Effect of saline water ionic strength on phosphorus recovery from synthetic swine wastewater.
Declining worldwide phosphate rock reserves has driven a growing interest in exploration of alternative phosphate supplies. This study involved phosphorus recovery from swine wastewater through precipitation of struvite, a valuable slow-release fertiliser. The economic feasibility of this process is highly dependent on the cost of magnesium source. Two different magnesium sources were used for phosphorus recovery: pure magnesium chloride and nanofiltration (NF) saline water retentate. The paper focuses on the impact of ionic strength on phosphorus recovery performance that has not been reported elsewhere. Experimental design with five numerical variables (Mg/P molar ratio, pH, PO43--P, NH4+-N, and Ca2+ levels) and one categorical variable (type of magnesium source) was used to evaluate the effect of ionic strength on phosphorus removal and struvite purity. The experimental data were analysed using analysis of variance (ANOVA) and principal component analysis (PCA). Results indicated that a magnesium source obtained from NF retentate was as effective as MgCl2 for struvite precipitation. It was also revealed that ionic strength had a more positive effect on struvite purity than on phosphorus removal. Within the range of parameters studied in this research, high ionic strength, high pH and wastewater with high phosphate, high ammonium and low calcium contents were found to be the most favourable conditions for struvite precipitation. Findings from this study will be beneficial to determine the feasibility of using high ionic strength saline water, such as NF seawater retentate, as a magnesium source for phosphorus recovery from wastewater that is rich in ammonium-nitrogen and phosphate.


Effectiveness of Intracanal Cryotherapy in Root Canal Therapy: A Systematic Review and Meta-analysis of Randomized Clinical Trials.
The effectiveness of intracanal cryotherapy for reducing postoperative pain is unclear. The objective of this systematic review was to evaluate the effect of intracanal cryotherapy on postoperative pain after root canal therapy in patients with pulpal or periradicular pathosis. We searched PubMed, Embase, Scopus, and the Cochrane Library as well as the top 3 endodontic journals for relevant articles. We included randomized controlled trials that included adults. Our main outcome was postoperative pain intensity measured with a validated scale. We assessed the risk of bias using the Cochrane criteria and the quality of the included studies using Grading of Recommendation Assessment, Development, and Evaluation. We used a random-effects model for meta-analysis. Eight studies involving 810 patients were included. The overall risk of bias was moderate. Seven of 8 studies used a visual analog scale to measure pain intensity. Compared with controls, intracanal cryotherapy significantly reduced postoperative pain at 6 (mean difference = -1.37; 95% confidence interval [CI], -0.61 to -2.14; P < .05; I2 = 76%; moderate-quality evidence) and 24 hours after the procedure (mean difference = -1.43; 95% confidence interval, -0.70 to -2.15; P < .05; I2 = 89%; moderate-quality evidence). There was no significant effect on pain at 48 and 72 hours and 7 days after the procedure. Moderate-quality evidence suggests that intracanal cryotherapy (ie, using cold saline irrigation as a final irrigant) significantly reduces the intensity of pain at 6 and 24 hours after root canal therapy. Future clinical trials assessing the effectiveness of intracanal cryotherapy are advocated.


Utilization of hybrid oak hosts by a monophagous gall wasp: How little host character is sufficient?
We examined the utilization by the cynipid gall former, Andricus californicus, of oak trees ranging across a hybrid continuum from pure Quercus dumosa to pure Q. engelmannii. Two components of utilization were considered, the proportion of trees parasitized and the density of galls on parasitized trees. Although the wasp normally only parasitizes Q. dumosa, galls were found on trees with up to 85% of the genetic character of the non-host, as determined by a hybrid index. The proportion of hybrids utilized did not differ statistically from the proportion of pure Q. dumosa utilized. We consider competing hypotheses about the genetic mechanism behind host choice in the light of our results. The model that is most consistent with the observed incidence pattern is based on a "cluster concept": A number of independent genetic factors in the host determine its acceptability, however, these factors are substitutable, such that no single factor is critical, but some threshold number of factors must be exceeded.


Determination of free levels of phenytoin in human plasma by liquid chromatography/tandem mass spectrometry.
A liquid chromatography combined with tandem mass spectrometry assay for the determination of free levels of the highly protein bound drug phenytoin (5,5-diphenylhydantoin) in human plasma is described. The assay was demonstrated to be reliable, accurate and precise, and specific for phenytoin. The procedure involves isolation of the unbound drug from the drug/protein complex by ultrafiltration. Liquid-liquid extraction was employed to extract the resultant ultrafiltrate. PHT was separated on a 50 x 3 mm reversed-phase column using isocratic mobile phase conditions that yielded a run time of 1.5 min, enabling high throughput sample analysis. Linearity was obtained over the range 5.00 to 500 ng/ml. Both between-run and within-run coefficients of variation were less than 15% and accuracy's across the assay range were all within 100 +/- 10%. The assay was successfully implemented to support a clinical interaction study with phenytoin.


Induced sputum in systemic sclerosis interstitial lung disease: comparison to healthy controls and bronchoalveolar lavage.
Induced sputum (IS) is a noninvasive tool, which can be used to collect cellular and soluble materials from lung airways. To evaluate if IS may be a useful and safe tool for the detection of airway inflammation in patients with interstitial lung disease (ILD) in systemic sclerosis (SSc). Sixty-eight patients with SSc and ILD as well as 18 healthy individuals (controls) were selected and submitted to IS examination. In 34 of 68 patients with SSc, bronchoalveolar lavage (BAL) was also performed. Safety of IS was assessed by comparison of forced expiratory volume in the first second (FEV(1)), FEV(1)/forced vital capacity ratio and peak expiratory flow before and after the IS procedure. Cell composition in samples collected by BAL and IS was correlated, and IS total and differential cell count in SSc patients and controls were compared. The total number of cells was significantly higher in IS samples of SSc patients compared to those of healthy controls. Mean percentage of neutrophils was also higher in SSc patients (41.79 +/- 23.89 vs. 27.37 +/- 17.90), as well as lymphocytes (17.42 +/- 19.70 vs. 3.13 +/- 2.28) and eosinophils (2.35 +/- 4.43 vs. 0.41 +/- 0.46). On the other hand, mean percentage of macrophages was higher in healthy individuals (69.10 +/- 19.15 vs. 36.96 +/- 20.68). In fluid recovered by BAL, the most frequent cells were macrophages (67.89% +/- 17.26), while neutrophils (14.77 +/- 17.18%) and lymphocytes (15.62 +/- 13.46%) were less frequent and eosinophils (1.66 +/- 2.08%) were rare. A similar pattern of cell composition was found in IS samples (41.15 +/- 21.67% of macrophages, 39.72 +/- 23.15% of neutrophils, 15.28 +/- 19.46% of lymphocytes and 2.56 +/- 5.03% of eosinophils). Strength of correlation between BAL and IS was significant for macrophages and neutrophils. After IS procedure was performed, improvement of FEV(1) (mean value before IS was 85.09 +/- 14.44 and 88.93 +/- 16.40 after IS) and FEV(1)/forced vital capacity (mean value before IS was 98.53 +/- 12.11 and 105.22 +/- 10.78 after IS) was observed. The IS method may allow a noninvasive assessment of cell composition in airway fluid and may contribute to the better understanding of upper/medium airway inflammation in SSc. Future studies are needed to verify whether IS can replace invasive procedures for the detection and monitoring of lung inflammation in SSc.


Bacterial infection of human hematopoietic stem cells induces monocytic differentiation.
Differentiation of hematopoietic stem cells (HSCs) can be influenced by different stimuli, including cytotoxic agents, certain cytokines, and contact with pathogens. Infection may result in dysregulation of these important progenitor cells and therefore interfere with the availability of blood cells. In this study we analyzed the effect of bacterial infection on HSCs concerning surface marker expression and cytokine release. Listeria monocytogenes and Yersinia enterocolitica accelerated maturation of hematopoietic progenitor cells along the myeloid lineage, as demonstrated by the upregulation of CD13, CD14, and costimulatory signals. By screening cytokine secretion, granulocyte-macrophage colony-stimulating factor, interleukin (IL)-6, IL-8, IL-10, IL-12, and tumor necrosis factor-alpha were found to be induced by bacterial infection. These data indicate that infection of HSCs with L. monocytogenes and Y. enterocolitica affects the differentiation of CD34(+) hematopoietic progenitors in vitro and may lead to secretion of cytokines that can influence the HSC differentiation capacity and immune response.


Nutritional correlates of fetal growth.
Fetal growth is regulated by an interplay of genetic and environmental factors. Fetuses with growth restriction secondary to decreased nutritional supply exhibit maturation whereas hyperglycemic fetuses of diabetic mothers show delayed lung and placental maturation. Membranes from fetuses of diabetics have a decrease in epidermal-growth-factor (EGF) binding, whereas EGF binding is increased in lung and placenta of growth-restricted fetuses. These results suggest that the EGF receptor is responsive to altered nutritional states and may be important to substrate flow to the fetus.


Amino acid incorporation into total protein and levels of S-100 protein in discrete rat brain areas after prolonged protein or amino acid restriction.
Young adult rats were fed an isocaloric diet for 28 days. The diet consisted of either 22% casein, or protein-restricted food consisting of a 5% mixture of soy and whey protein, or a synthetic amino acid mixed diet devoid of the essential amino acids tryptophan, valine, lysine, and threonine. The level of the nervous tissue-specific S-100 protein was quantified immunoelectrophoretically in 9 different brain areas. A marked decrease of S-100 was observed in hippocampus and posterior part of the cerebellar vermis per g wet weight in protein-restricted rats. An additional lowering was noticed in sensory motor cortex per mg soluble protein. This effect was potentiated with the amino acid-deficient diet. The in vitro incorporation of 3H-leucine into cerebellar proteins was slightly decreased in the low-protein-fed rats, and more markedly decreased in those receiving an amino acid-restricted diet.


Human papillomavirus type 11 in multiple squamous cell carcinomas in a patient with subacute cutaneous lupus erythematosus.
Squamous cell carcinoma (SCC) is a rare complication of cutaneous lupus erythematosus (LE). Aside from the documented role of ultraviolet light, SCC may arise in areas of chronic scarring, such as in lesions of discoid LE. Iatrogenic immunosuppression associated with organ transplantation also results in a predisposition to SCC, often with multiple tumors. A role for certain human papillomaviruses (HPV) in the development of squamous cell carcinoma has been documented; specifically, HPV types 5 and 8 are detected in SCCs in patients with epidermodysplasia verruciformis and in recipients of organ transplants. HPV-11 is generally found in benign genital condylomata or laryngeal papillomas, but has not yet been associated with malignancy. We describe a patient with non-scarring cutaneous LE who was treated with azathioprine and prednisone and developed multiple SCCs. HPV-11 DNA and the target oncogenes neu and Ki-ras were detected in tumor tissue with the polymerase chain reaction. The HPV may have been involved in tumor induction and the azathioprine may have been involved in tumor promotion.


Promoter-specific co-activation by Drosophila mastermind.
Mastermind (Mam) is a co-activator protein of binary complexes consisting of Suppressor of Hairless (Su(H)) and Notch Intracellular Domain (NICD) proteins assembled on cis-regulatory regions of target genes activated by Notch signaling. Current evidence indicates that Mastermind is necessary and sufficient for the formation of a functional Su(H)/NICD/Mam ternary complex on at least one specific architecture of Su(H) binding sites, called the SPS element (Su(H) Paired Sites). However, using transcription assays with a combination of native and synthetic Notch target gene promoters in Drosophila cultured cells, we show here that co-activation of Su(H)/NICD complexes on SPS elements by Mam is promoter-specific. Our novel results suggest this promoter specificity is mediated by additional unknown cis-regulatory elements present in the native promoters that are required for the recruitment of Mam and formation of functional Su(H)/NICD/Mam complexes on SPS elements. Together, the findings in this study suggest Mam is not always necessary and sufficient for co-activation of binary Su(H)/NICD complexes on SPS elements.


Incidence and recurrence of depression from adolescence to early adulthood: A longitudinal follow-up of the Mexican Adolescent Mental Health Survey.
Depression is a leading cause of disease burden around the globe, often develops during adolescence and is recurrent. Thus, disentangling risk factors for incidence from those of recurrence during adolescence is relevant and might suggest different strategies for prevention of onset than for relapse. The aim was to evaluate the relative risk of socio-demographic and clinical factors and traumatic events associated to incidence and recurrence of depression in youth from Mexico City. This is a prospective longitudinal general population survey in which 1071 respondents from the Mexican Adolescent Mental Health Survey were interviewed between the ages of 12 and 17 and again eight years later when they were between 19 and 26 years of age. The World Mental Health Composite International Diagnostic Interview evaluated incidence and persistence of major depression and risk factors. Eight-year incidence was 12.9% while recurrence was 46.1%. Risk factors for incidence (female sex, any incident trauma, and specifically sexual abuse and an other/private event) differed from the risk factors for recurrence (childhood onset and domestic violence) with the exception of having a parent with depression, which was associated to increased risk for both. The follow-up response rate was limited by inability to locate participants at wave II. Statistical power was limited for persistence due to low rate of depression at wave I. Intervening with both depressed and non-depressed children of parents with depression may have beneficial effects on both the development of depression as well as recurrence.


Mandibular fractures - towards a national standard for "time to theatre" - national audit by the BAOMS Trauma Specialist Interest Group.
Recent studies have shown that in most patients, a delay of several days in the treatment of mandibular fractures is not associated with adverse outcomes, and this has challenged the traditional practice of recommending treatment within 24hours. Longer hospital stays cost more and lower the patients' quality of life, but we know of no standard recommendation about when these patients should be treated. Our aim therefore was to find out how many patients had reduction and fixation of a fractured mandible by the end of the next working day, with a view to developing a national standard. We invited all oral and maxillofacial surgery (OMFS) units in the UK to participate in a prospective audit over two months, and 35 agreed. Overall, 506 patients (80%) were operated on by the end of the next working day. The time to theatre varied from 1 hour 15minutes to 11 days, 20hours and 51minutes (median 22hours 7minutes). Patients admitted to units with an OMFS trauma list were more likely to be operated on by the next working day (p=0.011) as were those operated on at the weekend (p=0.019). We think that early fixation, return of function, and discharge, benefit patients most in terms of quality of life. Also, shorter hospital stays and reduced costs increase the availability of resources for elective operations. Setting a standard will improve our service and the care we deliver.


Holt-Oram Syndrome: Hands are the Clue to the Diagnosis.
Holt-Oram syndrome or heart-hand syndrome consists of phenotypic and genotypic abnormalities. It is characterized by abnormalities of upper limbs and congenital cardiac defects. It is an autosomal dominant disorder due to a mutation in TBX5 gene located on chromosome 12, but sporadic cases have also been reported. We describe a 26-year-old female with a history of shortness of breath for 5 years. She had bilateral hand deformities, and on evaluation, found to have ostium secundum atrial septal defect which is common cardiac defect in Holt-Oram syndrome.


[Simultaneous comparison of periodograms and performance spectra to distinguish periodical from statistical curve portions of vegetative rhythms].
The differences between corresponding data of power spectral densities and quadrated periodograms were computed delimiting periodical and statistical parts of curves of mean arterial pressure, heart rate, and respiration rhythms. The statistical parts of the curves show similar density distributions in the investigated frequency range as the periodical parts (power spectra). In patients with autonomic disorders these statistical parts of the curves are higher than in healthy volunteers.


Inferior alveolar nerve function after mandibular osteotomies.
A total of 1034 patients who had undergone orthognathic surgery were examined after 2 years; 818 had been treated with varying types of mandibular osteotomy such as vertical ramus osteotomy, sagittal split ramus osteotomy, and genioplasty. Neurosensory function in the mental nerve region was assessed by evaluating light touch perception. The incidence of neurosensory deficiency was 216/548 (39%) after sagittal split ramus osteotomy, 26/140 (19%) after extraoral vertical ramus osteotomy, 9/78 (12%) after genioplasty and 60/650 (9%) after intraoral vertical ramus osteotomy. Additional genioplasty increased both the incidence and severity of neurosensory disturbance after intraoral vertical ramus osteotomy but did not significantly influence the neurosensory function after sagittal split ramus osteotomy. The incidences of neurosensory disturbance after mandibular osteotomies in this report correspond well with those previously reported, but the incidence of almost 40% after sagittal split ramus osteotomy must be considered a disquieting drawback of the procedure.


Neprilysin and Natriuretic Peptide Regulation in Heart Failure.
Neprilysin is acknowledged as a key player in neurohormonal regulation, a cornerstone of modern drug therapy in chronic heart failure. In the cardiovascular system, neprilysin cleaves numerous vasoactive peptides, some with mainly vasodilating effects (natriuretic peptides, adrenomedullin, bradykinin) and other with mainly vasoconstrictor effects (angiotensin I and II, endothelin-1). For decades, neprilysin has been an important biotarget. Academia and industry have combined active efforts to search for neprilysin inhibitors (NEPIs) that might be useful in clinical practice. NEPI monotherapy was initially tested with little success due to efficacy issues. Next, combination of NEPI and ACE-inhibiting activity agents were abandoned due to safety concerns. Recently, the combination of NEPI and ARB, also known as ARNI, has shown better than expected results in heart failure with reduced ejection fraction, and multitude of ongoing studies are set to prove its value across the heart failure spectrum.


L-2-Hydroxyglutaric aciduria: MRI in seven cases.
The MRI findings in 7 patients with L-2-Hydroxyglutaric aciduria (L-2-OHG aciduria) are described and compared with previous neuroradiological reports and the only three published pathological cases. Signal abnormalities involved peripheral subcortical white matter, basal ganglia and dentate nuclei. Cerebellar atrophy was present. Although similar appearances may be seen in other metabolic disorders, the distribution of signal abnormalities in L-2-OHG aciduria is highly characteristic and may suggest the correct diagnosis.


Visualization of breast lesions with an advanced ultrasonic device: results of a pilot study.
A pilot study is described in which a new design of a sensitive ultrasonic device was used to visualize breast lesions in nine patients. The results were in general accord with clinical, histologic, and x-ray examinations, although ultrasound was superior to x-ray mammography in the visualization of discrete cysts in breasts having a "dense" background. As the device provides an indication of the capabilities of ultrasonic equipment which will be generally available within the next two years, projections are made on the impact of this equipment on the earlier diagnosis and prognosis of cancer, together with a discussion of the negligible radiation bio-hazards posed by devices of this type, in the light of present knowledge.


Enrichment of C-type virus mRNA from immunochemically separated polyribosomes.
A method for the isolation of mRNA from a c-type virus-positive cell (JLS-V6) has been developed. This method consisted of (i) specific immunochemical precipitation of polyribosomes synthesizing viral proteins, (ii) extraction of the mRNA from the polyribosome/antigen/antibody complex, and (iii) separation of poly-A containing RNA by affinity chromatography on oligo-d(T)-cellulose. Three size classes of virus specific poly-A containing mRNA are identified and they are 35S, 20S-25S, and 10S-15S.


Relation of interleukin-6 levels in COVID-19 patients with major adverse cardiac events.
Elevated interleukin-6 (IL-6) levels may correlate with disease severity in COVID-19. We analyzed whether there was an association between elevated IL-6 levels and major adverse cardiac events (MACE) and/or mortality in COVID-19 patients. A retrospective chart review was performed on COVID-19 patients among four hospitals in one health system from March to May 2020, extracting information on baseline characteristics, MACE (i.e., myocardial infarction, stroke, deep venous thrombosis/pulmonary embolism, or shock requiring vasopressor support), mortality, and IL-6 levels. Of the 496 patients hospitalized with COVID-19, 191 patients had an IL-6 level drawn and 68% had elevated IL-6 levels. The elevated IL-6 population had higher odds of developing a MACE compared to the normal IL-6 population (P < 0.0001, odds ratio [OR] = 5.91, 95% confidence interval [CI] = 2.65-14.11). The elevated IL-6 population also had higher mortality rates (28.2% vs 5%, P = 0.0001, OR = 7.47, 95% CI = 2.19-39.32) and an increased incidence of a MACE and/or mortality (58.78% vs 20.00%, P < 0.0001, OR = 5.7, 95% CI 2.65-12.83) compared to the normal IL-6 population. Elevated IL-6 levels in COVID-19 patients may be associated with MACE and/or mortality. Monitoring IL-6 levels in COVID-19 patients may help risk-stratify patients.


Surface distribution of flash-evoked and pattern reversal-evoked potentials in hooded rats.
Simultaneous recording from 21 electrode sites in a 4 X 4 mm area over the posterior cortex was used to determine the surface distribution of all major peaks which constitute flash-evoked potentials (FEPs) and pattern reversal evoked-potentials (PREPs) in hooded rats. Topographical maps were constructed with respect to Bregma and midline reference points. The data indicate that not all of the peaks which constitute either evoked potential have their greatest amplitude within the classically defined primary visual cortex. Further, since the FEPs were produced by uniform stimulation, the data suggest that surface regions of the rat visual cortex differ in ways other than simply the portion of the visual field from which information is received.


[Skin necrosis with vitamin K antagonists: An imbalance between coagulant and anticoagulant factors].
Skin necrosis with vitamin k antagonists are rare. They affect more frequently middle-aged and obese women, often within 10 days after initiating of treatment. They occur most often in a context of thrombophilia. An 18-year-old obese woman was treated with heparin and fluindione for a lower limb deep venous thrombosis. On day 5, the patient presented fever and skin necrosis, which extended rapidly. We identified an activated protein C resistance and a major inflammatory syndrome related to Mycoplasma pneumoniae infection. The outcome was favorable after discontinuation of the fluindione, introduction of heparin and vitamin K, despite amputation of a toe. Skin necrosis is due to a transient hypercoagulable state during the initiation of vitamin K antagonist treatment due to an imbalance between pro- and anticoagulant factors. In our case, it was caused by an activated protein C resistance and an inflammatory syndrome.


CCl4-induced alterations in Ca++ homeostasis in chlordecone and phenobarbital pretreated animals.
Male S-D rats were maintained on normal powdered diet or on the same diet containing 10 ppm chlordecone or 225 ppm phenobarbital for 15 days. On day 15, all the animals received a single ip injection of either corn oil or a subtoxic dose of CCl4 (25-200 microliter/kg) in corn oil vehicle (1 ml/kg). The animals were sacrificed 12 hrs later. Liver microsomal cytochrome P-450 and Ca++ levels in whole liver, mitochondria, microsomes and cytosol were determined. Cytochrome P-450 induction was greater with phenobarbital pretreatment than with chlordecone but the CCl4 induced destruction of cytochrome P-450 was almost similar in both groups and progressive with the dose of CCl4. CCl4 given to animals on normal diet in a dose range of 25-200 microliter/kg did not significantly alter the cytochrome P-450 levels. These findings are consistent with greater bioactivation of CCl4 after the above two pretreatments. There was a massive accumulation of Ca++ in chlordecone and phenobarbital pretreated animals after CCl4 administration. Cytosolic Ca++ levels remained high despite the mitochondrial and microsomal sequestration. This perturbation of hepatocellular Ca++ homeostasis might lead to hepatic lesion and hepatic failure. Chlordecone or phenobarbital alone do not alter hepatic Ca++ levels. These findings suggest that excessive accumulation of Ca++ may be causally related to the progression of hepatotoxic response due to CCl4 in chlordecone treated animals.


Diagnosis of nosocomial pneumonia in mechanically ventilated patients by the blind protected telescoping catheter.
To demonstrate that blind insertion of the protected telescoping catheter (PTC-NB) through the orotracheal tube can provide reliable pulmonary samples for the diagnosis of nosocomial pneumonia (NP) in ventilated patients. We performed a random comparison between the protected telescoping catheter introduced through a bronchofiberscope (PTC-B) and the PTC-NB to diagnose NP. A general intensive care unit of a University Hospital. 40 consecutive patients on mechanical ventilation and with suspicion of NP. The diagnosis of NP was suspected by clinical and chest X-ray findings. NP was confirmed microbiologically in 26 (65%) patients and maintained in 8 patients by clinical and radiological criteria. PTC-NB confirmed the microbiological diagnosis of PN in 21 (80%) patients. The use of antibiotics prior taking respiratory samples reduced the sensitivity of PTC-NB and PTC-B from 100-74% and from 94-70% (p = 0.001). Both techniques agreed in 24 of 33 (73%) patients but such agreement was better when PN was on the right lung. Two patients developed a self-limiting hemoptysis after the PTC-B procedure. PTC-NB is as sensitive as specific as PTC-B for diagnosing PN in mechanically ventilated patients, being a much easier technique to use.


Microcornea, iris and choroidal coloboma, and global developmental delay caused by TENM3 pathogenic variants in a Chinese patient.
Biallelic TENM3 pathogenic variants cause isolated or syndromic microphthalmia. Syndromic microphthalmia 15 (MCOPS15) is characterized by microphthalmia, coloboma, and developmental delay. Currently, only four cases of MCOPS15 have been reported and the clinical features varied among the patients indicating potential broad phenotypic spectrum. The present case was a 6-month-old male at diagnosis. The patient exhibited long philtrum, large ears, bilateral ptosis, and nystagmus. Ophthalmic tests showed that he had microcornea, iris and choroidal coloboma. The patient presented with global developmental delay (GDD). Trio-whole exome sequencing and genome copy number sequencing were conducted to explore the disease-causing mutations. Exome sequencing and genome copy number sequencing showed the presence of L1471F and E661G compound mutations in TENM3, which were inherited from the mother and father, respectively. Sanger sequencing was conducted to verify association of the mutations with the disease in the present family. Two TENM3 variants were identified in a patient with Syndromic microphthalmia 15 in the present study. However, further studies should be conducted to explore the pathogenicity of the variants.


Effects of drugs that influence eucaryotic motile processes on motility of Cystobacter fuscus (Myxobacterales).
Cytochalasin B, dbcAMP and EGTA were found to inhibit the motility of Cystobacter fuscus completely whereas colchicine and cAMP only reduced velocity of movement.


ARGX-117, a therapeutic complement inhibiting antibody targeting C2.
Activation of the classical and lectin pathway of complement may contribute to tissue damage and organ dysfunction of antibody-mediated diseases and ischemia-reperfusion conditions. Complement factors are being considered as targets for therapeutic intervention. We sought to characterize ARGX-117, a humanized inhibitory monoclonal antibody against complement C2. The mode-of-action and binding characteristics of ARGX-117 were investigated in detail. Furthermore, its efficacy was analyzed in in vitro complement cytotoxicity assays. Finally, a pharmacokinetic/pharmacodynamic study was conducted in cynomolgus monkeys. Through binding to the Sushi-2 domain of C2, ARGX-117 prevents the formation of the C3 proconvertase and inhibits classical and lectin pathway activation upstream of C3 activation. As ARGX-117 does not inhibit the alternative pathway, it is expected not to affect the antimicrobial activity of this complement pathway. ARGX-117 prevents complement-mediated cytotoxicity in in vitro models for autoimmune hemolytic anemia and antibody-mediated rejection of organ transplants. ARGX-117 exhibits pH- and calcium-dependent target binding and is Fc-engineered to increase affinity at acidic pH to the neonatal Fc receptor, and to reduce effector functions. In cynomolgus monkeys, ARGX-117 dose-dependently reduces free C2 levels and classical pathway activity. A 2-dose regimen of 80 and 20 mg/kg separated by a week, resulted in profound reduction of classical pathway activity lasting for at least 7 weeks. ARGX-117 is a promising new complement inhibitor that is uniquely positioned to target both the classical and lectin pathways while leaving the alternative pathway intact.


Adenocarcinoma arising from short-segment Barrett's esophagus in a young man.
We report herein a case of adenocarcinoma arising from short-segment Barrett's esophagus (SSBE) in a 36-year-old man. An elevated tumor was found at the esophagogastric junction, and a histological evaluation of the biopsy specimen led to a diagnosis of adenocarcinoma. The tumor was found to be confined to the mucosa surrounding the SSBE, and endoscopic submucosal dissection was done without complications. Histological examination of the resected specimen showed that the adenocarcinoma had also invaded the muscularis mucosae and provided evidence of lymphovascular invasion. Additional surgical resection and regional lymph node dissection were therefore carried out; however, no lymph node metastasis was found. Adenocarcinoma arising from Barrett's mucosa is rare in young patients, especially in Japan, and this case is therefore particularly noteworthy.


Seeing invisible light: 2-photon microperimetry to measure visual function.
The accuracy of conventional visual function tests, which emit visible light, decreases in patients with corneal scars, cataracts, and vitreous hemorrhages. In contrast, infrared (IR) light exhibits greater tissue penetrance than visible light and is less susceptible to optical opacities. We therefore compared conventional visual function tests against infrared 2-phton microperimetry (2PM-IR) in a subject with a brunescent nuclear sclerotic and posterior subcapsular cataract before and after cataract surgery. Testing using infrared light microperimetry from a novel device (2PM-IR), visible light microperimetry from a novel device (2PM-Vis), conventional microperimetry, and the cone contrast threshold (CCT) test were performed before and after cataract surgery. Retinal sensitivity assessed using 2PM-IR, 2PM-Vis, and cMP improved by 3.4 dB, 17.4 dB, and 18 dB, respectively. Cone contrast threshold testing improved for the S-cone, M-cone, and l-cone by 111, 14, and 30. 2PM-IR, unlike conventional visual function tests, showed minimal variability in retinal sensitivity before and after surgery. Thus, IR visual stimulation may provide a more accurate means of measuring neurosensory retinal function by circumventing optical media opacities, aiding in the diagnosis of early macular disease.


Relationship between histamine-induced changes of cyclic AMP and mechanical activity on smooth muscle preparations of the guinea-pig ileum and the rabbit mesenteric artery.
On guinea-pig ileum and rabbit mesenteric artery contracted by high potassium (100 mM) histamine produced relaxations which were inhibited by the H2-receptor antagonist metiamide. These results are thus indicative for the role of H2-receptors in mediating relaxation and for H1-receptors in mediating contraction on smooth muscle. Time course studies for the relaxing and cyclic AMP responses to histamine showed that the cyclic AMP increase preceded the H2-receptor mediated relaxation. The cyclic AMP increase in response to histamine was prevented by metiamide, but remained unaffected by mepyramine on both the guinea-pig ileum and the rabbit mesenteric artery. In addition, dose-response curves obtained on the mesenteric artery demonstrated that the H2-receptor mediated depressor responses coincided with cyclic AMP increases. Thus, these results gave clear-cut evidence that cyclic AMP is an intracellular metabolic event only implicit in the H2-receptor mediated relaxation, but not in the H1-receptor mediated contraction on smooth muscle preparations.


Quantization of Optic Disc Characteristics in Young Adults Based on Artificial Intelligence.
This study aimed to automatically and quantitatively analyse the characteristics of the optic disc by applying artificial intelligence (AI) to fundus images. A total of 1084 undergraduates were recruited in this cross-sectional study. The optic disc area, cup-to-disc ratio (C/D), optic disc tilt, and the area, width, and height of peripapillary atrophy (PPA) were automatically and quantitatively detected using AI. Based on axial length (AL), participants were divided into five groups: Group 1 (AL ≤ 23 mm); Group 2 (23 mm < AL≤ 24 mm); Group 3 (24 mm < AL≤ 25 mm); Group 4 (25 mm < AL< 26 mm) and Group 5 (AL ≥ 26 mm). Relationships between ocular parameters and optic disc characteristics were analysed. A total of 999 undergraduates were included in the analysis. The prevalence of optic disc tilting and PPA were 47.1% and 92.5%, respectively, and increased with the severity of myopia. The mean optic disc area, PPA area, C/D, and optic disc tilt ratio were 1.97 ± 0.46 mm2, 0.84 ± 0.59 mm2, 0.18 ± 0.07, and 0.81 ± 0.08, respectively. In Group 5, the average optic disc area (1.84 ± 0.41 mm2) and optic disc tilt ratio (0.79 ± 0.08) were significantly smaller and the PPA area (1.12 ± 0.61 mm2) was significantly larger than those in the other groups. AL was negatively correlated with optic disc area and optic disc tilt ratio (r=-0.271, -0.219; both p < 0.001) and positively correlated with PPA area, width, and height (r = 0.421, 0.426, 0.345; all p < 0.01). A greater AL (β = 0.284, p < 0.01) and a smaller optic disc tilt ratio (β=-0.516, p < 0.01) were related to a larger PPA area. The characteristics of the optic disc can be feasibly and efficiently extracted using AI. The quantization of the optic disc might provide new indicators for clinicians to evaluate the degree of myopia.


Cost-effectiveness of full medicare coverage of angiotensin-converting enzyme inhibitors for beneficiaries with diabetes.
Angiotensin-converting enzyme (ACE) inhibitors slow renal disease progression and reduce cardiac morbidity and mortality in patients with diabetes. Patients' out-of-pocket costs pose a barrier to using this effective therapy. To estimate the cost-effectiveness to Medicare of first-dollar coverage (no cost sharing) of ACE inhibitors for beneficiaries with diabetes. Markov model with costs and benefits discounted at 3%. Published literature and Medicare claims data. 65-year-old Medicare beneficiary with diabetes. Lifetime. Medicare and societal. We evaluated Medicare first-dollar coverage of ACE inhibitors compared with current practice (no coverage) and the new Medicare drug benefit. Costs (2003 U.S. dollars), quality-adjusted life-years (QALYs), life-years, and incremental cost-effectiveness. Compared with current practice, first-dollar coverage of ACE inhibitors saved both lives and money (0.23 QALYs gained and 1606 USD saved per Medicare beneficiary). Compared with the new Medicare drug benefit, first-dollar coverage remained a dominant strategy (0.15 QALYs gained, 922 USD saved). Results were most sensitive to our estimate of increase in ACE inhibitor use; however, if ACE inhibitor use increased by only 7.2% (from 40% to 47.2%), first-dollar coverage would remain life-saving at no net cost to Medicare. In analyses conducted from the societal perspective, benefits were similar and cost savings were larger. Results depend on accuracy of the underlying data and assumptions. The effect of more generous drug coverage on medication adherence is uncertain. Medicare first-dollar coverage of ACE inhibitors for beneficiaries with diabetes appears to extend life and reduce Medicare program costs. A reduction in program costs may result in more money to spend on other health care needs of the elderly.


The biochemistry and clinical application of urinary oestriol measurement during late pregnancy in the 1990's.
Part 1. The present disillusionment with oestriol measurement as a test of fetoplacental function could be explained by the use of poor methodology and inappropriate normal ranges rather than that the test has lost its usefulness. We have updated the Lever method for measuring oestriol in urine, and examined the automatic TDX system supplied by Abbott Laboratories. The precision of the methods and consistency of results between methods have been determined and normal ranges have been established for both methods. The overall accuracy of collection of 24-hour urine specimens in a routine laboratory setting has also been calculated. The normal ranges suggested as a guide for the TDX method by Abbott were based on those derived from the original method of Brown and were found to be too low and therefore unsuitable for clinical use. This study reports appropriate lower limits of normal for both the updated Lever and the TDX methods. Part 2. The results obtained using the updated Lever method since its introduction in 1991 have been compared with those obtained by the original Brown method during the years 1971-1989. The new, user-friendly Lever method of oestriol assay measurement used in 1991-1993 gave results of equivalent clinical value to the Brown method used in 1971-1989, although the perinatal mortality rates in the tested populations fell from 0.95% to 0.37%. During 1971-1989, low oestriol excretion on 1 or more occasions was associated with a 5.6-fold increase in the perinatal mortality rate (0.66% to 3.67%), whereas in 1991-1993, the factor was 4.4 (0.27% to 1.2%).(ABSTRACT TRUNCATED AT 250 WORDS)


Toxicities From Antibody-Drug Conjugates.
Antibody-drug conjugates are becoming increasingly important in the treatment of many cancer types. The 3 main structural components-antibody, linker, and payload-each contribute to the toxicity profiles of these drugs. In addition to cytopenias and gastrointestinal adverse effects attributed to the chemotherapy payloads, each drug has specific toxicities that are not commonly described in oncology. Ocular, pulmonary, dermatologic, and neurologic toxicities are particularly nuanced. This review provides a framework for clinicians to analyze current and future antibody-drug conjugates and a description of the unique monitoring, preventive, and supportive care measures for these agents.


An ontology-based exploration of the concepts and relationships in the activities and participation component of the international classification of functioning, disability and health.
The International Classification of Functioning, Disability and Health (ICF) is a classification of health and health-related issues, aimed at describing and measuring health and disability at both individual and population levels. Here we discuss a preliminary qualitative and quantitative analysis of the relationships used in the Activities and Participation component of ICF, and a preliminary mapping to SUMO (Suggested Upper Merged Ontology) concepts. The aim of the analysis is to identify potential logical problems within this component of ICF, and to understand whether activities and participation might be defined more formally than in the current version of ICF. In the relationship analysis, we used four predicates among those available in SUMO for processes (Patient, Instrument, Agent, and subProcess). While at the top level subsumption was used in most cases (90%), at the lower levels the percentage of other relationships rose to 41%. Chapters were heterogeneous in the relationships used and some of the leaves of the tree seemed to represent properties or parts of the parent concept rather than subclasses. Mapping of ICF to SUMO proved partially feasible, with the activity concepts being mapped mostly (but not totally) under the IntentionalProcess concept in SUMO. On the other hand, the participation concept has not been mapped to any upper level concept. Our analysis of the relationships within ICF revealed issues related to confusion between classes and their properties, incorrect classifications, and overemphasis on subsumption, confirming what already observed by other researchers. However, it also suggested some properties for Activities that could be included in a more formal model: number of agents involved, the instrument used to carry out the activity, the object of the activity, complexity of the task, and an enumeration of relevant subtasks.


[Effect of the endoexpander pressure of continuous and constant pressure expansion on the drug permeability].
To investigate the effect of the endoexpander pressure of continuous and constant pressure expansion on the drug permeability. The expanders were divided into two groups, the normal expansion and the continuous and constant pressure expansion (4.6 kPa). Each expander was filled with 0.2% Metronidazole, then the expanders were immersed wholly in normal saline and sealed totally. At several intervals over 72 hours, the surrounding saline was sampled and the drug concentration of the sample was measured respectively. Both groups were permeable to the Metronidazole and the concentration outside the expander would reach the effective concentration in 48 hours. The drug concentration of the continuous and constant pressure expansion was higher than that of the normal one and there was significant difference between the two groups (P < 0.01). The endoexpander pressure in continuous and constant pressure expansion can enhance the drug permeability. In view of this, in the course of continuous and constant pressure expansion, 0.2% Metronidazole can be used to prevent and control the infection.


Structure-function studies on phytochrome. Preliminary characterization of highly purified phytochrome from Avena sativa enriched in the 124-kilodalton species.
A new protocol for the purification of phytochrome from etiolated Avena sativa L. seedlings in 15-25% yield is described. This preparation exhibits molecular properties dissimilar to those previously reported from oats. Phytochrome prepared by this method contains a dominant species having a Mr = 124,000 (70% of total) on sodium dodecyl sulfate-polyacrylamide gels, in addition to a chromoprotein species with Mr = 118,000 (30%). A blocked NH2 terminus is indicated by amino acid sequencing of the purified chromoprotein preparation. By ultraviolet-visible spectroscopy, this preparation displays a 730-nm absorption maximum for Pfr, an enhanced APfr730/APfr668 ratio under saturating red light illumination, and a reduced amount of dark reversion. Circular dichroism reveals a new absorption band for Pfr in the blue spectral region. These spectral properties and electrophoretic behavior are consistent with available information on phytochrome in vivo or in rapidly prepared extracts from oat seedlings. Thus, the molecular properties described here may more accurately reflect those of phytochrome in vivo in etiolated A. sativa shoots than those of phytochrome species isolated by previous methodologies.


Factors affecting the effectiveness of the physical activity counselling intervention implemented in primary health care in adults with type 2 diabetes.
Type 2 diabetes (T2D) has become a major public health threat; physical inactivity and obesity are both independent risk factors. Increasing daily physical activity (PA) significantly benefits treatment. Individual PA counselling is helpful for people with T2D, especially those with previous inactivity or with diabetes complications. This study evaluated factors contributing to effectiveness of PA counselling in primary health care (PHC) patients with T2D in a real-world setting and using data elicited from electronic health records (EHRs). All patients with T2D were offered the opportunity to participate in a PA program organized as part of basic PHC services in the Siun sote region in North Karelia, Finland, from October 2016 to December 2018. The study population consists of patients aged 19 to 87 years (n = 546). During the intervention information on possible other factors in addition to age and sex influencing the intervention effect such as amount of counselling sessions, changes in PA and patients´ motivation was gathered. Changes in the participants' PA activity was generated by following the predefined rules from patient records and by assessing the descriptive documentation of activity patterns. The patients' motivation level was assessed using a Likert scale. Over 60% of participants who attended PA counselling more than three times increased their PA compared with 1% of participants with one counselling session. Of the whole intervention group, the participants experiencing the largest weight loss were those with an increased level of PA (-1.36 kg vs. -0.63 kg among those with no change in PA). Age, sex, and baseline motivation did not affect the change the PA nor the main intervention outcomes. Patients' compliance with the intervention was reflected in the number of PA counselling sessions attended which in turn was seen as increased levels of PA as well as better treatment outcomes. In the implementation of lifestyle counselling interventions attention should be paid on sufficient amount and frequency of counselling sessions. The individually tailored PA counselling provided in PHC has similar effects regardless of sex and age.


Superior operational stability of immobilized L-asparaginase over surface-modified carbon nanotubes.
L-asparaginase (ASNase, EC 18.104.22.168) is an enzyme that catalyzes the L-asparagine hydrolysis into L-aspartic acid and ammonia, being mainly applied in pharmaceutical and food industries. However, some disadvantages are associated with its free form, such as the ASNase short half-life, which may be overcome by enzyme immobilization. In this work, the immobilization of ASNase by adsorption over pristine and modified multi-walled carbon nanotubes (MWCNTs) was investigated, the latter corresponding to functionalized MWCNTs through a hydrothermal oxidation treatment. Different operating conditions, including pH, contact time and ASNase/MWCNT mass ratio, as well as the operational stability of the immobilized ASNase, were evaluated. For comparison purposes, data regarding the ASNase immobilization with pristine MWCNT was detailed. The characterization of the ASNase-MWCNT bioconjugate was addressed using different techniques, namely Transmission Electron Microscopy (TEM), Thermogravimetric Analysis (TGA) and Raman spectroscopy. Functionalized MWCNTs showed promising results, with an immobilization yield and a relative recovered activity of commercial ASNase above 95% under the optimized adsorption conditions (pH 8, 60 min of contact and 1.5 × 10-3 g mL-1 of ASNase). The ASNase-MWCNT bioconjugate also showed improved enzyme operational stability (6 consecutive reaction cycles without activity loss), paving the way for its use in industrial processes.


Three novel cyclic hexapeptides from Streptomyces alboflavus 313 and their antibacterial activity.
Three novel cyclic hexapeptides, designated NW-G05 (1), NW-G06 (2) and NW-G07 (3), were isolated from the fermentation broth of Streptomyces alboflavus 313. Their structures were elucidated on the basis of extensive spectroscopic analysis, MS experiments, and chemical analysis. Their antibacterial activities against several strains of bacteria were evaluated by micro-broth dilution method. Among these compounds, NW-G06 (2) and NW-G07 (3) displayed highly antibacterial activity against gram-positive bacteria, but not gram negative ones. However, NW-G05 (1) was not active against all tested microorganisms.


The extinct Sicilian wolf shows a complex history of isolation and admixture with ancient dogs.
The Sicilian wolf remained isolated in Sicily from the end of the Pleistocene until its extermination in the 1930s-1960s. Given its long-term isolation on the island and distinctive morphology, the genetic origin of the Sicilian wolf remains debated. We sequenced four nuclear genomes and five mitogenomes from the seven existing museum specimens to investigate the Sicilian wolf ancestry, relationships with extant and extinct wolves and dogs, and diversity. Our results show that the Sicilian wolf is most closely related to the Italian wolf but carries ancestry from a lineage related to European Eneolithic and Bronze Age dogs. The average nucleotide diversity of the Sicilian wolf was half of the Italian wolf, with 37-50% of its genome contained in runs of homozygosity. Overall, we show that, by the time it went extinct, the Sicilian wolf had high inbreeding and low-genetic diversity, consistent with a population in an insular environment.


Considering agitation in ultrasonic electroplating through observation of cavitation.
Ultrasonic electroplating produces various effects, including refinement of the plating film structure, by generating localized agitation through cavitation bubbles. However, details of the agitation mechanism have not been clarified because ultrasonic cavitation is very small in scale and occurs rapidly, and its reproducibility is low. Therefore, using laser-induced cavitation, which can generate cavitation similar to ultrasonic waves with high reproducibility, the author attempted to elucidate the conditions and frequency of cavitation generation that affect the agitation phenomenon in ultrasonic electroplating. By controlling the laser irradiation position, three different cavitation conditions were established, and the microstructures of the plated films produced were compared. Microstructural refinement was the most advanced under the condition of microjet generation. The frequency of cavitation generation at any position in the ultrasonic electroplating was estimated to be < 1 Hz.


Health status of non-descript goats travelling long distances to water source.
The objective of the study was to determine the influence of distance to water source on health status of non-descript weaners and does. The goats were situated at 0.25, 0.75, 1.25, 1.75, 2.25, 2.75 and 3.25 km from the Pongola river. Body condition score (BCS) declined faster in male weaners than female weaners as the distance to water source increased (P < 0.001). The rate of decline in BCS was similar between does and female weaners as the distance to water source increased (P > 0.05). Rectal temperature (RT) of all goat classes increased with an increase in distance to water source (P < 0.05). Rate of change in RT was higher in female weaners than male weaners and does as the distance to water source increased (P < 0.01). The increase in FAMACHA scores was higher in male weaners than does and female weaners as the distance to water source increased (P < 0.05). Does had the smallest drop in packed cell volume (PCV) than female and male weaners as the distance to water source increased (P > 0.05). All goat classes were severely affected by the distance to water source; however, the effects were more adverse in male weaners than in female weaners and does. Body condition score and PCV declined, whereas RT and FAMACHA increased with an increase in distance travelled by goats to the water source. It can be concluded that both male and female weaners were more susceptible to increasing distance to water source.


Metreleptin improves blood glucose in patients with insulin receptor mutations.
Rabson-Mendenhall syndrome (RMS) is caused by mutations of the insulin receptor and results in extreme insulin resistance and dysglycemia. Hyperglycemia in RMS is very difficult to treat, and patients are at risk for early morbidity and mortality from complications of diabetes. Our objective was to study 1-year effects of recombinant human methionyl leptin (metreleptin) in 5 patients with RMS and 10-year effects in 2 of these patients. We conducted an open-label nonrandomized study at the National Institutes of Health. Patients were adolescents with RMS and poorly controlled diabetes. Two patients were treated with escalating doses (0.02 up to 0.22 mg/kg/d) of metreleptin for 10 years, including 3 cycles of metreleptin withdrawal and reinitiation. In all 5 patients, 1-year effects of metreleptin (0.22 mg/kg/d) were studied. Hemoglobin A1c (HbA1c) and body mass index (BMI) z-scores were evaluated every 6 months. HbA1c decreased from 11.4% ± 1.1% at baseline to 9.3% ± 1.9% after 6 months and 9.7% ± 1.6% after 12 months of metreleptin (P = .007). In patients treated for 10 years, HbA1c declined with each cycle of metreleptin and rose with each withdrawal. BMI z-scores declined from -1.4 ± 1.8 at baseline, to -2.6 ± 1.6 after 12 months of metreleptin (P = .0006). Changes in BMI z-score correlated with changes in HbA1c (P < .0001). Metreleptin treatment for 12 months was associated with a 1.7% reduction in HbA1c; part of this improvement was likely mediated via decreased BMI. Metreleptin is a promising treatment option for RMS, but additional therapies are needed to achieve HbA1c targets.


Aspects of Anesthesia for Breast Surgery during Pregnancy.
Non-obstetric surgery is needed in 0.75-2% of pregnant women, and safety of anesthesia for mother and child are key points at this time. Some breast diseases need to be approached in a short time interval, and surgery must be performed during pregnancy . In these cases, the technique of anesthesia regarding local, regional or general anesthesia and type of anesthetic medicine are selected based on the extent of the procedure, gestational age, and condition of the mother and child. The ideal timing for any surgery during pregnancy is in the second trimester because the risk of fetal adverse effects as well as preterm labor are lower. However, surgery of breast cancer during pregnancy is performed in any trimester as guided by treatment guidelines and is not deferred based on anesthesia preferences. Various types of anesthesia for breast surgery during pregnancy , preoperative and postoperative considerations are discussed in this chapter.


Triage Travel Screening in the Pediatric ED: A Cross-Sectional Analysis to Evaluate Current Use and Effectiveness in Identifying Travel Related Illness.
In 2014 the Center for Disease Control and Prevention recommended emergency departments (EDs) implement triage travel screening to identify persons at risk for Ebola Virus Disease (EVD). EVD remains rare in the United States, and in practice the triage travel screen serves as a de facto screen for all travel-related illnesses. This study seeks to determine the current use and effectiveness of the triage travel screen to detect travel-related illness in the pediatric ED. This was a retrospective, cross-sectional study of visits across three pediatrics EDs in 2019 in Atlanta, GA. Prevalences of travel-related illnesses were compared between patients with positive and negative travel screens. Patient charts with diagnoses of travel-related illness were then reviewed. Out of 244,841 patient encounters during the study period, 13 patients with travel-related illness were identified. 5/13 cases of travel-related illness were not diagnosed at the initial ED visit. Of these 5 cases, 2 had correctly negative travel screens (as travel was not within the specified timeframe) and 3 had correctly positive travel screens, but none had a clinician-documented travel history in the ED clinical notes. Of the 8/13 cases that were diagnosed at the initial ED visit, 7/8 had a clinician-documented travel history in the ED note. This study highlights the limitations of the current pediatric ED triage travel screen to detect travel-related illness and reinforces the importance of a provider-taken travel history. Strategies to increase provider-administered travel history documentation and revisions to increase triage travel-screen efficacy should be considered.


Characterization of a newly identified rice chitinase-like protein (OsCLP) homologous to xylanase inhibitor.
During rice blast fungal attack, plant xylanase inhibitor proteins (XIPs) that inhibit fungal xylanase activity are believed to act as a defensive barrier against fungal pathogens. To understand the role of XIPs in rice, a xylanase inhibitor was cloned from rice. The expression of this gene was examined at the transcriptional/translational levels during compatible and incompatible interactions, and the biochemical activity of this protein was also examined. Sequence alignment revealed that the deduced amino acid sequence of OsCLP shares a high degree of similarity with that of other plant TAXI-type XIPs. However, recombinant OsCLP did not display inhibitory activity against endo-1,4-β-xylanase enzymes from Aureobasidium pullulans (A. pullulans) or Trichoderma viride (T. viride). Instead, an in-gel activity assay revealed strong chitinase activity. The transcription and translation of OsCLP were highly induced when rice was exposed to pathogens in an incompatible interaction. In addition, exogenous treatment with OsCLP affected the growth of the basidiomycete fungus Rhizoctonia solani through degradation of the hyphal cell wall. These data suggest that OsCLP, which has chitinase activity, may play an important role in plant defenses against pathogens. Taken together, our results demonstrate that OsCLP may have antifungal activity. This protein may directly inhibit pathogen growth by degrading fungal cell wall components through chitinase activity.


Gu Ling Pian, a traditional Chinese medicine, regulates function and OPG/RANKL synthesis of osteoblasts via the p38 MAPK pathway.
Osteoporosis is a common disease that makes bones prone to fracture and can affect both men and women. Many traditional Chinese medicine formulations have the potential effect of preventing osteoporosis. Gu Ling Pian (GLP), a traditional Chinese medicine formulation, comprised of tonifying kidney herbal medicines, has been demonstrated to prevent osteoporosis by increasing bone mineral density, however the exact mechanism has not yet been elucidated. Osteoprotegerin (OPG), a receptor activator of NF-kappaB (RANK), and RANK ligand (RANKL) play critical roles in bone remodelling by regulating the function of osteoclasts. In this study, we investigated the effect of GLP on osteoblasts, namely MG-63 cells. The cell proliferation and differentiation, synthesis of OPG/RANKL and p38 expression were tested on MG-63 cells exposed to serum from rats fed with GLP or not. The results showed that GLP significantly promoted MG-63 cell proliferation and differentiation. Upregulation of OPG and down-regulation of RANKL at the protein and mRNA level were observed in GLP serum treated MG-63 cells using an enzyme-linked immunosorbent assay and real-time polymerase chain reaction. Further, treatment with GLP serum increased the level of p38 phosphorylation but did not affect the total p38 expression. These effects can be blocked by the p38 specific inhibitor SB203580. The results indicate that GLP can effectively promote the proliferation and differentiation of osteoblasts and regulate their OPG/RANKL expression, while the effects may be mediated via the p38 MAPK pathway. The findings suggest that GLP induces bone formation and may be beneficial for patients with osteoporosis.


Perfluoroalkyl chemicals in vacuum cleaner dust from 39 Wisconsin homes.
Perfluoroalkyl chemicals (PFCs) have been used as surfactants and stain repellants in a variety of consumer products for more than 50years and there is growing concern regarding their persistence and toxicity. Human exposure to these chemicals is essentially universal in North America and researchers have linked them to a variety of health problems ranging from higher rates of cancer, to developmental and reproductive problems, and higher cholesterol levels. Major exposure pathways are food and water ingestion, dust ingestion via hand to mouth transfer. In an effort to assess residential exposure, the Wisconsin Department of Health Services tested vacuum cleaner contents from thirty-nine homes for 16 perflouroalkyl chemicals. PFOS, PFOA, PFHxS, PFHpA and PFNA were found in all of the vacuum dust samples and dust from eight homes contained all 16 PFCs included in our analysis. The most commonly detected compounds were perfluorooctanesulfonate (PFOS), perfluorohexanesulfonate (PFHxS) and perfluorooctanoic acid (PFOA) which together made up 70% of the total PFC residues in dust from these homes. Summed PFC concentrations in these dust samples ranged from 70 to 2513ng/g (median 280ng/g). Our investigation suggests that these chemicals may be ubiquitous contaminants in US homes.


Does housing chronically homeless adults lead to social integration?
Supported housing programs have been successful in helping homeless adults obtain housing. This study examined whether improvements in social integration occur after clients obtain supported housing. Measures of social integration were examined for 550 chronically homeless adults with mental illness who participated in the 11-site Collaborative Initiative to Help End Chronic Homelessness. Social integration was conceptualized as a multidimensional construct of variables in six domains: housing, work, social support, community participation, civic activity, and religious faith. Changes in baseline measures related to the six domains and their interrelationships were examined at six and 12 months after entry into the supported housing program. Chronically homeless adults showed substantial improvements in housing but remained socially isolated and showed limited improvement in other domains of social integration, which were only weakly correlated with one another. More attention is needed to develop rehabilitation interventions in supported housing programs to improve social integration of chronically homeless adults. Because improvements in some domains of social integration were only weakly related, it may be necessary to intervene in multiple domains simultaneously.


Evaluation of clinical and electroencephalographic findings in patients with early childhood epilepsy and inborn errors of metabolism.
Epilepsy is one of the leading chronic diseases of childhood, and an underlying IEM is an etiology that can easily be overlooked. The aim of this study was to determine the frequency of metabolic disease in patients diagnosed with epilepsy in the first two years of life, as well as to determine the clinical, radiological, and electroencephalographic (EEG) characteristics of the metabolic disease subtypes associated with epilepsy and evaluate treatment response in our study. The records of patients diagnosed with epilepsy before the age of 2 years in our pediatric neurology clinic between 2014 and 2021 were reviewed retrospectively. Those diagnosed with an IEM and followed up in the pediatric neurology and pediatric metabolism departments of our hospital were included in the study. A total of 990 patients under the age of 2 years were diagnosed with epilepsy in the pediatric neurology clinic of our hospital and 74 (7.5%) of them had IEM. Thirty-nine (52.7%) of the 74 patients were female. The median age at admission was 144 days (min-max: 0-284). Of the 74 patients diagnosed with metabolic epilepsy, 38 patients were diagnosed with amino acid metabolism disorder, 17 with lysosomal storage disease, 9 with energy metabolism disorder, 5 with vitamin/cofactor/trace element metabolism disorders, 2 with fatty acid metabolism disorder, 2 with peroxisomal disease, and 1 with carbohydrate metabolism disorder. Epilepsy was refractory despite appropriate treatment in 39 patients (52.7%). Inborn errors of metabolism are a rare cause of epilepsy, in regions like our country with high rates of consanguineous marriage, IEM should be considered in patients presenting with seizures that do not respond to conventional antiepileptic treatments.


Indirect spectrophotometric determination of sodium ceftriaxone with n-propyl alcohol-ammonium sulfate-water system by extraction flotation of copper(II).
Although the determination methods of sodium ceftriaxone has been increasingly reported, these methods have their inherent limits preventing them from being broadly applied in common laboratories. In order to circumvent this problem, a rapid and simple method for the indirect spectrophotometric determination of sodium ceftriaxone is reported. Sodium ceftriaxone was degraded completely in the presence of 0.20 mol/l sodium hydroxide in boiling water bath for 20 min. The thiol group (-SH) of the degradation product (I) of sodium ceftriaxone could reduce cupric to cuprous ions, and the resulting which was precipitated with the thiol group (-SH) of the degradation product (II) at pH 4.0. By determining the residual amount of copper (II), the indirect determination of sodium ceftriaxone can be achieved. Standard curve of sodium ceftriaxone versus the flotation yield of copper(II) showed that sodium ceftriaxone could be determined in low concentrations. The linear range of sodium ceftriaxone was 0.70-32 microg/ml and the detection limit evaluated by calibration curve (3sigma/k) was found to be 0.60 microg/ml. A simple and efficient method was developed and it has been successfully applied to the determination of sodium ceftriaxone in human serum and urine samples, respectively. It is expected that this method will find broad applications in the detection of cephalosporin derivatives with similar structure.


A new species of the rodent genus Hylomyscus from Angola, with a distributional summary of the H. anselli species group (Muridae: Murinae: Praomyini).
A new species of Hylomyscus, H. heinrichorum, is described from mountains in western Angola. Based on morphological traits and cranial morphometry, the new species is assigned to the H. anselli species group and is hypothesized to be most closely related to H. anselli Bishop proper, a species named from Zambia. Members of both the H. anselli and H. denniae species groups occupy the Afromontane Biotic Zone, found in various mountain systems to the south and east of the Congo Basin. Evidence is reviewed that supports the independent radiation of these two species groups within montane forest from different Guineo-Congolian ancestral stocks.


[P. Minonzio's ideas about contagion].
Paolo Minonzio was a physician working in a little country town near Varese in XIX century. He wrote a diary illustrating his medical experience which represents an interesting document of the spreading of bacteriological theories in a provincial context.


Pars plana vitrectomy in ocular trauma.
Visual improvement was achieved in 62% of 100 consecutive patients with ocular trauma treated by pars plana vitrectomy. Anterior segment injuries had a better prognosis than posterior segment injuries, and retinal detachment was a poor prognostic sign. Patients undergoing vitrectomy during the two weeks after injury had a better visual prognosis than those who had delayed vitrectomy. Pars plana vitrectomy has increased the recovery rate in traumatized eyes which previously were deemed inoperable and frequently were enucleated. Most such eyes have intraocular fibrocellular proliferations, resulting in traction retinal detachments, cyclitic membranes, and phthisis, as documented in clinicopathological and experimentally produced specimens of penetrating ocular trauma. Vitrectomy can interrupt this sequence, if performed one to 14 days after injury, by removing the vitreous scaffold onto which proliferation occurs, together with the elements of hemorrhage, damaged lens, vitreous, and foreign material which may incite proliferation. We believe four to ten days after injury to be the optimal time for vitrectomy to avoid the hazards of immediate intervention, while removing damaged tissue before serious sequenlae occur.


Transcatheter anastomosis connector system for vascular access graft placement: results from a first-in-human pilot study.
A lengthy healing and maturation period follows standard surgical preparation of a permanent arteriovenous access, often requiring or extending use of a venous catheter (VC) for hemodialysis. The InterGraft™ Anastomotic Connector System was developed for minimally invasive anastomosis of an arteriovenous graft (AVG). The venous and arterial InterGraft™ connectors are designed to provide optimized flow dynamics and may result in reduction of AVG stenosis. This pilot study evaluated placement procedure success, patency and safety of the InterGraft™ connectors. Nine AVGs were implanted in nine patients currently receiving dialysis with a VC. The study allowed use of both connectors (n = 5) or use of the venous connector with a sutured arterial anastomosis (n = 4). Monthly ultrasound examinations were performed throughout the six-month follow-up. AVG angiography was performed at five months. Endpoints included procedure success (acceptable graft flow at end of procedure, without significant bleeding or need for emergent surgery), patency, and device-related major adverse events. Procedure success was attained in all patients. AVGs were used for dialysis within 17 days, on average, and VCs were removed. Three patients exited the study early for reasons unrelated to the InterGraft™ connectors. The remaining six patients had patent grafts: two with assisted and four with unassisted patency. AVG flow rates were greater than 1 L/minute. No dilatations or aneurysms were observed by angiography. There were no device-related major adverse events. The InterGraft™ connectors can be safely and successfully used for AVG anastomoses, with acceptable near-term patency. Further clinical evaluation is warranted.


[Prognostic significance of the area of myocardial lesion and the status of the coronary bed during restoration of work capacity in patients with a complicated course of acute myocardial infarction].
The effect of heart failure and acute left-ventricular aneurysm on the recovery of working capacity was assessed with reference to the size of necrotic focus and the extent of coronary arterial involvement in 117 patients with acute myocardial infarction. The size of necrotic focus and magnitude of coronary arterial affection were shown to be the principal determinants of heart failure in acute myocardial infarction. The presence of heart failure and acute left-ventricular aneurysm in combination with multiple coronary-arterial lesions is an adverse predictive sign in the assessment of the severity of acute myocardial infarction and the recovery of patients' working capacity. On the contrary, the presence of a local aneurysm in combination with an isolated coronary-arterial lesion should not be regarded as an unequivocal indicator of disability.


Immunoregulation: the key to transplantation and autoimmunity.
Immune responses depend on a unique set of recognition structures, namely, antibody molecules embedded in the B cell membrane for antibody formation and alpha-beta chain heterodimers of the T cell receptor for cellular immune receptors. These structures are coded for by genes, which undergo rearrangements during the differentiation of B- and T-lymphocytes known as somatic translocations. The end result of this process is the creation of separate repertoires of B and T cells, each single cell displaying a unique receptor. Antigen acts by selecting preexisting antigen-reactive cells for division and further differentiation. Accessory cells such as macrophages are essential for the initiation of most immune responses. Different subsets of T-lymphocytes play a vital regulatory role, not only in controlling cell-mediated immunity as such, but also in guiding B cell function. Understanding the roles of accessory cells, regulatory T cells, and the molecules on their surface is essential for understanding immunoregulation. At present, immunosuppression in organ transplantation and therapy of autoimmune diseases are largely nonspecific and empirical. As the rules of the interactive immunoproliferative cascade are progressively unraveled, more targeted immune manipulation will become possible, and some future avenues of this sort are described.


Utilization of warning lights and siren based on hospital time-critical interventions.
The objective of this study was to evaluate the time saved by usage of lights and siren (L&S) during emergency medical transport and measure the total number of time-critical hospital interventions gained by this time difference. A retrospective study was performed of all advanced life support (ALS) transports using lights and siren to this university emergency department during a three-week period. Consecutive times were measured for 112 transports and compared with measured transport times for a personal vehicle traveling the same day of the week and time of day without lights and siren. The time-critical hospital interventions are defined as procedures or treatments that could not be performed in the prehospital setting requiring a physician. The project assessed whether the patients received the hospital interventions within the average time saved using lights and siren transport. The average difference in time with versus without L&S was -2.62 minutes (95% CI: -2.60- -2.63, paired t-test p<0.0001). The average transport time with L&S was 14.5±7.9 minutes (min) (1 standard deviation/minute (min), range=1-36 min.). The average transport time without L&S was 17.1±8.3 min (range=1-40 min). Of the 112 charts evaluated, five patients (4.5%) received time-critical hospital interventions. No patients received time-critical interventions within the time saved by utilizing lights and siren. Longer distances did not result in time saved with lights and siren. Limiting lights and siren use to the patients requiring hospital interventions will decrease the risks of injury and death, while adding the benefit of time saved in these critical patients.


Synergistic Growth Inhibition by Afatinib and Trametinib in Preclinical Oral Squamous Cell Carcinoma Models.
Given that aberrant activation of epidermal growth factor receptor family receptors (ErbB) is a common event in oral squamous cell carcinoma, and that high expression of these receptor proteins is often associated with poor prognosis, this rationalizes the approach of targeting ErbB signaling pathways to improve the survival of patients with oral squamous cell carcinoma. However, monotherapy with the ErbB blocker afatinib has shown limited survival benefits. This study was performed to identify mechanisms of afatinib resistance and to explore potential afatinib-based combination treatments with other targeted inhibitors in oral squamous cell carcinoma. We determined the anti-proliferative effects of afatinib on a panel of oral squamous cell carcinoma cell lines using a crystal violet-growth inhibition assay, click-iT 5-ethynyl-2'-deoxyuridine staining, and cell-cycle analysis. Biochemical assays were performed to study the underlying mechanism of drug treatment as a single agent or in combination with the MEK inhibitor trametinib. We further evaluated and compared the anti-tumor effects of single agent and combined treatment by using oral squamous cell carcinoma xenograft models. In this study, we showed that afatinib inhibited oral squamous cell carcinoma cell proliferation via cell-cycle arrest at the G0/G1 phase, and inhibited tumor growth in xenograft mouse models. Interestingly, we demonstrated reactivation of the mitogen-activated protein kinase (ERK1/2) pathway in vitro, which possibly reduced the effects of ErbB inhibition. Concomitant treatment of oral squamous cell carcinoma cells with afatinib and trametinib synergized the anti-tumor effects in oral squamous cell carcinoma-bearing mouse models. Our findings provide insight into the molecular mechanism of resistance to afatinib and support further clinical evaluation into the combination of afatinib and MEK inhibition in the treatment of oral squamous cell carcinoma.


Chemical and antigenic characterization of the carbohydrate side chains of an Asian (N2) influenza virus neuraminidase.
The Pronase-released neuraminidase heads from the Asian influenza virus A/Tokyo/3/67 contain four oligosaccharide units attached at asparagine residues 86, 146, 200, and 234. Chemical analysis of the isolated tryptic, chymotryptic, or thermolytic glycopeptides shows that the oligosaccharide side chains attached at residues 86 and 200 are essentially of the oligomannoside (simple or Type II) variety containing two residues of N-acetylglucosamine, five residues of mannose, and less than molar ratios of galactose and fucose. The carbohydrate side chains attached at residues 146 and 234 are of the N-acetyllactosamine (complex or Type I) type and contain N-acetylglucosamine, mannose, galactose, and fucose. The complex oligosaccharide unit at residue 146 is unusual in that it also contains N-acetylgalactosamine, a sugar residue rarely found in N-glycosidically linked carbohydrates. Antigenic analysis of these four isolated glycopeptides showed that only the N-acetyllactosamine oligosaccharide unit at asparagine residue 146 was capable of binding to antibodies raised against uninfected chick chorioallantoic membranes and is hence antigenically related to chick embryo host antigen.


Overexpression of synthesized cephalosporin C acylase containing mutations in the substrate transport tunnel.
Cephalosporin C (CPC) acylase converts CPC into 7-aminocephalosporanic acid (7-ACA) by single-step enzymatic catalysis. An optimized CPC acylase gene with substituted codons and a reduced GC content was artificially designed, synthesized and overexpressed in recombinant Escherichia coli. The synthetic CPC acylase (sCPCAcy) exhibited 2.3 times more CPC specific deacylation activity with substrate CPC than with substrate glutaryl-7-ACA (GL-7-ACA). Site-directed mutagenesis of the residues around the active center showed that not only the residues that were adjacent to the CPC D-α-aminoadipyl moiety, but also the residues that were in the substrate transport tunnel (Leu666, Ala675, Leu677), played crucial roles in catalysis as the ones locating in active center. Mutant sCPCAcy(Leu666Phe) and sCPCAcy(Leu677Ala) exhibited significantly reduced specific enzymatic activity, while mutant sCPCAcy(Ala675Gly) demonstrated enhanced activity. The specific activity of purified sCPCAcy and sCPCAcy(Ala675Gly) was 10.0 U/mg and 11.3 U/mg, respectively. The optimal CPC acylase productivity of mutant sCPCAcy(Ala675Gly) reached 5349 U/l after 24h in culture, which was a 35% increase over the activity of sCPCAcy.


Comparison of alternative analytical techniques for the characterisation of the human serum proteome in HUPO Plasma Proteome Project.
Based on the same HUPO reference specimen (C1-serum) with the six proteins of highest abundance depleted by immunoaffinity chromatography, we have compared five proteomics approaches, which were (1) intact protein fractionation by anion-exchange chromatography followed by 2-DE-MALDI-TOF-MS/MS for protein identification (2-DE strategy); (2) intact protein fractionation by 2-D HPLC followed by tryptic digestion of each fraction and microcapillary RP-HPLC/microESI-MS/MS identification (protein 2-D HPLC fractionation strategy); (3) protein digestion followed by automated online microcapillary 2-D HPLC (strong cation-exchange chromatography (SCX)-RPC) with IT microESI-MS/MS; (online shotgun strategy); (4) same as (3) with the SCX step performed offline (offline shotgun strategy) and (5) same as (4) with the SCX fractions reanalysed by optimised nanoRP-HPLC-nanoESI-MS/MS (offline shotgun-nanospray strategy). All five approaches yielded complementary sets of protein identifications. The total number of unique proteins identified by each of these five approaches was (1) 78, (2) 179, (3) 131, (4) 224 and (5) 330 respectively. In all, 560 unique proteins were identified. One hundred and sixty-five proteins were identified through two or more peptides, which could be considered a high-confidence identification. Only 37 proteins were identified by all five approaches. The 2-DE approach yielded more information on the pI-altered isoforms of some serum proteins and the relative abundance of identified proteins. The protein prefractionation strategy slightly improved the capacity to detect proteins of lower abundance. Optimising the separation at the peptide level and improving the detection sensitivity of ESI-MS/MS were more effective than fractionation of intact proteins in increasing the total number of proteins identified. Overall, electrophoresis and chromatography, coupled respectively with MALDI-TOF/TOF-MS and ESI-MS/MS, identified complementary sets of serum proteins.


Using three-dimensional printed models for trainee orbital fracture education.
Three-dimensional printing is an underutilized technology in ophthalmology training; its use must be explored in complex educational scenarios. This study described a novel approach to trainee education of orbital fracture repair utilizing three-dimensional (3D) printed models as a teaching tool. Ophthalmology residents and oculoplastic fellows from multiple training institutions underwent an educational session on orbital fractures, learning through four different models. Participants analyzed orbital fractures through computerized tomography (CT) imaging alone and then utilizing CT imaging with the aid of a 3D printed model. Participants completed a questionnaire assessing their understanding of the fracture pattern and surgical approach. After the training, participants were surveyed on the impact of the educational session. Components of the training were rated by participants on a 5-point Likert scale. A statistically significant difference (p < .05) was found in participant confidence conceptualizing the anatomic boundaries of the fracture and planning the orbital fracture approach for repair of three out of four models on pre-test post-test analysis. On exit questionnaire, 84.3% of participants thought the models were a useful tool for surgical planning, 94.8% of participants thought the models were a useful tool for conceptualizing the anatomic boundaries of the fracture, 94.8% of participants thought the models were a useful tool for orbital fracture training, and 89.5% of participants thought the exercise was helpful. This study supports the value of 3D printed models of orbital fractures as an effective tool for ophthalmology trainee education to improve understanding and visualization of complex anatomical space and pathology. Given the limited opportunities trainees may have for hands-on orbital fracture practice, 3D printed models provide an accessible way to enhance training.


Immunoglobulin heavy-chain switching in pre-B leukaemias.
Immunoglobulin gene expression is initiated in pre-B cells by rearrangements of heavy-chain variable genes V, D and J, for transcription together with the constant region gene C mu (refs 1-7). The subsequent joining of light-chain V-J genes in the kappa or lambda families leads to formation of complete IgM molecules, which are then expressed on the surface of B cells. Heavy-chain isotype switching has been thought to occur later and to involve CH gene rearrangement via deletion of DNA between a switch site 5' to C mu and a switch site 5' to the downstream C gamma, C epsilon or C alpha gene expressed by a mature plasma cell. On the other hand, isotype switching has been seen in human pre-B-cell leukaemias and in a murine pre-B-cell line before light-chain gene rearrangements and without C mu gene deletion. To explore further the isotype switching in pre-B cells, we used monoclonal antibodies in immunofluorescence assays to allow unambiguous assignment of the heavy-chain isotypes expressed by individual leukaemic cells in 11 pre-B-cell leukaemias. Switching in these leukaemic clones invariably led to expression of gamma 1 heavy-chain and kappa light-chain determinants, occasionally together with gamma 4 and alpha. These results indicate a nonrandom order for heavy-chain isotype switching and for light-chain isotype expression, and also suggest that a mechanism exists for coordinating the two events.


Anatomic skull base education using advanced neuroimaging techniques.
The goal of the present article was to describe our dissection training system applied to a variety of endoscopic endonasal approaches. It allows one to perform a 3D virtual dissection of the desired approach and to analyze and quantify critical surgical measurements. All the human cadaveric heads were dissected at the Laboratory of Surgical Neuro-Anatomy (LSNA) of the University of Barcelona (Spain). The model surgical training protocol was designed as follows: 1) virtual dissection of the selected approach using our dissection training 3D model; 2) preliminary exploration of each specimen using a second 3D model based on a preoperative computed tomographic scan; 3) cadaveric anatomic dissection with the aid of a neuronavigation system; and 4) quantification and analysis of the collected data. The virtual dissection of the selected approach, preliminary exploration of each specimen, a real laboratory dissection experience, and finally, the analysis of data retrieved during the dissection step was a complete method for training manual dexterity and hand-eye coordination and to improve the general knowledge of surgical approaches. The present model results are found to be effective, providing a valuable representation of the surgical anatomy as well as a 3D visual feedback, thus improving study, design, and execution in a variety of approaches. Such a system can also be developed as a preoperative planning tool that will allow the neurosurgeon to practice and manipulate 3D representations of the critical anatomic landmarks involved in the endoscopic endonasal approaches to the skull base.


Incidence and risk factors for radioactive iodine-induced sialadenitis.
Radioactive iodine (131I) is one of the treatments of hyperthyroidism and differentiated thyroid carcinoma (DTC). Swelling of salivary glands are one of the possible side effects of this treatment, known as radioactive iodine-induced sialadenitis (RAIS). The prevalence of RAIS varies widely and no specific risk ratio has been established. To determine the incidence of RAIS, analysing the epidemiological data and tumour- and treatment-related factors that may influence the development of the disease. 197 patients who received radioiodine treatment between 2015 and 2017 were studied (76.6% women). The variables studied were age, gender, weight, height, and body mass index; presence of high blood pressure, dyslipidemia, diabetes, and thyroid diseases; cumulative radioiodine dose, presence of sialadenitis, affected salivary gland, and the time of onset. 14 patients developed sialadenitis (78.6% women), all with DTC. The incidence of sialadenitis was 3.4% overall and 6.3% among DTC patients. Furthermore, we found that higher cumulative radioiodine doses confer a greater risk of developing sialadenitis, with a hazard ratio of 1.009 (p = .001). No association was found between the epidemiologic data studied and sialadenitis. In this series, a dose-dependent relationship was found between radioiodine treatment and sialadenitis.


Inhibitory effects of peptide YY on basal and VIP-stimulated short-circuit current in the rat jejunum: influence of technical conditions on observed results.
The interaction of PYY and VIP was studied in stripped and intact rat jejunum preparations mounted in Ussing chambers. PYY decreased basal Isc in intact as well as in stripped jejunum. Stripping was necessary to evidence a stimulation of basal Isc by VIP. When PYY and VIP were administered at the same time in the serosal bath, their effects seemed additive; VIP stimulation took over when VIP was present in ten times larger amounts than PYY, while PYY inhibition predominated at isomolar concentrations (10(-7) M) of both peptides. However, when PYY was administered three to six minutes before isomolar amounts of VIP, the VIP stimulation developed without being notably hampered. At this time, however, the amount of radioimmunoassayable PYY in the serosal compartment represented still 60% of the added amount. In conclusion, the experimental conditions can significantly change the results: stripping the longitudinal muscle/myenteric plexus impairs the effect of PYY and VIP in a different fashion, while the timing and order of administration of the peptides may change the apparent interaction between VIP stimulation and PYY inhibition.


Neural mechanisms and management of obesity-related hypertension.
The sympathetic nervous system is activated in human obesity and in the analogous experimental obesity produced by overfeeding. The causes remain uncertain and may be multiple. The consequences include hypertension, probably attributable to activation of the sympathetic outflow to the kidneys, and, more disputed, insulin resistance. The pattern of sympathetic activation in normal-weight and obesity-related hypertension differs in terms of the firing characteristics of individual sympathetic fibers (increased rate of nerve firing in normal-weight hypertensives, increased number of active fibers firing at a normal rate in obesity-hypertension) and the sympathetic outflows involved. The underlying mechanisms and the adverse consequences of the two modes of sympathetic activation may differ. Should antihypertensive drug therapy in obesity-hypertension specifically target the existing neural pathophysiology? Such an approach can be advocated on theoretical grounds. Perhaps more important is the requirement that chosen antihypertensives do not cause weight gain or insulin resistance.


The effect of oil pulling with coconut oil to improve dental hygiene and oral health: A systematic review.
Coconut oil is a cheap and accessible oil for many people around the world. There are numerous advocates for the practice of oil pulling to prevent common oral diseases. Therefore determining the effectiveness of oil pulling with coconut oil could potentially have monumental benefits. This review aimed to assess the effect of oil pulling with coconut oil in improving oral health and dental hygiene. We included randomized controlled trials comparing the effect of oil pulling with coconut oil on improving oral health and dental hygiene.No meta-analysis was performed due to the clinical heterogeneity and differences in the reporting of data among the included studies. Six electronic databases were screened: PubMed, Medline, EMBASE, AMED, CENTRAL and CINAHL. Electronic searches yielded 42 eligible studies, of which four RCTs including 182 participants were included. The studies lasted between 7 and 14 days. Significant differences were demonstrated for a reduction in salivary bacterial colony count (p = 0.03) and plaque index score (p=<0.001). One study also demonstrated a significant difference in staining compared to using Chlorhexidine (p = 0.0002). However, data was insufficient for conclusive findings, the quality of studies was mixed and risk of bias was high. The limited evidence suggests that oil pulling with coconut oil may have a beneficial effect on improving oral health and dental hygiene. Future clinical trials are of merit considering the universal availability of the intervention. Prospective research should have a robust design with rigorous execution to provide a higher quality of evidence. Oil pulling with coconut oil could be used as a adjunct to normal preventative regimes to improve oral health and dental hygiene although further studies are needed to determine the level of effectiveness.


Induction of a gene encoding an oleosin homologue in cultured citrus cells exposed to salt stress.
A cDNA clone (C3) with high homology to plant oleosins was isolated from citrus cultured cells. The 827-bp cDNA insert has an open reading frame of 144 amino-acid residues. The central hydrophobic domain of the protein is nearly identical to oleosins from Brassica napus and maize, and the C-terminal hydrophilic region following the hydrophobic domain is also highly conserved. The steady-state level of mRNA hybridizing to C3 was significantly increased upon exposure of citrus cells to 0.2 M NaCl. A lower level of transcript was found in seeds, but none could be detected in any other vegetative tissue (leaves, roots or fruit) even in the presence of salt under the conditions used. The induction of the oleosin homologue in citrus cells by salt does not depend on the developmental stage of the cells.


Potassium ion channel openers, Maxipost and Retigabine, protect against peripheral salicylate ototoxicity in rats.
Sodium Salicylate (SS) reliably induces a sensorineural hearing loss and tinnitus when administered in high doses. Recent animal modeled studies indicate that potassium channel openers such as Maxipost and Retigabine (RTG) can block SS- or noise-induced tinnitus respectively; however, the origins and mechanisms are poorly understood. Since SS blocks the same potassium channels that Maxipost and RTG open, we postulated that these drugs might influence peripheral auditory function. To test this hypothesis Maxipost or RTG were administered alone or in combination with SS in rats. When administered alone, Maxipost and RTG had no effect on distortion product otoacoustic emissions (DPOAE) or compound action potentials (CAPs). However when Maxipost or RTG were administered with SS, Maxipost prevented the SS-reduced CAP amplitudes at high frequencies (≥20 kHz) and RTG prevented SS-reduced CAP amplitudes at low frequencies (≤8 kHz). These results suggest that Maxipost and RTG can protect against peripheral damage and therefore reduce the incidence of tinnitus.


Total right ventricular dependent coronary circulation in pulmonary atresia with intact ventricular septum.
This report describes the case of a full-term gestational female with a prenatal diagnosis of pulmonary atresia with intact ventricular septum. Cardiac ultrasound at birth confirmed the diagnosis with no evidence of coronary artery fistulas. The patient died 6 hours after a central aortic to pulmonary artery shunt had been created with bypass support. Postmortem examination showed a coronary artery fistula rising from the right ventricle and a complete absence of both coronary ostia. This rare finding has been reported sporadically in the English literature.


Eltrombopag in paediatric immune thrombocytopenia: Iron metabolism modulation in mesenchymal stromal cells.
Immune thrombocytopenia (ITP) is an autoimmune disease caused by platelet destruction mediated by auto-antibody production. It is characterized by a compromised immune system and alteration of the inflammatory response. Mesenchymal stromal cells (MSCs) play an important role in modulating immune and inflammatory processes, exerting immune-suppressing and anti-inflammatory properties. In ITP-MSCs the activity and survival are strongly impaired. Eltrombopag (ELT) is a thrombopoietin receptor agonist approved in chronic ITP for stimulating platelet production. It has immunomodulating properties by stimulating T and B regulatory cell activity and by promoting a macrophage switch from the pro-inflammatory to the anti-inflammatory phenotype. ELT also exhibits iron-chelating properties. Iron is a crucial element involved in several physiologic processes, but its intracellular accumulation determines cell damages. Therefore, for the first time we analysed the effect of ELT on ITP-MSCs demonstrating its ability to restore survival and activity of MSCs directly and to promote their survival and proliferation indirectly, by iron metabolism modulation.