insurance (NHI) was implemented in Taiwan in 1995, and covers most of the population (>99%). We use the NHI database to investigate the epidemiological features of BA and compare Taiwan's annual BA incidence with that of other countries. We identified 327 new BA cases during the period from 1996 to 2003. The overall incidence of BA was 1.46 cases per 10 000 live births (0.89-1.90 per 10 000). The estimation was 1.32-1.65 per 10 000 after adjustment for the misdiagnosis rate. The peak incidence occurred in 2002 (1.90 per 10 000), accompanying Taiwan's dengue fever epidemic in 2002. The 5-year overall survival rate during 1999-2003 was higher than that during 1996-1998 (74.8% vs 61.1%, P = 0.014). Taiwan has the second-highest incidence of BA reported in world literature. Viral infection outbreaks remain a potential candidate as a cause of BA. The management of BA has been improving, with a better 5-year overall survival rate.


Maintained function of foreign and appropriate junctions on reinnervated goldfish extraocular muscles.
1. The ability of a multiply innervated muscle to become dually innervated, that is to accept a functional innervation from both its original and a foreign nerve, was investigated using the superior oblique muscle (s.o. muscle) of the goldfish.2. Dual innervation of s.o. muscles was achieved by allowing the original nerve (cranial NIV) to regenerate to its s.o. muscle which had been previously denervated and cross-innervated by a foreign nerve (cranial NIII), or by allowing the original and the foreign nerve to regenerate simultaneously to a denervated muscle.3. Behavioural observations suggested that in some fish reinnervation of the s.o. muscle by its original nerve repressed the function of a previously established foreign innervation. However, physiological tests which involved the stimulation of both foreign and appropriate nerves, and the recording of mechanical and electrical activity of the s.o. muscle, demonstrated that there was no functional displacement of foreign innervation on these muscles, even on individual dually innervated fibres.4. Dual innervation of the s.o. muscle persisted, apparently unchanged, for as long as the observations were continued (up to 7 months). The s.o. muscle contains two populations of fibres, fast and slow, and both types became and remained dually innervated.5. When both NIII and NIV were allowed to regenerate simultaneously to a denervated s.o. muscle there was no obvious selectivity in the final pattern of innervation. On the average both nerves elicited approximately equal tension from s.o. muscles, and evoked excitatory junctional potentials (e.j.p.s) of similar mean quantal contents.6. ;Myotypic respecification' was shown not to be responsible for the discrepancy between the behavioural results which sugested that repression of foreign innervation had occurred, and the physiological results which demonstrated that this was not the case. Anatomical and physiological findings indicated that the discrepancy was attributable to eye rotation produced by regenerated inferior oblique muscle fibres which contracted simultaneously with the cross-innervated s.o. muscle. The net result was an eye movement in which the activity of the s.o. muscle was masked.7. It is concluded that repression of established foreign neuromuscular connexions following reinnervation by the embryologically correct nerve does not occur on goldfish extraocular muscles. The s.o. muscle can become non-selectively innervated by both foreign and appropriate axons, and remains so, at least for several months.


Genetically incorporated crosslinkers identify regulators of membrane protein PD-L1 in mammalian cells.
Profiling membrane proteins' interacting networks is crucial for understanding their regulatory mechanisms and functional characteristics, but it remains a challenging task. Here, by combining genetic incorporation of crosslinkers, tandem denatured purification, and proteomics, we added interaction partners for PD-L1, a cancer cell surface protein that inhibits T cell activity. The site-specifically incorporated crosslinker mediates the covalent capture of interactions under physiological conditions and enabled the PD-L1 complexes to withstand the harsh extraction conditions of membrane proteins. Subsequent experiments led to the identification of potential PD-L1 interaction candidates and verified membrane-associated progesterone receptor component 1 as a novel PD-L1 interaction partner in mammalian cells. Importantly, we demonstrated that PGRMC1 positively regulates PD-L1 expression by regulating GSK3β-mediated PD-L1 degradation in cancer cells. Furthermore, PGRMC1 knockdown results in dramatically enhanced T cell-mediated cytotoxicity in cancer cells. In conclusion, our study elucidated the interactome of PD-L1 and uncovered a new player in the PD-L1 regulation mechanism.


Increased serum aminotransferases associated with anti-mitochondrial antibodies in systemic lupus erythematosus patients with autoimmune liver disease.
Serum aminotransferase activities are increased in many liver diseases, but the causes for the elevation might be difficult to determine. Whether the elevation of aminotransferases correlates with anti-mitochondrial antibodies (AMA) in systemic lupus erythematosus (SLE) patients with autoimmune liver disease deserves further consideration. A meticulous review was done in a large SLE cohort searching for laboratory features of the presence of AMA. Forty-eight hospitalized SLE patients with AMA and 60 randomly selected SLE patients without AMA as a matched case control were enrolled into the retrospective study. Laboratory data were collected, analyzed and compared in SLE patients with and without AMA. Serum activities of aminotransferases were significantly increased in the 48 SLE patients with AMA compared with the 60 subjects without AMA. Meanwhile, we found a positive correlation between serum AMA titers and serum aminotransferase activities. Although much remains to be learned about the pathogenesis of autoimmune liver disease associated with AMA, it is possible to suggest that AMA might contribute to the elevation of aminotransferases in SLE patients with the progressive disease.


A fully integrated continuous-time 50-Hz notch filter with center frequency tunability.
A novel continuous-time notch filter based on current steering technique was described in this paper. The second-order notch filter consisted of two integrators, one unity-gain inverter and two alpha blocks that were fully integrated onto a silicon chip. The circuit was implemented in SMIC mixed-signal 0.18 nm 1P6M process with the die area of 0.06 mm(2). Post-annotated simulation indicated the continuous-time notch filter was capable of providing 55.4 dB attenuation for the 50 Hz power line interference and its center frequency was tunable against process variations.


Antennal sensilla of the green bottle fly, Lucilia sericata (Meigen) (Diptera: Calliphoridae).
Lucilia sericata (Meigen) is a cosmopolitan synanthropic fly of forensic and medical importance, which can work as a mechanic vector of pathogens or cause myiasis of both human and sheep. As essential olfactory organs, antennae of adult L. sericata were examined with stereoscopic microscope, scanning electron microscope, and laser scanning confocal microscope. On antennal scape and pedicel, both microtirchiae and several bristles are detected, while another two structures, setiferous plaques and pedicellar buttons, are also found on the antennal pedicel. Seven subtypes of antennal sensilla are observed on antennal funiculus including one subtype of trichoid sensilla, two subtypes of basiconic sensilla, two subtypes of coeloconic sensilla, and two subtypes of sensory pits. Size and density of the former four types of sensilla on antennal funiculus are measured. Three distinctive sensillar characters of L. sericata are detected, which may contribute to greater olfactory sensitivity of this species and their wide distribution throughout the world. Unlike the common poreless pedicellar button with mechanoreceptor function, every pedicellar button in L. sericata is perforated by three pores, which might indicate potential chemoreceptor function of this structure. Besides, another unique feature is greater number of setiferous plaques in genus Lucilia than calliphorids of other genera. Expect for the common sensory pits with basiconic or basiconic-like sensilla in them, sensory pits filled with rarely described coeloconic-like sensilla are founded in L. sericata as well. After comparison with previous equivalent findings, the functions of these specific structures are discussed according to the life history of this calliphorid.


Polyacrylamide gel electrophoresis: reaction of acrylamide at alkaline pH with buffer components and proteins.
The chemical reaction of monomeric acrylamide with primary, secondary, and tertiary amines, used as buffer components in polyacrylamide gel electrophoresis systems, was investigated in the basic pH range. Adduct formation proceeded for several minutes up to weeks, depending on the reactivity of the amino groups. A pH shift in the reaction mixture due to an altered pK value of the reaction product was observed. However, a few primary amines (tris(hydroxymethyl)aminomethane, 2-amino-2-methyl-1,3-propanediol) and secondary amines 3-([2-hydroxy-1,1-bis(hydroxymethyl)ethyl]amino)-1-propanesulfonic acid, 3-(dimethyl(hydroxymethyl)methylamino)-2-hydroxypropanesulfonic acid) showed negligible shifts of pH. They are, therefore, useful as components in the polymerization mixture; whereas some tertiary amines showing complete pH stability as well (e.g., triethanolamine) are not suitable, as they acted as accelerators of gel polymerization. Acrylamide can also covalently bind to proteins by reacting with the epsilon-amino group of lysine residues, especially. Bovine serum albumin, having an acidic isoelectric point, and the basic protein cytochrome c were treated with different acrylamide concentrations at alkaline pH yielding modified protein molecules with altered electrophoretic mobilities in different polyacrylamide gel electrophoresis systems. This reaction gave rise to artifacts in alkaline polyacrylamide gels and isoelectric focusing systems when residual acrylamide monomers were still present in the gel matrix after the polymerization process ceased.


Impact of hyperoxia on patients hospitalized in an intensive care unit for acute heart failure.
Oxygen therapy remains a cornerstone of treatment for acute heart failure in patients with pulmonary congestion. While avoiding hypoxaemia has long been a goal of critical care practitioners, less attention has been paid to the potential hazard related to excessive hyperoxia. To evaluate the impact of early hyperoxia exposure among critically ill patients hospitalized in an intensive care unit for acute heart failure. In this preliminary study conducted in a Parisian intensive care unit, we assessed patients with acute heart failure admitted with pulmonary congestion and treated with oxygen therapy from 1 January 2015 to 31 December 2016. The hyperoxia group was defined by having at least one partial pressure of oxygen measurement>100mmHg on the first day following admission to the intensive care unit. The primary endpoint was 30-day all-cause mortality. Secondary endpoints were 30-day unplanned hospital admissions, occurrence of infections and intensive care unit and hospital lengths of stay. Seventy-five patients were included. Forty-three patients (57.3%) presented hyperoxia, whereas 32 patients (42.7%) did not (control group). The baseline clinical characteristics did not differ between the two groups. The primary endpoint was not statistically different between the two groups (14.0% in the hyperoxia group vs 18.8% in the control group; P=0.85). The secondary endpoints were also not significantly different between the two groups. In the multivariable analysis, hyperoxia was not associated with increased 30-day mortality (odds ratio 0.77, 95% confidence interval 0.24-2.41). In patients referred to an intensive care unit for acute heart failure, we did not find any difference in outcomes according to the presence of hyperoxia.


Nitric oxide as an early marker of human embryo metabolic cleavage in ART using fresh or thawed oocytes.
To study a possible role of nitric oxide (NO) as a marker of development in the early phases of human embryo cleavage during assisted reproduction. 179 women having ART were included. 123 women used fresh oocytes and 56 oocyte thawing cycles in the Center of Reproductive Medicine, Department of Obstetrics and Gynecology, Arcispedale S. Maria Nuova, between July 2005 and June 2006; 57 patients had IVF and 122 patients had ICSI. NO concentrations in IVF or ICSI embryo culture media were assessed by monitoring levels of NO stable oxidation products (nitrites/nitrates). Analysis of embryo quality was performed. Student's t-test or Mann-Whitney and logistic regression model tests were applied to the data. In patients using fresh oocytes, there were greater NO production in embryos derived from ICSI than from IVF after 52 h of culture (38.64 micromol/L vs 11.2 micromol/L, p<0.05). No correlation with embryo quality was observed. Embryos derived from fresh oocytes produce more NO than embryos from thawed oocytes both after 48 and 52 h of culture (16.12 micromol/L vs 6.83 micromol/L and 25.93 micromol/L vs 2.98 micromol/L respectively, p<0.05). NO in embryo culture media is not a metabolic cleavage marker or a marker of embryo quality in ART. However, it could be an important parameter in the investigation of metabolism in frozen/thawed oocytes.


Relationships between personality traits and disordered eating among Chinese female exercisers: the role of symptoms of exercise dependence and obsessive-compulsiveness.
Although numerous studies have examined associations between personality traits and eating disorders in females, few studies have been conducted on female exercisers. Given the high risk of disordered eating in female exercisers, this study investigated the associations between the Big Five personality traits and disordered eating in female exercisers, and further explored the potential mediators, namely exercise dependence symptoms, and obsessive-compulsive symptoms underlying this association. A total of 295 female exercisers aged between 18 to 67 years (M = 22.11, SD = 6.65) participated in this study. Negative and statistically significant correlations between conscientiousness (r = - 0.17, p < 0.01), emotional stability (r = - 0.27, p < 0.001) and agreeableness (r = - 0.18, p < 0.01) and disordered eating were observed in our sample of female exercisers. The multiple mediation analyses revealed that exercise dependence symptoms and obsessive-compulsive symptoms mediate the relationship between conscientiousness (β = 0.016, CI = [0.003, 0.031]), emotional stability (β = -0.012, CI = [- 0.028, - 0.002]), and disordered eating in female exercisers, whereas obsessive-compulsive symptoms (β = - 0.041, CI = [- 0.088, - 0.001]) but not exercise dependence symptoms are a mediator of the relationship between agreeableness and disordered eating. Our findings can be used to improve the screening procedures for eating disorders in female exercisers as they contribute to a better understanding of the psychological mechanisms that underlie the associations between the Big Five personality traits and disordered eating.


Establishment of monolayer culture of pig pancreatic endocrine cells by use of nicotinamide.
A method for the isolation and primary monolayer culture of adult pig pancreatic endocrine (PE) cells was established. Cells were dissociated from the pancreas by autodigestion without addition of proteolytic enzymes and separated into distinct bands in a single centrifugation step using Histopaque-1077 (a mixture of polysucrose and sodium diatrizoate). The cells collected from an interfacial fraction were suspended in RPMI 1640 containing 11 mmol/l D-glucose with or without nicotinamide (0, 10, 20, 40 mmol/l), and then placed in culture dishes. Pancreatic cells formed a monolayer while fibroblasts became detached from the bottom of the dish when cultured in the presence of nicotinamide. More than 80% of monolayer-forming cells were stained for insulin, using an enzymatic method, and were identified as B-cells. Morphologically, the PE cells extended multiple processes terminating in growth-cone-like structures, as visualized by both light microscopy and scanning electron microscopy. Insulin secretion in response to glucose stimulation occurred for 35 days of incubation in the RPMI 1640 medium, with or without nicotinamide. Exposure of the cells to nicotinamide for 35 days resulted in a 2-3-fold increase in insulin secretion in response to high glucose stimulus (16.7 mmol/l) compared with low glucose (5.5 mmol/l). Glucose-induced Ca2+ responses were examined in individual cells cultured for 35 days in the presence of 10 mmol/l nicotinamide, using Ca2+ imaging with fura-2. These results indicate that it is possible to prepare pig PE cells in monolayer culture with low fibroblast contamination and to maintain functioning B-cells in vitro for relatively long periods. The present method provides useful preparations for further morphological and physiological studies on the differentiation, growth and regenerative capacity of islet cells.


Defining the key parameters for comparing reactions among acellular and whole-cell pertussis vaccines.
To facilitate future vaccine reaction data collection and analysis, we sought to determine the minimum data set required to describe accurately and to compare common reactions after the administration of acellular (DTaP) or whole-cell (DTP) pertussis vaccine with diphtheria and tetanus toxoids combined. Thirteen DTaP and 2 DTP vaccines were studied in a multicenter trial involving 2342 infants who received a primary series of vaccinations at 2, 4, and 6 months of age. Temperature, fussiness, redness, swelling and pain at the injection site, antipyretic use, drowsiness, loss of appetite, and vomiting were evaluated. Reactions were assessed at 3 hours and (if not immunized in the evening) 6 hours after immunization, at bedtime each evening for 7 evenings, and on the 14th evening after immunization. Two reaction assessment approaches were compared: (1) analysis of all reactions, regardless of the degree of severity; and (2) a condensation of the data to five key reactions (fever > 100 degrees F, moderate or more fussiness, any local redness, any local swelling, and moderate or more local pain). We found that the onset of reactions was infrequent beyond the second evening, and that collection and analysis of reaction data beyond that time did not further discriminate among the vaccines. Information regarding antipyretic use, loss of appetite, drowsiness, or vomiting did not assist in differentiating among these vaccines. Monitoring the occurrence of fever greater than 100 degrees F, moderate or severe fussiness, injection site redness or swelling, and moderate or severe injection site pain occurring through the second evening after immunization will provide the minimum data set needed to discriminate among DTaP and DTP vaccines with respect to the common adverse reactions.


Raising the Evidentiary Bar for Guideline Recommendations for TAVR: JACC Review Topic of the Week.
On August 16, 2019, the U.S. Food and Drug Administration approved expanding the indication for transcatheter aortic valve replacement (TAVR) to low-risk patients with symptomatic severe aortic stenosis. The decision was based on the results of 2 pivotal trials that confirmed superiority (PARTNER [Placement of Aortic Transcatheter Valves] 3) or noninferiority (Evolut Low Risk [LR]) of TAVR as compared with SAVR at 1- and 2-year follow-up, respectively. As compared with intermediate-risk cohorts, the sample size in these trials was smaller and the total number of primary endpoint events was nearly 3 times as low (193 vs. 615). The total number of deaths from any cause or disabling stroke at 1 year in the low-risk cohorts was 62, which is substantially lower than the numbers in intermediate-, high-, and inoperable-risk cohorts. In Evolut LR, only 137 of 1,403 patients (9.8%) completed the 2-year follow-up, with 91.2% requiring model-based imputation. Thus, the quantum of evidence is insufficient for endorsing TAVR as the preferred intervention for these patients.


Separation and purification of S49 mouse lymphoma histones by reversed-phase high-performance liquid chromatography.
A rapid reversed-phase high-performance liquid chromatography procedure for the fractionation of histones from S49 mouse lymphoma cells is reported. The system utilizes a Vydac C4 macroporous column, heptafluorobutyric acid as solubilizing and ion-pairing agent, and an acetonitrile gradient. All five histone classes and several subclass species are separated, including two H1 species, H2B, two H2A species, H4, and two H3 species. Analytical to multimilligram semipreparative scale fractionations are demonstrated while maintaining resolution of all histone types.


Vasculitis related to viral and other microbial agents.
Vasculitis due to infection may occur as a consequence of the inflammation of vessel walls due to direct or contiguous infection, type II or immune complex-mediated reaction, cell-mediated hypersensitivity, or inflammation due to immune dysregulation triggered by bacterial toxin and/or superantigen production. As immunosuppressive therapy administered in the absence of antimicrobial therapy may increase morbidity and fail to effect the resolution of infection-associated vascular inflammation, it is important to consider infectious entities as potential inciting factors in vasculitis syndromes. The causality between infection and vasculitis has been established in hepatitis B-associated polyarteritis nodosa (HBV-PAN) and hepatitis C-associated (cryoglobulinemic) vasculitis (HCV-CV). The review summarizes the recent literature on the pathophysiological mechanisms and the approaches to the management of HBV-PAN and HCV-CV. Roles of other viral and microbial infections, which either manifest as vasculitic syndromes or are implicated in the pathogenesis of primary vasculitides, are also discussed.


The short-lip deformity after triangular flap repair: a lengthening technique.
A method for lengthening of the short lip after triangular-flap repair of the unilateral cleft lip is documented. This technique offers a minimal additional scar line and a maximum effect.


[Acrodermatitis enteropathica (author's transl)].
In connection with the clinical observation of their five patients suffering from AE the authors summarize current questions related to this disease. They examined the function of the cellular immunity in this disease. They call attention to dangers of oxychinoline treatment, and to benefits of zinc administration. They established that the introduction of zinc therapy indicates a progress in the treatment of AE.


Investigation of the prognostic value of CD4 T cell subsets expanded from tumor-infiltrating lymphocytes of colorectal cancer liver metastases.
The positive role of CD8+ tumor-infiltrating lymphocytes (TIL) in patients with colorectal cancer (CRC) has been well described but the prognostic value of CD4 T cell subsets remained to be investigated. In this study, we expanded TIL from surgically resected liver metastases of patients with CRC and characterized the phenotype and the prognostic value of expanded-CD4 T cells. Liver metastases were surgically resected from 23 patients with CRC. Tumors were enzymatically digested and cultured in high dose of interleukin-2 for up to 5 weeks. T cell phenotype and reactivity of cultured-T cells were measured by flow cytometry and correlated with patients' clinical outcomes. We successfully expanded 21 over 23 TIL from liver metastases of patients with CRC. Interestingly, we distinguished two subsets of expanded T cells based on T cell immunoglobulin mucin domain-containing protein 3 (TIM-3) expression. Medians fold expansion of expanded T cells after rapid expansion protocol was higher in CD3+TIM-3low cultures. In an attempt to investigate the correlation between the phenotype of expanded CD4 T cells and clinical outcomes, we observed on one hand that the level of Tregs in culture as well as the expression of both PD1 and TIM-3 by expanded T cells was not correlated to the clinical outcomes. Interestingly, on the other hand, cultures containing high levels of Th17 cells were associated with a poor prognosis (p=0.0007). Our data confirmed the presence of Th17 cells in expanded T cells from liver metastases. Among CD4 T cell characteristics investigated, TIM-3 but not programmed cell death protein 1 predicted the expansion capacity of TIL while only the Th17 phenotype showed correlation with patients' survival, suggesting a particular role of this T cell subset in CRC immune contexture. NCT02817178.


DHA regulates angiogenesis and improves the efficiency of CDDP for the treatment of lung carcinoma.
Dihydroartemisinin (DHA), a semisynthetic derivative of artemisinin, has been shown to exhibit anti-angiogenic and anti-tumor effects apart from its antimalarial activity. In this study, we demonstrate that the combined treatment of cisplatin (CDDP) and DHA exerts a strong, synergistic anti-proliferative effect in human lung carcinoma cells, including A549 and A549/DDP cells, with an average combination index below 0.7. Moreover, the in vivo anti-tumor efficacy of CDDP treatment was increased by DHA. The enhanced anti-cancer activities were also accompanied by reduced tumor microvessel density, increased CDDP concentration within A549 and A549/DDP xenograft BALB/c athymic mice models and suppressed expression of the vascularization-related proteins HIF-1α and VEGF both in vivo and in vitro. Furthermore, the level of apoptosis in the tumor cells increased with the combined treatment of DHA and CDDP. Taken together, our results indicate that a combination of DHA and CDDP treatments synergistically affects tumor angiogenesis, and these results provide a clear rationale for the investigation of these drugs in future clinical trials.


Proinflammatory maternal diet and early weaning are associated with the inflammatory diet index of Brazilian children (6-12 mo): A pathway analysis.
The aim of this study was to assess the dietary inflammatory index (DII) and its association with maternal factors and excess body weight in Brazilian children aged <2 y during complementary feeding. This was a cross-sectional study (2016-2019), conducted with 231 mothers and children ages 6 to 24 mo. The food consumption of the mother-child dyad was obtained through the mean of three 24-h recalls, as well as information on the consumption of breast milk. The DII was used to verify the quality of the diet. Children's weight and length were measured, and the weight/height index was calculated. Path analysis was used to assess the interrelationships between variables. Multiple linear regression was conducted to identify the components of the child's DII (C-DII) that contributed the most to explaining its variation. The children had an anti-inflammatory diet (C-DII -0.37 ± 0.91) whereas the mothers had a proinflammatory diet (M-DII +0.24 ± 0.86). Fiber was the nutrient that contributed most to the variations in the C-DII. Approximately 28% of children were overweight. In the pathway analysis, we verified a direct negative effect of education on excess body weight (standardized coefficients [SC], -0.180; P = 0.034) and C-DII (SC, -0.167; P = 0.002); negative direct effect of breastfeeding on the C-DII (SC, -0.294; P < 0.001); and positive direct effect of M-DII on C-DII (SC, 0.119; P = 0.021). Children's proinflammatory diet during the period of complementary feeding was associated with maternal proinflammatory diets, lower education, and absence of breastfeeding practice.


A case of enteroviral meningoencephalitis presenting as rapidly progressive dementia.
A 70-year-old immunocompetent male presented to a memory disorders clinic with a 7-month illness that had begun with somatic complaints including transient right temporal head pain, left buttock pain, and right conjunctival injection. About 3 months after the first signs of illness, the patient had begun to develop insidious cognitive and behavioral decline, which progressed most rapidly in the 2 months before presentation. An assessment completed during hospitalization for intermittent fevers and confusion had not revealed an infectious etiology, although mild pleocytosis in the cerebrospinal fluid had been noted. Upon presentation to the memory disorders clinic, the patient was disoriented, distractible, laughed at inappropriate moments, and followed only one-step commands. He had hypophonic speech and had mildly increased axial tone. He scored 5 out of 30 on the Mini Mental State Examination and was admitted for expedited evaluation. Physical examination, brain MRI, electroencephalogram, lumbar puncture, autoimmune and paraneoplastic testing, cerebral angiogram, cerebrospinal fluid analysis, enterovirus group-specific reverse transcriptase polymerase chain reaction assay, and RNA sequencing in brain biopsy samples. Enteroviral meningoencephalitis. Intravenous steroids with oral taper and intravenous immunoglobulin.


Neuronal cell-based medicines from pluripotent stem cells: Development, production, and preclinical assessment.
Brain degeneration and damage is difficult to cure due to the limited endogenous repair capability of the central nervous system. Furthermore, drug development for treatment of diseases of the central nervous system remains a major challenge. However, it now appears that using human pluripotent stem cell-derived neural cells to replace degenerating cells provides a promising cell-based medicine for rejuvenation of brain function. Accordingly, a large number of studies have carried out preclinical assessments, which have involved different neural cell types in several neurological diseases. Recent advances in animal models identify the transplantation of neural derivatives from pluripotent stem cells as a promising path toward the clinical application of cell therapies [Stem Cells Transl Med 2019;8:681-693; Drug Discov Today 2019;24:992-999; Nat Med 2019;25:1045-1053]. Some groups are moving toward clinical testing in humans. However, the difficulty in selection of valuable critical quality criteria for cell products and the lack of functional assays that could indicate suitability for clinical effect continue to hinder neural cell-based medicine development [Biologicals 2019;59:68-71]. In this review, we summarize the current status of preclinical studies progress in this area and outline the biological characteristics of neural cells that have been used in new developing clinical studies. We also discuss the requirements for translation of stem cell-derived neural cells in examples of stem cell-based clinical therapy.


Skeletal muscle ergoreflex overactivity is not related to exercise ventilatory inefficiency in non-hypoxaemic patients with COPD.
Increased ventilatory response to the metabolic demand ("ventilatory inefficiency") is commonly found during dynamic exercise in patients with chronic obstructive pulmonary disease (COPD). However, the role of enhanced muscle ergoreflex activity on this phenomenon is yet unknown. Ten non-hypoxaemic patients with varying degrees of disease severity (median and range of post-bronchodilator FEV(1) = 37.5 (27 to 70%) predicted) and 7 age- and gender-matched controls were studied. Subjects were submitted to wrist flexion tests to the limit of tolerance (Tlim) with and without post-exercise regional circulatory occlusion (PE-RCO) for 3 min. The muscle ergoreflex activity was quantified as the difference in ventilation between PE-RCO and control recovery periods corrected for the resting values (ergoreflex Delta). In addition, the area under the ventilatory curve in the recovery period was calculated in both conditions. We found that Tlim and the physiological stress associated with localized exercise did not differ between patients and controls. However, patients had increased ventilatory response to a given metabolic demand (VCO(2)), either at rest or during exercise (P < 0.05). There were no significant differences in ergoreflex Delta in patients and controls (-2.2 to 2.4 (0.2) vs. -0.6 to 1.8 (0.3) l/min, respectively). In addition, the area under the ventilatory curve in the recovery period did not differ between control and PE-RCO tests in patients and healthy subjects (P > 0.05). We conclude that increased muscle ergoreflex activity did not contribute to an excessive ventilatory response to exercise in patients with COPD-at least in non-hypoxaemic and non-cachetic subjects.


Gene expression of collagenase and stromelysin in skin fibroblasts derived from dystrophic epidermolysis bullosa.
We studied expression of collagenase gene and stromelysin gene in skin fibroblasts derived from patients with recessive dystrophic epidermolysis bullosa (RDEB) and dominant dystrophic epidermolysis bullosa (DDEB). Northern blot analyses revealed that collagenase gene expression was markedly increased in two of four RDEB cells, as compared with three normal control cells. Moreover, stromelysin gene expression was also markedly increased in two RDEB cells, as compared with normal controls. In contrast, collagenase and stromelysin gene expression levels in three DDEB cells did not show any significant difference from those of normal controls, except one cell line which showed mild increase of both collagenase and stromelysin mRNA. Quantitative estimates of collagenase mRNA (U/micrograms RNA) determined by slot blot hybridizations showed that those of RDEBs: 0.92-1.81 (mean 1.3 +/- 0.45); DDEBs: 0.18-0.73 (mean 0.60 +/- 0.37); normal controls: 0.26-0.93 (mean 0.64 +/- 0.34). Stromelysin mRNA levels showed that those of RDEBs: 1.75-6.62 (mean 4.06 +/- 2.00); DDEBs: 0.55-3.78 (mean 1.69 +/- 1.81); normal controls: 1.27-2.08 (mean; 1.55 +/- 0.45). These data demonstrated that collagenase and stromelysin gene expression was increased in some, but not all, RDEB cell lines. Our data suggested that collagenase and/or stromelysin could play a certain role for blister formation in RDEB, coordinately or in a distinct manner.