MicroRNA-155 may affect allograft survival by regulating the expression of suppressor of cytokine signaling 1.
Immune rejection of organ transplants has life-threatening implications. It is believed that allograft rejection is initiated by the activation of lymphocytes following recognition of donor antigens, leading to generation of effector T lymphocytes, alloantibody production, and graft infiltration by alloreactive cells. There is solid evidence that miRNAs are integral for maintaining immune homeostasis and self-tolerance. A deeper understanding of the regulation of the immune response by miRNAs could define new mechanisms for manipulating graft immunity and preventing rejection. The miRNA miR-155 is of particular interest due to its known roles in regulating the expression of genes relevant to allograft rejection and the induction of immune tolerance. Indeed, miR-155 has been shown to dramatically impact both innate and adaptive immune processes, including inflammation, antigen presentation, T-cell differentiation, cytokine production, and T regulatory cell (Treg) functions. The suppressor of cytokine signaling 1 (SOCS1) is a critical regulator of immune cell function and an evolutionarily conserved target of miR-155 in breast cancer cells. We propose that suppression of miR-155 could enhance SOCS1 expression in immune cells and suppress allograft rejection. Further studies on the specific role of miR-155 in allograft rejection may lead to the identification of new targets for therapeutic intervention.


p300 mediates the histone acetylation of ORMDL3 to affect airway inflammation and remodeling in asthma.
Bronchial asthma is affected by both environmental and genetic factors. The orosomucoid 1-like protein 3 (ORMDL3) gene is related to childhood asthma and is involved in airway inflammation and airway remodeling. The ORMDL3 promoter contains binding sites for the histone acetylase p300. Gene expression can be affected by epigenetic modifications. This study aimed to investigate whether the p300-mediated histone acetylation (HAT) of ORMDL3 gene affects airway inflammation and remodeling in asthma. 16HBE14o- cells were transfected with various concentrations of a wild-type p300 plasmid or p300HAT-deletion plasmids. A dual luciferase reporter assay was used to examine the effect of p300-mediated HAT on the ORMDL3 promoter. Thirty BALB/c mice were randomly divided into a control group, an ovalbumin (OVA)-induced asthma group and an asthma + C646 (a selective inhibitor of p300) group. Noninvasive lung function tests were conducted to examine airway hyperreactivity (AHR) in the different groups. HE and Masson's trichrome staining was performed to examine airway remodeling and inflammation. Immunohistochemistry, western blotting and real-time PCR were used to analyze ORMDL3 expression in lung tissues. ELISA and western blotting were used to evaluate the HAT status in lung tissue. The ChIP assay was used to determine the relationship of the ORMDL3 promoter to p300 or acetylated histone H3 (aceH3). p300 activated transcription from the ORMDL3 promoter, resulting in an increase in endogenous ORMDL3 mRNA levels. ORMDL3 promoter activity was reduced when the HAT activity of p300 was lost. ORMDL3 expression was elevated, and HAT activity was high in the lung tissues of asthmatic mice. p300 and aceH3 bound to the promoter region of ORMDL3. In the asthma group, the amounts of p300 and aceH3 recruited to the ORMDL3 promoter were increased. C646 inhibited p300 expression and reduced HAT activity and aceH3 levels in asthmatic mice, thereby reducing ORMDL3 expression and relieving AHR and airway remodeling. p300-mediated HAT modulates the expression of the asthma susceptibility gene ORMDL3, thereby improving the process of airway inflammation and remodeling in asthma.


Nanoplateletsomes restrain metastatic tumor formation through decoy and active targeting in a preclinical mouse model.
Platelets buoy up cancer metastasis via arresting cancer cells, enhancing their adhesion, and facilitating their extravasation through the vasculature. When deprived of intracellular and granular contents, platelet decoys could prevent metastatic tumor formation. Inspired by these, we developed nanoplatesomes by fusing platelet membranes with lipid membranes (P-Lipo) to restrain metastatic tumor formation more efficiently. It was shown nanoplateletsomes bound with circulating tumor cells (CTC) efficiently, interfered with CTC arrest by vessel endothelial cells, CTC extravasation through endothelial layers, and epithelial-mesenchymal transition of tumor cells as nanodecoys. More importantly, in the mouse breast tumor metastasis model, nanoplateletsomes could decrease CTC survival in the blood and counteract metastatic tumor growth efficiently by inhibiting the inflammation and suppressing CTC escape. Therefore, nanoplatelesomes might usher in a new avenue to suppress lung metastasis.


Modeling protein folding: the beauty and power of simplicity.
It is argued that simplified models capture key features of protein stability and folding, whereas more detailed models may be more appropriate for protein structure prediction. A brief overview of experimental and theoretical results is presented that corroborates these points. I argue that statistical models capture the key principle of protein stability-cooperativity- and therefore provide a reasonable estimate of protein free energy whereas more detailed but less physically transparent calculations fail to do so. I also explain that the previously published claim that simple models give predictions that are inconsistent with experiments on polypeptide block-copolymers is based on incomplete analysis of such experiment.


Hybrid procedures combining conventional and thoracic endovascular aortic repair for thoracic aortic aneurysms.
To minimize surgical invasiveness for extensive aortic aneurysms and expand the indications for thoracic endovascular aortic repair (TEVAR), we evaluated outcomes of hybrid procedures combining conventional surgical aortic repair and TEVAR for thoracic aortic aneurysms. The following hybrid procedures were performed: second-stage TEVAR after total aortic arch replacement using the elephant trunk as the landing zone in 17 patients; and for multiple aortic aneurysms, vascular graft replacement and TEVAR in 13 patients, vascular graft replacement and TEVAR with bypass in 2 patients, and TEVAR with bypass in 23 patients. There were three (5.3%) hospital deaths, from serious complications including stroke, paraplegia, paraparesis, and aspiration pneumonia; and eight late deaths. There was only one aneurysm-related death, of a patient who underwent emergency surgery for an esophageal fistula resulting from enlargement of a residual false lumen of a thoracoabdominal aorta after second-stage TEVAR. Hybrid procedures minimize surgical invasiveness in thoracic aortic aneurysm repair, but further evaluation of a larger number of patients is necessary.


Effects of multidisciplinary interventions on weight loss and health outcomes in children and adolescents with morbid obesity.
Morbid obesity is the fastest growing subcategory of childhood obesity, associated with an increased health risk that persists into adulthood. There is an urgent need to develop multifaceted interventions that target initial and long-term lifestyle changes. This review investigates the effects of multidisciplinary interventions on weight loss and health outcomes in children and adolescents with morbid obesity. The influence of age, gender and family participation on health outcomes and intensive treatment alternatives are explored. The review includes 16 studies conducted between 1995 and 2017. Studies examined youth with morbid obesity, 4-18 years old, undergoing multidisciplinary treatment. All studies found a reduction in body mass index (BMI or z-score) and if measured, cardiovascular risk factors. Physical activity, nutrition education, behavioural modification and family involvement are commonly included treatment components and have improved weight loss and health-related outcomes. However, initial weight loss was often not sustainable, despite the favourable interventional effect on cardiometabolic risk markers. Weight loss was prolonged in younger children and among the male sex. There is not a 'one-size-fits-all' treatment approach, and matched care to personal needs is preferable. The integration of a chronic care approach is critical for the successful adaption of sustainable health behaviours.


Successful rescue of a lethal Griscelli syndrome type 2 presenting with neurological involvement and hemophagocytic lymphohistiocytosis: a case report.
Griscelli syndrome type 2 (GS2) is a rare autosomal recessive disease caused by mutations in RAB27A gene. It is primarily characterized by a combination of partial albinism, hemophagocytic lymphohistiocytosis (HLH) or other immunodeficiency. However, neurological involvement at onset in GS2 and treatment has rarely been described. We describe a 3-year-old boy with GS2 in an Asian Chinese family. He presented with progressive neurological abnormalities following unremitting fever at onset. He developed HLH during the clinical course. A novel homozygous mutation (c.1 A > G) in RAB27A gene was subsequently identified. He was then treated by HLH-1994 protocol combined with ruxolitinib and experienced a dramatic remission. He subsequently underwent a successful haploidentical hematopoietic stem cell transplantation and stayed at a good condition. We reported an atypical form of GS2 manifesting as severe central nervous system involvement at onset and subsequent HLH, which was successfully rescued in time. This case also highlights the need for early consideration of immunologic and genetic evaluation for HLH in unexplained neuroinflammation in the diagnostic work up.


Safer outcomes for placenta accreta spectrum disorders: A decade of quality improvement.
To describe the evolution and evaluation of protocol-based multidisciplinary quality improvement (QI) in women undergoing cesarean hysterectomy for radiologically suspected and pathologically confirmed placenta accreta spectrum (PAS) disorders. A single-center, retrospective cohort study was conducted of all patients undergoing cesarean hysterectomy for PAS disorders between March 2009 and June 2018. Two distinct periods were defined to compare outcomes: 2009-2011 (initial period) and 2017-2018 (current period). Primary outcomes included blood loss and administration of blood products. Secondary outcomes included perioperative levels of hemoglobin, adverse events and complications, time to mobilization, and length of hospitalization. Among the 105 consecutive patients identified, there were 26 in the initial period and 32 in the current period. With the implementation of all QI care bundles, median estimated surgical blood loss halved from 2000 ml in the initial period to 1000 ml in the current period, and fewer patients required allogenic blood transfusion (61.5% vs 25%). Patients in the current period demonstrated improved postoperative levels of hemoglobin compared to those in the initial period (101 g/L vs 89 g/L) and had a shorter median postoperative hospital stay (3 days vs 5 days). These results support the implementation of a multifaceted QI and patient care initiative for women with PAS disorders.


Arguments raised by the recent discovery that insulin and leptin are expressed in and secreted by human ejaculated spermatozoa.
The recent findings demonstrating that insulin and leptin are expressed in and secreted by human ejaculated spermatozoa raise the controversial issue related to mRNA function in male gamete. Capacitated sperm display an increased metabolism and overall energy expenditure presumably to affect the changes in sperm signaling and function during capacitation. However the relationship between the signaling events associated with capacitation and the change in sperm metabolism energy is poorly understood. It emerges from the findings here reported that both leptin and insulin may be crucial in ejaculated spermatozoa to manage their energy status. Immunoistochemical analysis revealed that in uncapacitated sperm insulin was located at the subacrosomial level, in the midpiece and through the tail while leptin was immunodetected at the equatorial segment and at the midpiece. Capacitated sperm display an overall decrease and a more uniform distribution in the signal for both hormones and this is in agreement with their enhanced release in the medium. Both hormones in ejaculated sperm somehow recapitulate the cross-talk between their signalling transductional pathways in somatic cells, resulting in the increase of phosphoinositide 3-kinase (PI3K) activity, AKT S473 and Glycogen synthase kinase 3 (GSK-3)-S9 phosphorylations. During capacitation GSK-3 phosphorylation was abolished suggesting how in capacitating sperm there is a block in glycogen synthesis. This reasonably indicates how during capacitation glycogen reserve is mobilized and this makes the glucose as energy substrate available. For instance insulin dismissed by ejaculated spermatozoa up-regulates Glucose 6-Phosphate Dehydrogenase (G6PDH), the rate-limiting enzyme in the pentose phosphate pathway (PPP), which has be shown to be crucial in the acquisition of fertilizing capability as well as to mediate gamete fusion. Insulin immunoneutralization or blockage of its release, dramatically down regulated G6PDH. Interestingly, in the presence of a disruptor of insulin signaling wortmannin, an inhibitor of PI3K, the intrinsic activity of G6PDH drops. Leptin appears to play similar action to that of insulin on G6PDH in sperm (data in progress). The enhanced activity of this enzyme induced by both hormones produces an increase of NADPH that is essential for fatty acid synthesis from acetyl CoA. These fatty acids have two possible fates: beta-oxidation to produce ATP or reesterification back into triacylglycerol. Inter-relationships of the classes of substrates of free fatty acids (FFA) and glucose utilized for energy, has been long established [Randle, P.J., 1964. The interrelationships of hormones, fatty acid and glucose in the provision of energy. Postgrad. Med. J. 40, 457-463]. The authors observed in ejaculated spermatozoa what it occurs in somatic cells: FFA beta-oxidation tested utilizing the octanoil-CoA as substrate, appears to be stimulated by leptin and down-regulated by the contemporaneous presence of insulin in uncapacitated sperms. FFA beta-oxidation activity dramatically increases when capacitation starts, so it may be assumed the possibility that leptin may work to stimulate such enzymatic activity providing additional metabolic fuel to triggering capacitation process. The autonomous capability of sperm to release insulin and leptin suggests that they through an autocrine short loop may provide the recruitment of energy substrate according to sperm metabolic needs. This occurs independently by the systemic regulation and may represent a protective mechanism which preserves sperm fertilizing capability by any detrimental effects produced by long calorie restriction or by alterations occurring in the energy homeostasis at systemic level.


Electrical coupling and gap junctions between neurosecretory cells in an insect.
Intracellular injections of Lucifer yellow into single neurosecretory cells in the posterior (glandular) lobe of the corpus cardiacum of locusts resulted in dye transfer between these cells. Passage of hyperpolarizing or depolarizing current into one cell resulted in changes in the membrane potential of other cells. Freeze-fracture replicas of these cells revealed gap junctions which probably mediate the electrical and dye coupling. It seems apparent from these data that coupling may synchronize the neurosecretory cells' activity.


Effects of thalassemia on pregnancy outcomes of women with gestational diabetes mellitus.
To explore the effect of thalassemia on pregnancy outcomes of women with gestational diabetes mellitus (GDM). This retrospective study reviewed the medical records of women with GDM delivered at the Chongqing Maternal and Child Health Hospital in China between July 2017 and December 2020. The live singleton pregnancies with α or β-thalassemia were identified as the thalassemia group, included α-thalassemia subgroup and β-thalassemia subgroup, whereas pregnant women without thalassemia were randomly selected as the non-thalassemia group according to a control-to-case ratio of 10:1 by computerized randomization. Logistic regression analyses were used to explore the potential association between thalassemia and pregnancy outcomes. A total of 223 pregnant women with GDM and thalassemia were analyzed, including women with α-thalassemia (n = 143) and β-thalassemia (n = 80). There were no significant differences in the incidence of adverse neonatal outcomes such as preterm birth and low-birth weight among groups. However, among pregnancy complications, significant differences were detected in the incidence of placenta increta, polyhydramnios, and postpartum anemia between the thalassemia group and the non-thalassemia group. Logistic regression results indicated that β-thalassemia increased the risk of polyhydramnios (odds ratio [OR] = 3.95, 95% confidence interval [CI]: 1.14-13.65, p = 0.030) and chorioamnionitis (OR = 3.61, 95%CI: 1.04-12.49, p = 0.043) compared with the non-thalassemia group. In our study, thalassemia did not increase adverse neonatal outcomes, but β-thalassemia increased the risk of pregnancy complications, including polyhydramnios and chorioamnionitis.


Recent Advances on the Role of EGFR Tyrosine Kinase Inhibitors in the Management of NSCLC With Uncommon, Non Exon 20 Insertions, EGFR Mutations.
The first-line treatment of choice for patients with EGFR mutation-positive NSCLC is an EGFR tyrosine kinase inhibitor (TKI), of which five as follows are predominantly available in practice: gefitinib, erlotinib, afatinib, dacomitinib, and osimertinib. Most prospective clinical trial data with these agents are limited to patients with the common activating and sensitizing EGFR mutations as follows: exon 19 deletions and exon 21 L858R point mutations. However, 10% to 20% of patients with NSCLC harbor uncommon EGFR mutations that have variable sensitivity to different EGFR TKIs. Owing to their molecular structures, afatinib, dacomitinib, and osimertinib have broader inhibitory profiles than the first-generation agents, gefitinib and erlotinib. Nevertheless, the paucity of prospective clinical data, the wide heterogeneity of uncommon mutations, and the existence of compound mutations in up to 25% of the cases complicate treatment decisions in this patient subgroup. Here, we collate the latest preclinical and clinical data regarding the activity of different TKIs against major uncommon EGFR mutations including compound mutations, but excluding exon 20 insertions which are generally insensitive to TKIs. On the basis of these data, we offer suggestions regarding treatment strategies for uncommon EGFR mutations. Moving forward, it will be important to include uncommon EGFR mutations in the first-line molecular analysis of all patients with adenocarcinoma of the lung, as this will help optimize patient outcomes according to their precise genotype.


[DIFFERENTIAL APPROACH TO THE EVALUATION OF RIGHT VENTRICULAR SYSTOLIC FUNCTION BY PULSED WAVE DOPPLER ULTRASOUND].
A method for diagnostics of systolic function of the right ventricle of the heart in patients with cardiovascular disease is proposed. Its application expands possibilities for detecting disorders of the discharge RV function using a conventional pulsed wave Doppler ultrasonography.


Angiotensin converting enzyme inhibition unmasks the sympathofacilitatory effect of bradykinin in human right atrium.
To investigate the role of angiotensin converting enzyme (ACE) inhibition in bradykinin-mediated modulation of noradrenaline release in human and rat atrium. Human and rat atrial slices were incubated with [3H]-noradrenaline, superfused with Krebs-Henseleit solution and stimulated electrically at 5 Hz. The stimulation-induced outflow of radioactivity was taken as an index of endogenous noradrenaline release. In the absence of ACE inhibition 0.01-1 micromol/l bradykinin failed to alter the release of noradrenaline in human atrium. In contrast, 0.001-0.1 micromol/l bradykinin enhanced the release of noradrenaline in rat atrium. In the presence of 3 micromol/l of the ACE inhibitor captopril, however, bradykinin significantly enhanced the release of noradrenaline in human atrium. The bradykinin B1-receptor agonist (Des-Arg9)-bradykinin (0.01-1 micromol/l) had no effect on the release of noradrenaline in human atrium both in the absence and in the presence of 3 micromol/l captopril. Captopril (3 micromol/l) potentiated the facilitatory effect of bradykinin in rat atrium. The selective bradykinin B2-receptor antagonist D-Arg[Hyp3,Thi5, D-Tic7,Oic8]-bradykinin (Hoe 140, 0.3 micromol/l) and the cyclo-oxygenase inhibitor indomethacin (10 micromol/l) reduced the facilitatory effect of bradykinin significantly in the presence of captopril in rat and human atrium. Prostaglandin F2alpha (0.1 micromol/l), prostaglandin E2 (0.3 micromol/l) and the thromboxane A2 receptor agonist U-46 619 (0.1 micromol/l) enhanced the release of noradrenaline in human atria, whereas 0.1 micromol/l prostaglandin I2 had no effect. These data suggest that bradykinin facilitates the release of noradrenaline in human and rat atrium by activation of bradykinin receptors of the B2-subtype and subsequent release of facilitatory prostaglandins. The facilitatory effect of bradykinin in human atrium can only be demonstrated when its enzymatic degradation is prevented by ACE inhibition.


Verbal fluency and agrammatism.
Since the beginning of this century it has been documented that cerebellar lesions induce speech deficits but these were thought to result from lack of motor coordination in the muscular activity needed for phonation. The pure motor nature of the cerebellum has been challenged on different grounds, and cerebellar activation has been documented in language-related tasks independently from motor activity. This chapter reviews the available evidence in favor of a cerebellar contribution to linguistic processing, focusing mainly on clinical observations in patients. The clinical findings are discussed in the light of recent theories on cerebellar functions.


Leveraging Quality Improvement Principles for Radiology Sustainability: Bridging Advocacy and Action.
The healthcare industry is a top polluter, and the United States healthcare is among the worst offenders worldwide. Radiology contributes disproportionately to the carbon footprint of healthcare and may contribute up to 1% of global greenhouse gas emissions. This commentary underscores the untapped potential within radiology departments to integrate quality improvement principles with sustainability. By embracing these principles and setting environmental quality standards, radiologists can transition from sustainability advocacy to improvements in their radiology practices.


Ethyl p-coumarate exerts antifungal activity in vitro and in vivo against fruit Alternaria alternata via membrane-targeted mechanism.
The fungus Alternaria alternata can cause food contamination by black spot rot and food safety issues due to the production of mycotoxins. In particular, A. alternata can infect many fresh fruits and vegetables and lead to considerable postharvest decay during storage and processing. The use of plant-derived products in postharvest disease management may be an acceptable alternative to traditional chemical fungicides. The aim of this study was to assess the antifungal activity of ethyl p-coumarate (EpCA) against Alternaria alternata in vitro and in vivo, and to determine the underlying mechanism. Results indicated that EpCA exhibited pronounced antifungal activity against in vitro mycelial growth of A. alternata, with half-inhibition concentration of 176.8 μg/mL. Spore germination of the pathogen was inhibited by EpCA in a dose-dependent manner. Moreover, in vivo test confirmed that both 100 and 800 μg/mL EpCA significantly reduced disease development of black spot rot in jujube fruit caused by A. alternata. The EpCA treatments increased plasma membrane permeability as great leakage of intercellular electrolytes, soluble proteins and sugars of A. alternata occurred during incubation. The EpCA treatments also caused increase of the influx of propidium iodide, a fluorescence dye binding nucleus DNA, into the affected spores, indicating the disrupted plasma membrane integrity. Observations of ultrastructure further evidenced the damage to plasma membrane and morphology of A. alternata caused by EpCA, which resulted in distortion, sunken and shrivelled of spores and mycelia of the pathogen. In addition, fluorometric assay by confocal laser scanning microscopy confirmed that the EpCA treatments induced endogenous reactive oxygen species (ROS) formation in the spores of A. alternata, with stronger and more stable accumulation of ROS at higher concentration of EpCA. Therefore, heavy oxidative damage to cellular membranes and organelles might happen as demonstrated by the severe occurrence of lipid peroxidation of the pathogen treated with EpCA. Taken together, these results indicated that EpCA exerts antifungal activity via membrane-targeted mechanism and it would be a promising candidate to control postharvest diseases of fruits.


HeartCode BLS with voice assisted manikin for teaching nursing students: preliminary results.
The purpose of this study was to evaluate the effectiveness of HeartCode BLS, a self-directed, computer-based course for obtaining basic life support (BLS) certification. For part 2 of the course, students learned and practiced their cardiopulmonary resuscitation (CPR) psychomotor skills on a voice assisted manikin (VAM). Students from 10 schools of nursing were randomly assigned to two types of CPR training: HeartCode BLS with VAM or the standard, instructor-led (IL) course with manikins that were not voice assisted; 264 students trained using HeartCode BLS and 339 had an IL course. When students passed their respective courses and were certified in BLS, their CPR skills were tested using the Laerdal PC SkillReporting System. Students who trained using HeartCode BLS and practiced their CPR skills on VAMs were significantly more accurate in their ventilations, compressions, and single-rescuer CPR than students who had the standard, IL course with regular manikins.


Nonneoplastic diseases of aorta and pulmonary trunk--Part IV.
This five-part review focuses on selected nonneoplastic diseases of the aorta and pulmonary trunk. Because many more diseases affect the aorta compared with the pulmonary trunk and right and left main pulmonary arteries, most of this review will be devoted to disorders of the aorta. Part IV of the series discusses cystic medial degeneration, trauma, and congenital diseases of the aorta.


The prevalence of supracondyloid process in the living: a radiographic study.
The spur or the supracondyloid process of the humerus has been of special interest to anatomists, anthropologists and clinicians. Apart from the anthropological research by ancient authors and clinical studies carried out half a century ago, no study of this variation appear in the literature. The aim of the present work is to investigate this variation in the living subjects. The present information was performed on direct radiograms of the elbow obtained from the volunteer individuals. This study was carried out over a 3-year period from 2005-2008. The spur was found in 9 cases among the 903 persons examined. Bilateral occurrence of the process was higher than that reported in the literature. The cases with the spur reported mild pain in the forearm over a long period. This study showed a higher occurrence of bilateral supracondyloid process than previously reported. It is also suggested that the cases reported as asymptomatic may not be fully free of the complaint of pain which might assist the clinician in their diagnosis.


Serum cholesterol and aggressive behavior in psychiatrically hospitalized children.
The relationship between serum cholesterol and a number of measures of impulsiveness and aggression was examined in 38 prepubertal, psychiatrically hospitalized children. Although care was taken to use reports and direct observations of both variables within 2 weeks of admission and 8 weeks later, no consistent relationship was found. The reasons for these findings are discussed.


Is the Vazirani-Akinosi Nerve Block a Better Technique Than the Conventional Inferior Alveolar Nerve Block for Beginners?
This study was performed to compare the efficacy and comfort of the inferior alveolar nerve (IAN) block and the Vazirani-Akinosi (VA) nerve block when administered by dental trainees. In this prospective, randomized controlled trial, patients requiring extraction of mandibular teeth received either the conventional IAN block (IAN group) or VA nerve block (VA group). Objective parameters evaluated included ease of locating landmarks, incidence of positive aspiration, and failure rate. Patient comfort during injection was assessed with a visual analog scale. Statistical analysis was performed with the unpaired t test and Fisher exact test. One hundred patients were included in each group. Landmarks were easier to locate in the VA group. The incidence of positive aspiration was higher in the IAN group (0.08%) than in the VA group (0.01%, P < .05). The incidence of failed blocks was higher in the IAN group than in the VA group. Patients appeared to experience less pain with the VA injection than with the IAN injection. This study showed that the dental trainees found the VA technique more straightforward to perform. It had a higher success rate and lower incidence of positive aspiration and was more comfortable for patients than the conventional IAN block.


Prostate-specific antigen nomogram to predict advanced prostate cancer using area under the receiver operating characteristic curve boosting.
For prostate cancer, accurate prediction of the pathological stage before surgery is very important. Therefore, the aim of the present study was establishing the prostate-specific antigen (PSA) threshold nomogram to predict pathologically advanced prostate cancer using the novel method of area under the receiver operating characteristic curve boosting (AUCBoost). The medical records of patients with clinically localized prostate cancer who underwent robot-assisted radical prostatectomy were retrospectively reviewed. Multivariate logistic regression analysis was performed to identify clinical covariates significantly associated with pathological tumor stage ≥3a. The best combination of the variables was determined by validated values of the area under the curve (AUC). The optimal individualized PSA threshold values were developed using AUCBoost. In the multivariate logistic regression analysis, PSA, prostate volume, clinical tumor stage, Gleason Grade Group, the number of positive cores, and the percentage of positive cores were independent predictive factors for pathological tumor stage ≥3a. A combination model comprising PSA, prostate volume, clinical tumor stage, percent positive core, and Gleason Grade Group produced the highest AUC for predicting pathological tumor stage ≥3a (AUC = 0.777). The PSA threshold values for detecting pathological tumor stage ≥3a were calculated and a table of individualized PSA threshold nomogram was developed using AUCBoost. We developed a nomogram of the PSA threshold values for predicting adverse pathological tumor stages of prostate cancer using a novel statistical method. Further validation is necessary; however, the individualized PSA threshold nomogram may be useful in determining treatment strategies before surgery.


H-Ras selectively up-regulates MMP-9 and COX-2 through activation of ERK1/2 and NF-kappaB: an implication for invasive phenotype in rat liver epithelial cells.
One of the most frequent events in carcinogenesis is uncontrolled activation of Ras signaling pathway. A previous study demonstrated that the introduction of H-Ras into the normal WB-F344 rat liver epithelial (WB) cell line and adult male F344 rats resulted in tumorigenicity. The present study investigated whether H-Ras induced the invasive and migrative phenotypes in WB cells, and subsequently aimed at characterizing the underlying mechanisms. H-Ras induced the invasive and migrative phenotypes of WB cells with a selective up-regulation of matrix metalloproteinase (MMP)-9, but not MMP-2. Cyclooxygenase (COX)-2 and the subsequent production of prostaglandin E2 (PGE2) were also induced by H-Ras. Treatment of H-Ras WB cells with GM6001 and NS398, the inhibitors of MMPs and COX-2, respectively, significantly inhibited the H-Ras-induced invasive and migrative phenotypes. DNA binding activity of nuclear factor (NF)-kappaB, but not that of activator protein (AP)-1, was increased by H-Ras. Caffeic acid phenethyl ester and Bay 11-7082, specific inhibitors of NF-kappaB and IKK, respectively, significantly inhibited the expression of MMP-9 and COX-2, invasion and migration of H-Ras WB cells, revealing NF-kappaB as a transcriptional factor responsible for H-Ras-induced malignant phenotypic conversion of WB cells. Activation of ERKs pathway was critical for H-Ras-induced invasive and migrative phenotypes, up-regulation of MMP-9 and COX-2 as well as enhanced DNA binding activity of NF-kappaB in WB cells. Taken together, these results demonstrate that H-Ras up-regulates MMP-9 and COX-2 through activation of ERKs and IKK-IkappaBalpha-NF-kappaB signal pathway which may contribute to the malignant progression of WB rat liver epithelial cells.


Chorionic villus sampling: diagnostic uses and limitations of enzyme assays.
Control ranges for enzymes in uncultured chorionic villi were established, based on: (1) 21 of 22 enzymes (mainly lysosomal) in villi had similar properties to the enzyme in cultured fibroblasts; (2) isoenzyme patterns in villi were similar to those in fibroblasts for five lysosomal enzymes but different for aryl sulphatases; (3) control ranges were determined for 12 enzymes in abortion villi and for 21 enzymes in biopsy villi, values tending to be higher in the latter for those enzymes studied in both types of sample; (4) storage of samples under various conditions revealed no major changes in activity of seven lysosomal enzymes. A number of potential pitfalls in the use of chorionic villus samples for diagnosis of metabolic disorders by enzyme assay are described: (1) the presence of aryl sulphatase C in chorionic villi, an isoenzyme which may interfere in assays of aryl sulphatase A; (2) the presence of maternal enzyme in chorionic villus material illustrated by the detection of the A isoenzyme of B-hexosaminidase in chorionic villus from a pregnancy affected with Sandhoff's disease; (3) the finding of falsely normal levels of alpha-iduronidase in chorionic villus samples from a pregnancy affected with Hurler's disease, probably due to contamination with maternal tissue which has relatively high levels of this enzyme compared with fetal chorionic material: (4) the inadequacy of indirect assays of incorporation of radiolabel into macromolecules using chorionic villi, for example [14C]propionate incorporation for prenatal diagnosis of methylmalonic aciduria. Provided that such pitfalls are recognized and great care is taken in selection of villus samples and interpretation of results, chorionic villus sampling allows reliable prenatal diagnosis of a large number of disorders using enzyme assays.


Hydrogen sulfide: effects on avian respiratory control and intrapulmonary CO2 receptors.
The respiratory response to acute inhalation of hydrogen sulfide (H2S) and the response of pulmonary CO2 receptors to this gas were studied in male White Leghorn chickens. Inhaling low concentrations of H2S (0.05%) for 30 min had no effect on ventilation, but respiratory frequency and tidal volume became irregular and variable in birds that inhaled 0.2% and 0.3% H2S for that period. All birds that inhaled 0.4% H2S died within 15 min. H2S, presented in the gas stream of unidirectionally ventilated birds, caused an increase in the discharge frequency of intrapulmonary CO2 receptors and an increase in the amplitude of sternal movements. Because an increase in the discharge of these receptors normally inhibits the central respiratory neurons and may lead to apnea, it is clear that H2S also has actions that increase the output from these central neurons. The possibility that H2S affects the intrapulmonary CO2 receptors by inhibiting carbonic anhydrase in them is discussed.


Association of phase angle with muscle strength and aerobic fitness in different populations: A systematic review.
The aim of this study was to summarize the evidence on the association of phase angle (PhA) with muscle strength and aerobic fitness in different populations. A systematic search on this topic was performed in nine electronic databases (CINAHL, LILACS, PubMed, SciELO, Scopus, SPORTDiscus, ScienceDirect, MEDLINE, and Web of Science) in January 2021. Studies with different designs that permitted extraction of information about the relationships between PhA and muscle strength and between PhA and aerobic fitness were included. A total of 4446 studies were initially identified; 34 were included after reading of the title, abstract, full text, and references. Four of the studies included had a longitudinal design, with samples consisting of participants ages 6 to 92 years. Thirty-two of the 34 studies evaluated the relationship between PhA and muscle strength, two cross-sectional studies investigated only PhA and aerobic fitness, and three cross-sectional studies evaluated both components (muscle strength and aerobic fitness). PhA was directly associated with muscle strength in 30 cross-sectional studies and two longitudinal studies; the two studies that did not find a direct relationship had a cross-sectional design. For aerobic fitness, the five studies identified reported a direct relationship with PhA. PhA is directly associated with muscle strength and aerobic fitness in different age groups (children, adolescents, adults, and older adults) and in people with different health conditions (human immunodeficiency virus, Crohn's disease, chronic obstructive pulmonary disease, bariatric surgery, kidney transplant, cancer, hemodialysis, and sarcopenia).


Selection of surfactants for enhancing diesel hydrocarbons-contaminated media bioremediation.
The use of surfactants represents a valuable method to enhance the access of the microorganisms to low-soluble and recalcitrant compounds in bioremediation techniques. The choice of surfactants is the first step of feasibility studies for this application. So far, no defined procedures are present in literature to select the most suitable surfactant for the treatment of a specific contaminated site. Furthermore, the characterisation of physico-chemical parameters is important to understand the reason of successes and failures. In this paper a step procedure to select and characterise a commercial surfactant to be used in bioremediation enhancement of hydrocarbon-contaminated media was developed. Among the commercial surfactants, the procedure was applied to alkyl polyethoxylates (Brij family) and sorbitan derivates (Tween family). The selection resulted in the application of Brij 56 and Tween 80 as biodegradation-enhancer in different lab scale systems for remediation of diesel contamination. In liquid systems, Tween 80 greatly increased biodegradation of highly branched and high-molecular weight hydrocarbons, while Brij 56 enhanced degradation of highly branched hydrocarbons. Based on these results, the potential applications and the limitations of these surfactants at full scale level were estimated.


Microbial community fingerprinting by differential display-denaturing gradient gel electrophoresis.
Complex microbial communities exhibit a large diversity, hampering differentiation by DNA fingerprinting. Herein, differential display-denaturing gradient gel electrophoresis is proposed. By adding a nucleotide to the 3' ends of PCR primers, 16 primer pairs and fingerprints were generated per community. Complexity reduction in each partial fingerprint facilitates sample comparison.


Geographical variation in the epidemiology of esophageal cancer in Pakistan.
To evaluate whether factors such as the geographic area of residence, sex, and anatomic subsite of esophagus can prognosticate the histologic subtype of esophagus cancer. To study the major histologic subtypes of esophagus cancer stratified by various factors through multivariate analyses using morphology as the dependent factor and gender, province, and subsite of esophagus as independent factors. A tertiary care cancer hospital situated in the city of Lahore in Pakistan. Three hundred and thirty five patients diagnosed either with esophageal squamous cell carcinoma or adenocarcinoma, from December 1994 to April 2004, were included. Subjects were residents of either Punjab or the Northwest Frontier Province in Pakistan. An excessive likelihood of development of squamous cell carcinoma versus adenocarcinoma was established for the Northwest Frontier Province as compared to Punjab (odds ratio 2.7, 95 percent confidence interval: 1.2, 6.2, p = 0.02), and in the upper-third of the esophagus relative to the lower-third of the organ (odds ratio 8.8, 95 percent confidence interval: 2.8, 28.3, p < 0.001). This histologic variation may be explained by environmental and lifestyle factors peculiar to geographical regions.


An improved bioprocess for synthesis of acetohydroxamic acid using DTT (dithiothreitol) treated resting cells of Bacillus sp. APB-6.
Acyltransferase activity of amidase from Bacillus sp. APB-6 was enhanced (24 U) by multiple feedings of N-methylacetamide (70 mM) into the production medium. Hyperinduced whole resting cells of Bacillus sp. APB-6 corresponding to 4 g/L (dry cell weight), when treated with 10mM DTT (dithiothreitol) resulted in 93% molar conversion of acetamide (300 mM) to acetohydroxamic acid in presence of hydroxylamine-HCl (800 mM) after 30 min at 45°C in a 1L reaction mixture. After lyophilization, a 62 g powder containing 34% (wtwt(-1)) acetohydroxamic acid was recovered. This is the first report where DTT has been used to enhance acyltransfer reaction and such high molar conversion (%) of amide to hydroxamates was recorded at 1L scale.


Prospective, multicentre, randomised controlled trial comparing the seroclearance of HBsAg between combination therapy of peg-interferon alpha and tenofovir with tenofovir monotherapy in nucleos(t)ide analogue-experienced patients with HBV-related liver fibrosis: a study protocol.
Combination antiviral therapy of nucleos(t)ide analogue (NA) and pegylated interferon alpha (peg-IFN alpha) decrease hepatitis B virus (HBV) surface antigen (HBsAg) levels to achieve functional cure and improve long-term prognosis in chronic hepatitis B patients. However, for hepatitis B-related liver fibrosis, studies on combination of these two medicines are limited. This study was designed to compare the efficacy between peg-IFN alpha combined with tenofovir (TDF) and TDF monotherapy for the clearance of HBsAg in NA-experienced patients with HBV-related liver fibrosis. This study was designed to be a prospective, multicentre, open, randomised controlled study. A total of 272 patients with HBV-related liver fibrosis will be randomised into the combination therapy group or the monotherapy group at a 1:1 ratio. Participants in the combination group will receive subcutaneous injections of peg-IFN alpha 180 µg per week for 48 weeks combined with oral TDF 300 mg daily. Participants in the monotherapy group will receive 300 mg oral TDF daily alone. All participants will undergo long-term treatment with TDF and will be followed up at the outpatient department for 144 weeks after randomisation. Clinical symptoms, laboratory tests and examination indicators will be collected at each follow-up time point, and adverse events will be recorded. The primary endpoint is serological clearance rate of HBsAg at 48 weeks. The ethics committee of the Third Affiliated Hospital at Sun Yat-sen University approved this study (Approval Number: (2020)02-183-01). The results of the study will be presented at relevant meetings and published in an appropriate journal after the completion of the trial and the analysis of the data. NCT04640129.


The burden of skeletal-related events in patients with prostate cancer and bone metastasis.
To assess contemporary characteristics, hospital admissions, charges, and mortality in patients with prostate cancer (CaP) who have bone metastases and skeletal-related events in an observational study. Relying on the Nationwide Inpatient Sample (NIS), patients with CaP with bone metastases between 1998 and 2010 were abstracted. Patients who experienced skeletal-related events were identified, and hospital charges were calculated. Generalized linear regression analyses focused on in-hospital mortality. Between 1998 and 2010, a weighted estimate of 443,929 CaP visits with bone metastases was recorded. Of these, 15.9% experienced at least 1 SRE. The rate of SRE decreased from 18% to 15.4% (1998-2010, estimated annual percent change [EAPC] =-1.44%, P = 0.005) and the SRE-associated mortality decreased from 8.5% to 4.7% (1998-2010, EAPC =-3.68%, P = 0.004). Nevertheless, the inflation-adjusted charges associated with hospital visits of patients with CaP with bone metastases rose by 92% to $1,512,449,106 (EAPC = +8.82%, P<0.001), and SRE charges rose by 94% to $369,256,799 (EAPC =+7.62%, P<0.001). Predictors of in-hospital mortality in patients with SRE included age (odds ratio [OR] = 1.02), comorbidities (≥3 vs. 0-1, OR = 1.72), SRE of the upper limb (OR = 1.75), SRE of the lower limb (OR = 1.35), spinal cord compression (OR = 1.48), radiation (OR = 0.68), surgery (OR = 0.32), and year of hospitalization (2010 vs. 1998, OR = 0.54; all P< 0.03). From 1998 to 2010, the incidence of SRE and SRE-associated mortality in patients with CaP and bone metastases decreased. However, charges for SRE-associated hospitalizations have increased alarmingly. Future health care policies should strive to provide cost-effective prevention and management of SREs in this population.


Physical determinants of β-barrel membrane protein folding in lipid vesicles.
The spontaneous folding of two Neisseria outer membrane proteins, opacity-associated (Opa)(60) and Opa(50) into lipid vesicles was investigated by systematically varying bulk and membrane properties. Centrifugal fractionation coupled with sodium dodecyl sulfate polyacrylamide gel electrophoresis mobility assays enabled the discrimination of aggregate, unfolded membrane-associated, and folded membrane-inserted protein states as well as the influence of pH, ionic strength, membrane surface potential, lipid saturation, and urea on each. Protein aggregation was reduced with increasing lipid chain length, basic pH, low salt, the incorporation of negatively charged guest lipids, or by the addition of urea to the folding reaction. Insertion from the membrane-associated form was improved in shorter chain lipids, with more basic pH and low ionic strength; it is hindered by unsaturated or ether-linked lipids. The isolation of the physical determinants of insertion suggests that the membrane surface and dipole potentials are driving forces for outer membrane protein insertion and folding into lipid bilayers.


Proteomics-based network analysis characterizes biological processes and pathways activated by preconditioned mesenchymal stem cells in cardiac repair mechanisms.
We have demonstrated that intramyocardial delivery of human mesenchymal stem cells preconditioned with a hyaluronan mixed ester of butyric and retinoic acid (MSCp+) is more effective in preventing the decay of regional myocardial contractility in a swine model of myocardial infarction (MI). However, the understanding of the role of MSCp+ in proteomic remodeling of cardiac infarcted tissue is not complete. We therefore sought to perform a comprehensive analysis of the proteome of infarct remote (RZ) and border zone (BZ) of pigs treated with MSCp+ or unconditioned stem cells. Heart tissues were analyzed by MudPIT and differentially expressed proteins were selected by a label-free approach based on spectral counting. Protein profiles were evaluated by using PPI networks and their topological analysis. The proteomic remodeling was largely prevented in MSCp+ group. Extracellular proteins involved in fibrosis were down-regulated, while energetic pathways were globally up-regulated. Cardioprotectant pathways involved in the production of keto acid metabolites were also activated. Additionally, we found that new hub proteins support the cardioprotective phenotype characterizing the left ventricular BZ treated with MSCp+. In fact, the up-regulation of angiogenic proteins NCL and RAC1 can be explained by the increase of capillary density induced by MSCp+. Our results show that angiogenic pathways appear to be uniquely positioned to integrate signaling with energetic pathways involving cardiac repair. Our findings prompt the use of proteomics-based network analysis to optimize new approaches preventing the post-ischemic proteomic remodeling that may underlie the limited self-repair ability of adult heart.


Spatial and temporal genetic variation of Echinostoma revolutum (Trematoda: Echinostomatidae) from Thailand and the Lao PDR.
A total of 314 individual Echinostoma revolutum were collected at different locations and times from domestic ducks from Khon Kaen Province, Thailand and Vientiane Province, the Lao People's Democratic Republic (PDR). Genetic variation of these parasites was analyzed using multilocus enzyme electrophoresis at three polymorphic loci namely, glucose-6-phosphate dehydrogenase (G6pd), malic enzyme (Me) and peptidase valine-leucine (PepA). High levels of genetic variability were found within and between populations. Significant heterozygote deficiencies compared with the predictions under Hardy-Weinberg equilibrium were detected in populations from Thailand and the Lao PDR for all loci except G6pd-1. Significant genetic differentiation was observed between spatially separated populations from Thailand and the Lao PDR. This as also true for some samples collected at different times in Thailand. The variability found may be consistent with a Wahlund effect, genetic drift and/or other factors such as the population structure of snail hosts. Our data provide further insight into the process of genetic divergence within and among geographically and temporally isolated populations of E. revolutum, and potentially other medically important echinostomes in Southeast Asia.


Microbial Treatments for the Mind.
For $99, you can obtain a kit that includes two cotton swabs and instructions for properly collecting your own stool sample, along with oral and skin samples. Upon shipping those specimens to the Knight Lab in La Jolla, CA, you will join the ranks of "citizen scientist," becoming a contributor to the world's largest crowd-sourced microbiome research project. In return, should you have accepted this mission, you will receive a report that offers you a "snapshot" of the microbes found in your fecal matter, and compares it to that of the rest of the population.


Differentiation of the humoral immune response in herpes simplex encephalitis.
Six patients with herpes simplex encephalitis were investigated. Antibody activities against different viral antigens were determined in serum and cerebrospinal fluid with an enzyme-linked immunosorbent assay after adjusting both fluids to identical immunoglobulin G concentrations. In serum, the strength of the antiviral reaction remained low and no qualitative changes became detectable. In cerebrospinal fluid, at first locally synthesized antibodies were directed against the same antigens as in serum. Ten days later, the intrathecal reaction increased with additional antibodies against at least two antigens. Once established, this expanded heterogeneity remained stable during the course of the disease.


New methodology for obtaining CdTe quantum dots by using ultrasound.
Luminescent CdTe quantum dots (Qdots) have been produced at few minutes by using a new, simple and fast methodology in an aqueous medium by using ultrasound irradiation to accelerate the process of tellurium reduction. The structural and optical properties were characterized by TEM, XRD, absorption and fluorescence spectrocopy. The produced Qdots are in a strong quantum confinement regime and have only one fluorescence band. Moreover, the nanoparticles seem to be monodispersed, which is in accordance with the fluorescence results. We have developed a simple route for preparing monodispersed CdTe Qdots in an aqueous media. The use of ultrasound allows the morphology to be better controlled and the surfaces defects of Qdots to be reduced.


Long noncoding RNA LINC02582 acts downstream of miR-200c to promote radioresistance through CHK1 in breast cancer cells.
Radiotherapy is essential to treat breast cancer and microRNA (miRNA) miR-200c is considered as a radiosensitizer of breast cancer. However, the molecular mechanisms by which miR-200c regulates radiosensitivity remain largely unknown. In the present study, we showed that induction of miR-200c led to widespread alteration in long noncoding RNA (lncRNA) expression in breast cancer cells. We identified lncRNA LINC02582 as a target of miR-200c. Inhibition of LINC02582 expression increased radiosensitvity, while overexpression of LINC02582 promoted radioresistance. Mechanistically, LINC02582 interacts with deubiquitinating enzyme ubiquitin specific peptidase 7 (USP7) to deubiquitinate and stabilize checkpoint kinase 1 (CHK1), a critical effector kinase in DNA damage response, thus promoting radioresistance. Furthermore, we detected an inverse correlation between the expression of miR-200c vs. LINC02582 and CHK1 in breast cancer samples. These findings identified LINC02582 as a downstream target of miR-200c linking miR-200c to CHK1, in which miR-200c increases radiosensitivity by downregulation of CHK1.


Comparison of corneal storage in K-Sol and chondroitin sulfate corneal storage medium in human corneal transplantation.
Fifty-one pairs of corneas, stored in either K-Sol or CSM (chondroitin sulfate corneal storage medium) from 8 to 97 hours (mean +/- standard deviation, 58 +/- 21 and 57 +/- 21 hours, respectively), were transplanted in a prospective, randomized manner into 99 patients (n = 102 eyes), paired by diagnostic group and procedure. Ninety-six percent of K-Sol grafts (n = 51) and 94% of the CSM grafts (n = 51) were clear at 6 months; 92% of both the K-Sol (n = 38) and CSM (n = 35) grafts were clear at 12 months. One primary donor failure occurred, a K-Sol cornea stored for 76 hours. The CSM group experienced a greater number of persistent epithelial defects beyond 2 weeks (7 versus 4 defects) and graft reaction episodes (7 versus 3 episodes) than the K-Sol group; however, an equal number of late graft failures (3) occurred in both groups. No significant differences by paired t test analyses were found in endothelial cell density, area, coefficient of variation, or figure coefficient at 3 (n = 37 pairs), 6 (n = 36 pairs), and 12 (n = 26 pairs) months between the two groups. Mean endothelial cell density significantly decreased by 11% +/- 22 by 3 months in the K-Sol group, whereas the 7% +/- 24 decrease in the CSM group was insignificant. By 12 months, both groups experienced a significant decrease: K-Sol, 27% +/- 22; CSM, 17% +/- 26. A significant decrease in the mean coefficient of variation (polymegathism) was noted after 3 months in the K-Sol group which returned to the preoperative mean by 1 year, whereas this parameter remained unchanged in the CSM group. Both chondroitin sulfate-based media result in successful corneal transplantation with storage up to 4 days; however, endothelial survival with both media are comparable with previous studies with McCarey-Kaufman (M-K) medium.


The influence of maternal weight, smoking, vascular complications and glucose regulation on the birth weight of infants of type 1 diabetic women.
The influence of maternal blood glucose regulation, weight gain, pre-pregnancy weight, vascular complications and smoking on the birth weight of infants was investigated in 72 type 1 (insulin-dependent) pregnant diabetic women. In patients with vascular complications (n = 23) the birth weight was significantly lower than in patients without vascular involvement (n = 49) (mean 380 g, P less than 0.05). The mean RBWR (relative birth weight ratio) of infants of patients who smoked more than 10 cigarettes per day was statistically significant lower compared to the mean RBWR of infants of non-smokers (P less than 0.025). A significant correlation was present between haemoglobin A1c (HbA1c) and RBWR (r = 0.28, P less than 0.02) and between maternal net weight gain and RBWR (r = 0.36, P less than 0.005) and this correlation became even stronger when only patients without vascular lesions were considered (n = 49) (r = 0.51, P less than 0.005) and (r = 0.50, P less than 0.005), respectively. In contrast no correlation was found between pre-pregnancy weight and RBWR. The study suggests that factors other than maternal hyperglycaemia stimulate fetal growth and may explain why fetal macrosomia may occur despite of strict blood glucose regulation.


[Isolation and characterisation of L-ascorbic acid oxidase (EC 18.104.22.168) from wheat flour (author's transl)].
Wheat flour (Caribo, 0.55% ash) is extracted with 0.4 M-NaCl-solution, the L-ascorbic acid oxidase precipitated with (NH4)2SO4 and this concentrate separated by thinlayer isoelectric focussing on polyacrylamid- and dextrangel. 8-12 active fractions (isoenzymes) are detected with a high specifity for L-ascorbic acid in respect in L-isoascorbic acid activity). The molecular weights are 165,000-175,000 (determined by dextran gel-thin layer chromatography). In fresh flour the activity is near 28 mg L-ascorbic acid per kg flour in 30 min, after 30 days the activity has diminished to 5% after 60 days no activity is detectable.


[Characterization and analysis of the aggregation of a single-chain chimeric anti-ErbB2 antibody].
We studied the aggregation of a recombinant engineering antibody (chA21). Anti-ErbB2 antibody chA21 was produced by fusing single-chain Fv (scFv) with human IgG1 Fc fragment, and it was proved to be a drug candidate for cancer therapy. We characterized the aggregation of chA21 by high performance sized-exclusive chromatography (HPSEC), dynamic light scattering (DLS), SDS-PAGE, indirect ELISA assay, and compared the influence of temperature and additive on the level of aggregation and binding activity. Conformation changes of different levels of aggregation were also analyzed via circular dichroism (CD). Finally, we analyzed which part of chA21 was involved in aggregation by cleaving it into scFv and Fc fragments. The results showed that chA21 could form aggregates in the storage solution. The aggregates interacted through non-covalent bonds and remained binding activity. Temperature and additive could slightly affect the level of aggregation and binding activity, while the conformations of chA21 were stable. Aggregation propensity of scFv fragment was almost same as chA21, indicating that scFv may be the major part to form the aggregates. The research on aggregation may be helpful to develop a suitable formulation for chA21 clinical application as well as provide direction for future antibody design and reconstruction.


Urinary tract infection due to Aeromonas species: An uncommon causative agent.
Members of the genus Aeromonas are Gram-negative bacilli, belonging to family Aeromonadaceae, and are widely found in various aquatic environments. The most common species associated with human infections are A. hydrophila, A. caviae, and A. veronii biovar sobria. Aeromonas species are recognized as emerging opportunistic pathogens in humans mainly causing gastrointestinal infections and wound infections with or without progression to septicaemia. Aeromonas organisms rarely cause urinary tract infection (UTI) and are not known uropathogens. We report a series of UTI due to Aeromonas species in three adult patients, specifically identified as A. veronii biovar sobria in two patients and A. hydrophila in one patient. Two patients had history of occupational exposure to aquatic environment. The cases highlight another expanded range of infections caused by Aeromonas spp. that can be encountered in a community setting and indicate that infections with Aeromonas spp. should be kept in mind while investigating for the etiology of UTI, especially in adult patients with occupational exposure to aquatic ecosystems.


Normal oxygen saturation trend in healthy term newborns within 30 minutes of birth.
To determine normal arterial oxygen saturation (SpO(2)) trend during first 30 min of life and to evaluate for difference in SpO(2) trends in healthy term newborns of normal vaginal delivery (NVD) and elective cesarean section (CS). This Prospective Cross-sectional Observational study was conducted in Department of Pediatrics and Obstetrics, Gandhi Medical College, Bhopal. Newborns born of NVD and elective CS in first 30 min of life, complying with the study criteria were included in the study. Soon after birth, newborns with Apgar score ≥ 7 were given routine care and pulse-oximeter probe was applied on wiped right hand continuously for 30 min. Readings were obtained at an interval of 5 min. Among NVD, the mean SpO(2) at 1, 5, 10, 15, 20, 25 and 30 min were 64.26%, 76.23%, 86.05%, 90.78%, 91.41%, 91.73% and 93.48%, respectively. The mean SpO(2) for CS was 67.43%, 78.50%, 88.44%, 90.81%, 91.46%, 91.83% and 92.88%, respectively. There was no significant difference in the SpO(2) between NVD and CS [95% CI = 74.8612-94.8359 in NVD and 77.1231-94.6912 in CS] and the correlation between NVD and CS being significant [r = 0.997 at 0.01 level]. There exists a strong positive correlation between Apgar and SpO(2) [r = 0.995, significant at 0.01 level (1-tailed) in NVD and r = 0.980, significant at 0.01 level (2-tailed) in CS]. The study defines the normal SpO(2) in healthy term newborns of NVD and CS delivered newborns and also concludes that there is no significant difference in SpO(2) among NVD and CS.


Biotransformation of d-xylose to d-xylonate coupled to medium-chain-length polyhydroxyalkanoate production in cellobiose-grown Pseudomonas putida EM42.
Co-production of two or more desirable compounds from low-cost substrates by a single microbial catalyst could greatly improve the economic competitiveness of many biotechnological processes. However, reports demonstrating the adoption of such co-production strategy are still scarce. In this study, the ability of genome-edited strain Pseudomonas putida EM42 to simultaneously valorize d-xylose and d-cellobiose - two important lignocellulosic carbohydrates - by converting them into the platform chemical d-xylonate and medium-chain-length polyhydroxyalkanoates, respectively, was investigated. Biotransformation experiments performed with P. putida resting cells showed that promiscuous periplasmic glucose oxidation route can efficiently generate extracellular xylonate with a high yield. Xylose oxidation was subsequently coupled to the growth of P. putida with cytoplasmic β-glucosidase BglC from Thermobifida fusca on d-cellobiose. This disaccharide turned out to be a better co-substrate for xylose-to-xylonate biotransformation than monomeric glucose. This was because unlike glucose, cellobiose did not block oxidation of the pentose by periplasmic glucose dehydrogenase Gcd, but, similarly to glucose, it was a suitable substrate for polyhydroxyalkanoate formation in P. putida. Co-production of extracellular xylose-born xylonate and intracellular cellobiose-born medium-chain-length polyhydroxyalkanoates was established in proof-of-concept experiments with P. putida grown on the disaccharide. This study highlights the potential of P. putida EM42 as a microbial platform for the production of xylonate, identifies cellobiose as a new substrate for mcl-PHA production, and proposes a fresh strategy for the simultaneous valorization of xylose and cellobiose.


Use of nutritional supplements based on melatonin, tryptophan and vitamin B6 (Melamil Tripto®) in children with primary chronic headache, with or without sleep disorders: a pilot study.
Headache is one of the main complaints in pediatric neurology. Exogenous melatonin has been shown to be useful and safe in improving sleep-wake cycles and sleep quality in children. Tryptophan as well plays a key role in sleep regulation. So far, no studies tried to analyze the effects of a combination of both melatonin and tryptophan in treating chronic headache in children affected also by night-time awakenings. Thirty-four children with a diagnosis of chronic headache (with or without sleep disorders) have been enrolled. The study was articulated in two steps: 1) each child was observed for one month without any intervention; 2) children have been then randomized into two groups: the "ME-group", which received the nutritional supplement melatonin for two months and the "MET-group", which received the nutritional supplements melatonin, tryptophan, and vitamin B6 for two months. In terms of changes in number of headache events, responders in the ME-group were 91.7% and those in the MET-group were 66.7% (P=0.113). In terms of changes in number of night awakenings, in the ME group, mean number at baseline, after 30 days, and after 60 days were 3.6±3.2, 3.2±3.5, and 2.7±3.4 (P=0.495). In the MET group, mean number of night awakenings was 7.4±8.1, 4.0±4.4, and 3.3±2.9 (P=0.041). Using either nutritional supplement for two months can help in decreasing the monthly number of headache episodes and night awakenings. The addition of tryptophan and vitamin B6 appears to have stronger influence on night awakenings reduction than melatonin only.


Histopathological Terminology Standards for the Reporting of Prostatic Epithelial Lesions in Dogs.
The terminology applied to canine prostatic epithelial lesions, especially carcinomas, is currently not standardized and this hampers the ability of pathologists to study the biological and clinical significance of these lesions. The aim of this review is to present the essential histomorphological diagnostic attributes of a wide spectrum of prostatic epithelial lesions in dogs. In addition to the traditionally recognized prostatic hyperplasia, hormonal atrophy, prostatitis, squamous metaplasia, adenocarcinoma and transitional cell (urothelial) carcinoma, new entities are described and discussed in order to provide veterinary pathologists with a basic atlas of common histological lesions of the canine prostate that is comprehensive and easy to use.


Splenic abscess. Report of 10 cases and review of the literature.
Ten cases of splenic abscess seen between 1964 and 1974 are reviewed. Pain referable to the abscess was the most common symptom, but was present in only five cases. Fever was present in all but one case. Tenderness in the region of the spleen was noted in six cases, in three cases the spleen was palpable and in one case a large mass in the upper left quadrant of the abdomen was palpated. Abdominal films were suggestive of the diagnosis in two cases, and the liver-spleen scan demonstrated a defect in three cases. Seven abscesses were caused by gram-negative bacilli of bowel origin; the etiologic agents in the other three were Staphylococcus aureus, Streptobacillus moniliformis and a Nocardia species. Associated conditions predisposing to splenic abscess included trauma in three cases, splenic arteritis or embolization in five cases, and foci of infection elsewhere in the body in six, including two cases of endocarditis. The mortality was 60 per cent. Half of the deaths were due to the underlying illness, but failure to diagnose splenic abscess contributed to a fatal outcome in three cases.


Lymphatic microcirculation profile in the progression of hypertension in spontaneously hypertensive rats.
The contractile behavior of collecting lymphatic vessels occurs in essential hypertension in response to homeostasis, suggesting a possible role for microcirculation. We aimed to clarify the nature of the lymphatic microcirculation profile in spontaneously hypertensive rats (SHRs) and normotensive controls. The vasomotion of collecting lymphatic vessels in eight- and thirteen-week-old SHRs and age-matched Wistar-Kyoto rats (WKYs, n = 4 per group) was visualized by intravital video and VasTrack. The lymphatic vasomotion profile (frequency and amplitude) and contractile parameters (contraction fraction and total contractility activity index) were compared. Plasma nitrite/nitrate levels were assessed by the Griess reaction, and plasma endothelin-1 was measured by enzyme-linked immunosorbent assay. WKYs and SHRs differed in the vasomotion of collecting lymphatic vessels. Both eight- and thirteen-week-old WKYs revealed a high-amplitude pumping pattern, whereas a low-amplitude pattern was observed in SHRs. Moreover, compared with age-matched WKYs, SHRs exhibited deteriorated output and reflux capability and lost the ability to regulate collecting lymphatic vasomotion. Additionally, the chemistry complements the microcirculatory lymphatic profile as demonstrated by an increase in plasma nitrite, nitrate, and endothelin-1 in SHRs. ET-1 inhibitor meliorated the lymphatic contractile capability in SHRs partially through regulating frequency of lymphatic vasomotion. We used an intravital lymphatic imaging system to observe that SHRs exhibit an impaired collecting lymphatic vasomotion profile and deteriorated contractility and reflux.


Prisoners with psychosis in England and Wales: diversion to psychiatric inpatient services?
The prevalence of psychosis among prisoners in England and Wales is ten times that in the household population and UK government policy is that prisoners should receive equivalent care to those in the community. This study investigated the implications of policy to divert more from the criminal justice system for psychiatric treatment. Psychotic prisoners were compared with psychotic persons in households and with other prisoners in two surveys of psychiatric morbidity in representative samples of the UK population. Psychotic prisoners were younger, more from ethnic minorities, with comorbid anxiety, substance misuse, ASPD, and childhood behavioural problems compared to psychotic persons in households. Less than a third had received previous inpatient treatment. Psychotic prisoners had similar criminal histories and higher psychopathy scores than non-psychopathic prisoners. Diversion is unfeasible without improved screening for psychosis and increasing bed numbers at higher levels of security to accommodate more patients who would pose high risk to the public. Future research should investigate why UK psychiatric services fail to identify psychotic prisoners and provide aftercare.


Prevalence of pregnancy-relevant infections in a rural setting of Ghana.
Although infectious diseases still account for a high burden of morbidity and mortality in sub-Saharan Africa, simultaneous investigations on multiple infections affecting maternal and child health are missing. We conducted a cross-sectional, single-centre pilot study in a rural area of Ghana to assess the infectiological profile during pregnancy. Screening of 180 expectant mothers was done by vaginal swabs and serology to detect the most common pregnancy-relevant infections. They were also interviewed for potential risk factors, outcome of previous pregnancies, and socio-economic aspects. We found a high prevalence of infections caused by hepatitis B virus (16.7% HBs antigen positive). In contrast, infections caused by hepatitis C virus (1.1% anti-HCV) and HIV (0.6%) were rare. Maternal malaria was frequent (10.6%), despite increasing acceptance of intermittent preventive treatment during pregnancy (IPTp). Group B streptococci were present in 10.6% of all pregnant women. Absence of antibodies against varicella zoster virus in 43.2%, Toxoplasma gondii in 26.8%, parvovirus B19 in 20.0%, and rubella virus in 15.7% makes a significant proportion of pregnant women susceptible for acquiring primary infections. Whereas all study participants had specific IgG antibodies against human cytomegalovirus, infections with Listeria, Brucella, or Neisseria gonorrhoeae as well as active syphilis were absent. Our pilot study in a rural community in Ghana indicates an urgent need for action in dealing at least with high-prevalent pregnancy-relevant infections, such as hepatitis B, malaria and those caused by group B streptococci. In addition, the resulting prevalence rates of various other infections may offer guidance for health officials to prioritize possible future intervention schemes.


Variation in work-up and treatment procedures among types of radiation therapy facilities: the patterns of care process survey for three head and neck sites.
The PCS Process Survey analyzed radiation therapy facilities to evaluate procedures in work-up and treatment of patients with cancer of the larynx, tongue, and nasopharynx. Types of facilities are compared to establish bench marks in performance of work-up and treatment procedures that can be used as a foundation for upgrading care and for adjusting studies to follow this paper. A statistical method is demonstrated that provides a "signature" of relative performance over a standardized set of procedural criteria. Facilities with resident training programs perform nearly all of these procedures much more consistently than do nontraining facilities. Facilities with full-time head therapists perform most procedures more consistently than do facilities with part-time heads. A third comparison of large versus small facilities shows that among training facilities size has no effect and that among full-time facilities size has a slight effect. Among part-time facilities, however, smaller ones fail to perform most procedures more often than larger facilities. The size difference is confounded with the full-time/part-time difference because part-time facilities are on the average smaller than facilities with full-time head therapists.


Association of Maternal Serum Uric Acid and Cystatin C Levels in Late Pregnancy with Adverse Birth Outcomes: An Observational Cohort Study in China.
To investigate the associations between serum uric acid (UA) and cystatin C (CysC) levels in late pregnancy with major unfavorable birth outcomes. We retrospectively analyzed the maternal UA and CysC levels during late pregnancy and their relationship with unfavorable birth outcomes in a Chinese population (n = 11,580). Women with the highest quartile of UA had higher risks of low birth weight (LBW) and small for gestational age (SGA) babies and a lower risk of preterm birth (PTB) compared to women with the lowest quartile [for LBW, adjusted-odds ratio (OR) = 2.63, 95% CI: 1.76, 3.95; for SGA, adjusted-OR = 2.11, 95% CI: 1.73, 2.57; for PTB, adjusted-OR = 0.55, 95% CI: 0.45, 0.69; all P for trend <0.001]. Compared to women in the lowest quartile of CysC, higher risks of macrosomia and large for gestational age (LGA) and lower risks of PTB and SGA were observed for those in the highest quartile (for macrosomia, adjusted-OR = 2.01, 95% CI: 1.60, 2.51; for LGA, adjusted-OR = 1.97, 95% CI: 1.67, 2.32; for PTB, adjusted-OR = 0.32, 95% CI: 0.26, 0.41; all P for trend <0.001; for SGA, adjusted-OR = 0.78, 95% CI: 0.64, 0.96; P for trend <0.05). This study reports the associations of maternal UA and CysC with adverse birth outcomes, and suggests that routine determination of maternal UA and CysC in late pregnancy is beneficial for assessing the risks of these outcomes.


Combined deletions of pfhrp2 and pfhrp3 genes result in Plasmodium falciparum malaria false-negative rapid diagnostic test.
We report a case of misdiagnosis of Plasmodium falciparum malaria from Brazil with negative PfHRP2-based rapid diagnostic tests (RDTs), leading to inappropriate case management. Genetic tests showed the deletion of both pfhrp2 and pfhrp3 genes. The detection of two distinct P. falciparum target antigens is then advisable.


The quantification of ormazans in tissue sections by microdensitometry. III. The effect of objective power and scanning spot size.
In this article, it is reported that the formazans derived from neotetrazolium chloride (NT) and 2-(2-benzothiazolyl)-3-(4-phthalhydrazidyl)-5-styryl-tetrazolium chloride (BPST) can be measured by microdensitometry of tissue sections with a wide range of scanning spot sizes, without any significant effect on the recorded extinctions. The spot sizes tested ranged from 0.20 to 16 mum. Thus when large fields have to be measured, it is possible to use low-power objectives and still obtain valid results.


School food in Mexican children.
To establish the school eating habits of Mexican children, who are prone to obesity and later to high rates of adult chronic diseases. Questionnaires for students and parents with staff questionnaires and interviews. Randomly sampled schools in a socio-economically representative district of Mexico City. Subjects were 1504 adolescents aged 10-19 years attending schools in Mexico City, 27 teachers and seven headmasters, sampled from both public and private schools and from the full range of socio-economic groups. Foods brought from home were of a higher nutritional quality than those purchased at school, where purchases were dominated by crisps, soft drinks and other items with high energy density. Girls were more inclined to purchase inappropriately; those from poorer homes purchased less. Private-school students irrespective of socio-economic grade brought more food from home and purchased more expensive food at school. School policies allowed food and drink vendors to market any products within the schools, which benefited financially from these activities. Current school food policies are conducive to amplifying the current epidemic of obesity and related adult chronic diseases, and need to change.


R factor-mediated aminoglycoside antibiotic resistance in Pseudomonas aeruginosa: a new aminoglycoside 6'-N-acetyltransferase.
The newly introduced semisynthetic aminoglycoside antibiotics, i.e., 3',4'-dideoxykanamycin B (DKB), 6'-N-methyl DKB (6'-Me-DKB) and amikacin (AK) have been found to be effective against gram-negative pathogens including Pseudomonas aeruginosa, which are resistant to the known aminoglycoside antibiotics. We have demonstrated in our stock cultures two types of P. aeruginosa strains resistant to DKB, i.e., (DKB(r).AK(r).6'-Me-DKB(s)) and (DKB(r).AK(s).6'-Me-DKB(r)) (where r = resistant; s = sensitive). Both groups of strains inactivate the drugs by acetylation. The acetylating enzyme was extracted from GN4925(DKB(r).AK(s).6'-Me-DKB(r)) and purified by affinity chromatography. Enzymatic studies of the inactivation reaction and chemical studies of the inactivated products indicated that DKB and 6'-Me-DKB were inactivated by acetylation of the 6'-amino group of the drugs. This enzyme acetylates kanamycin A (KM-A), KM-B, DKB, 6'-Me-DKB, 6'-N-methyl kanamycin B, but not KM-C, AK, and gentamicin C(1). The enzyme is named aminoglycoside 6'-N-acetyltransferase 3. Genetic studies of two strains resistant to DKB and 6'-Me-DKB disclosed that the enzyme catalyzing inactivation of both DKB and 6'-Me-DKB was mediated by an R factor, i.e., R(ms167) and R(ms168), capable of conferring resistance to KM, DKB, and 6'-Me-DKB, in addition to resistance to gentamicin, streptomycin, and sulfanilamide, and resistance to tetracycline, chloramphenicol, streptomycin and sulfanilamide respectively.


[Consequences of tobacco, cocaine and cannabis consumption during pregnancy on the pregnancy itself, on the newborn and on child development: A review].
Substance use has increased worldwide. Based on these data, we may think that substance use has also increased during pregnancy, but epidemiological data are scarce in this population. The potential consequences of tobacco, cocaine or cannabis use during pregnancy are a major public health concern. The combined use of different substances during pregnancy may have serious consequences on the pregnancy and on child development. In this paper, we will describe the potential consequences for the newborn, child and adolescent after being exposed to tobacco, cannabis and cocaine in utero. For this purpose, we will review all retrospective and prospective studies (in English and French) referenced in PubMed reporting on the somatic or psychiatric consequences of alcohol, tobacco and drug consumption by pregnant women on newborn and children. Consumption during pregnancy was assessed in these studies using simple questionnaires, biomarkers analysis or both. Generally speaking, these pregnancies are at high risk for both the mother and the foetus: for example, an increased risk of miscarriage or of reduced length of gestation, an increased risk of uterine apoplexy and placenta praevia, more premature births and/or hypotrophy were reported. The occurrence of a newborn's withdrawal syndrome may be misdiagnosed. Many consequences on child development may be observed such as growth disorders, learning or motor disorders, language disorders, cognitive disorders (attention, memory, executive functions), attention deficit disorders with impulsivity or with hyperactivity (ADHD), and memory disorders. The prevalence of depressive or anxiety disorders may also be increased in these children. The risk of addictive disorders or schizophrenia in children exposed in utero to illicit drugs or tobacco is still unknown. The combined use of different substances increases, consequently it is difficult to disentangle the consequences on child development of each of the drugs used during pregnancy owing to potential interactions between these drugs. The consequences on child development will also depend on the dose and on the time of drug use during pregnancy. The National Institute of Drug Abuse reported that 75% of the infants exposed in utero to one or more substances will present medical problems during childhood, as compared to only 27% of the non-exposed infants. However, the medical consequences are still a matter of controversies. Methodological biases, such as the use of different rating scales among studies, and the heterogeneity of the populations included are main limitations. Further studies are needed using larger cohorts and longer follow-up periods.


Trafficking of a dual-modality magnetic resonance and fluorescence imaging superparamagnetic iron oxide-based nanoprobe to lymph nodes.
This study aims to develop and characterize the trafficking of a dual-modal agent that identifies primary draining or sentinel lymph node (LN). Herein, a dual-reporting silica-coated iron oxide nanoparticle (SCION) is developed. Nude mice were imaged by magnetic resonance (MR) and optical imaging and axillary LNs were harvested for histological analysis. Trafficking through lymphatics was observed with intravital and ex vivo confocal microscopy of popliteal LNs in B6-albino, CD11c-EYFP, and lys-EGFP transgenic mice. In vivo, SCION allows visualization of LNs. The particle's size and surface functionality play a role in its passive migration from the intradermal injection site and its minimal uptake by CD11c+ dendritic cells and CD169+ and lys+ macrophages. After injection, SCION passively migrates to LNs without macrophage uptake and then can be used to image LN(s) by MRI and fluorescence. Thus, SCION can potentially be developed for use in sentinel node resections or for intralymphatic drug delivery.


Application of Near-Infrared Spectroscopy and Fuzzy Improved Null Linear Discriminant Analysis for Rapid Discrimination of Milk Brands.
The quality of milk is tightly linked to its brand. A famous brand of milk always has good quality. Therefore, this study seeks to design a new fuzzy feature extraction method, called fuzzy improved null linear discriminant analysis (FiNLDA), to cluster the spectra of collected milk for identifying milk brands. To elevate the classification accuracy, FiNLDA was applied to process the near-infrared (NIR) spectra of milk acquired by the portable near-infrared spectrometer. The principal component analysis and Savitzky-Golay (SG) filtering algorithm were employed to lower dimensionality and eliminate noise in this system, respectively. Thereafter, improved null linear discriminant analysis (iNLDA) and FiNLDA were applied to attain the discriminant information of the NIR spectra. At last, the K-nearest neighbor classifier was utilized for assessing the performance of the identification system. The results indicated that the maximum classification accuracies of LDA, iNLDA and FiNLDA were 74.7%, 88% and 94.67%, respectively. Accordingly, the portable NIR spectrometer in combination with FiNLDA can classify milk brands correctly and effectively.


Musculoskeletal symptoms in patients with long COVID: A cross-sectional study on Iranian patients.
Latest studies have revealed that an increasing number of Corona Virus Disease of 2019 (COVID-19) patients may continue to feel symptoms after the acute phase. This study aimed to evaluate the prevalence of musculoskeletal symptoms after the acute phase of COVID-19 and its associated factors. We designed a cross-sectional study from January 2021 to April 2021. An online questionnaire was designed and sent to patients who had recovered from COVID-19. The questionnaire contained questions on participants' demographic characteristics, COVID-19 course at its acute phase, and musculoskeletal symptoms after recovering from COVID-19. Musculoskeletal symptoms associations with patients' characteristic and COVID-19 course was evaluated. 239 patients, including 72 (30.1%) males and 167 (69.9%) females with a mean age of 37.96 years (SD = 11.19), were included in the study. 98.74% of our patients had experienced at least one musculoskeletal symptom after recovering from COVID-19, and the most common symptom was fatigue, as 91.2% of participants experienced this symptom, followed by myalgia, headache, and low back pain. High BMI, hospitalization, and ICU admission were associated with a higher risk of musculoskeletal symptoms. This study indicated a high prevalence of persistent musculoskeletal symptoms among patients who recovered from COVID-19. Modifiable factors, such as BMI, can be targeted to reduce the prevalence of musculoskeletal symptoms in COVID-19 survivors and reduce its burden.


A comparison of two proposed definitions for metabolic syndrome in the Chinese adult population.
The metabolic syndrome is a major risk factor for cardiovascular disease (CVD). We estimated the prevalence of the metabolic syndrome using the definitions proposed by the International Diabetes Federation (IDF) and the American Heart Association and the National Heart, Lung, and Blood Institute (revised ATP III), and compared the 2 definitions in the Chinese adult population. We conducted a cross-sectional study among a nationally representative sample of 15,838 Chinese adults ages 35 to 74 years in 2000 to 2001. Waist girth, blood pressure, and blood levels of HDL-cholesterol, triglycerides, and glucose were measured according to standard methods. The overall age-standardized prevalence of the metabolic syndrome by the IDF and revised-ATP III definitions was 16.5% and 23.3%, respectively. The overall agreement of being classified as having or not having the metabolic syndrome was 93.2% for the 2 definitions, with a Kappa coefficient of 0.80. The prevalence significantly increased with age and was higher in women than in men by both definitions (23.3% vs 10.0% for IDF and 29.1% vs 17.7% for revised ATP III). Compared with men, women had a significantly higher prevalence of central obesity (37.6% vs 16.0%) and reduced HDL-cholesterol (46.5% vs 21.9%), whereas men had a significantly higher prevalence of raised blood pressure (44.2% vs 38.0%) compared with women. The metabolic syndrome is very common in China regardless of the definition used. Prevention and treatment of the metabolic syndrome should become a public health priority to reduce the CVD-related burden in China.


What to expect from medical treatment of otitis media.
1. To state the expected rates of spontaneous improvement for untreated acute otitis media (AOM), recurrent AOM, and otitis media with effusion (OME). 2. To state the expected impact of antibiotic therapy on AOM, recurrent AOM, and OME in terms of the number of children needed to be treated to cure or prevent a single episode. 3. To explain why oral steroids are a promising, but unproven, treatment for OME. 4. To update and modify expectations for medical treatment of otitis media based on meta-analysis of randomized clinical trials.


Functional selectivity of adenosine receptor ligands.
Adenosine receptors are plasma membrane proteins that transduce an extracellular signal into the interior of the cell. Basically every mammalian cell expresses at least one of the four adenosine receptor subtypes. Recent insight in signal transduction cascades teaches us that the current classification of receptor ligands into agonists, antagonists, and inverse agonists relies very much on the experimental setup that was used. Upon activation of the receptors by the ubiquitous endogenous ligand adenosine they engage classical G protein-mediated pathways, resulting in production of second messengers and activation of kinases. Besides this well-described G protein-mediated signaling pathway, adenosine receptors activate scaffold proteins such as β-arrestins. Using innovative and sensitive experimental tools, it has been possible to detect ligands that preferentially stimulate the β-arrestin pathway over the G protein-mediated signal transduction route, or vice versa. This phenomenon is referred to as functional selectivity or biased signaling and implies that an antagonist for one pathway may be a full agonist for the other signaling route. Functional selectivity makes it necessary to redefine the functional properties of currently used adenosine receptor ligands and opens possibilities for new and more selective ligands. This review focuses on the current knowledge of functionally selective adenosine receptor ligands and on G protein-independent signaling of adenosine receptors through scaffold proteins.


A novel use of infra-red spectroscopy (NIRS and ATR-FTIR) coupled with variable selection algorithms for the identification of insect species (Diptera: Sarcophagidae) of medico-legal relevance.
Unequivocal identification of fly specimens is an essential requirement in forensic entomology. Herein, a simple, non-destructive and rapid method based on two vibrational spectroscopy techniques [Near-Infrared Spectroscopy (NIRS) and attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy] coupled with variable selection techniques such as genetic algorithm-linear discriminant analysis (GA-LDA) and successive projection algorithm-linear discriminant analysis (SPA-LDA) were applied for identifying and discriminating six species of flesh flies (Diptera: Sarcophagidae) native to Neotropical regions. This novel approach is based on the unique spectral "fingerprints" of their biochemical composition. One hundred sixty (160) NIRS and FT-IR specimens (120 male, 40 female) were acquired; different pre-processing methods such as baseline correction, derivative and Savitzky-Golay smoothing were also performed. In addition, the multivariate classification accuracy results were tested based on sensitivity, specificity, positive (or precision) and negative predictive values, Youden index, positive and negative likelihood ratios. Principal components analysis (PCA) was employed for male vs. female category using NIRS, strongly showing the separation between the classes with only three principal components and 99% explained variance. Differentiation between the genera Oxysarcodexia, Peckia and Ravinia was efficiently confirmed by both techniques. In comparison with other biological methods, this approach represents an effective choice for fast and non-destructive identification in forensic entomology.


Focal encephalopathy with recurrent episodes of epileptic status and cluster mimicking hemiconvulsion-hemiplegia-epilepsy syndrome.
Hemiconvulsion-hemiplegia-epilepsy syndrome is characterized by unilateral convulsions during fever, transient hemiplegia, and subsequent partial epilepsy with atrophy in the cerebrum. A 9-year-old boy with a history of West syndrome and hypoglycemic attacks had three episodes of epileptic status and clusters mimicking HHE syndrome over a 2-year period. Magnetic resonance imaging revealed the involvement of the right and left cerebrums. Because no abnormalities were detected in an endocrine examination, screening tests for metabolic errors, or magnetic resonance spectroscopy, a diagnosis of metabolic errors was not supported. Immunohistochemistry using the patient's sera showed binding of the serum immunoglobulin with neurons in the temporal and occipital cerebral cortices, indicating the possible involvement of autoimmune mechanisms in this case. Focal encephalopathy should be considered in children showing convulsions, psychiatric disorders, and/or involuntary movements for several months in a row. In such cases, immunohistochemistry using the patient's sera may be useful for the investigation of the pathogenesis of the illness.


Helicobacter pylori infection in children with abdominal ailments in a developing country.
Helicobacter pylori commonly infects children in developing countries. To determine the frequency of this infection and its potential role in specific gastrointestinal entities, all patients requiring upper gastrointestinal endoscopy for the evaluation of abdominal ailments in a gastroenterology practice in Lima, Peru, were evaluated during a 1-year period. Gastric biopsies were obtained for each child and were stained with hematoxylin-eosin and Warthin-Starry stains. Of the 107 evaluable patients (mean age 7.4 years, 58% boys), 52 (49%) were infected. The infection rate increased with older patients (P = 0.004). Children with recurrent abdominal pain (P = 0.04), an endoscopic finding of nodular gastritis (P = 0.007), and a histologic finding of chronic active gastritis (P < 0.0001) were infected more commonly.


Multiple coronary aneurysms and acute myocardial infarction in a female patient with rhupus: case report and literature review.
Coronary artery aneurysms (CAA) are an infrequent cause of coronary artery disease in both systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), most occurring as a result of acute coronary syndromes (ACS). Until now, no cases of CAA have been described in a patient with rhupus syndrome (RhS). Differentiating whether CAA stem from primary vasculitis, atherosclerosis, or a combination of both continues to pose a significant challenge. We present the first described clinical case of a 43-year-old patient with RhS and multiple CAA identified by the presentation of an acute myocardial infarction. The presence of multiple cardiovascular risk factors and the absence of inflammatory findings, both in PET-CT and arterial biopsy, favored an atherosclerotic versus a vasculitic etiology of the CAA. At the time of the aneurysms diagnosis, the patient showed no signs of SLE activity and only moderate RA activity, which underscores the importance of screening for silent coronary aneurysms in these patients, even in subjects exhibiting little apparent activity from their underlying disease. This case also exemplifies the severe impact of atherosclerotic burdens on such patients, demanding vigilance and aggressiveness in its prevention, early diagnosis, and treatment. We hypothesize that RhS could engender an even greater risk of presenting CAA than either SLE or RA on their own, which therefore warrants more careful follow-up in these patients.


Routine interval appendectomy in children is not indicated.
This study evaluates outcomes for children treated without interval appendectomy (IA) after successful nonoperative management of perforated appendicitis. A retrospective study of pediatric patients with appendicitis was performed from 12 regional acute-care hospitals from 1992 to 2004 with mean length of follow-up of 7.5 years. Main outcomes were recurrent appendicitis and cumulative length of hospital stay. The study included 6439 patients, of which 6367 (99%) underwent initial appendectomy. Seventy-two (1%) patients were initially managed nonoperatively and 11 patients had IA. Of the remaining 61 patients without IA, 5 (8%) developed recurrent appendicitis. Age, sex, type of appendicitis, and abscess drainage had no influence on recurrent appendicitis. Cumulative length of hospital stay was 6.6 days in patients without IA, 8.5 days in patients with IA, and 9.6 days in patients with recurrent appendicitis. Recurrent appendicitis is rare in pediatric patients after successful nonoperative management of perforated appendicitis. Routine IA is not necessarily indicated for these children.