[Therapeutic modalities of nasopharyngeal adenoid cystic carcinoma].
To grasp clinical characteristics, therapeutic methods and prognosis of the patients with nasopharyngeal adenoid cystic carcinoma, and explore the optimal therapeutic modalities. Twenty one cases with nasopharyngeal adenoid cystic carcinoma were retrospectively reviewed. The treatment results were compared between radiotherapy alone and combined therapy. The cases with nasopharyngeal adenoid cystic carcinoma in T1, T2 phases was 28.6%, the cases in T3, T4 phases was 71.4%. The lymphatic node metastasis rate was 14.3%. The present symptoms were nasal discharge with blood, headache, nasal obstruction, deafness, double vision, facial insensibility, etc. One of 21 cases was lost follow up. Five years free-disease survival rates of the patients with nasopharyngeal adenoid cystic carcinoma was 42.9% (9/21). Five years free-disease survival rate of the patients with radiotherapy alone (RA) and the patients with radiotherapy combining surgery (R + S) were respectively 38.5% (5/12) and 50.0% (4/8), P = 0.472. Ten years free-disease survival rates of the patients was 16.7% (3/18). Ten years free-disease survival rates of the patients with RA and the patients with R + S were respectively 0/12 and 3/6, P = 0.025. The local recurrent rate was 50.0% (10/20). The local recurrent rates of the patients with RA and the patients with R + S were respectively 66.7% (8/12) and 25.0% (2/8), P = 0.085. The distant metastasis rate was 30. 0% (6/20). The distant metastasis rates of the patients with RA and the patients with R + S were respectively 25.0% (3/12) and 37.5% (3/8), P = 0.455. The course of nasopharyngeal adenoid cystic carcinoma is long, and it is prone to the local recurrence and the distant metastasis in advanced stage. Comparing with the radiotherapy alone, the radiotherapy combining surgery has better 10 years free-disease survival rate.


Neural crest derivatives and neuroendocrine cells in the gut of anencephalic and fetuses without congenital defects.
The enteric nervous system (ENS), a component of the peripheral nervous system in the intestinal walls, regulates motility, secretion, absorption, and blood flow. Neural crest (NC) migration, fundamental for ENS development, may be altered by central nervous system development alterations, such as neural tube defects (NTD). Intestinal innervation anomalies have been correlated to NTD. We aim to describe the ENS on a fetus with NTD and fetuses without congenital defects (FWCD). Two male and four female FWCD, 18-20 weeks-gestation (WG), and a 25 WG female anencephalic fetus. Samples from the pancreatoduodenal groove, jejunum, cecum, rectum, and appendix were analyzed by immunohistochemistry. Nervous plexuses were marked with Neuron-specific enolase and S-100; enteric glial cells with CD56; neuroendocrine cells with chromogranin and synaptophysin, and interstitial cells of Cajal (ICC) with CD117. The anencephalic fetus presented a rudimentary brainstem with a cerebellum. Partial frontal, temporal, and occipital bones were found. A large atrial septal defect, an enlarged kidney with a duplex collecting system and a single adrenal gland were found. NSE, S100, and CD56, showed the presence of the myenteric and submucous plexuses of the ENS; scarce interplexus reactivity may indicate inadequate development. Pancreatic and gut neuroendocrine cells, identified with chromogranin and CD56, showed that the enteroendocrine system is present. Findings on FWCD using these markers are consistent with literature descriptions. Vagal NC migration appears to be unaffected despite the presence of anencephaly, although maturation of the ENS may be altered.


A novel role of long non-coding RNAs in response to X-ray irradiation.
In the present study, the role of lncRNAs in response to radiation-induced DNA damage and oxidative stress were explored to improve our understanding of the biological pathways activated upon radiation-induced toxicity. The toxicity of X-ray radiation on human bronchial epithelial cell lines (HBE) was determined through a dose-dependent increase in ROS production and γ-H2AX formation and changes to lncRNA expression was observed and quantified using lncRNA-specific microarrays. 115 lncRNAs expression was increased in a dose-dependent manner following X-ray irradiation. Bioinformatic prediction algorithms determined that these lncRNAs significantly affect the p53 signaling pathway, and, more specifically, the BRCA 1 transcription factor and coding genes adjacent to BRCA 1. Our results highlight a previously uncharacterized role for lncRNAs to act via the p53-pathway in response to X-ray-induced DNA damage, and suggest lncRNAs may serve as novel indicators for radiation toxicity.


Biliary secretion of copper in healthy man. Quantitation by an intestinal perfusion technique.
A duodenal perfusion technique which permitted a normal daytime eating pattern of three liquid meals and an overnight fast was used to measure the 24-hr output of copper in bile in 19 studies in 14 persons with normal hepatic and gallbladder function. Daily biliary output was also determined by direct measurement on four 24-hr bile collections obtained from 3 patients with complete biliary diversion, and in 4 patients measurements of dietary copper intake and fecal copper output were also made. A mean bile copper output of 25 +/- 13 microng per kg-day (1.7 mg +/- 0.8) (mean +/- SD) was obtained in 19 perfusion studies; the range was 9.0 to 53.0 microng per kg-day. The values in the 24-hr bile collections were similiar to those obtained using the perfusion method. Biliary copper output was similar during the day and night, and there was no correlation between hourly rates of copper output and hourly rates of bile acid output, nor was there any correlation between daily copper output and daily bile acid output. The similar values for dietary intake, biliary output, and fecal output provide additional support for the current view that in healthy man copper balance is maintained by biliary secretion and subsequent fecal excretion of copper which has been absorbed in the stomach and proximal duodenum.


Morphology and Chemical Coding of Rat Duodenal Enteric Neurons following Prenatal Exposure to Fumonisins.
Fumonisins (FBs), including fumonisin B1 and B2 produced by the fungus Fusarium verticillioides, are widespread mycotoxins contaminating crop plants as well as processed food. The aim of the experiment was to determine whether the exposure of 5-week-old pregnant rats to FBs at 60 mg/kg b.w. (group FB60) or 90 mg/kg b.w. (group FB90) results in morphological changes in the duodenum of weaned offspring, particularly the enteric nervous system (ENS). In addition, the levels of expression of galanin and vasoactive intestinal polypeptide (VIP) in the ENS were analysed by immunofluorescence in the control and experimental groups of animals. No significant morphological changes in the thickness of the muscle layer or submucosa of the duodenum were noted in group FB60 or FB90. In group FB90 (but not FB60), there was a significant increase in the width of the villi and in the density of the intestinal crypts. Immunofluorescence analysis using neuronal marker Hu C/D showed no significant changes in group FB60 or FB90 in the morphology of the duodenal ENS, i.e., the myenteric plexus (MP) and submucosal plexus (SP), in terms of the density of enteric ganglia in the MP and SP, surface area of MP and SP ganglia, length and width of MP and SP ganglia, surface area of myenteric and submucosal neurons, diameter of myenteric and submucosal neurons, density of myenteric and submucosal neurons, and number of myenteric and submucosal neurons per ganglion. In both groups, there was an increase (relative to the control) in the percentage of Hu C/D-IR/VIP-IR (IR-immunoreactive) and Hu C/D-IR/galanin-IR myenteric and submucosal neurons in the ganglia of both the MP and SP of the duodenum. In addition, in groups FB60 and FB90, there was an increase in the number of nerve fibres showing expression of VIP and galanin in the mucosa, submucosa and circular muscle layer of the duodenum. The results indicate that prenatal exposure to FBs does not significantly alter the histological structure of the duodenum (including the ENS) in the weaned offspring. The changes observed in the chemical code of the myenteric and submucosal neurons in both experimental groups suggest harmful activity of FBs, which may translate into activation of repair mechanisms via overexpression of neuroprotective neuropeptides (VIP and galanin).


Lexipafant (BB-882), a platelet activating factor receptor antagonist, ameliorates mucosal inflammation in an animal model of colitis.
To assess the anti-inflammatory action of lexipafant (BB-882), a platelet activating factor antagonist, in an animal model of acute colitis. An animal intervention study. Following the rectal instillation of formalin 0.75% into male New Zealand White (NZW) rabbits, 0.85 ml of aggregated immunoglobulin was administered i.v. Treatment groups (0.8 mg/kg, n = 6; 2.4 mg/kg, n = 13; 3.2 mg/kg, n = 10) were given bolus doses of BB-882 two-hourly i.v. (control group, n = 25). Rectal dialysis was performed before induction of colitis and sacrifice. Dialysate leukotriene B4 (LTB4), prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) levels were determined. Tissue was saved for histology and measurement of myeloperoxidase content. There was a dose-dependent improvement in macroscopic scores (2.4 and 3.2 mg/kg: P < 0.02, P < 0.001) and myeloperoxidase levels (3.2 mg/kg: P < 0.04). Dialysate LTB4 levels fell (2.4 and 3.2 mg/kg: P < 0.03, P < 0.02) as did PGE2 levels. TXB2 concentrations remained unaffected. The PAF receptor antagonist BB-882 shows efficacy in treating inflammation in an animal model of acute colitis as evidenced by a dose-dependent fall in macroscopic mucosal damage, neutrophil infiltration and reduced generation of inflammatory mediators.


The Risk of Cardiovascular Events in Individuals With Primary Glomerular Diseases.
Little is known about the risk of cardiovascular disease (CVD) in patients with various primary glomerular diseases. In a population-level cohort of adults with primary glomerular disease, we sought to describe the risk of CVD compared with the general population and the impact of traditional and kidney-related risk factors on CVD risk. Observational cohort study. Adults with membranous nephropathy (n = 387), minimal change disease (n = 226), IgA nephropathy (n = 759), and focal segmental glomerulosclerosis (n = 540) from a centralized pathology registry in British Columbia, Canada (2000-2012). Traditional CVD risk factors (diabetes, age, sex, dyslipidemia, hypertension, smoking, prior CVD) and kidney-related risk factors (type of glomerular disease, estimated glomerular filtration rate [eGFR], proteinuria). A composite CVD outcome of coronary artery, cerebrovascular, and peripheral vascular events, and death due to myocardial infarction or stroke. Subdistribution hazards models to evaluate the outcome risk with non-CVD death treated as a competing event. Standardized incidence rates (SIR) calculated based on the age- and sex-matched general population. During a median 6.8 years of follow-up, 212 patients (11.1%) experienced the CVD outcome (10-year risk, 14.7% [95% CI, 12.8%-16.8%]). The incidence rate was high for the overall cohort (24.7 per 1,000 person-years) and for each disease type (range, 12.2-46.1 per 1,000 person-years), and was higher than that observed in the general population both overall (SIR, 2.46 [95% CI, 2.12-2.82]) and for each disease type (SIR range, 1.38-3.98). Disease type, baseline eGFR, and proteinuria were associated with a higher risk of CVD and, when added to a model with traditional risk factors, led to improvements in model fit (R2 of 14.3% vs 12.7%), risk discrimination (C-statistic of 0.81 vs 0.78; difference, 0.02 [95% CI, 0.01-0.04]), and continuous net reclassification improvement (0.4 [95% CI, 0.2-0.6]). Ascertainment of outcomes and comorbidities using administrative data. Patients with primary glomerular disease have a high absolute risk of CVD that is approximately 2.5 times that of the general population. Consideration of eGFR, proteinuria, and type of glomerular disease may improve risk stratification of CVD risk in these individuals. Patients with chronic kidney disease are known to be at high risk of cardiovascular disease. Cardiovascular risk in patients with primary glomerular diseases is poorly understood because these conditions are rare and require a kidney biopsy for diagnosis. In this study of 1,912 Canadian patients with biopsy-proven IgA nephropathy, minimal change disease, focal segmental glomerulosclerosis, and membranous nephropathy, the rate of cardiovascular events was 2.5 times higher than in the general population and was high for each disease type. Consideration of disease type, kidney function, and proteinuria improved the prediction of cardiovascular events. In summary, our population-level study showed that patients with primary glomerular diseases have a high cardiovascular risk, and that inclusion of kidney-specific risk factors may improve risk stratification.


The impact of a family history of type 2 diabetes on insulin secretion and insulin sensitivity in individuals with varying glucose tolerance.
This study was performed to investigate the impact of a family history of type 2 diabetes (T2DM) on insulin resistance and beta-cell dysfunction in populations with varying glucose tolerance. Among the total of 142 participants, 73 subjects with no family history of T2DM (FH-) included 42 with normal glucose tolerance (NGT/FH-) and 31 with impaired glucose tolerance (IGT/FH-); and 69 first-degree relatives of patients with T2DM (FH+) included 36 with NGT (NGT/FH+) and 33 with IGT (IGT/FH+). Insulin resistance was evaluated by Insulin Sensitivity Index (ISI) based on the euglycemic hyperinsulinemic clamp. Islet beta-cell function was assessed by disposition index (DI) for the acute insulin response to glucose (AIRg) using intravenous glucose tolerance test. Metabolic data were compared between groups after adjustment for age, sex, body mass index and waist-to-hip ratio. The NGT/FH+ group showed lower level of ISI (P = 0.023) than the NGT/FH- group, whereas no difference was found in AIRg or DI between these 2 subgroups. In the FH- individuals, both ISI and DI of the IGT/FH- group decreased compared with the NGT/FH- group (both P < 0.05). In the FH+ individuals, no difference was found in ISI between the IGT/FH+ and NGT/FH+ groups, whereas the IGT/FH+ group had a lower level of AIRg and DI than the NGT/FH+ group (both P < 0.0001). This study showed that the pathophysiological changes were different between individuals with and without a family history of T2DM during the glucose tolerance aggravation.


Mesoprefrontal dopamine neurons distinguish themselves.
By distinguishing groups of dopamine neurons that differ in their projection patterns and intrinsic properties, Lammel and colleagues report in this issue of Neuron that mesocorticolimbic dopamine neurons of the ventral tegmental area (VTA) form a distinct subclass of dopamine cells.


Sialadenitis in a patient with ulcerative colitis and autoimmune pancreatitis type 2.
Autoimmune pancreatitis (AIP) is a distinct form of chronic pancreatitis that has been increasingly recognised over the last decades and shows a good response to corticosteroid treatment. Two different forms of AIP have been characterized. Type 1 AIP is the pancreatic manifestation of IgG4-related disease and often affects multiple organ systems. In contrast, type 2 AIP is confined to the pancreas and involvement of extra-pancreatic organs has previously only very rarely been reported, except for an association with inflammatory bowel disease. The hallmark lesion of type 2 AIP is the granulocyte epithelial lesion (GEL), showing infiltration of neutrophilic granulocytes in the epithelium of pancreatic ducts and their accumulation in the duct lumen. We present a 61-year-old female patient who underwent pancreaticoduodenectomy with a postoperative histological diagnosis of type 2 AIP. Three months later, she underwent colectomy and was diagnosed with ulcerative colitis. One year later, she presented with swelling and pain of the right-sided submandibular salivary gland which was resected. Sialadenitis with lymphoplasmacytic inflammation, obliterative phlebitis, fibrosis and frequent accumulation of neutrophilic granulocytes in ducts, reminiscent of GELs, without IgG4-positivity or epitheloid cell granulomas, was found. Later, she presented with swelling and pain related to the left-sided submandibular gland, which resolved after steroid treatment. We describe the clinical, histological and immunohistochemical findings in this patient. It may be hypothesized that the sialadenitis may represent a rare extrapancreatic manifestation of, alternatively a rare association with, type 2 AIP or ulcerative colitis.


[Toxoplasma infection in males with sterility in Shenyang, China].
To investigate the Toxoplasma gondii (TOX) infection in males with sterility and the effect of the infection on the reproductive function of males. Enzyme linked immunoabsorbent assay (ELISA) was used to detect TOX-CAg, TOX-IgG and TOX-IgM in the peripheral blood of male patients with sterility. Among 100 cases of male sterility, 7 were TOX-IgG positive (7%), 16 TOX-IgM positive (16%) and 13 TOX-CAg positive (13%). Among 100 normal males, 7 were TOX-IgG positive (7%), 3 TOX-IgM positive (3%) and 1 TOX-CAg positive (1%). TOX infection may affect the fertility of males and cause male sterility. For this reason, males should prevent themselves from TOX infection.


Differential regulation of phenylalanine ammonia-lyase genes during plant development and by environmental cues.
Phenylalanine ammonia-lyase (PAL) catalyzes the first reaction in the biosynthesis from phenylalanine of a wide variety of phenylpropanoid natural products including lignin, flavonoid pigments, and phytoalexins. In bean (Phaseolus vulgaris L.), PAL is encoded by a family of three genes. We show here by RNase protection with gene-specific probes that these genes are expressed differentially during development and in response to different environmental cues. While all three genes are expressed at high levels in roots, only PAL1 and PAL2 are expressed in shoots and only PAL1 is expressed in leaves. Strikingly, PAL2 is expressed at very high levels in petals, where PAL1 is only very weakly expressed and PAL3 is not expressed. All three genes are induced by mechanical wounding of hypocotyls, but fungal infection only activates PAL1 and PAL3. Illumination of etiolated hypocotyls activates PAL1 and PAL2 but not PAL3. Corresponding differential patterns of synthesis of specific PAL polypeptide isoforms were observed by two-dimensional gel electrophoretic analysis of in vitro translation products encoded by RNA isolated from hypocotyls stimulated by light, wounding, or infection. The specific isoforms encoded by transcripts of the three PAL genes were identified by inhibition of synthesis in vitro with gene-specific anti-sense transcripts followed by comparative two-dimensional gel electrophoretic analysis of the pattern of translation products. These data indicate that selective expression of PAL genes encoding functional variants is governed by a complex set of regulatory networks for developmental and environmental control of phenylpropanoid biosynthesis.


Examining the correlation between the weather conditions and COVID-19 pandemic in India: A mathematical evidence.
In this article, for the analysis of Covid-19 progression in India, we present new insights to formulate a data-driven epidemic model and approximation algorithm using the real data on infection, recovery and death cases with respect to weather in the view of mathematical variables.


Reduction in early alcohol abstinence fits by administration of carbamazepine syrup instead of tablets.
All convulsive fits during ethanol abstinence in the acute ward of a Department of Alcohol Diseases were recorded during two 11-month periods. The patients and the treatment given were similar during the 2 periods, except that the initial dose of carbamazepine was given as tablets during the first period and as syrup during the second period. The rate of withdrawal fits between 2 and 10 h after the initial dose of carbamazepine was significantly lower in the group given the syrup, which is suggestive of greater efficacy. This is probably due to faster absorption of carbamazepine from the syrup, promoting more rapid attainment of an anticonvulsant concentration.


Three-dimensional analysis of pharyngeal airway volume in adults with anterior position of the mandible.
The purpose of this study was to examine whether the pharyngeal airway volume in adults with skeletal Class III malocclusion is greater than in subjects with Class I occlusion and whether the pharyngeal airway volume correlated with facial morphology. Cone-beam computed tomography scans were obtained from 60 subjects, who were assigned to 2 groups. The skeletal Class III malocclusion group consisted of 31 subjects (16 men, 15 women) who had planned on orthodontic treatment with orthognathic surgery. The Class I malocclusion group consisted of 29 subjects (14 men, 15 women). The pharyngeal airway volumes and areas were measured and compared with cephalometric variables. The cross-sectional areas of the lower part of the pharyngeal airway and the volume of the upper part of the pharyngeal airway were greater in skeletal Class III malocclusion patients than in Class I malocclusion patients. The volume of the upper part of the pharyngeal airway showed negative correlations with ANB angle and the Wits appraisal, and positive correlations with SNB, APDI, pogonion to N-perp, gonial angle, and FMA. The volume of the upper part of the pharyngeal space was greater in patients with skeletal Class III malocclusion, and the increased volume of the upper part of the pharyngeal airway showed significant correlations with measurements characterizing the anterior position of mandible.


Unsaturated amino acids derived from isoleucine trigger early membrane effects on plant cells.
Unsaturated amino acids (UnsAA) have been shown to affect the activity of various biological processes. However, their mode of action has been investigated poorly thus far. We show in this work that 2-amino-3-methyl-4-pentenoic acid (C2) and 2-amino-3-methyl-4-pentynoic acid (C3) structurally derived from isoleucine (Ile) exhibited a multisite action on plant cells. For one, C2 and C3 induced early modifications at the plasma membrane level, as shown by the hyperpolarization monitored by microelectrode implantation in the pulvinar cells of Mimosa pudica, indicating that these compounds are able to modify ionic fluxes. In particular, proton (H(+)) fluxes were modified, as shown by the pH rise monitored in the bathing medium of pulvinar tissues. A component of this effect may be linked to the inhibitory effect observed on the proton pumping and the vanadate-sensitive activity of the plasma membrane H(+)-ATPase monitored in plasma membrane vesicles (PMVs) purified from pulvinar tissues of M. pudica and leaf tissues of Beta vulgaris. This effect may explain, in part, the inhibitory effect of the compounds on the uptake capacity of sucrose and valine by B. vulgaris leaf tissues. In contrast, an unexpected action was observed in cell reactions, implicating ion fluxes and water movement. Indeed, the osmocontractile reactions of pulvini induced either by a mechanical shock in M. pudica or by dark and light signals in Cassia fasciculata were increased, indicating that, compared to Ile, these compounds may modify in a specific way the plasma membrane permeability to water and ions.


Electroencephalographic abnormalities in infants with hypoplastic left heart syndrome.
Electroencephalography (EEG) was performed on 16 neonates between 38-45 weeks conceptional age with hypoplastic left heart syndrome (HLHS). The findings were compared blindly with EEGs recorded from 16 infants with other congenital heart defects and 15 infants referred for EEGs with noncardiac diagnoses or problems. EEGs from HLHS infants demonstrated significantly decreased quiet sleep and increased indeterminate sleep, an abnormally discontinuous tracing in active and indeterminate sleep, and lack of response to stimulation. No significant differences were present in the amount of active sleep, sharp waves, focal slowing, or rhythmic theta activity. The distinctive abnormalities were unrelated to arterial blood gases or treatment with prostaglandin E at recording. Four HLHS infants had repeat recordings performed; there were serial increases in quiet sleep, decreases in indeterminate sleep, and improved continuity in all patients. Certain EEG abnormalities occur more frequently in infants with HLHS than in patients with other cardiac defects or noncardiac problems. These findings may result from the early onset of heart failure and abnormal cerebral perfusion due to hypoplasia of the ascending aorta and great arteries, conditions commonly associated with HLHS.


Parental and peer support in adolescents with a chronic condition: a typological approach and developmental implications.
Research has consistently demonstrated that contextual support is crucial towards the psychological functioning of adolescents with chronic conditions. However, the literature has predominantly focused on parental support instead of adopting an integrated approach to parental and peer support. The present manuscript with two longitudinal studies in adolescents with Type 1 diabetes and congenital heart disease examined the extent to which different clusters of maternal, paternal, and peer support at baseline were related to well- and ill-being over time. In both studies, four clusters emerged: combined support, parental support, peer support, and lack of support. Follow-up longitudinal analyses indicated that especially combined support from parents and peers proved to be of crucial importance towards psychological functioning. The present studies demonstrated the value of a typological approach for assessing social support in adolescents with chronic conditions. In addition to focusing on parental support, future research should assess peer support as well in these adolescents.


Computed tomographic diagnosis of pulmonary varix.
A solitary pulmonary nodule was shown by dynamic computed tomography to be vascular, to be enhanced during the pulmonary venous phase, and to be in continuity with the left inferior pulmonary vein. The diagnosis of pulmonary varix was confirmed by pulmonary angiography, an invasive procedure that can be avoided in the future.


Immunology in the clinic review series; focus on type 1 diabetes and viruses: role of antibodies enhancing the infection with Coxsackievirus-B in the pathogenesis of type 1 diabetes.
Type 1 diabetes results from an interaction between genetic and environmental factors. Coxsackieviruses B (CV-B) are major environmental candidates, as suggested by epidemiological and experimental studies. The mechanisms leading to the disease involve interactions between the virus, host target tissue (pancreas) and the immune system. The infection of target cells with viruses can be prevented by antibodies. Conversely, the infection can be enhanced by antibodies. The antibody-dependent enhancement (ADE) of infection has been described with various viruses, especially Picornaviruses. In mice infected with CV-B3 this phenomenon resulted in an extended inflammatory reaction and myocarditis. In the human system non-neutralizing antibodies can increase the infection of monocytes with CV-B4 and stimulate the production of interferon (IFN)-α by these cells in vitro. CV-B4/immunoglobulin (Ig)G immune complexes interacted with a specific viral receptor [Coxsackievirus and adenovirus receptor (CAR)] and with IgG Fc fraction receptors (FcγRII and FcγRIII) at the surface of monocytes. The virus-antibody complexes are internalized (CAR) and receptors for the Fc of IgG (FcγRII and FcγRIII). Such antibodies have been detected in patients with type 1 diabetes and they could be responsible for the presence of enteroviral RNA and IFN-α in peripheral blood mononuclear cells (PBMC) of these individuals. The target of enhancing antibodies has been identified as the VP4 protein, which allowed the detection of these antibodies by enzyme-linked immunosorbent assay (ELISA). It cannot be excluded that antibodies enhancing the infection with CV-B may play a role in the pathogenesis of type 1 diabetes, induced or aggravated by these viruses. They can cause a viral escape from the immune response and may participate in the spreading of viruses to β cells. Whether enhancing antibodies raised against VP4 can play a role in iterative homologous and/or heterologous CV-B infections and in the persistence of viruses within the host deserves further study.


Evaluating the clinical impact of routine whole genome sequencing in tuberculosis treatment decisions and the issue of isoniazid mono-resistance.
The UK has implemented routine use of whole genome sequencing (WGS) in TB diagnostics. The WHO recommends addition of a fluoroquinolone for isoniazid mono-resistance, so early detection may be of use. The aim of this study was to describe the clinical utility and impact of WGS on treatment decisions for TB in a low incidence high resource clinical setting. The clinical turnaround time (TAT) for WGS was analysed in comparison to TB PCR using Xpert MTB/RIF (Cepheid, Sunnyvale, CA) results where available and subsequent phenotypic drug susceptibility testing (DST) when required. This was a retrospective analysis of TB cases from January 2018 to March 2019 in London. Susceptibility and TAT by WGS, phenotypic DST, TB PCR using Xpert MTB/RIF were correlated to drug changes in order to describe the utility of WGS on treatment decisions on isoniazid mono-resistance in a low incidence high resource setting. 189 TB cases were identified; median age 44 years (IQR 28-60), m:f ratio 112:77, 7 with HIV and 6 with previous TB. 80/189 cases had a positive culture and WGS result. 50/80 were fully sensitive to 1st line treatment on WGS, and the rest required additional DST. 20/80 cases required drug changes; 12 were defined by WGS: 8 cases had isoniazid mono-resistance, 2 had MDR-TB, 1 had isoniazid and pyrazinamide resistance and 1 had ethambutol resistance. The median TAT for positive culture was 16 days (IQR 12.5-20.5); for WGS was 35 days (IQR 29.5-38.75) and for subsequent DST was 86 days (IQR 69.5-96.75), resulting in non-WHO regimens for a median of 50.5 days (IQR 28.0-65.0). 9/12 has TB PCRs (Xpert MTB/RIF), with a median TAT of 1 day. WGS clearly has a substantial role in our routine UK clinical settings with faster turnaround times in comparison to phenotypic DST. However, the majority of treatment changes defined by WGS were related to isoniazid resistance and given the 1 month TAT for WGS, it would be preferable to identify isoniazid resistance more quickly. Therefore if resources allow, diagnostic pathways should be optimised by parallel use of WGS and new molecular tests to rapidly identify isoniazid resistance in addition to rifampicin resistance and to minimise delays in starting WHO isoniazid resistance treatment.


Chemotherapy of advanced small-cell anaplastic carcinoma. Superiority of a four-drug combination to a three-drug combination.
A controlled clinical trial compared three-drug and four-drug combination chemotherapy in 109 patients with advanced small-cell anaplastic carcinoma of the lung. The combination of vincristine, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), cyclophosphamide, and methotrexate was significantly superior to the combination of the last three drugs alone with regard to median survival (230 versus 176 days) (P less than 0.01) and to duration of response (186 versus 112 days) (P less than 0.01). Objective response occurred in 78% and 75%, respectively. No significant difference in these values was observed in the comparison of the three subtypes of small-cell anaplastic carcinoma using the World Health Organization classification.


In vivo spreading of tau pathology.
Recent findings have suggested that tau pathology may spread in the brain by a prion-like mechanism. In this issue of Neuron, de Calignon et al. (2012) recreated an early stage of neurofibrillary tangle pathology to show that tau aggregates initially generated in a circumscribed area spread throughout the brain and lead to neurodegeneration.


Chorismate lyase: kinetics and engineering for stability.
By removing the enolpyruvyl group from chorismate, chorismate lyase (CL) produces p-hydroxybenzoate (p-HB) for the ubiquinone biosynthetic pathway. We have analyzed CL by several spectroscopic and chemical techniques and measured its kinetic (kcat=1.7 s(-1), K(m)=29 microM) and product inhibition parameters (K(p)=2.1 microM for p-HB). Protein aggregation, a serious problem with wild type CL, proved to be primarily due to the presence of two surface-active cysteines, whose chemical modification or mutation (to serines) gave greatly improved solution behavior and minor effects on enzyme activity. CL is strongly inhibited by its product p-HB; for this reason activity and inhibition measurements were analyzed by both initial rate and progress curve methods. The results are consistent, but in this case where the stable enzyme-product complex rapidly becomes the predominant form of the enzyme, progress curve methods are more efficient. We also report inhibition measurements with several substrate and product analogs that give information on ligand binding interactions of the active site. The biological function of the unusual product retention remains uncertain, but may involve a mechanism of directed delivery to the membrane-bound enzyme that follows CL in the ubiquinone pathway.


Niche segregation in high-altitude Himalayan chats (Aves, Turdidae): does morphology match ecology?
We investigated patterns of habitat segregation and morphological differentiation in syntopic, closely related turdid birds of the alpine zone of the Central Himalayas. Discriminant function analysis of 19 habitat structure parameters and comparisons of additional habitat features revealed that the species were distributed along gradients of vegetation height and vegetation density. In addition, non-vegetational structural habitat features, like microrelief variability or the presence of rocks and boulders, had strong discriminating power. In terms of habitat preferences the species of the guild investigated formed three subsets: shrubbery species (Erithacus pectoralis, E. chrysaeus and Hodgsonius phoenicuroides), species preferring open areas with higher surface roughness (Phoenicurus frontalis, Chaimarrornis leucocephalus) and the high-altitude species Grandala coelicolor. Using discriminant function analysis of 20 characters, morphology was analysed in relation to microhabitat utilization and foraging behaviour. Species inhabiting patches of shrubby thickets and foraging mainly by pedal movements (E. pectoralis, E. chrysaeus and H. phoenicuroides) have in common short rounded wings with high wing loading and strong legs and feet. Species preferably foraging by aerial hawking or "perch and pounce" techniques in more open areas (P. frontalis, C. chaimarrornis, and to some extent E. cyanurus) have longer wings, shorter tarsi and long rictal bristles. Grandala proved to be well adpated for long-distance flights at high altitudes (long, pointed wings) and for pedal foraging. Overall our results fit the basic assumption of ecomorphological theory that morphological distance reflects ecological distance. The ordination of each species in morphological space closely matched its distribution in ecological space (microhabitat, foraging strategies). Striking associations of morphology with ecology were not only evident for single traits but were also found in multidimensional comparisons: between-species Euclidian distances in ecology calculated from 19 habitat properties were in most cases equivalent to morphological distances calculated from 20 traits. In addition, in one of the two study areas species locations in the plane spanned by DFA axes of habitat use mirrored their positions in the morphological multivariate space. The observed distributions of the species in ecological and morphological space are interpreted as being mainly attributable to individualistic responses to the specific constraints of the alpine environment.


A judicial rashomon: on ageism and narrative justice.
How are old people treated in courts? How do judges construct old age? To what extent judicial decisions regarding older persons reflect ageist attitudes? Historically, these questions have received relatively little attention in gerontological literature. This Israeli case-study tries to add a new dimension to the growing literature in the field of jurisprudential gerontology, in a context that so far received little attention: narrative justice. More specifically, this study combines a narrative-justice theoretical approach, with a legal case-study methodology, in order to explore the relationships between judicial narratives and ageism. The narrative analysis presented in this case study exposes how in contrast to common perception, which views legal decisions as objective and unimaginative texts, reality is different. The judicial case studied in this article exemplify how in real life, judges often construct a socio-judicial narrative, embellished by personal bias and prejudices regarding old age.


The signature amidase from Sulfolobus solfataricus belongs to the CX3C subgroup of enzymes cleaving both amides and nitriles. Ser195 and Cys145 are predicted to be the active site nucleophiles.
The signature amidase from the extremophile archeum Sulfolobus solfataricus is an enantioselective enzyme that cleaves S-amides. We report here that this enzyme also converts nitriles in the corresponding organic acid, similarly to the well characterized amidase from Rhodococcus rhodochrous J1. The archaeal and rhodococcal enzymes belong to the signature amidases and contain the typical serine-glycine rich motif. They work at different optimal temperature, share a high sequence similarity and both contain an additional CX3C motif. To explain their dual specificity, we built a 3D model of the structure of the S. solfataricus enzyme, which suggests that, in addition to the classical catalytic Ser-cisSer-Lys, a putative additional Cys-cisSer-Lys catalytic site, likely to be responsible for nitrile hydrolysis, is present in these proteins. The results of random and site-directed mutagenesis experiments, as well as inhibition studies support our hypothesis.


Analysis of gene expression in MOG-induced experimental autoimmune encephalomyelitis after treatment with a novel brain-penetrating antioxidant.
Accumulating data from experimental studies indicate that oxidative stress has a major role in the pathogenesis of multiple sclerosis (MS). It has been suggested that local production of reactive oxygen species, probably by macrophages, mediates axonal damage in both MS patients and the mouse model experimental autoimmune encephalomyelitis (EAE). We have shown previously that our novel brain-penetrating antioxidant, N-acetylcysteine amide (AD4), reduces the clinical and pathological symptoms, including inflammation and axonal damage in myelin oligodendrocyte glycoprotein (MOG)-induced chronic EAE in mice. The aim of this study was to examine the molecular mechanism by which AD4 exerts protection in MOG-induced EAE mice. Therefore, we analyzed gene-expression profile in the spinal cords of MOG-induced chronic EAE mice and compared them with MOG-induced mice treated with AD4, using a cDNA microarray. We found that MOG treatment up-regulated genes encoding growth factors, cytokines, death receptors, proteases, and myelin structure proteins, whereas MOG- and AD4-treated mice demonstrated gene expression profiles similar to that seen in naive healthy mice. In conclusion, our study shows that chronic AD4 administration suppresses the induction of various pathological pathways that play a role in EAE and probably in MS.


Splenectomy for cytopenias associated with systemic lupus erythematosus.
Splenectomy was performed in 20 patients with refractory cytopenias associated with systemic lupus erythematosus. An immediate and sustained increase in platelet count (greater than 150,000 cells/mm3) was achieved in 12 of 18 patients whose principal indication for operation was thrombocytopenia. Of seven patients with hemolytic anemia, which was linked with thrombocytopenia in five, six had an increase in the hematocrit value of 20 percent or more after operation. The white blood count increased to normal values in three leukopenic patients. We believe that although removal of the spleen is not uniformly successful in correcting cytopenias in patients with systemic lupus erythematosus, splenectomy should be considered in patients refractory to other modalities of treatment.


Cardiac tamponade following varicella.
An 18-month-old girl presented with cardiac tamponade five weeks after varicella. An emergency pericardiocentesis was performed and, subsequently, an anterior pericardiectomy. She eventually made a complete recovery following corticosteroid treatment.


Hypocalcemic toxicity and atypical reactions in therapeutic plasma exchange.
Hypocalcemic toxicity accounts for the most common adverse effects of therapeutic plasma exchange. The symptoms can be related to a fall in plasma ionized calcium. Citrate-based anticoagulants, notably sodium citrate and ACD formula A, have been indicated as the major cause of hypocalcemic toxicity, but colloid replacement fluids containing human serum albumin are also at fault. Recognition of the signs and symptoms of hypocalcemic toxicity is important because several clinical measures are available to deal with them and to ensure patient comfort. A typical reactions, characterized by flushing and hypotension during plasma exchange, have been attributed to the effects of angiotensin converting enzyme inhibitors. Both exchange and adsorption apheresis procedures can result in atypical reactions in patients who have been taking this class of drugs within 48 to 72 hours of an apheresis procedure. These reactions are less common than hypocalcemic toxicity, but can be prevented by paying attention to detail.


Integrins in the normal and healing corneal epithelium.
Integrins are heterodimeric plasma membrane glycoproteins involved in cell-matrix and cell-cell interactions. The present communication reviews the distribution of several of the currently known integrin subunits in the corneal epithelium. The corneal epithelium contains the following integrin heterodimers: alpha 2 beta 1, alpha 3 beta 1, and alpha 6 beta 4. The expression of alpha v with an unknown beta subunit is also recognized, whereas the expression of alpha 4 and alpha 5 subunits remains controversial. Some of the changes occurring in the distribution of integrins in response to wounding will also be discussed.


Neighbors ameliorate local salinity stress for a rhizomatous plant in a heterogeneous environment.
The selection pressures experienced by clonal plants in heterogeneous environments may be significantly affected by physiological integration among ramets via rhizome connections. We experimentally examined how connections affected the response to saline soil conditions in Ambrosia psilostachya clones from natural saline basins in eastern Nebraska. Paired stems connected by uniform lengths of rhizome were grown in partitioned pots in 3 watering regimes: (1) both stems watered with tapwater, (2) both stems watered with salt water (1% NaCl), and (3) one stem watered with salt water and one with tapwater. All plants survived and grew in salt water, yet dry weight gain of salt-salt plants was only 34% of that for plants in uniform tapwater. Salt plants connected to tapwater plants had 2-fold higher dry weight gain than salt-salt plants. Their tapwater neighbors had significantly smaller biomass than pairs with both stems growing in tapwater. Measurements of leaf stomatal conductance, transpiration rate and water potential, together with root-shoot allocation patterns, suggest that rhizomes transported both water and photosynthate from tapwater plants to their neighbors in saline soil. These results indicate that ramets in a locally inferior environment can be helped by their neighbors, but at some cost to the contributing ramet. We discuss the consequences of this phenomenon for the evolution of local adaptation in populations of rhizomatous plants.


Modulation of GPC-4 and GPLD1 serum levels by improving glycemic indices in type 2 diabetes: Resistance training and hawthorn extract intervention.
This study was designed to investigate the effects of resistance training (RT) and hawthorn extract (Ha) on Glypican-4 (GPC-4) and Insulin-regulated glycosylphosphatidylinositol-specific phospholipase D (GPLD1) serum levels in T2DM and to examine the relationship of these variables with glycemic indexes. 40 male Wistar rats were divided into five equal groups: Healthy Control (H-C), Diabetes Control (D-C), Diabetes Resistance training (D-RT), Diabetes Hawthorn (D-Ha), and Diabetes Resistance training Hawthorn (D-RT-Ha). T2DM was induced with a 4-week high-fat diet (HFD) and one dose of STZ intraperitoneal injection (35 mg/kg). 1-week after the injection, RT (with a range of 50%-100%1RM/3 day/week) and gavage of Ha extract (100 mg/kg/day) was performed for 12 weeks. The glycemic indices improvement (reducing blood glucose and increasing serum insulin level) caused by RT and/or Ha increased GPC-4 and decreased GPLD1 in the T2DM rats, but these positive changes were more effective in the combination of RT + Ha. A strong correlation was also observed between GPC-4 and GPLD1 with blood glucose and insulin. The increase in serum GPC-4 levels was probably due to the direct effect of RT + Ha, and the improvement of glycemic indexes after RT and Ha. The double effect of RT + Ha can be a regulatory mechanism for GPC-4 and its related factors in controlling T2DM complications.


Predicting breast cancer risk in a racially diverse, community-based sample of potentially high-risk women.
Identifying women with high risk of breast cancer is necessary to study high-risk experiences and deliver risk-management care. Risk prediction models estimate individuals' lifetime risk but have rarely been applied in community-based settings among women not yet receiving specialized care. Therefore, we aimed: (1) to apply three breast cancer risk prediction models (i.e., Gail, Claus, and IBIS) to a racially diverse, community-based sample of women, and (2) to assess risk prediction estimates using survey data. An online survey was administered to women who were determined by a screening instrument to have potentially high risk for breast cancer. Risk prediction models were applied using their self-reported family and medical history information. Inclusion in the high-risk subsample required ≥20% lifetime risk per ≥1 model. Descriptive statistics were used to compare the proportions of women identified as high risk by each model. N = 1053 women were initially eligible and completed the survey. All women, except one, self-reported the information necessary to run at least one model; 90% had sufficient information for >1 model. The high-risk subsample included 717 women, of which 75% were identified by one model only; 96% were identified by IBIS, 3% by Claus, <1% by Gail. In the high-risk subsample, 20% were identified by two models and 3% by all three models. Assessing breast cancer risk using self-reported data in a community-based sample was feasible. Different models identify substantially different groups of women who may be at high risk for breast cancer; use of multiple models may be beneficial for research and clinical care.


METHODS FOR ESTIMATION OF BLOOD GLUCOSE : A COMPARATIVE EVALUATION.
Glucose in blood is the most frequent analyzed parameter in a clinical chemistry laboratory. In Armed Forces Laboratories, copper reduction method (Modified Folin Wu) is commonly used. Here we have compared this method as well as O-Toluidine and GOD-POD method with reference UV-Hexokinase method. Both Modified Folin Wu and O-Toluidine showed upward deviation with substantial imprecision (CV=4.9% - 3.5% and 6% - 5.8% respectively) and inaccuracy (Average deviation = 5.76% and 10.68% respectively). GOD-POD method was found linear (up to 500 mg/dl), with good precision (CV=0.7% to 1.4%) and accuracy (Average deviation= -0.97%). This method is simple, rapid, economical and sensitive, and can be adopted to a routine colorimeter.


A multi-institutional study of the Family Conference Objective Structured Clinical Exam: a reliable assessment of professional communication.
To test the value of a simulated Family Conference Objective Structured Clinical Exam (OSCE) for resident assessment purposes, we examined the generalizability and construct validity of its scores in a multi-institutional study. Thirty-four first-year (PG1) and 27 third-year (PG3) surgery residents (n = 61) from 6 training programs were tested. The OSCE consisted of 2 cases (End-of-Life [EOL] and Disclosure of Complications [DOC]). At each program, 2 clinicians and 2 standardized family members rated residents using case-specific tools. Performance was measured as the percentage of possible score obtained. We examined the generalizability of scores for each case separately. To assess construct validity, we compared PG1 with PG3 performance using repeated measures multivariate analysis of variance (MANOVA). The relative G-coefficient for EOL was .890. For DOC, the relative G-coefficient was .716. There were no significant performance differences between PG1 and PG3 residents. This OSCE provides reliable assessments suitable for formative evaluation of residents' interpersonal communication skills and professionalism.


Energy requirements, length of digestive tract compartments and body mass in six gerbilline rodents of the Negev Desert.
Energy requirements of an animal are size dependent and, in this study, the average daily metabolic rate (ADMR) of six Negev Desert gerbilline rodents, ranging in body mass (mb) from 10g to over 200g, scaled to mb0.57. Although gerbilline rodents are considered 'granivores', these rodents consume substantial amounts of green vegetation and the largest gerbil is a strict herbivore. We predicted that the lengths of the compartments of the digestive tract would scale allometrically to mb0.33 and that ADMR would scale allometrically to the lengths of the compartments to the exponent of 1.73. Using log-transformed data, the length of the colon scaled to mb0.50 (r2adj = 0.74; p= 0.02), of the caecum to mb0.45 (r2adj=0.80; p= 0.01) and of the small intestine to mb0.30 (r2adj=0.59; p < 0.05). Therefore, the exponents for the colon and caecum were higher than predicted and were close to the exponent for ADMR generated for the rodents. The absolute lengths of the colon (r2adj=0.68; p= 0.03; slope = 0.99) and of the caecum (r2adj=0.79; p= 0.01; slope = 1.19) were related significantly to ADMR, but of the small intestine was not (r2adj=0.04; p=0.33; slope = 0.85). The exponents implied that the relationships were isometric and not allometric as predicted and that the rates of increase of the lengths of the intestine compartments were at the same rate as the increase in ADMR. The lengths of the colon and caecum were highly correlated between each other (r2adj=0.98; p< 0.001; slope = 1.12) and explained most of the variation in ADMR. Green vegetation could be a nutritional bottleneck for rodents as it is bulky and, consequently, limits the dietary intake, and fermentation occurs in the caecum and colon, whereas seeds, which are compact and are digested in the small intestine, would limit intake to a much lesser degree. However, when the effect of body mass was eliminated by using residuals of the variables on body mass, only the length of the small intestine was significant (r2adj=0.86; p< 0.005; slope = -1.33) and was related negatively to ADMR. Therefore, when effects of body size were removed, most of the variation in ADMR was explained by the length of the small intestine and implied that the length of the small intestine increased with a decrease in ADMR. A higher energy expenditure was related to a shorter small intestine and, therefore, by implication, a higher concentration of metabolizable energy yield of the diet. We also questioned whether there are differences in the morphology of the digestive tract due to differences in dietary consumption. The digestive tracts of the gerbils were not diverse and could be characterized as structurally homogenous. All the gerbils had a uni-locular, hemi-glandular stomach and the differences in the digestive tract among species did not seem to be of functional importance, but rather were related to the taxon. However, some important morpho-functional characteristics of the digestive tract emerged that apply to the whole group.


Relationship between chest expansion and respiratory muscle strength in patients with primary fibromyalgia.
In this paper the assessment of the relationship between chest expansion with maximal inspiratory (MIP) and expiratory pressures (MEP) in primary fibromyalgia (FM) syndrome is discussed. Chest expansion (CE) measurements, spirometric values, and MIP and MEP values in 30 female patients with primary FM are compared with 29 healthy age-matched female controls. Patients with FM had lower CE, MEP and MIP values than controls. CE correlated significantly with MIP and MEP values. There was no significant difference between groups in spirometric values. Our results indicate that patients with FM have impaired respiratory muscle strength, and measurement of CE may be a useful clinical parameter. Despite its limitations CE may reflect respiratory muscle strength. It is worth following up these data in a wider and controlled series, with ancillary tests in addition to the MIP and MEP.


Gingivitis around the deciduous teeth of sheep.
Two-hundred and eight sheep from two farms were killed mostly in age-matched groups of 6 between the ages of 6 and 141 weeks. Sheep from one farm (W) had excessive tooth wear whilst sheep from the other (G) had little. The four deciduous incisor teeth and the third premolar from one side of the mandible of each sheep were examined by light microscopy. The inflammatory reaction in the gingiva around the sulcus and sulcular epithelial proliferation were subjectively assessed. Sheep from both farms initially showed a neutrophilic reaction. From approximately 25 to 100 weeks of age, sheep from farm G had a more extensive reaction than those from farm W involving neutrophils and mononuclear cells. The latter showed a more frequent tendency to spread on farm G than on farm W. The length of the sulcus was also more often greater on farm G. In contrast, the proliferation of the sulcular epithelium in both width and length was not greater on farm G. It is suggested that the severity of the gingivitis was arrested at a less severe stage on farm W than on farm G and that the pathogenesis of sulcular epithelial proliferation may different from that of gingival inflammation.


Genomic selection for white spot syndrome virus resistance in whiteleg shrimp boosts survival under an experimental challenge test.
White spot syndrome virus (WSSV) causes major worldwide losses in shrimp aquaculture. The development of resistant shrimp populations is an attractive option for management of the disease. However, heritability for WSSV resistance is generally low and genetic improvement by conventional selection has been slow. This study was designed to determine the power and accuracy of genomic selection to improve WSSV resistance in Litopenaeus vannamei. Shrimp were experimentally challenged with WSSV and resistance was evaluated as dead or alive (DOA) 23 days after infestation. All shrimp in the challenge test were genotyped for 18,643 single nucleotide polymorphisms. Breeding candidates (G0) were ranked on genomic breeding values for WSSV resistance. Two G1 populations were produced, one from G0 breeders with high and the other with low estimated breeding values. A third population was produced from "random" mating of parent stock. The average survival was 25% in the low, 38% in the random and 51% in the high-genomic breeding value groups. Genomic heritability for DOA (0.41 in G1) was high for this type of trait. The realised genetic gain and high heritability clearly demonstrates large potential for further genetic improvement of WSSV resistance in the evaluated L. vannamei population using genomic selection.


Corticosteroids for Blastomycosis-Induced Acute Respiratory Distress Syndrome: A Case Report and Literature Review.
We describe a case report of a patient with Blastomycosis-induced acute respiratory distress syndrome (ARDS) and severe hypoxemia requiring mechanical ventilation, prone positioning, and neuromuscular blockade whose clinical condition rapidly improved with the use of corticosteroids resulting in the patient being discharged home without the need for supplemental oxygen.


Comparative immunohistochemical investigation of markers for malignant histiocytes.
The presence of lysozyme, alpha 1-antitrypsin (AT), alpha 1-antichymotrypsin (ACT), and cytoplasmic receptors for peanut and soy bean agglutinin and for concanavalin A (PNA, SBA, and ConA, respectively) was investigated in formalin-fixed, paraffin-embedded material from 16 cases of malignant histiocytosis. The tumors in these cases did not show phenotypic characteristics of T or B cells. Lysozyme and AT especially were found less frequently in tumor cells from malignant histiocytosis than in normal histiocytes, whereas ACT and binding sites for the lectins were maintained during malignancy. Specimens from 44 per cent of the cases were positive for lysozyme, 56 per cent for AT, 82 per cent for ACT, 88 per cent for PNA receptors, 94 per cent for SBA receptors, and 100 per cent for ConA receptors. Tumor cells from B- and T-cell lymphomas were negative for these markers. Plasma cells, granulocytes, and fibroblasts sometimes bound ConA, but not PNA or SBA. The cases of malignant histiocytosis were subdivided into three groups on the basis of grade of differentiation. The tumor cells from the cases in group 1 showed the highest degree of differentiation, those from group 2 an intermediate degree, and those from group 3 the lowest degree. Mitotic activity was present mainly in groups 1 and 2. Lysozyme was present most frequently in groups 1 and 3 and in cases with the least mitotic activity. Expression of AT was decreased in groups 2 and 3. The presence of phagocytosis, which is not obligatory for the diagnosis, was always correlated with ACT staining. The presence of binding sites for these lectins can be considered a useful marker for malignant histiocytes.


Accuracy of the medication history at admission to hospital in Saudi Arabia.
Inaccurate medication history at admission to hospitals leads to preventable adverse drug events, which in turn increase mortality, morbidity, and health care costs. The objective of this study was to investigate the role of pharmacists in identifying discrepancies in medication histories at admission to a tertiary referral hospital in Saudi Arabia. We performed a prospective observational study in a 1200 bed tertiary hospital in Riyadh, Saudi Arabia. Patients were included if they were aged 16 years or older, were taking 5 or more medications, and were able to communicate or were accompanied by a caregiver who could communicate. Over 2 months in 2009, a pharmacist interviewed patients to ascertain all medications used prior to hospitalization, then all discrepancies were discussed with the admitting physician and unintended discrepancies were reported as errors. A pharmacist interviewed 60 patients who were taking 564 medications total. Of these patients, 65% were male, and their mean age was 62. Patients were taking an average of 9.4 medications. Twenty-two (37%) patients had at least one discrepancy, with the most common being omissions of medications (35%) and dosage errors (35%). The mean age for patients with discrepancies was 64.6 years, and without discrepancies, 60.8 years (P = 0.37). Inaccurate medication history at admission to a hospital was common in Saudi Arabia. This has the potential to cause harm to patients if it remains undetected. Pharmacists could potentially play a major role in obtaining this medication history at the time of hospital admission.


Correlation of aqueous solubility of salts of benzylamine with experimentally and theoretically derived parameters. A multivariate data analysis approach.
Twenty two salts of benzylamine and p-substituted benzoic acids were prepared and characterized. The p-substituent was varied with regard to electronic, hydrophobic, and steric effects as well as hydrogen bonding potential. A multivariate data analysis was used to describe the relationship between the aqueous solubility of the salts and experimentally determined physicochemical parameters and theoretically derived molecular descriptors. The model, based on all descriptors, gave R(2)=0.86 and Q(2)=0.72. The most significant descriptors exhibiting VIP (variance of importance) values above 1.0 were intrinsic dissolution rate, intrinsic solubility of the unionized acids (S(0)), Hansch's hydrophobic parameter, Charton's steric parameter and molecular weight (MW). Statistically good models for predicting solubility of a selected test set were obtained by using simple models consisting of a few descriptors only: (i) Charton, Hansch and MW (R(2)=0.73; Q(2)=0.70), and (ii) Charton and S(0) (R(2)=0.74; Q(2)=0.72).


Effects of Head and Neck Alignment and Pharyngeal Anatomy on Epiglottic Inversion During Swallowing in Dysphagic Patients.
The effects of head and neck alignment and pharyngeal anatomy on epiglottic inversion remain unclear. This study investigated the factors involved in epiglottic inversion, including head and neck alignment and pharyngeal anatomy, in patients with dysphagia. Patients with a chief complaint of dysphagia and who underwent videofluoroscopic swallowing study at our hospital from January to July 2022 were enrolled. They were divided into three groups based on the degree of epiglottic inversion as the complete-inversion (CI), partial-inversion (PI), and non-inversion group (NI) groups. Data were compared among the three groups; a total of 113 patients were analyzed. The median age was 72.0 (IQR: 62.0-76.0) years; 41 (36.3%) and 72 (63.7%) were women and men, respectively. There were in 45 (39.8%) patients in the CI, 39 (34.5%) in the PI, and 29 (25.7%) in the NI groups, respectively. Single-variable analysis revealed significant relation to epiglottic inversion of Food Intake LEVEL Scale score, penetration-aspiration score with 3-mL thin liquid bolus, epiglottic vallecula and pyriform sinus residue, hyoid position and displacement during swallowing, pharyngeal inlet angle (PIA), epiglottis to posterior pharyngeal wall distance, and body mass index. Logistic regression analysis with complete epiglottic inversion as the dependent variable revealed the X coordinate at maximum hyoid elevation position during swallowing and PIA as significant explanatory variables. These results suggest that epiglottic inversion is constrained in patients with dysphagia who have poor head and neck alignment or posture and a narrow pharyngeal cavity just before swallowing.


Intersex: four cases in one family.
Intersex presents a unique challenge to modern medicine. Generally, patients with ambiguous genitalia present in the neonatal period. Due to functional failure of the assigned gender role, some patients may be discovered later in life, as in the presented cases. The four patients, all members of the same family and aged 23, 15, 13 and 4 years, presented with ambiguous genitalia. The family history revealed parental consanguinity and one additional case of genital ambiguity. The eldest two patients had developed gynaecomastia during puberty. Examination of the genitalia revealed penoscrotal hypospadias and bifid scrotum in all the four. Gonads were palpable bilaterally in three of the patients, but in the fourth only one gonad was palpable. Buccal smear was negative for sex chromatin in all the cases. On abdominal ultrasound Müllerian structures were found in the two eldest patients. The karyotype in all four cases was determined as 46XY. Gonadal biopsies revealed immature testicular tissue and azoospermia, as sometimes seen in cryptorchidism. We conclude that these cases should be classified as dysgenetic male pseudohermaphrodites, a rare variety of ambiguous genitalia. In agreement with the patients and their parents, they were assigned the male gender and surgery was performed accordingly. We stress the need for active involvement of patient and parents in the process of gender assignment and awareness of hasty decision making.


Collaborative Innovation Strategy of Supply Chain in the Context of MCU Domestic Substitution : A Differential Game Analysis.
The domestic substitution of the IC (the Integrated Circuit) industry improves economic efficiency and is significant in ensuring national security, which has gradually become an essential strategy for countries worldwide. Based on the background of domestic substitution of integrated circuits, we select a typical component Micro Controller Unit) as the research object, construct a three-level supply chain game model under different scenarios in a dynamic architecture, and analyze the game problem of collaborative innovation of the MCU supply chain. We fully consider the impact of factors such as time, cost and the innovation and collaborative innovation efforts of various supply chain members on the level of domestic substitution. Moreover, we put forward a two-part pricing + cost-sharing contract to achieve supply chain coordination. We found that: (1) Collaborative innovation of the supply chain in the centralized decision-making scenario achieves the highest level, followed by the cost-sharing scenario; (2) The two-part pricing + cost-sharing contract can help achieve supply chain coordination; (3) The trend of the MCU domestic substitution level with manufacturing cost is U-shaped, which means the increase of manufacturing cost may have a positive impact on the process of domestic substitution.


Mining featured biomarkers associated with prostatic carcinoma based on bioinformatics.
To analyze the differentially expressed genes and identify featured biomarkers from prostatic carcinoma. The software "Significance Analysis of Microarray" (SAM) was used to identify the differentially coexpressed genes (DCGs). The DCGs existed in two datasets were analyzed by GO (Gene Ontology) functional annotation. A total of 389 DCGs were obtained. By GO analysis, we found these DCGs were closely related with the acinus development, TGF-β receptor and signal transduction pathways. Furthermore, five featured biomarkers were discovered by interaction analysis. These important signal pathways and oncogenes may provide potential therapeutic targets for prostatic carcinoma.


Effect of carrier composition on 2,6-dimethylaniline degradation in aqueous solution by fluidized-bed Fenton process.
The fluidized-bed Fenton process is an alternative process that decreases iron sludge from the Fenton reaction by using carriers to crystallize iron on to the surface of the carrier. In this study, the target compound is 2,6-dimethylaniline, which is a carcinogen and difficult to degrade. This study examined the effect of different carriers on the degradation of 2,6-dimethylaniline by a fluidized-bed Fenton process. The six carriers were alumina dioxide (Al2O3), silica dioxide (SiO2), and black, white, brown and coloured gravels. The results revealed that differences in the composition of elements and the structures of each carrier have different effects on the oxidation of 2,6-dimethylaniline. The carriers containing Ca were not suitable for use in the fluidized-bed Fenton process. In contrast, Al2O3 and SiO2 were more efficient at removing 2,6-dimethylaniline, and the pH value was almost stable. Moreover, 2,6-dimethylanililne removal efficiency of Al2O3 was higher compared with the other carriers. Therefore, in this study, Al2O3 was an optimum carrier for the oxidation of 2,6-dimethylaniline.


Low-grade mucosa-associated lymphoma of the breast: radiological-pathological correlation.
Primary breast lymphoma generally is a rare disease. We present a case of a low-grade mucosa-associated (MALT) lymphoma of the breast in a 32-year-old woman, a distinctive type of localized non-Hodgkin's lymphoma (NHL), which is very seldom located in the breast. We performed differential diagnosis and radiological-pathological correlation with regard to typical microscopic criteria and clinical relevance that apply for that special entity.


Study on the synthesis and PKA-I binding activities of 5-alkynyl tubercidin analogues.
5-alkynyl tubercidin analogues were synthesized and their biological activities were evaluated. It was found that protein kinase A could be activated by 5-alkynyl tubercidin (9a) and cAMP-binding ability to PKA-I was selectively inhibited by it. Molecular modeling showed that the interaction of 9a and PKA-I was associated with the existence of hydrophobic alkynyl group. During the synthesis of tubercidin analogues, a pair of 2'-carbonyl participating abnormal coupling products (11a, 11b) was obtained, the structure was identified by X-ray crystalline diffraction.


Errors in longitudinal measurements of bone mineral: effect of source strength in single and dual photon absorptiometry.
The effect of changing strength during the useful life of a radiation source was evaluated in studies performed on four dual photon (DPA) and two single photon (SPA) bone absorptiometry instruments. Two DPA units and one SPA unit did not show any systematic dependence of measured bone mineral content or bone mineral areal density (BMD) on source activity when evaluated over an entire source life. One DPA and one SPA instrument, however, showed significant time trends associated with source activity. The fourth DPA instrument had a significant linear decrease in BMD over a source life in the automatic mode but performed better in the manual mode.


Gene therapy to target dendritic cells from blood to lymph nodes.
Peripheral lymph nodes (PLN) are strategic microenvironments where antigen-presenting dendritic cells (DC), loaded with environmental antigens, and naive lymphocytes meet to initiate immune responses. The unique capacity of DC to induce primary immune responses has led to their use in clinical medicine; however, delivering DC to lymph nodes is problematic. Intravenously injected DC cannot access to PLN, while DC injected into tissue migrate inefficiently through lymphatics to PLN. We achieved DC targeting to T-cell areas of PLN by endowing DC with a novel receptor for peripheral node addressin (PNAd), an adhesion molecule present on the lymph node venular endothelium. This novel receptor is a chimeric E/L-selectin (ELS) that, we have previously shown, binds to PNAd. DC were genetically modified by retroviral transduction to express ELS. ELS expression was targeted to tips of microvilli, and mediated rolling of DC on PNAd both in vivo and in vitro. Such genetically engineered DC could extravasate directly from blood through the lymph node endothelium as opposed to nontransduced DC. This study provides evidence that the trafficking of DC can be modified using gene transfer technologies. More efficient delivery of DC to PLN should assist the development of improved vaccination strategies.


Hernandulcin: an intensely sweet compound discovered by review of ancient literature.
Ancient Mexican botanical literature was systematically searched for new plant sources of intensely sweet substances. Lippia dulcis Trev., a sweet plant, emerged as a candidate for fractionation studies, and hernandulcin, a sesquiterpene, was isolated and judged by a human taste panel as more than 1000 times sweeter than sucrose. The structure of the sesquiterpene was determined spectroscopically and confirmed by chemical synthesis. Hernandulcin was nontoxic when administered orally to mice, and it did not induce bacterial mutation.


Childhood adversity, parental stress, and depression of negligent mothers.
The objective of this study was to identify major childhood events that were experienced by negligent mothers matched with non-negligent mothers as well as to define the existing link between those events, depression of the mother and parental stress. The sample was composed of 80 French-speaking Canadian families. The measures used were the Parental Stress Index (Abidin, 1983), the Psycho-Social Interview (Ethier et al., 1989) and the Beck Depression Inventory (1961). The results have shown an extreme level of parental stress and a high level a depression for negligent mothers. The negligent mothers had a history of placements, violence and sexual abuse, but they did not differ from control mothers for parental breakups and nonavailability. We have also shown a significant link between childhood events, depression, and parental stress even more so for the control group than for the negligence group. The results are discussed in the perspective of attachment theory.


Germline-restricted chromosome shows remarkable variation in size among closely related passerine species.
Passerine birds have a supernumerary chromosome in their germ cells called the germline-restricted chromosome (GRC). The GRC was first discovered more than two decades ago in zebra finch but recent studies have suggested that it is likely present in all passerines, the most species rich avian order, encompassing more than half of all modern bird species. Despite its wide taxonomic distribution, studies on this chromosome are still scarce and limited to a few species. Here, we cytogenetically analyzed the GRC in five closely related estrildid finch species of the genus Lonchura. We show that the GRC varies enormously in size, ranging from a tiny micro-chromosome to one of the largest macro-chromosomes in the cell, not only among recently diverged species but also within species and sometimes even between germ cells of a single individual. In Lonchura atricapilla, we also observed variation in GRC copy number among male germ cells of a single individual. Finally, our analysis of hybrids between two Lonchura species with noticeably different GRC size directly supported maternal inheritance of the GRC. Our results reveal the extraordinarily dynamic nature of the GRC, which might be caused by frequent gains and losses of sequences on this chromosome leading to substantial differences in genetic composition of the GRC between and even within species. Such differences might theoretically contribute to reproductive isolation between species and thus accelerate the speciation rate of passerine birds compared to other bird lineages.


The Forever War: understanding, science fiction, and thought experiments.
The aim of this paper is to show that scientific thought experiments and works of science fiction are highly suitable tools for facilitating and increasing understanding of science. After comparing one of Einstein's most famous thought experiments with the science fiction novel "The Forever War", I shall argue that both proceed similarly in making some of the more outlandish consequences of special relativity theory intelligible. However, as I will also point out, understanding in thought experiments and understanding in science fiction differ in one important respect: While the former aim at what I shall call "physical understanding", science fiction novels typically have "existential understanding" as their target.


Effect of a plano-convex posterior chamber lens on capsular opacification from Elschnig pearl formation.
Opacification of the posterior capsule occurs most commonly from Elschnig pearl migration or fibrosis. The physical contact of a posterior chamber lens, particularly one with a reverse optic, has been postulated to decrease the rate of capsular opacification by creating a barrier to Elschnig pearl migration. This randomized prospective clinical study comparing the 3M style 34S convex-plano optic and style 34R plano-convex (reverse) optic posterior chamber lens demonstrated a statistically significant reduction in capsular opacification by Elschnig pearls at one year in the reverse optic lenses (18.2% versus 7.6%, P = .03). No statistically significant difference in capsular fibrosis rates was noted (2.5% versus 4.5%, P = .48). The reverse optic implant also demonstrated greater iris to implant optic clearance.


Scoping review: Diagnostic reasoning as a component of clinical reasoning in the U.S. primary care nurse practitioner education.
Diagnostic Reasoning (DR) is an essential competency requiring mastery for safe, independent Nurse Practitioner (NP) practice, but little is known about DR content included in NP education programs. The aims of this study were to identify whether and how the concept of DR is addressed in NP education. We conducted a scoping review on DR-related content and teaching innovations in U.S. primary care NP education programs, with implications for NP education programs worldwide. Concepts and principles with global applicability include: conducting focused and hypothesis-directed histories and exams, generating the problem statement, formulating the differential diagnosis, appropriate and relevant diagnostic testing, determining the working diagnosis and developing evidence-based, patient-centred management plans. N = 1115 articles retrieved from Medline, Embase, PsycINFO, and CINAHL for the period 2005-2021. Forty-one scholarly articles met inclusion/exclusion criteria. Data were extracted, synthesized and grouped by theoretical frameworks, content included, educational interventions and assessment measures. Most articles provided descriptions of approaches for teaching NP clinical or diagnostic reasoning. Ten papers directly referenced the current science and theory of DR. The US NP education literature addressing DR is limited and demonstrates a lack of shared conceptualizations of DR. Whilst numerous components of DR are identifiable in the literature, a robust teaching/learning scholarship for DR has not yet been established in the US NP education literature. Whilst primary care NP education programs are beginning to incorporate DR education into their curricula, little research has been conducted to demonstrate the effectiveness of educational outcomes. Increased integration of DR content into NP education is needed, including increased educational research on teaching DR competencies. No patient or public contribution was included in this review, as the public is generally not familiar with DR or its teaching approaches.


Correction of 'Culture moderates changes in linguistic selfpresentation and detail provision when deceiving others'.
[This corrects the article DOI: 10.1098/rsos.170128.].


Results of radiotherapy in oropharyngeal carcinomas.
To present the results of radiotherapy treatment in patients with oropharyngeal carcinomas. Retrospective study of a cohort of 359 patients treated with radiotherapy, including chemo- and bio-radiotherapy, during the period 2000-2019. Information on human papillomavirus (HPV) status was available for 202 patients, of whom 26.2% were HPV-positive. Five-year local recurrence-free survival was 73.5% (95% CI: 68.8%-78.2%). The variables that were related to local disease control in a multivariate study were the local tumor extension category and the HPV status. Five-year local recurrence-free survival for patients with cT1 tumors was 90.0%, for cT2 88.0%, for cT3 70.6%, and for cT4 42.3%. Five-year local recurrence-free survival for HPV-negative tumors was 67.2% and for HPV-positive tumors 93.3%. Five-year specific-disease survival was 64.4% (95% CI: 59.1%-69.7%). Variables that were related to specific survival in a multivariate study were the patient's general condition, local and regional extent of the tumor, and HPV status. Five-year local recurrence-free survival of patients with oropharyngeal carcinomas treated with radiotherapy was 73.5%. Variables that were related to local control were local tumor extension and HPV status.


In silico analysis of ubiquitin/ubiquitin-like modifiers and their conjugating enzymes in Entamoeba species.
Covalent modification of proteins by ubiquitin (Ub) and ubiquitin-like modifiers (Ubls) regulates many cellular functions in eukaryotes. These modifications are likely to be associated with pathogenesis, growth, and development of many protozoan parasites but molecular details about this pathway are unavailable for most protozoa. This study presents an analysis of the Ub pathway in three members of the Entamoeba species. Using bioinformatics tools we have identified all Ub and Ubl genes along with their corresponding activating, conjugating, and ligating enzymes (E1, E2s, and E3s) in three Entamoeba species, Entamoeba histolytica, Entamoeba dispar, and Entamoeba invadens. Phylogenetic trees were established for the identified E2s and RING finger E3s using maximum-likelihood method to infer the relationship among these proteins. In silico co-domain analysis of RING finger E3s implicates these proteins in a variety of functions. Several known and putative regulatory motifs were identified in the upstream regions of RING finger domain containing E3 genes. All E2 and E3 genes were analyzed in genomic context in E. histolytica and E. dispar. Most E2s and E3s were in syntenic positions in the two genomes. Association of these genes with transposable elements (TEs) was compared between E. histolytica and E. dispar. A closer association was found between RING finger E3s with TEs in E. histolytica. In summary, our analyses suggests that the complexity of the Ub pathway in Entamoeba species is close to that observed in higher eukaryotes. This study provides important data for further understanding the role of Ub pathway in the biology of these organisms.


Si-Ni-SAN ameliorates obesity through AKT/AMPK/HSL pathway-mediated lipolysis: Network pharmacology and experimental validation.
Si-Ni-San (SNS) is a famous Chinese herbal formula used in China for thousands of years. It has clinical effects on a variety of lipid metabolism disorders, but the ameliorating effects of SNS on obesity and underlying mechanisms remained poorly elucidated. This study aims to explore the therapeutic effect and mechanism of SNS on obesity from multiple perspectives in vitro and in vivo. The high-fat diet (HFD)-induced obesity mouse model was established to evaluate the effect of SNS. Then network pharmacologic methods were performed to predict underlying mechanisms, and the core pathways were verified in animal and cell studies. Our results demonstrated that SNS significantly reduced body weight, body fat content, white adipose tissue (WAT) expansion in obese mice, and lipid accumulation in primary mouse embryonic fibroblasts (MEFs) cells. Network pharmacologic analysis identified 66 potential therapeutic targets, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of these genes revealed that the most important signaling pathway includes AMP-activated protein kinase (AMPK) signaling pathway, regulation of lipolysis in adipocytes, lipid and atherosclerosis. Western blot assay confirmed that SNS activated hormone-sensitive triglyceride lipase (HSL) and adipose triglyceride lipase (ATGL) activity and promoted lipolysis through AMPK signaling pathway. The results confirmed that SNS improves lipid accumulation through AKT/AMPK/HSL axis mediated lipolysis, which opens a new option for clinical treatment of obesity and associated complications.


Mortality trends for 23,505 Medicare patients hospitalized with heart failure in Northeast Ohio, 1991 to 1997.
Clinical trials have identified major therapeutic advances for heart failure (HF), but the degree to which survival has improved among the general population of patients with HF is not known. This study analyzed mortality trends from 1991 to 1997 for 23,505 Medicare patients hospitalized with a first admission for HF at 29 Northeast Ohio hospitals. We linked databases from the Cleveland Health Quality Choice (CHQC) program and Medicare to allow identification of first admissions for HF and death date. We adjusted for changes in admission illness severity using chart data from CHQC (eg, vital signs, do-not-resuscitate status, comorbid conditions, and laboratory results). Logistic regression was used to analyze trends in risk-adjusted mortality. At baseline (1991), crude inhospital, 30-day and 1-year mortality rates were 6.4%, 8.6% and 36.5%, respectively. Between 1991 and 1997, mean length of stay declined steeply from 9.2 days to 6.6 days (P <.001 for trend). Risk-adjusted inhospital mortality also declined markedly (absolute-decline -3.7%, 95% CI -4.3 to -3.0), a 52.8% relative decrease. However, the decline in 30-day mortality was only -1.4% (95% CI -2.5 to -0.1, P <.05), a 15.3% relative decrease. The 1-year mortality declined -5.3% (95% CI -3.2 to -7.4, P <.001), a 14.6% relative decrease. Long-term mortality for patients hospitalized with HF improved from 1991 to 1997, although mortality remains very high. The 30-day mortality declined far less than inhospital mortality, indicating that mortality shortly after discharge increased. This raises concerns that the marked reduction in length of stay is causing adverse consequences.


Long distance transport of irradiated male Glossina palpalis gambiensis pupae and its impact on sterile male yield.
The application of the sterile insect technique (SIT) requires mass-production of sterile males of good biological quality. The size of the project area will in most cases determine whether it is more cost effective to produce the sterile flies locally (and invest in a mass-rearing facility) or import the sterile flies from a mass-rearing facility that is located in another country. This study aimed at assessing the effect of long distance transport of sterile male Glossina palpalis gambiensis pupae on adult male fly yield. The male pupae were produced at the Centre International de Recherche-Développement sur l'Elevage en zone Subhumide (CIRDES), Bobo-Dioulasso, Burkina Faso, and shipped with a commercial courier service in insulated transport boxes at a temperature of ±10°C to Senegal (±36 h of transport). Upon arrival in the insectary in Dakar, the pupae were transferred to an emergence room and the flies monitored for 3-6 days. The results showed that the used system of isothermal boxes that contained phase change material packs (S8) managed to keep the temperature at around 10°C which prevented male fly emergence during transport. The emergence rate was significantly higher for pupae from batch 2 (chilled at 4°C for one day in the source insectary before transport) than those from batch 1 (chilled at 4°C for two days in the source insectary before transport) i.e. an average (±sd) of 76.1 ± 13.2% and 72.2 ± 14.3%, respectively with a small proportion emerging during transport (0.7 ± 1.7% and 0.9 ± 2.9%, respectively). Among the emerged flies, the percentage with deformed (not fully expanded) wings was significantly higher for flies from batch 1 (12.0 ± 6.3%) than from batch 2 (10.7 ± 7.5%). The amount of sterile males available for release as a proportion of the total pupae shipped was 65.8 ± 13.3% and 61.7 ± 14.7% for batch 1 and 2 pupae, respectively. The results also showed that the temperature inside the parcel must be controlled around 10°C with a maximal deviation of 3°C to maximize the male yield.


Salivary changes associated with seasickness.
Salivary composition and flow rate were measured in 13 healthy male volunteers exposed to a real seasickness situation. The flow rates of whole unstimulated and stimulated saliva were significantly reduced at sea in about 80% of the subjects. Salivary flow rate was negatively correlated with seasickness severity. These results contrast with the classic concept of increased salivation during seasickness. At sea, the potassium concentration of both unstimulated and stimulated saliva was significantly reduced, while sodium concentration was consistently elevated. The sodium and protein concentrations were positively correlated with seasickness severity. Thus, objective measurements of salivary flow rate and composition may be recommended for evaluation of the seasickness syndrome.


Impact of axial length on visual outcomes and complications in phacoemulsification surgery: a multicenter database study.
To analyze the impact of axial length (AL) on the visual outcome and rate of perioperative complications in phacoemulsification surgery. Retrospective clinical database study. Cataract surgery data of 217,556 eyes was extracted from the electronic medical records of 8 ophthalmic centers in the United Kingdom from July 2003 to March 2015. A total of 88,774 eyes without ocular co-pathologies were grouped eyes according to AL (mm): short AL (< 22), average AL (22-26; reference group), and long AL (> 26). We analyzed visual acuity (VA) outcomes at 4 weeks, 4-12 weeks, and 12-24 weeks postoperatively, as well as the incidence of posterior capsular rupture (PCR), torn iris (TI), cystoid macular edema (CME), and retinal detachment (RD). Mean pre-operative VA (logMAR) was the worst in eyes with long AL compared to average and short AL eyes (VA 0.59 vs. 0.58 and 0.56; p < 0.001). However, post-operative VA at 4-12 weeks was slightly better in the long AL group (0.14 in short and average AL; 0.12 in long AL, p < 0.001). We observed an increased odds of TI in the short AL group (OR 2.09, 95% CI 1.60-2.75). There was increased risk of RD in long AL eyes (p < 0.001). However, PCR and CME rates were not different. In the absence of any coexisting ocular pathology, AL alone did not have an impact on VA improvement or the risk of encountering PCR or CME. The risk of TI was greater in the short AL group, and the risk of RD was higher in the long AL group.


The first skull and other new discoveries of Australopithecus afarensis at Hadar, Ethiopia.
The Hadar Formation in Ethiopia is a prolific source of Pliocene Hominidae attributed to the species Australopithecus afarensis. Since 1990, three seasons of field work have contributed 53 new specimens to the hominid inventory from Hadar, including the first fairly complete adult skull. Ranging from 3.0 to 3.4 million years in age (Fig. 1), the new specimens bear on key debates in hominid palaeontology, including the taxonomic implications of sample variation and the reconstruction of locomotor behaviour. They confirm the taxonomic unity of A. afarensis and constitute the largest body of evidence for about 0.9 million years of stasis in the earliest known hominid species.


rDNA units are highly polymorphic in Scutellospora castanea (glomales, zygomycetes).
The ribosomal DNA (rDNA) units in the glomalean zygomycete fungus Scutellospora castanea were analyzed. Dot-blot assays allowed an estimation of 75 copies per genome. After constructing a genomic library in a phage lambdaEMBL3 vector, 13 rDNA clones were screened and explored. PCR experiments confirmed their nature and allowed homologous probes to be obtained. Restriction-fragment length polymorphism (RFLP) analysis and hybridizations with 18 s and 25 s probes allowed their grouping into nine families. The 18 s gene from these 13 clones was partially sequenced. The resulting 550 bases sequences were analyzed, and a phylogenetic tree was inferred. This revealed that two clones contain one highly divergent rDNA family (rUSc1) by comparison with other known 18 s sequences from the database. A phylogenetic tree was constructed with the entire 18 s sequences of rUSc1, rUSc3 and those of seven species representative of the glomalean fungi, Glomus, Entrophospora, Acaulospora, Scutellospora and Gigaspora. This tree confirmed that the rUSc1 sequence is the neighbor of 18 s sequences from Glomus (Glomineae), while rUSc3 remained in the group of the Gigaspora and Scutellospora (Gigasporineae). A specific primer, rUSc1-1, was generated from the ITS region of rUSc1, and used for PCR amplification from single spores, depicting the presence of rUSc1 in the genome of S. castanea at a lower frequency than other units.


The distended neonate.
A prospective study, followed by a retrospective audit, was made of the radiographs and clinical features of 225 consecutive neonates with abdominal distension presenting during a period of 4 years. More than one major cause for the distension was found in a third of cases. Excluding cases of ano-rectal atresia, diagnostic difficulties were encountered in 31% of cases and, occasionally, the diagnosis was revised several times as investigations proceeded. Neuhauser's sign of 'bubbly' meconium is unreliable, being found in cases of meconium ileus, ileal atresia, Hirschsprung's disease and necrotising enterocolitis. Concomitant small-bowel atresia should be suspected in all cases of meconium ileus; intestinal malrotation should be considered in association with duodenal and intestinal atresias. In the absence of an obvious anatomical defect, it is difficult to differentiate between the various causes of functional obstruction by radiological means alone and all such infants should be referred to a specialised centre for intensive investigation and treatment. Very often, the skills of a neonatologist, paediatric surgeon and, especially, an experienced pathologist will be required in addition to those of the radiologist.


Protein patterns obtained from support-bound gels by combining the images at different stages of destaining.
A more informative method for the visualization of proteins on thin-layer gels, based on combining the images of the gel at different stages of destaining, is presented. It is useful whenever important information seems to be lost after prolonged destaining. The method, which makes it unnecessary to run different loads in different channels, has been developed utilizing isoelectric focusing on polyester film-bound agarose gels. The strongly destained gel is superimposed on a negative image of the same gel made at an earlier phase of destaining, thus showing white spots on a gray background for minor components and dark bands in a white field surrounded by the grey background for the abundant ones. In general, the method may be applied to gel images obtained by different staining procedures.


Synthesis and pharmacological evaluation of several ring-contracted amantadine analogs.
The synthesis of several (3-noradamantyl)amines, [(3-noradamantyl)methyl]amines, (3,7-dimethyl-1-bisnoradamantyl)amines, and [(3,7-dimethyl-1-bisnoradamantyl)methyl]amines is reported. They were evaluated against a wide range of viruses and one of them inhibited the cytopathicity of influenza A virus at a concentration similar to that of amantadine. Several of the new polycyclic amines show an interesting activity as NMDA receptor antagonists. A rimantadine analogue displayed significant trypanocidal activity. Moreover, to further characterize the pharmacology of these compounds, their effects on dopamine uptake were also assessed.


Flexible electrical stimulation device with Chitosan-Vaseline® dressing accelerates wound healing in diabetes.
The healing process of diabetic wounds is typically disordered and prolonged and requires both angiogenesis and epithelialization. Disruptions of the endogenous electric fields (EFs) may lead to disordered cell migration. Electrical stimulation (ES) that mimics endogenous EFs is a promising method in treating diabetic wounds; however, a microenvironment that facilitates cell migration and a convenient means that can be used to apply ES are also required. Chitosan-Vaseline® gauze (CVG) has been identified to facilitate wound healing; it also promotes moisture retention and immune regulation and has antibacterial activity. For this study, we created a wound dressing using CVG together with a flexible ES device and further evaluated its potential as a treatment for diabetic wounds. We found that high voltage monophasic pulsed current (HVMPC) promoted healing of diabetic wounds in vivo. In studies carried out in vitro, we found that HVMPC promoted the proliferation and migration of human umbilical vein endothelial cells (HUVECs) by activating PI3K/Akt and ERK1/2 signaling. Overall, we determined that the flexible ES-chitosan dressing may promoted healing of diabetic wounds by accelerating angiogenesis, enhancing epithelialization, and inhibiting scar formation. These findings provide support for the ongoing development of this multidisciplinary product for the care and treatment of diabetic wounds.


Adult-onset Still's disease complicated by macrophage activation syndrome.
Young patients with persistent rash and fevers despite antibiotic treatment should be evaluated for non-infectious etiologies. In our patient's case, these findings led to a diagnosis of MAS, which ultimately affected how she was managed. Adult-onset Still's disease (AOSD) is a rare, often difficult to diagnose autoimmune disease that typically presents as a rash, unresolving fevers and joint pains capable of mimicking a number of autoimmune diseases. Here, we present the case of a young postpartum woman whose clinical presentation, which included a pruritic maculopapular rash that evolved to include a flagellate component, and serological studies, chief among them cytopenias and a Ferritin >15,000 nm/mL) allowed us to make an early diagnosis of AOSD complicated by macrophage activation syndrome. We discuss the treatment for AOSD complicated by MAS with Hydrocortisone and Anakinra, the final discharge regimen prescribed for our patient, and report on her state 3 months post-hospitalization, which was favorable. Our case is unique because we ultimately believe that pregnancy itself triggered her ASOD, because of how the quality of the flagellate component of her rash allowed us to narrow the differential diagnosis, and because of how the significant cytopenias and significant liver dysfunction alerted us to the possibility of MAS.


Effect of sodium butyrate in combination with prostaglandin E1 and inhibitors of cyclic nucleotide phosphodiesterase on human amelanotic melanoma cells in culture.
Sodium butyrate and cyclic AMP-stimulating agents (prostaglandin E1, papaverine, theophylline, and RO20-1724) caused reductions in the cell number (primarily due to reduction in cell division) when added individually to human melanoma cells in culture. However, the combination of sodium butyrate with one of the cyclic AMP-stimulating agents produced a marked reduction in cell number (primarily due to cell death).