Molecular form of human lymphocyte membrane-bound acetylcholinesterase.
The membrane-bound acetylcholinesterase (AchE) from human peripheral blood lymphocyte gives only one symmetrical peak on sucrose density gradient centrifugation in the presence of Triton X-100 detergent, with the calculated sedimentation coefficient of 6.5 S. However, this dimeric form of AchE was converted to a monomeric 3.8 S form when treated with 2-mercaptoethanol and iodoacetic acid. The results are consistent with studies which have shown by sodium dodecyl sulfate gel electrophoresis that the enzyme is built up of two identical monomers inter-linked by disulfide bond(s). Under reducing conditions, revealed a single species of 70,000 molecular weight, whereas under non-reducing conditions, another species of 140,000 molecular weight of the AchE was found. Polyacrylamide gel electrophoresis indicated a single band with AchE activity in the presence of Triton X-100. In contrast, in the absence of the same detergent multiple band pattern could be observed. These results suggest that membrane-bound AchE enzyme is present in homogenous dimeric form on human lymphocyte membrane.


Applying the behavioral economics principle of unit price to DRO schedule thinning.
Within the context of behavioral economics, the ratio of response requirements to reinforcer magnitude is called unit price. In this investigation, we yoked increases in reinforcer magnitude with increases in intervals of differential reinforcement of other behavior (DRO) to thin DRO intervals to a terminal value.


Otolaryngologic surgery in children with trisomy 18 and 13.
Trisomy 18 and 13 are the most common autosomal trisomy disorders after Down syndrome. Given the high mortality rate (5-10% one-year survival), trisomy 18 and 13 were historically characterized as uniformly lethal and palliation was the predominant management approach. Management strategy has shifted with recognition that through medical and surgical intervention, children with trisomy 18 and 13 can achieve developmental milestones, live meaningful lives, and exhibit long-term survival. Otolaryngologic surgery in children with trisomy 18 and 13 has not been described. The objective of this article is to describe the role of the otolaryngologist in the management of children with trisomy 18 and 13. Retrospective cohort analysis of the surgery registry for the Support Organization for Trisomy 18, 13 and Related Disorders for otolaryngologic surgeries reported from 1988 through June 1, 2014. In the database of approximately 1349 children, 1380 procedures were reported, 231 (17%) of which were otolaryngologic. The most common otolaryngologic procedures were tympanostomy tube placement (57/231, 25%), cleft lip repair (40/231, 17%), tracheostomy (38/231, 16.5%), tonsillectomy and/or adenoidectomy (37/231, 16%), and cleft palate repair (30/231, 13%). Of the ten most common procedures reported, four were otolaryngologic. Seventeen percent of procedures performed in children with trisomy 18 and 13 were otolaryngologic, highlighting the significant role of the otolaryngologist in the treatment of these patients. Surgical intervention may be considered as part of a balanced approach to patient care.


Clinical Sensitivity of Severe Acute Respiratory Syndrome Coronavirus 2 Nucleic Acid Amplification Tests for Diagnosing Coronavirus Disease 2019.
Utilizing 34 348 severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) nucleic acid amplification test (NAAT) results from 2 health systems, we estimated the clinical sensitivity of a single SARS-CoV-2 NAAT. We found that SARS-CoV-2 NAAT has 82%-97% sensitivity for diagnosing coronavirus disease 2019 among symptomatic patients.


Balancing the risk and benefits of low-dose aspirin in clinical practice.
Antiplatelet agents are widely used in primary and secondary prevention of cardiovascular events. The scientific evidence has provided strong support for the benefits of aspirin in decreasing the risk of cardiovascular events in a wide range of pathologies. The relatively rare occurrence of major bleeding complications should not be underestimated, mainly due to its high morbi-mortality. The assessment of both gastrointestinal risk and cardiovascular benefits of low-dose aspirin for any individual patient may be difficult in clinical practice. In this review, we summarize the evidence supporting the efficacy of aspirin and the risks of side effects due to hemorrhagic complications. This article proposes a unifying framework for application to help the clinician in the decision making process of individuals who have different risk of cardiovascular and bleeding events with different examples. Finally, new developments in the field directed towards individualized risk assessment strategies are described.


VBP15, a novel dissociative steroid compound, reduces NFκB-induced expression of inflammatory cytokines in vitro and symptoms of murine trinitrobenzene sulfonic acid-induced colitis.
The goal of this study was to assess the capacity of VBP15, a dissociative steroidal compound, to reduce pro-inflammatory cytokine expression in vitro, to reduce symptoms of colitis in the trinitrobenzene sulfonic acid-induced murine model, and to assess the effect of VBP15 on growth stunting in juvenile mice. In vitro studies were performed in primary human intestinal epithelial cells. Colitis was induced in mice by administering trinitrobenzene sulfonic acid. Growth stunting studies were performed in wild type outbred mice. Cells were treated with VBP15 or prednisolone (10 μM) for 24 h. Mice were subjected to 3 days of VBP15 (30 mg/kg) or prednisolone (30 mg/kg) in the colitis study. In the growth stunting study, mice were subjected to VBP15 (10, 30, 45 mg/kg) or prednisolone (10 mg/kg) for 5 weeks. Cytokines were measured by PCR and via Luminex. Colitis symptoms were evaluated by assessing weight loss, intestinal blood, and stool consistency. Growth stunting was assessed using an electronic caliper. VBP15 significantly reduced the in vitro production of CCL5 (p < 0.001) IL-6 (p < 0.001), IL-8 (p < 0.05) and reduced colitis symptoms (p < 0.05). VBP15 caused less growth stunting than prednisolone (p < 0.001) in juvenile mice. VBP15 may reduce symptoms of IBD, while decreasing or avoiding detrimental side effects.


[Characteristics of clinical manifestations of closed abdominal injuries in combined cranio-abdominal trauma].
The analysis of the results of treatment of 818 sufferers with severe craniocerebral trauma was carried out. Among the patients, 102 had associated injuries to the abdominal organs. The difficulties of timely diagnosis were related to atypical manifestation of intraabdominal complications, insufficient pronouncement of clinical symptoms; therefore, the special methods of investigation--roentgenologic, instrumental, the use of liquid-crystal colour thermography acquire special value. The lethality was 37.2%.


Enhanced mechanism of calcium towards uranium incorporation and stability in magnetite during electromineralization.
Doping uranium into a room-temperature stable Fe3O4 lattice structure effectively reduces its migration. However, the synergistic or competitive effects of coexisting ions in an aqueous solution directly affect the uranium mineralization efficiency and the structural stability of uranium-bearing Fe3O4. The effects of calcium, carbonate, and phosphate on uranium electromineralization were investigated via batch experiments and theoretical calculations. Calcium incorporated into the Fe3O4 lattice increased the level and stability of doped uranium in Fe3O4. Uranium and calcium occupied the octahedral and tetrahedral sites of Fe3O4, respectively; the formation energy was only -10.23 eV due to strong hybridization effects between Fe1s, U4f, O2p, and Ca3d orbitals. Compared to the uranium-doped Fe3O4, uranium leaching ratios decreased by 19.2 % and 48.9 % under strongly acidic and alkaline conditions after 120 days. However, high concentrations of phosphate inhibited Fe3O4 crystallization. These results should provide new avenues for the development of multi-metal co-doping technologies and mineralization optimization to treat uranium-containing complex wastewater.


Utilization of the walking oximetry test to allow safe ambulation after pulmonary resection.
Supplemental oxygen therapy after pulmonary resection can generally be tapered according to arterial blood gases at rest or pulse oximetry (SpO2). However, detecting exercise-induced oxygen desaturation can be difficult. We developed the walking oximetry test (WOT) so that thoracotomy patients could be rehabilitated without the risk of undetected ambulatory hypoxemia. The subjects were 58 patients who had undergone pulmonary resection and could walk at the bedside, with oxygen at 3 l/min via a nasal cannula. Patients with a value of more than 100 torr were allowed to walk with assistance for 6 min in the corridor. The oxygen flow rate was kept at 3 l/min and the walking pace was less than 50 m/min. SpO2 was determined using a wristwatch pulse oximeter. The test was stopped if the SpO2 fell below 90% or there was a score of 5 or more on the Borg scale (range 1-10). Oxygen desaturation occurred in six patients (10%) during the WOT. These patients underwent ambulatory training with sufficient oxygen supplementation and were then tested again. Patients whose SpO2 values remained higher than 90% and who showed no more than 5% desaturation were permitted to walk in the corridor with oxygen at 3 l/min via a nasal cannula. All these patients had a Borg score of 4 or lower. The WOT is a reliable, nonvasive method for detecting exercise-induced oxygen desaturation during ambulation after pulmonary resection.


One Notable Complication of Nasopharyngeal Airway: A Case Report.
The nasopharyngeal airway (NPA) is used by emergency providers and first responders to assist with oxygenation in obtunded, critically ill patients. There are few recorded NPA complications. We describe a unique case in which a patient went multiple days with recurrent symptoms of upper airway obstruction secondary to retained NPA. Nasopharyngeal airways may be uniquely prone to being displaced and retained due to their use in emergent situations, their small size, and time of insertion in the field prior to emergency department (ED) contact where handoff is not often standardized. The use of large-flanged NPAs might reduce incidences of displacement into the nasal cavity. This case highlights the need for improved handoff communication between emergency medical services and ED staff, especially to account for all inserted devices to prevent foreign body retention.


Novel splice site mutation at IVS8 nt 5 of HEXB responsible for a Greek-Cypriot case of Sandhoff disease.
Sandhoff disease is caused by abnormalities in HEXB gene encoding the beta-subunit of beta-hexosaminidase. In this study, we analyzed the HEXB gene of a Sandhoff carrier in the Greek-Cypriot community. A G to C transversion was identified in one allele of her HEXB gene at position 5 of the 5'-splice site of intron 8 (IVS8 nt5). One of 13 cDNA clones derived from her lymphocyte HEXB mRNA lacked the last four nucleotides "GTTG" of exon 8, which created a premature termination codon at 11 codons downstream. In vivo transcription of the mutant HEXB gene fragment in CHO cells resulted in deletion of the "GTTG." The mutation has not been found in 40 DNA samples from anonymous donors, indicating that this is not a polymorphism in the Cypriot population. These results clearly indicate that the splice site mutation at IVS8 nt5 is responsible for this case of Sandhoff disease.


Precise determination of the molybdenum isotopic composition of urine by multiple collector inductively coupled plasma mass spectrometry.
Molybdenum (Mo) is predominantly expelled from the human body in urine. Consequently, urinary variability in the concentration and isotopic composition of Mo may encode valuable clinical information. To access this information, however, it is first necessary to develop and demonstrate a rapid, accurate and precise methodology capable of concentrating Mo from urine for isotope analysis. The utility of N-benzoyl-N-phenylhydroxylamine (BPHA) to effectively separate and purify Mo from urine samples without the need for acid digestion was tested. Following this approach, applying a double-spike mass bias correction, we determined the Mo isotopic compositions of a set of urine samples by multiple collector inductively coupled plasma mass spectrometry (MC-ICP-MS). Based on replicate analyses of an in-house urine standard, this approach demonstrates an external precision on δ98/95 Mo values of better than 0.08‰ (2SD, n = 15). Application to a sample set collected from healthy individuals in Guangzhou, China, provides the first suite of δ98/95 Mo measurements from urine samples. Samples from the female participants show δ98/95 Mo (‰) values (1.31 ± 0.19‰, Ave ± 2SD, n = 14) that are consistently lower than those from the male participants (1.55 ± 0.16‰, Ave ± 2SD, n = 17). The employed methodology is suitable for rapid, low-blank and high-throughput Mo isotope analysis of urine samples. Although resolvable δ98/95 Mo variability is seen in this preliminary dataset, the mechanism driving this variability is unknown. High-precision Mo isotopic analysis might be added to the urinalysis tool-kit, with the potential to provide valuable clinical information in the future.


Evaluating the compatibility of three colorimetric protein assays for two-dimensional electrophoresis experiments.
To evaluate compatibility of commonly used colorimetric protein assays for 2-DE experiments, we investigated the interfering mechanisms of major 2-DE component(s) in the Lowry-based assay, the Bradford assay and the bicinchoninic acid (BCA) assay. It was found that some 2-DE components did not directly interfere with the assays' color development reaction, but possibly influenced the quantitation results by interacting with proteins. Generally, simultaneous presence of 2-DE components in the samples demonstrated a cooperative rather than additive interference. Interference by reductants in the Lowry-based assay and the BCA assay were too prominent and could not be completely eliminated by either the reported alkylation procedure or the water dilution procedure. The Bradford assay however, presented a more suitable method for quantitating 2-DE samples because it was less interfered by most 2-DE components. Furthermore, despite slightly compromising protein solubility, utilization of reductant free 2-DE sample buffers conferred application of the Lowry-based and BCA assays in the 2-DE experiments.


A national study on the residential impact of biological aerosols from the land application of biosolids.
The purpose of this study was to evaluate the community risk of infection from bioaerosols to residents living near biosolids land application sites. Approximately 350 aerosol samples from 10 sites located throughout the USA were collected via the use of six SKC Biosamplers. Downwind aerosol samples from biosolids loading, unloading, land application and background operations were collected from all sites. All samples were analysed for the presence of HPC bacteria, total coliform bacteria, Escherichia coli, Clostridium perfringens, coliphage, enteroviruses, hepatitis A virus and norovirus. Total coliforms, E. coli, C. perfringens and coliphage were not detected with great frequency from any sites, however, biosolids loading operations resulted in the largest concentrations of these aerosolized microbial indicators. Microbial risk analyses were conducted on loading and land application operations and their subsequent residential exposures determined. The greatest annual risks of infection occurred during loading operations, and resulted in a 4 x 10(-4) chance of infection from inhalation of coxsackievirus A21. Land application of biosolids resulted in risks that were <2 x 10(-4) from inhalation of coxsackievirus A21. Overall bioaerosol exposure from biosolids operations poses little community risk based on this study. This study evaluated the overall incidence of aerosolized micro-organisms from the land application of biosolids and subsequently determined that microbial risks of infection were low for residents close to biosolids application sites.


Electrophysiological responses in hydranencephaly.
We recorded electrophysiological responses, both electroretinograms (ERGs) and visual evoked responses (VER), at 4 and 21 months of age in a child with hydranencephaly. As expected, the ERG was normal. Despite the apparent absence of most of the cerebral cortex, a VER was present at both visits. The child's visual performance definitely improved both subjectively and electrophysiologically. The VER contained multiple early components in contrast to previous reports, where only a slow, monophasic response was detected.


Changing etiologies and outcome of liver failure in Southwest China.
The prognosis of liver failure depends greatly on the underlying cause, and there were few data about the prognosis, etiologies or trigger factors of liver failure in China based on long-term and large samples cohorts. We screened out 3171 liver failure cases from 25467 patients hospitalized in our department between 2000 and 2012 according to Chinese criteria, and determined their etiologies and prognosis. 97.3 % cases were associated with at least one of 25 identified factors. The 3 leading etiologies were HBV (91.6 %), alcohol (18.1 %) and antiviral therapy (AVT) related hepatitis B flares (6.7 %). Acute-on-chronic liver failure (ACLF) accounted for 92.1 % of all cases. 96.5 % ACLF cases were associated with HBV, in which the percentage of AVT related flares increased from 0 % in 2000 up to 11.5 % in 2012, and hepatitis virus superinfection declined from peak 19.3 % in 2002 down to 2.5 % in 2012. Three-month spontaneous survival (SS) rate of 3171 cases was 31.4 %, but improved from 17.4 % in 2000 up to 40.4 % in 2012. SS was significantly different among various etiological groups (P = 0.000). In HBV related liver failure aged 25 to 54 years, males accounted for 87.6 %, and had a progressively decreased SS with increasing age. From 25 to 54 years, SS was lower in male than in female HBV related liver failure, and having significant difference in cases of ages 40 to 44 years (27.6 % versus 50.9 %, P = 0.001). Etiologies of liver failure were numerous and varied in southwest China. HBV was the most leading cause of liver failure, especially in ACLF. AVT related flares had become the third leading cause of ACLF. The prognosis of liver failure remained poor, but had markedly improved in recently 3 years. Middle-aged male HBsAg carriers had an extremely higher risk for liver failure and worse prognosis compared to female. 1. Etiologies of liver failure were numerous and varied in southwest China. HBV infection is the main cause of liver failure in southwest China, especially the major cause of ACLF. Antiviral related liver failure, especially the NUCs withdrawal induced ACLF were extremely increased, which has replaced the superinfection as the third important cause of HBV-ACLF. 2. The prognosis of liver failure is still poor, but the spontaneous survival rate showed a trend of steady rise in recent years. The prognosis of patients with liver failure caused by different causes also exists certain difference, the more damage factors bulls the worse prognosis. 3. The prognosis of the HBV and HCV reactivation induced by the steroids was poor.Interferon treatment of CHB in ACLF although rare, but should be taken into consideration seriously. 4. Patients with liver failure caused by different etiologies showed larger differences of gender and age distribution. Gender and age are the important factors with the occurrence and prognosis of HBV-ACLF.


Monoclonal antibodies (McAbs) to determinants on human gamma chains: properties of antibodies showing subclass restriction or subclass specificity.
Thirteen monoclonal antibodies (McAbs) showing subclass-specific and subclass-restricted reactivity to human IgG have been produced by the hybridoma technique. Their specificity has been defined by passive haemagglutination (HA) and haemagglutination-inhibition (HAI) assays using a large panel pf purified IgG paraproteins of known subclass. Their use in assaying human IgG subclasses in radial immunodiffusion (RID) and in purifying human subclasses by both positive and negative immunoabsorption chromatography is illustrated.


Development and validation of a five-lncRNA signature with prognostic value in colon cancer.
Dysregulation of long noncoding RNAs (lncRNAs) has been found in a large number of human cancers, including colon cancer. Therefore, the implementation of potential lncRNAs biomarkers with prognostic prediction value are very much essential. GSE39582 data set was downloaded from database of Gene Expression Omnibus. Re-annotation analysis of lncRNA expression profiles was performed by NetAffx annotation files. Univariate and multivariate Cox proportional analyses helped select prognostic lncRNAs. Algorithm of random survival forest-variable hunting (RSF-VH) together with stepwise multivariate Cox proportional analysis were performed to establish lncRNA signature. The log-rank test was carried out to analyze and compare the Kaplan-Meier survival curves of patients' overall survival (OS). Receiver operating characteristic (ROC) analysis was used for comparing the survival prediction regarding its specificity and sensitivity based on lncRNA risk score, followed by calculating the values of area under the curve (AUC). The single-sample GSEA (ssGSEA) analysis was used to describe biological functions associated with this signature. Finally, to determine the robustness of this model, we used the validation sets including GSE17536 and The Cancer Genome Atlas data set. After re-annotation analysis of lncRNAs, a total of 14 lncRNA probes were obtained by univariate and multivariate Cox proportional analysis. Then, the RSF-VH algorithm and stepwise multivariate Cox analysis helped to build a five-lncRNA prognostic signature for colon cancer. The patients in group with high risk showed an obviously shorter survival time compared with patients in group with low risk with AUC of 0.75. In addition, the five-lncRNA signature can be used to independently predict the survival of patients with colon cancer. The ssGSEA analysis revealed that pathways such as extracellular matrix-receptor interaction was activated with an increase in risk score. These findings determined the strong power of prognostic prediction value of this five-lncRNA signature for colon cancer.


Progressive metastatic pheochromocytoma induced by multiple endocrine neoplasia type 2A with a lethal outcome.
Patients with multiple endocrine neoplasia type 2A (MEN2A) harboring a pathological variant in the RET gene are characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism. Although pheochromocytoma is currently defined as a malignant tumor, MEN2A-associated pheochromocytoma is known to have a small risk of metastasis. The case was a 62-year-old Japanese male with bilateral pheochromocytoma, multiple metastases in the liver and bones, and a cardiac thrombus. Genetic testing revealed a pathological variant at codon 634 of the RET gene, thereby leading a diagnosis of MTC. We considered that the multiple metastases were due to MTC; however, a liver biopsy revealed metastasis of pheochromocytoma. When pheochromocytoma precedes MTC, the diagnosis of MEN2A may be difficult.


Prevalence of Falls in an Urban Community-Dwelling Older Population of Cape Town, South Africa.
Falls are a major cause of disability and mortality in older adults. Studies on falls in this population have mainly been conducted in high income countries, and scant attention has been given to the problem in low and middle income countries, including South Africa. The aim of the study was to establish a rate for falls in older adults in South Africa. A cross-sectional survey with a 12-month follow-up survey. Three purposively selected suburbs of Cape Town: Plumstead, Wynberg Central and Gugulethu. Eight hundred and thirty seven randomly sampled ambulant community-dwelling subjects aged ≥ 65 years grouped according to ethnicity in three sub-samples: black Africans, coloureds (people of mixed ancestry) and whites. Data were collected on socio-demographic and health characteristics, and history of falls using a structured questionnaire and a protocol for physical assessments and measurements. Of the total baseline (n=837) and follow-up (n=632) survey participants, 76.5% and 77.2 % were females with a mean (S.D) age of 74 years (6.4) and 75 years (6.2), respectively. Rates of 26.4% and 21.9% for falls and of 11% and 6.3% for recurrent falls, respectively, were calculated at baseline and follow-up. Fall rates differed by ethnic sub-sample at baseline: whites 42 %, coloureds 34.4% and black Africans 6.4 % (p=0.0005). Rates of 236, 406 and 354 falls per 1000 person years were calculated for men, women and both genders, respectively. Recurrent falls were more common in women than in men. Falls are a significant problem in older adults in South Africa. Effective management of falls and falls prevention strategies for older people in South Africa, need to be developed and implemented.


A specific role for cyclin D1 in mammary gland development.
Cyclin D1 is a critical component of the core cell cycle machinery. Mice lacking cyclin D1 develop mammary glands that fail to undergo normal lobuloalveolar proliferation during pregnancy. Thus, cyclin D1 seems to play a critical role in pregnancy-induced proliferation of mammary epithelium. Cyclin D1 also participates in neoplasia, as the majority of human mammary carcinomas contain elevated levels of this cyclin.


The regulation of glucose transport by cAMP stimulators via three different mechanisms in rat and human adipocytes.
The regulation of glucose transport by a beta-adrenergic agonist and other cAMP stimulators was assessed by kinetic analyses of 3-O-methylglucose (MG) transport in rat and human adipocytes and in isolated rat plasma membrane vesicles. Basal MG transport was biphasically affected by L-isoproterenol in rat adipocytes: lower concentrations (10-25 nM) of L-isoproterenol stimulated the basal rate by increasing the Vmax, but higher concentrations (0.5-2 microM) of L-isoproterenol inhibited the basal rate. On the other hand, the maximum insulin-stimulated MG transport rate was not affected by 25 nM L-isoproterenol, but was suppressed by 2 microM L-isoproterenol in rat adipocytes. In the presence of adenosine deaminase plus L-isoproterenol (25 nM and 2 microM), dibutyryl cyclic AMP (Bt2cAMP), 3-isobutyl-1-methylxanthine, or forskolin, both basal and the maximum rates of MG transport were suppressed in rat adipocytes. However, from kinetic experiments, both L-isoproterenol plus adenosine deaminase and Bt2cAMP decreased the Vmax. On the other hand, isobutymethylxanthine and forskolin decreased the Vmax as well as increased the K8. MG transport in plasma membrane vesicles was directly inhibited by either forskolin or isobutylmethylxanthine. In contrast, both 25 nM and 2 microM L-isoproterenol with or without adenosine deaminase, Bt2cAMP, or cAMP had no effect on MG transport in rat plasma membrane vesicles. In human adipocytes, L-isoproterenol always stimulated basal MG transport and did not suppress the maximum rate of MG transport, even though cAMP production was maximally stimulated by L-isoproterenol. Both adenosine deaminase plus L-isoproterenol and Bt2cAMP did not suppress the basal rate, but did show a modest suppression (40%) of the maximum insulin effect on MG transport in human adipocytes. However, both isobutylmethylxanthine and forskolin remarkably suppressed (85%) both the basal and the maximum rate of MG transport by both increasing the K8 and decreasing the Vmax. These results indicate MG transport in both rat and human adipocytes is regulated by 3 different mechanisms: (I) L-isoproterenol, a beta-adrenergic agonist, stimulates basal MG transport by increasing the Vmax, (II) cAMP mediates a decrease in MG transport by decreasing the Vmax, and (III) both forskolin and isobutylmethylxanthine also decrease MG transport by directly inhibiting the binding of MG molecules to transporters, resulting in a decrease in the Vmax and an increase in the K8.


High-dose methotrexate, high-dose cytarabine and temozolomide for the treatment of primary central nervous system lymphoma (PCNSL).
Treatment of primary central nervous system lymphoma (PCNSL) associates with low response rates and poor survival using conventional radio and chemotherapy. Due to its favorable toxicity profile, temozolomide has emerged as a new option for treatment of PCNSL in young patients. In this study, we report a series of PCNSL patients treated with an innovative regimen combining high dose of both cytarabine and methotrexate with temozolomide without radiotherapy or intrathecal chemotherapy. To evaluate a new intensive chemotherapy with temozolomide, trying to assess response and progression-free survival rates and if the results are promising, we are aiming at evaluating the overall survival (OS) taking into consideration the toxicity profile. The study was performed at Al Mowassa Charity Hospital in Damascus (Syria). Forty patients with histologically confirmed PCNSL median age 52 years (range 20-65) years were included. Biopsies were cultured, and a karyotyping was made in 32 patients. An induction chemotherapy was started, and methotrexate 3 gr/m² over 12 h on day 1, cytarabine 3 gr/m² every 12 h on day 1 and temozolomide 150 mg/m² from day 2 through day 6 with a total of 6 cycles were given on a monthly basis. Among the 40 patients included in the study, a complete response was observed in 34 patients (85%) and a partial response in the remaining 6 patients (15%). Disease progressed in 8 out of 40 patients (20%) while 32 patients are still living at 5 years making the OS reaching 77%. Grade II nephrotoxicity was observed in 2 patients while grade III and IV hematotoxicity was observed in 5 patients. High dose of both Ara-C and MTX combined with temozolomide appears to be a good choice in the treatment of PCNSL, in the light of good response and OS rates, taking into consideration the acceptable toxicity profile. However, a larger trial is needed to make it an acceptable new combination as a first line for PCNSL patients.


The erythrocytic schizogony of two synchronized strains of plasmodium berghei, NK65 and ANKA, in normocytes and reticulocytes.
By a modified Percoll-glucose centrifugation technique the rings and young trophozoites of two strains of Plasmodium berghei, NK65 and ANKA, were separated from the other erythrocytic stages and inoculated into mice. The subsequent infection was followed for ANKA in normal mice and for NK65 in normal mice and in mice with high-grade reticulocytosis induced by injections of phenylhydrazine. The duration of the erythrocytic schizogony of the NK65 strain was shown to be independent of the age of the host cell, and the hour of inoculation did not influence the cycle of the ANKA strain.


Stereoisomeric engineering of aggregation-induced emission photosensitizers towards fungal killing.
Fungal infection poses and increased risk to human health. Photodynamic therapy (PDT) as an alternative antifungal approach garners much interest due to its minimal side effects and negligible antifungal drug resistance. Herein, we develop stereoisomeric photosensitizers ((Z)- and (E)-TPE-EPy) by harnessing different spatial configurations of one molecule. They possess aggregation-induced emission characteristics and ROS, viz. 1O2 and O2-• generation capabilities that enable image-guided PDT. Also, the cationization of the photosensitizers realizes the targeting of fungal mitochondria for antifungal PDT killing. Particularly, stereoisomeric engineering assisted by supramolecular assembly leads to enhanced fluorescence intensity and ROS generation efficiency of the stereoisomers due to the excited state energy flow from nonradiative decay to the fluorescence pathway and intersystem (ISC) process. As a result, the supramolecular assemblies based on (Z)- and (E)-TPE-EPy show dramatically lowered dark toxicity without sacrificing their significant phototoxicity in the photodynamic antifungal experiments. This study is a demonstration of stereoisomeric engineering of aggregation-induced emission photosensitizers based on (Z)- and (E)-configurations.


Comparison of inpatient versus post-discharge venous thromboembolic events after spinal surgery: A single institution series of 6869 consecutive patients.
retrospective chart review. We aimed to determine the perioperative risk factors that lead to inpatient or post-discharge venous thromboembolism (VTE) events after spinal surgery. While many studies relate the risk factors in a post-surgical setting to the incidence of VTE, this study aims to separate these VTE into inpatient and post-discharge categories to examine timing and risk factors. We analyzed 6869 patients from 2009 to 2015 using Current Procedural Technology codes from a single tertiary academic institution. Patients were stratified based on occurrence and setting of VTE then controlled for perioperative characteristics with exclusion criteria being patients undergoing minor spine surgeries or secondary procedures. In 170 VTE events, these factors were associated with increased risk for: Inpatient DVT only: IVC filter (OR 6.380 [3.414-11.924]), longer length of hospital stay (OR 1.083 [1.047-1.120]), a prior history of DVT (OR 3.640 [1.931-6.856]). Post-discharge DVT only: history of PE (OR 45.142 [6.785-300.351]), having a corpectomy (OR 26.670 [3.477-204.548]), and having an osteotomy (OR 18.877 [1.129-315.534]). Inpatient PE only: surgery >4 h (OR 30.820, p < 0.001), fracture (OR 6.913, p = 0.004), IVC filter (OR 3.135, p = 0.029). Post-discharge PE only: corpectomy (OR 541.271, p = 0.009), foraminotomy (OR 40.137, p = 0.013), EBL > 500cc (OR 2467.798, p = 0.002). Time to onset of VTE events was significantly longer for patients undergoing osteotomy (7.43 days) than for patients with fracture (4.28 days), which is consistent with our findings that fracture was an independent predictor of inpatient VTE, and osteotomy was an independent predictor of post-discharge VTE (p = 0.018). Time-to-VTE varies between types of surgeries. Some risk factors are independently associated with VTE at all times during the 30-day postoperative period, while other factors are only associated with either inpatient or post-discharge VTE. Those patients with high-risk features for post-discharge VTE merit increased study for thromboprophylaxis management.


The expression of melanosomal matrix protein in the transdifferentiation of pigmented epithelial cells into lens cells.
A monoclonal antibody (MC/1) was constructed against melanosomes purified from the chicken pigmented epithelial cells (PECs) in order to characterize the differentiative phenotypes of PEC in the process of transdifferentiation into lens cells. Immunofluorescent studies revealed that MC/1 antibody specifically stains both retinal PECs in the eye and melanocytes in the skin, of chicken embryos. Immunoelectron microscopy showed that the antigen molecules are located on the peripheral region of the melanosomal matrix. A single protein band with an apparent molecular weight of 115,000 was labelled by MC/1 in Western blotting. The 115 kDa polypeptide identified by MC/1 is considered to be a member of the melanosomal matrix proteins. The maintenance of specificity of pigment cell nature is followed in the system of transdifferentiation of PEC into lens in vitro, utilizing 115 kDa protein as a marker. In the dedifferentiated PECs, this protein was undetectable.


Do metoprolol and carvedilol have equivalent effects on diurnal heart rate in patients with chronic heart failure?
Carvedilol exerted a greater reduction in mortality than metoprolol tartrate in the Carvedilol or Metoprolol European Trial (COMET). However, it is unclear if the degree and time course of beta1-blockade during a 24-h period was similar with each agent at the doses used. Therefore we analyzed 24-h ECG Holter recordings from a study which compared the long-term clinical efficacy of metoprolol tartrate to carvedilol in chronic heart failure patients using the same dosing regimen as in COMET. Fifty-one patients with chronic heart failure with a mean LVEF 26+/-1.8% were randomized in a double-blind fashion to receive metoprolol tartrate 50 mg bid or carvedilol 25 mg bid. 24-h ECG monitoring (Holter) was performed at baseline, 12 weeks and 1 year. Adequate quality recordings for analysis were obtained from 43 subjects at baseline, 42 at 12 weeks and 29 subjects at 1 year. Both drugs produced a fall in average 24-h heart rate from baseline at 12 weeks and at 1 year: metoprolol 88+/-3 to 71+/-2 and 69+/-3 bpm; carvedilol 83+/-3 to 70+/-2 and 70+/-3 bpm respectively (all p<0.001). The pattern of suppression of heart rate during the 24-h period was similar for both drugs. Metoprolol tartrate 50 mg bid and carvedilol 25 mg bid had similar effects on 24-h heart rate. This result suggests that the degree of beta1-blockade produced by these two drugs in these doses is comparable and the superior survival effect of carvedilol compared to metoprolol seen in COMET is likely to be due to actions of carvedilol other than beta1-blockade.


Distribution of Drosophila melanogaster transposable element sequences in species of the obscura group.
Fifteen species belonging to the obscura group of the genus Drosophila were screened for sequences homologous to Drosophila melanogaster transposable elements (TEs) as an initial step in the examination of the possible occurrence of TEs at chromosomal inversion breakpoints. Blots of genomic DNAs from species of the obscura group were hybridized at three different stringencies with 14 probes representing the major families of TEs described in D. melanogaster. The probe DNAs included copia, gypsy, 412, 297, mdg1, mdg3, 3S18, F, G, I, jockey, P, hobo, and FB3. D. melanogaster TEs were not well represented in the species of the obscura group analyzed. The TEs that were observed generally exhibited heterogeneous distributions, with the exception of F, gypsy and 412 which were ubiquitous, and 297, G, Sancho 2, hobo and FB which were not detected.


Author Correction: Genomic Prediction of 16 Complex Disease Risks Including Heart Attack, Diabetes, Breast and Prostate Cancer.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Feasibility of the semi-opened method of specimen resection for a circumferential resection margin in rectal cancer surgery: a multicenter study.
A circumferential resection margin (CRM) > 1 mm is a surrogate marker of oncologic outcomes in rectal cancer patients. In Japan, because the mesentery is removed from the rectum, the CRM cannot be measured. This multicenter prospective study evaluates the feasibility of a resected specimen processing method that allows CRM measurement. Fifty patients with rectal cancer were enrolled. Resected specimens were processed as previously reported. The primary outcomes were CRM measurement and the rate of CRM positivity. The secondary outcomes were the quality of total mesorectal excision, the possibility to visualize and sample the tumor, the number of harvested lymph nodes, and comparison between the pathological CRM and preoperative mesorectal fascia (MRF) involvement. This study was registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry under identification number UMIN000031735. The CRM was measurable in all patients and found to be positive in three (6%). We confirmed tumor localization, sampled the tumor, and measured the distal margin in all patients. A median of 20 lymph nodes were harvested. The concordance rate between preoperative MRF involvement and pathological CRM status was 90%. A semi-opened rectal specimen with transverse slicing is a feasible method for measuring the CRM.


Transport of micron-sized polyethylene particles in confined aquifer: Effects of size, aging, and confining pressure.
Contamination of groundwater by microplastics (MPs) is increasingly reported and attracts a growing attention due to their potential risks. To understand how MPs migrate into groundwater, many previous works have investigated their transport using man-made microspheres of few microns or smaller as models. However, MPs observed in the environment are more diverse in size, shape, and type, which may have different migration behaviors. In this work, the transports of irregularly shaped polyethylene (PE) particles in the sand packed column were studied. Small MPs (22-37 μm) generally have high mobility than large MPs (44-74 μm) but can also be affected by aging. Aging decreased the hydrophobicity of the MPs and increased their surface negative charge, which can facilitate the transport of MPs. However, the physical barrier of space in the porous media might have a greater influence on their transport. The retention of the MPs was enhanced with the increase of pressure due to compression that decreased pore size. Results from this study showed that MPs of environmental features can also be transported in the groundwater but the processes could be governed by different factors, such as physical interception and steric hindrance.


Are certain HLA haplotypes responsible for low testosterone levels in males?
The level of testosterone on 138 HLA typed healthy males and 71 male rheumatoid arthritis patients were analysed. HLA-B15 was associated with a lower mean serum testosterone level in males than any other tissue type. This was observed in both the normal and RA groups.


Bacillus cereus AR156 activates PAMP-triggered immunity and induces a systemic acquired resistance through a NPR1-and SA-dependent signaling pathway.
Induced resistance responses play a potent role in plant defense system against pathogen attack. Bacillus cereus AR156 is a plant growth promoting rhizobacterium (PGPR) that installs induced systemic resistance (ISR) to Pseudomonas syringae pv. tomato (Pst) in Arabidopsis. Here, we show that AR156 leaf infiltration enhances disease resistance in Arabidopsis through the activation of a systemic acquired resistance (SAR). PR1 protein expression and reactive oxygen species (ROS) burst are strongly induced in plants treated with AR156 and inoculated with Pst than that in plants inoculated with Pst only. Moreover, AR156 can trigger SAR in jar1 or ein2 mutants, but not in the NahG transgenic and NPR1 mutant plants. Our results indicate that AR156-induced SAR depends on SA-signaling pathway and NPR1, but not JA and ET. Also, AR156-treated plants are able to rapidly activate MAPK signaling and FRK1 gene expression, which are involved in pathogen associated molecular pattern (PAMP)-triggered immunity (PTI). Altogether, our results indicate that AR156 can induce SAR by the SA-signaling pathways in an NPR1-dependent manner and involves multiple PTI components.


Epigenetic Repression of STING by MYC Promotes Immune Evasion and Resistance to Immune Checkpoint Inhibitors in Triple-Negative Breast Cancer.
The MYC oncogene is frequently amplified in triple-negative breast cancer (TNBC). Here, we show that MYC suppression induces immune-related hallmark gene set expression and tumor-infiltrating T cells in MYC-hyperactivated TNBCs. Mechanistically, MYC repressed stimulator of interferon genes (STING) expression via direct binding to the STING1 enhancer region, resulting in downregulation of the T-cell chemokines CCL5, CXCL10, and CXCL11. In primary and metastatic TNBC cohorts, tumors with high MYC expression or activity exhibited low STING expression. Using a CRISPR-mediated enhancer perturbation approach, we demonstrated that MYC-driven immune evasion is mediated by STING repression. STING repression induced resistance to PD-L1 blockade in mouse models of TNBC. Finally, a small-molecule inhibitor of MYC combined with PD-L1 blockade elicited a durable response in immune-cold TNBC with high MYC expression, suggesting a strategy to restore PD-L1 inhibitor sensitivity in MYC-overexpressing TNBC.


Anti-inflammatory activity of hydroxycinnamic acid derivatives isolated from corn bran in lipopolysaccharide-stimulated Raw 264.7 macrophages.
In this study, the effect of the 80% ethanolic extract of corn bran (EECB) on inhibition of nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in lipopolysaccharide (LPS)-stimulated Raw 264.7 cells was investigated. The EECB inhibited LPS-induced NO production and iNOS expression in a dose-dependent manner. Four hydroxycinnamic acid derivatives (HADs), including two free cinnamic acids, p-coumaric acid (CA) and ferulic acid (FA), and their conjugate phenolic amides, p-dicoumaroyl-putrescine (DCP) and diferuloylputrescine (DFP), were found to be present in the EECB by LC-MS analysis, and DFP (378.66 μg/g) was the predominant phenolic compound, followed by DCP (7.83 μg/g)>CA (5.58 μg/g)>FA (1.84 μg/g). The four HADs significantly inhibited NO production and iNOS expression in a dose-dependent manner. Among the four HADs tested, DFP showed the most potent inhibition on NO production and iNOS mRNA and protein expression, followed by DCP>FA ≥ CA. DFP also exhibited the strongest inhibition on LPS-induced iNOS and NF-κB luciferase activity, which was followed by DCP ≥ FA (CA)>CA (FA). Thus, these results suggest that phenolic amides in the corn bran may be a potential source of natural anti-inflammatory agents.


Gingival augmentation with an acellular dermal matrix: human histologic evaluation of a case--placement of the graft on bone.
The importance of gingival augmentation to increase the amount of keratinized tissue is a controversial subject. In this case report, an acellular dermal matrix was used to obtain an increase in the amount of keratinized tissue around four implants. In this case, the acellular dermal matrix was placed on bone. The surgical procedure resulted in an increase in the amount of keratinized tissue. Therefore, it met the clinical goals of the surgical procedure. However, the clinical findings and patient pain levels during the healing seemed to resemble a denudation procedure. Additionally, the histologic evaluation of the tissue that formed around the implants showed that the acellular dermal matrix was not incorporated into the result. Based on this case, the use of an acellular dermal matrix placed on bone does not seem to be a good technique to increase the amount of keratinized tissue.


The role of macrophages in T cell-mediated autoimmune diabetes in nonobese diabetic mice.
We have shown previously that the inactivation of macrophages in nonobese diabetic (NOD) mice results in the prevention of diabetes; however, the mechanisms involved remain unknown. In this study, we found that T cells in a macrophage-depleted environment lost their ability to differentiate into beta cell-cytotoxic T cells, resulting in the prevention of autoimmune diabetes, but these T cells regained their beta cell-cytotoxic potential when returned to a macrophage-containing environment. To learn why T cells in a macrophage-depleted environment lose their ability to kill beta cells, we examined the islet antigen-specific immune response and T cell activation in macrophage-depleted NOD mice. There was a shift in the immune balance, a decrease in the T helper cell type 1 (Th1) immune response, and an increase in the Th2 immune response, due to the reduced expression of the macrophage-derived cytokine IL-12. As well, there was a deficit in T cell activation, evidenced by significant decreases in the expression of Fas ligand and perforin. The administration of IL-12 substantially reversed the prevention of diabetes in NOD mice conferred by macrophage depletion. We conclude that macrophages play an essential role in the development and activation of beta cell-cytotoxic T cells that cause beta cell destruction, resulting in autoimmune diabetes in NOD mice.


Experimental study on the apoptosis of the astrocytes and the oligodendrocytes induced by Ca(2+) reperfusion.
To investigate the apoptosis rules of the astrocytes and oligodendrocytes induced by Ca(2+) reperfusion. The apoptosis of purified cultured astrocytes and oligodendrocytes induced by Ca(2+) reperfusion and the relationship between the development of the cell apoptosis and post-reperfusion time was observed. Both the astrocytes and oligodendrocytes were obviously in a time-dependent fashion, and the apoptosis ratios of the oligodendrocytes (39.73%+/-4.16%) were higher than the astrocytes (19.64%+/-4.67%) 24 hours after Ca(2+) reperfusion. The TUNEL positive cells were 13.6+/-1.82 and 21.4+/-1.95 at every visual field of astrocytes and oligodendrocytes respectively 24 hours after Ca(2+) reperfusion. The astrocytes and oligodendrocytes are similar wi th the development rules on apoptosis and have different susceptiveness to the situation.


Improvement of the red blood cell O2 release capacity by lipid vesicle-mediated incorporation of inositol hexaphosphate.
Fusion of unilamellar lipid vesicles with red blood cells has been used to deliver entrapped inositol hexaphosphate (IHP) to the cells. Incorporated IHP tightly bound to hemoglobin produces a significant and lasting "right-shift" of the O2-binding curve of red blood cells. The O2 release capacity of red blood cells is increased by this method up to 270% of the normal value. The Bohr effect is increased so that carbon dioxide transport is also enhanced. The fine structure of the erythrocytes does not seem to be altered by the lipid vesicle incorporation.


Endobronchial ultrasound-guided transbronchial needle aspirate (EBUS-TBNA): a proposal for on-site adequacy criteria.
This is a retrospective study of 48 patients who underwent EBUS-TBNA procedure between the periods January 2008 to September 2009 at Long Island Jewish Medical Center. The study was undertaken with the following objectives: First, to define practical and useful on-site adequacy criteria for EBUS-TBNA samples; Second, to understand the diagnostic pitfalls associated with accurate interpretation of EBUS-TBNA samples. EBUS-TBNA procedure was able to diagnose 24/48 (50%) patients with malignancy, 1/48 (2%) suspicious for malignancy, 9/48 (19%) with granulomatous process, and 9/48 (19%) negative for disease. Only five cases (10%) could not be diagnosed with this procedure. Based on our experience, any smear with presence of > 5 low power fields (×100) with ≥ 100 lymphocytes in each and containing < 2 groups of bronchial cells/low power field (×100) can be considered adequate for evaluation. Also, the presence of germinal center fragments renders a smear adequate for evaluation, irrespective of the above mentioned criteria. Adequacy criteria are to be applied only to the smears not showing any identifiable pathology such as malignancy or granuloma. An understanding of diagnostic pitfalls associated with accurate interpretation of EBUS-TBNA samples is essential to avoid false-positive and false-negative diagnosis. To conclude, an effective communication between the clinician and cytologist, an algorithmic approach to diagnosis, and the on-site adequacy criteria proposed in this study can markedly improve the diagnostic yield of the procedure.


Considerations on Listing's Law and the primary position by means of a matrix description of eye position control.
Voluntary gaze control obeys the law of Listing. This law specifies the torsion of the eye in every direction of gaze, when the so-called "primary position" of the eye is known. In the present article, some interesting relations between Listing's Law and the primary position on the one hand, and eye muscle innervation on the other hand are derived. A new vectorial description of eye position is introduced which permits to represent Listing's Law by a very simple equation. It also allows to approximate the transformation between eye muscle innervation and eye position by a 3 x 3-matrix in a large field of gaze and with quantities of innervation which are directly related to motoneuron firing rates. It is shown that these innervation quantities must be linearly coupled to yield Listing's Law and that the parameters of this coupling determine the primary position. Finally, relations between innervations and eye muscle forces are considered, and a hypothesis concerning the cooperation of voluntary gaze control and otolith or vergence inputs is presented.


Sensitivity to capreomycin and prothionamide in strains of Mycobacterium, Nocardia, Rhodococcus, and related taxa for taxonomical purposes.
Sensitivity to capreomycin and to prothionamide was analysed for 150 strains belonging to the genera Mycobacterium, Nocardia, Rhodococcus, and related taxa. The analyses showed, e.g., that strains of Mycobacterium chelonei and Nocardia brasiliensis were more resistant to capreomycin than the other strains tested and that M. farcinogenes differed from M. senegalense concerning sensitivity to this drug. The analysis showed, furthermore, that strains of Mycobacterium differ from those of Nocardia, Rhodococcus, "Mycobacterium album", and "Gordona aurantiaca" in being more sensitive to prothionamide than these organisms. Strains designated N. amarae were more sensitive to both drugs than were the other tested strains of Nocardia, which indicates that N. amarae diverges from the other species of this genus.


Influence of a detergent on the catfish olfactory mucosa.
The olfactory mucosa of the catfish (Ictulurus punctatus) has been briefly exposed to various concentrations of the non-ionic detergent Triton X-100. At high concentrations (1-4%) the upper layer of cells constituting the sensory and non-sensory areas of the lamellae is extensively damaged and new receptor cells do not appear in significant number before 2 months after treatment. Respiratory cells regenerate first followed by sustentacular and olfactory receptors. The regenerative process is very similar to that described previously after prolonged contact between the mucosa and ZnSO4. Low detergent concentrations 0.03-0.1% affect only the sensory area. Olfactory and sustentacular microvilli and cilia, are immediately severed by the chemical. Regeneration occurs within the next 4 days. The cellular membranes appear also to be affected. From anatomical, electrophysiological and biochemical studies both in vivo and in vitro, it can be hypothesized that a receptors involved in the transduction process are solubilized by the detergent but reappear at a level corresponding to 50-60% of their original activity within 2 h. Proteins, having an amino acid binding effectiveness correlated to the amino acid electrophysiological activities measured in vivo, can be isolated from the solubilized material. Further studies will be necessary to confirm that some of these molecules are involved in the olfactory transduction mechanism.


The promoted lateral root 1 (plr1) mutation is involved in reduced basal shoot starch accumulation and increased root sugars for enhanced lateral root growth in rice.
Lateral roots (LRs) are indispensable for plant growth, adaptability and productivity. We previously reported a rice mutant, exhibiting a high density of thick and long LRs (L-type LRs) with long parental roots and herein referred to as promoted lateral root1 (plr1). In this study, we describe that the mutant exhibited decreased basal shoot starch accumulation, suggesting that carbohydrates might regulate the mutant root phenotype. Further analysis revealed that plr1 mutation gene regulated reduced starch accumulation resulting in increased root sugars for the regulation of promoted LR development. This was supported by the exogenous glucose application that promoted L-type LRs. Moreover, nitrogen (N) application was found to reduce basal shoot starch accumulation in both plr1 mutant and wild-type seedlings, which was due to the repressed expression of starch biosynthesis genes. However, unlike the wild-type that responded to N treatment only at seedling stage, the plr1 mutant regulated LR development under low to increasing N levels, both at seedling and higher growth stages. These results suggest that plr1 mutation gene is involved in reduced basal shoot starch accumulation and increased root sugar level for the promotion of L-type LR development, and thus would be very useful in improving rice root architecture.


Circulating bioactive follicle stimulating hormone and immunoreactive inhibin levels during the normal human menstrual cycle.
To examine the relationship between circulating levels of bioactive FSH (B-FSH) and immunoactive inhibin and oestradiol we studied five women during ovulatory cycles. Daily blood samples were collected from each subject during one menstrual cycle. B-FSH was measured using a modified, highly sensitive in-vitro rat granulosa cell bioassay. The inclusion of IGF-1 (10 micrograms/l) and transferrin (50 mg/l) in the assay system enhanced granulosa cell responsiveness to FSH and resulted in increased assay sensitivity. Inhibin was measured by a heterologous radioimmunoassay (RIA) using an antibody raised against 31 kDa bovine inhibin. Bioactive FSH (B-FSH) levels were closely correlated to those of immunoactive FSH (I-FSH, r = 0.79, P less than 0.001) throughout the cycle. Peak levels of B-FSH were observed during the early follicular phase (day -13, 44.7 +/- 9.6 IU/l, mean +/- SEM) and during the midcycle surge (35.2 +/- 6.2 IU/l); lowest levels occurring during the luteal phase (nadir 3.9 +/- 0.27 IU/l). Plasma oestradiol levels increased significantly during the follicular phase (P less than 0.001) to a peak on day -1 and were negatively correlated with B-FSH during the late follicular phase (day -8 to -1; r = -0.45, P less than 0.02). There was no change in the concentration of inhibin (range 55.3-72.3 U/l) during the follicular phase until day -2 after which an increase to a midcycle peak of 139 +/- 10.6 U/l was observed. No correlation was observed between inhibin and B-FSH during the follicular phase. A second increase in the concentration of inhibin was seen during the luteal phase; peak levels occurred by day 6 (311 +/- 25.8 U/l), remained elevated until day 12, and were negatively correlated with B-FSH (r = -0.53, P less than 0.001). No correlation was observed between oestradiol and inhibin or B-FSH during the luteal phase. We conclude that (1) oestradiol secretion from the growing follicle is primarily responsible for the negative feedback regulation of B-FSH resulting in a change from peak levels in the early follicular phase to basal levels in the late follicular phase; (2) significant and sustained increase in peripheral inhibin concentrations occur mostly during the luteal phase; and (3) regulation of FSH secretion by inhibin occurs primarily in the luteal phase. These results suggest a temporal relationship between oestradiol and inhibin in the negative feedback regulation of FSH in vivo.


Cutaneous lupus erythematosus and autoimmune thyroiditis.
A 19-year-old girl presented with cutaneous lupus erythematosus and hypothyroidism, and developed a thyrotoxic crisis when chloroquine therapy was discontinued.


Smad4 (DPC4)--a potent tumour suppressor?
The recently described family of Smad molecules are essential mediators of transforming growth factor beta (TGF-beta) signalling. To date, seven members of this family have been identified, each of which plays a specific and separate role in mediating TGF-beta superfamily gene transcription. At least two different Smads, Smad2 and Smad4 (DPC4), have been implicated in human cancer and appear to have tumour-suppressor functions. Loss of function of Smad4 is most strongly associated with human pancreatic and colorectal malignancy. Furthermore, work from several different groups has suggested associations between Smad4 loss and malignancy in a number of other tissues. Here, we present a review of the current state of the literature implicating the central Smad mediator, Smad4, in the development of cancer.


Prognostic significance of whole-body MRI in patients with monoclonal gammopathy of undetermined significance.
Radiological skeletal survey or computed tomography are currently applied to assess bone diseases in patients with monoclonal plasma cell disorders. Whole-body magnetic resonance imaging (whole-body MRI) allows detecting the infiltration of clonal cells in nearly the whole bone marrow compartment even before bone destruction has occurred. Those MRI results (i.e., patterns of bone marrow infiltration) have been demonstrated to be of prognostic significance in patients with symptomatic as well as asymptomatic multiple myeloma. We have therefore analyzed the findings of whole-body MRI in 137 consecutive individuals with monoclonal gammopathy of undetermined significance (MGUS). A focal infiltration pattern was detected in 23.4% of patients. Presence and number of focal lesions as well as value of M-Protein were of independent prognostic significance for progression into a symptomatic disease requiring systemic treatment (P=0.02; P<0.0001 and P=0.0005, respectively). Lower homogeneous signal intensities in T1-weighted images were related to a physiologically higher bone marrow cellularity in younger individuals (P=0.002). We conclude that whole-body MRI identifies patients with focal accumulations of presumably monoclonal cells in bone marrow with prognostic impact concerning the risk of progression into symptomatic disease.


Oral microbiomes of patients with infective endocarditis (IE): a comparative pilot study of IE patients, patients at risk for IE and healthy controls.
Infective endocarditis (IE) is an uncommon disease with high morbidity and mortality rates, which often develops from oral bacterial species entering circulation. We compared oral microbiome profiles of three groups: IE patients (N 9 patients; n = 27 samples), disease controls at risk for IE (N = 28; n = 84), and healthy controls (N = 37; n = 111). Bacterial species in IE patients' blood cultures were identified for comparison with matched oral samples. Oral microbiome profiles were obtained from buccal mucosa, saliva, and tongue samples for all three groups and from sub- and supra-gingival plaque samples of the IE group (N = 9; n = 16) and disease controls (N = 28; n = 54). Alpha- and beta-diversities were determined based on relative abundance data. Discriminative species were identified by LEfSe, post hoc Mann-Whitney, and ROC analyses. Identity of the bacterial species in IE patients' blood cultures was confirmed by 16S-rRNA gene Sanger sequencing. Alpha- and beta-diversities differed between groups. Discriminative IE-associated species were identified, e.g. Haemophilus parainfluenzae and Streptococcus sanguinis. Two blood isolates were Staphylococcus aureus, also identified in one matched saliva sample. Streptococcus mutans was present in one patient's plaque samples and blood culture. Oral microbiomes of IE, non-IE disease controls, and healthy controls differed significantly. A better understanding of IE-related bacterial-host interactions is warranted.


Diagnostic and Prognostic Roles of GATA3 Immunohistochemistry in Urothelial Carcinoma.
This study aimed to evaluate the diagnostic and prognostic roles of GATA-binding protein 3 (GATA3) immunohistochemistry in urothelial carcinoma (UC) using a meta-analysis. We investigated GATA3 immunohistochemical expression rates and performed a subgroup analysis based on tumor site, study location, and histological subtypes. The overall survival rates of patients with GATA3-positive and -negative UC were compared. The estimated GATA3 expression rate was 0.748 (95% confidence interval [CI]: 0.704-0.787). GATA3 expression rates in the urinary bladder and urinary tract were 0.775 (95% CI: 0.727-0.818) and 0.614 (95% CI: 0.426-0.774), respectively. The GATA3 expression rates of noninvasive and invasive UCs were 0.965 (95% CI: 0.938-0.980) and 0.644 (95% CI: 0.581-0.702), respectively. In invasive UCs, there was a significant difference in GATA3 expression between non-muscular invasion and muscular invasion subgroups (0.937, 95% CI: 0.883-0.967 vs. 0.753, 95% CI: 0.645-0.836). GATA3 expression was the highest in the microcytic subtype among the histologic subtypes (0.952, 95% CI: 0.724-0.993). There was a significant correlation between GATA3 expression and better prognosis (hazard ratio: 0.402, 95% CI: 0.311-0.521). Taken together, GATA3 expression significantly correlated with low-stage and better prognosis in UC. GATA3 expression is highly variable across histological subtypes, and one should be careful while interpreting GATA3 expression.


Combined autologous cellular cardiomyoplasty with skeletal myoblasts and bone marrow cells in canine hearts for ischemic cardiomyopathy.
Cellular cardiomyoplasty with isolated skeletal myoblasts and bone marrow mononuclear cells is an encouraging therapeutic strategy for heart failure. We investigated the achievements accomplished with combined cell therapy of skeletal myoblast and bone marrow mononuclear cell transplantation to the ischemic canine myocardium. Autologous skeletal myoblasts (1 x 10(8)) and autologous bone marrow mononuclear cells (3 x 10(6)) were injected directly into the damaged myocardium of canine hearts that had undergone 2 weeks of left anterior descending coronary artery ligation. Treatment groups were as follows: skeletal myoblasts plus bone marrow mononuclear cells (combined cell therapy, n = 4), myoblasts (n = 4), bone marrow mononuclear cells (n = 4), and medium only (n = 4). In similarly designed supporting experiments, angiogenic factor expression was evaluated by enzyme-linked immunosorbent assay after cell transplantation in rat hearts that had undergone left anterior descending coronary artery ligation. Four weeks after cell implantation, echocardiography demonstrated better cardiac performance with reduced left ventricular dilation and significantly improved ejection fraction in the combined cell therapy group compared with that seen in the other groups (pretreatment, 37.7% +/- 1.1%, vs combined cell therapy, 55.4% +/- 8.6%; myoblasts, 47.4% +/- 7.4%; bone marrow mononuclear cells, 44.4% +/- 6.7%; medium only [control], 34.4% +/- 5.4%; P < .05). A significantly high number of neovessels were observed in the group receiving combined cell therapy only (combined cell therapy, 45.5 +/- 12 x 10(2)/mm2; myoblasts, 26.5 +/- 8 x 10(2)/mm2; bone marrow mononuclear cells, 30.7 +/- 15 x 10(2)/mm2; medium only [control], 7.1 +/- 1 x 10(2)/mm2; P < .05). Immunostained sections expressed the skeletal specific marker myosin heavy chain, although they did not express the cardiac specific marker troponin T. Results of enzyme-linked immunosorbent assay showed the highest expression of vascular endothelial growth factor (combined cell therapy, 2.9 +/- 0.7 ng/g tissue; myoblasts, 0.24 +/- 0.7 ng/g tissue; bone marrow mononuclear cells, 1.9 +/- 0.2 ng/g tissue; medium only [control], 0.19 +/- 0.004 ng/g tissue; P < .05) and hepatocyte growth factor in the combined cell therapy hearts. Combined autologous cellular therapy induced both myogenesis and angiogenesis with enhancement of cardiac performance and reduction of cardiac remodeling, suggesting a capable strategy for treating severe ischemic cardiomyopathy clinically.


Spontaneous extracranial decompression of epidural hematoma.
Epidural hematoma (EDH) is a common sequela of head trauma in children. An increasing number are managed nonsurgically, with close clinical and imaging observation. We report the case of a traumatic EDH that spontaneously decompressed into the subgaleal space, demonstrated on serial CT scans that showed resolution of the EDH and concurrent enlargement of the subgaleal hematoma.


Role of Nrf2 in cell senescence regulation.
Nuclear factor-E2-related factor 2 (Nrf2) is a key transcription factor known to be involved in maintaining cell redox balance and signal transduction and plays central role in reducing intracellular oxidative stress damage, delaying cell senescence and preventing age-related diseases. However, it has been shown that the level of Nrf2 decreases with age and that the silencing of the Nrf2 gene is associated with the induction of premature senescence. Therefore, a plethora of researchers have focused on elucidating the regulatory mechanism of Nrf2 in the prevention of cell senescence. This complex regulatory mechanism of Nrf2 in the cell senescence process involves coordinated regulation of multiple signaling molecules. After summarizing the function of Nrf2 and its relationship with cell senescence pathway, this review focuses on the recent advances and progress made in elucidating the regulatory mechanism of Nrf2 in the cell senescence process. Additionally, the information collected here may provide insights for further research on Nrf2, in particular, on its regulatory mechanism in the cell senescence process.


Mycobacterium scrofulaceum, serovar Cole.
Cole strains of Mycobacterium, originally introduced as M. scrofulaceum serovar No. 44 and later rejected as belonging to M. avium were re-investigated and compared with well-documented strains of M. scrofulaceum. Our data show that the Cole serovar belongs to M. scrofulaceum and should be re-introduced as serovar No. 44 of M. scrofulaceum.


Onboard early detection and mitigation of lithium plating in fast-charging batteries.
Fast-charging is considered as one of the most desired features needed for lithium-ion batteries to accelerate the mainstream adoption of electric vehicles. However, current battery charging protocols mainly consist of conservative rate steps to avoid potential hazardous lithium plating and its associated parasitic reactions. A highly sensitive onboard detection method could enable battery fast-charging without reaching the lithium plating regime. Here, we demonstrate a novel differential pressure sensing method to precisely detect the lithium plating event. By measuring the real-time change of cell pressure per unit of charge (dP/dQ) and comparing it with the threshold defined by the maximum of dP/dQ during lithium-ion intercalation into the negative electrode, the onset of lithium plating before its extensive growth can be detected with high precision. In addition, we show that by integrating this differential pressure sensing into the battery management system (BMS), a dynamic self-regulated charging protocol can be realized to effectively extinguish the lithium plating triggered by low temperature (0 °C) while the conventional static charging protocol leads to catastrophic lithium plating at the same condition. We propose that differential pressure sensing could serve as an early nondestructive diagnosis method to guide the development of fast-charging battery technologies.


[Complex immunochemical examination of patients with some liver disorders].
Complex differential-diagnostic immunodiffusional test for a number of blood plasma proteins, antigens of liver tissue and alpha-fetoprotein was used to evaluate the liver tissue functional state. The test characterized more distinctly the liver tissue function as compared with estimation of individual proteins and was more informative in diagnosis of liver tissue disorders.


Trunk, pelvic and hip kinematics during the Stork test in pregnant women with pelvic girdle pain, asymptomatic pregnant and non-pregnant women.
Pelvic girdle pain is prevalent during pregnancy, and women affected report weight-bearing activities to be their main disability. The Stork test is a commonly used single-leg-stance test. As clinicians report specific movement patterns in those with pelvic girdle pain, we aimed to investigate the influence of both pregnancy and pelvic girdle pain on performance of the Stork test. In this cross-sectional study, 25 pregnant women with pelvic girdle pain, 23 asymptomatic pregnant and 24 asymptomatic non-pregnant women underwent three-dimensional kinematic analysis of the Stork test. Linear mixed models were used to investigate between-group differences in trunk, pelvic and hip kinematics during neutral stance, weight shift, leg lift and single leg stance. Few and small significant between-group differences were found. Pregnant women with pelvic girdle pain had significantly less hip adduction during single leg stance compared to asymptomatic pregnant women (estimated marginal means (95% confidence intervals) -1.1° (-2.4°, 0.3°) and 1.0° (-0.4°, 2.4°), respectively; P = 0.03). Asymptomatic pregnant women had significantly less hip internal rotation compared to non-pregnant women 4.1° (1.6°, 6.7°) and 7.9° (5.4°, 10.4°), respectively (P = 0.04) and greater peak hip flexion angle of the lifted leg in single leg stance 80.4° (77.0°, 83.9°) and 74.1° (70.8°, 77.5°), respectively (P = 0.01). Variation in key kinematic variables was large across participants in all three groups. Our findings indicate that trunk, pelvic and hip movements during the Stork test are not specific to pregnancy and/or pelvic girdle pain in the 2nd trimester. Instead, movement strategies appear unique to each individual.


Neoadjuvant, adjuvant and palliative treatment of gastrointestinal stromal tumours (GIST) with imatinib: a centre-based study of 17 patients.
Malignant gastrointestinal stromal tumours (GIST) have a poor prognosis. Since these tumours are resistant to conventional radiation and chemotherapy, surgery has been the mainstay of treatment. However, surgery is usually inadequate for the treatment of malignant GIST. Imatinib, a KIT tyrosine kinase inhibitor, has recently been found to have a dramatic antitumour effect on GIST. In this centre-based study of 17 consecutive patients with high-risk or overtly malignant GIST, imatinib was used in three different settings - palliatively, adjuvantly, and neoadjuvantly. The treatment was found to be safe and particularly effective in tumours with activating mutations of exon 11 of the KIT gene. Clinical response to imatinib treatment correlated morphologically to tumour necrosis, hyalinisation, and reduced proliferative activity. The value of neoadjuvant imatinib treatment was illustrated in one case.


PM2.5 source apportionment identified with total and soluble elements in positive matrix factorization.
Source apportionments of urban aerosols identified with positive matrix factorization (PMF) are sensitive to input variables. So far, total elements were frequently included as effective factors in PMF-based source apportionment. We investigated the advances to involve soluble parts of elements in the source apportionment with four data sets of PM2.5 composition observed at a coastal city (Qingdao) in northern China: water-soluble ions plus organic and elemental carbon (IC set), the IC set plus total elements (ICTE set), the IC set plus soluble elements (ICSE set), and the IC set plus both total elements and soluble elements (ICAE set). The apportionments of six sources, including secondary sulfate, secondary nitrate, secondary oxalate, sea salt, biomass burning and dust, were identified with the IC set. In comparison, pollutants from vehicle + coal combustion, ship emissions, waste incineration and industrial activities were also identified with the ICTE, ICSE, or ICAE sets. We found that the PMF solutions of the ICAE set could distinguish aged and fresh dust, and identify fly ash and aged pollutants from industrial sources. The profiles and corresponding time series of vehicle + coal combustion, secondary aerosols, ship emissions, sea salt, and biomass burning emissions identified with the four data sets were very similar, while discrepancies were encountered for waste incineration, dust, and industrial sources. These results indicate the benefits and potentials with total and soluble elements involved in PMF-based source apportionments.


Point of care technology or standard laboratory service in an emergency department: is there a difference in time to action? A randomised trial.
Emergency Departments (ED) have a high flow of patients and time is often crucial. New technologies for laboratory analysis have been developed, including Point of Care Technologies (POCT), which can reduce the transport time and time of analysis significantly compared with central laboratory services. However, the question is if the time to clinical action is also reduced if a decisive laboratory answer is available during the first contact between the patient and doctor. The present study addresses this question: Does a laboratory answer, provided by POCT to the doctor who first attends the patient on admission, change the time to clinical decision in commonly occurring diseases in an ED compared with the traditional service from a central laboratory? We performed a randomised clinical trial with parallel design and allocation ratio 1:1. The eligibility Criteria were: All patients referred from General Practitioner or another referring doctor suspected for a deep venous thrombosis (DVT), acute coronary syndrome (ACS), acute appendicitis (AA) or acute infection (ABI). The outcome measure was the time spend from the blood sample was taken to a clinical decision was made. The study period took place in October--November 2009 and from February to April 2010. 239 patients were eligible for the study. There was no difference between the groups suspected for DVT, ACS and AA, but a significant reduction in time for the ABI group (p:0.009), where the median time to decision was reduced from 7 hours and 33 minutes to 4 hours and 38 minutes when POCT was used. Only in the confirmation of ABI the time to action was significantly shorter. Fast laboratory answers by POCT in an ED reduce the time to clinical decision significantly for bacterial infections. We suggest further studies which include a sufficient number of patients on deep venous thrombosis, acute appendicitis and acute coronary syndrome.


Follicular and Hürthle cell carcinoma: predicting outcome and directing therapy.
Follicular thyroid cancer is a heterogeneous disease including follicular and Hürthle cell and tumors with and without vascular and major capsular invasion. Analyses of prognosis and risk groups have been criticized for not taking these differences into account. Retrospective analysis was done of 240 patients treated from 1940 to 1997. Ninety-two patients without vascular or major capsular invasion followed up for a median of 14 years had no recurrences or deaths. In the remaining 148 patients, 32 had Hürthle cell and 116 had follicular cell carcinoma. Patients with Hürthle cell carcinoma were significantly older (55 vs 47 years; P = .0014). Lymphatic metastases did not influence outcome. Patients who were at high risk by age and sex, metastases, extent, and size had a 20-year survival rate of 36% for follicular and 35% for Hürthle cell carcinoma; patients at low risk had 20-year survival rates of 94% and 89%, respectively, with no significant difference between follicular and Hürthle cell carcinoma. Recurrences were treated successfully in 33% of patients with follicular carcinoma but never cured in patients with Hürthle cell carcinoma. Bilateral versus unilateral operation or radioiodine for ablation did not alter outcome. Follicular and Hürthle cell carcinoma with minimal capsular invasion behaved benignly. Age and sex, metastases, extent, and size risk criteria differentiate strongly between patients with high-risk and low-risk follicular and Hürthle cell carcinoma. Controlling for risk factors, Hürthle cell and follicular cell carcinomas have similar prognoses.


Longitudinal quality of life and quality adjusted survival in a randomised controlled trial comparing six months of bolus fluorouracil/leucovorin vs. twelve weeks of protracted venous infusion fluorouracil as adjuvant chemotherapy for colorectal cancer.
Longitudinal quality of life (QOL) assessment is infrequently made in adjuvant therapy for colorectal cancer (CRC). This analysis aims to assess QOL and quality adjusted survival (QAS) in patients receiving adjuvant 5-FU for stage II and III CRC. We performed a multicentre study in which 801 patients were randomised to 6 months of bolus 5-FU/leucovorin (LV n = 404) or 12 weeks of protracted venous infusion (PVI) 5-FU (n = 397). There were significant differences in the deterioration of QOL scores at week 2 with bolus 5-FU/LV compared to PVI 5-FU (P < 0.001), coinciding with toxicity peak during the first cycle. Following week 12, global QOL recovered to baseline when PVI 5-FU was stopped but this was delayed with bolus 5-FU/LV until completion at week 24. QOL scores significantly improved in both arms during follow-up (P < 0.001) and reached a plateau by year 1 without incremental improvement between years 2 and 5. There was a trend towards better QAS with PVI 5-FU. Twelve weeks of adjuvant PVI 5-FU was associated with significantly better QOL during treatment and faster time to recovery compared to 6 months of bolus 5-FU/LV.


Atrial fibrillation with rapid ventricular response in pregnancy.
To report a case of atrial fibrillation with rapid ventricular response occurring during pregnancy. A 35-year-old woman, gravida 3, para 1, abortus 1, with a history of persistent supraventricular arrhythmia, presented at 22 weeks' gestation. After adenosine administration, electrocardiography revealed atrial fibrillation with rapid ventricular response. The episode was complicated by hemodynamic instability and was refractory to verapamil. Sinus rhythm was restored after synchronized electrical cardioversion under sedation. Sotalol (80 mg) was given for arrhythmia and to control heart rate. The patient experienced a second episode of supraventricular arrhythmia at 26 weeks' gestation, which was also reversed after cardioversion. She delivered a healthy male baby at 38 weeks' gestation via scheduled cesarean section. Arrhythmias with underlying heart disease can result in serious hemodynamic deterioration. Electrical cardioversion is well-tolerated and effective in pregnant women and should not be withheld if clinically indicated.


Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy for the treatment of locally advanced esophageal cancer: a population-based analysis.
Currently, the optimal treatment strategy for locally advanced esophageal cancer (LAEC) remains controversial. We perform the present study to compare the outcomes of LAEC treated with neoadjuvant chemotherapy (neo-CT) or chemoradiotherapy (neo-CRT). A population cohort with histologically diagnosed of esophageal cancer was identified from SEER database between 2004 and 2015. The Kaplan-Meier method and Cox-regression proportional hazards model were used to assess the impact of neoadjuvant treatment regimens on the cause-specific survival (CSS) and overall survival (OS) of LAEC. A propensity score model was utilized to balance baseline covariates. After propensity score matching, a total of 1986 LAEC patients were included for analysis, 1,655 patients treated with neo-CRT and 331 with neo-CT, respectively. The survival outcomes of LAEC treated with neo-CRT were comparable to those treated with neo-CT in terms of 5-year OS (39% vs. 36%, p = 0.63) and CSS (51% vs. 51%, p = 0.77). In the multivariate Cox analyses, sex, histological grade, ypT stage, ypN( +), and number of LN examined were independent factors for predicting OS and CSS among LAEC treated with neoadjuvant treatment. The present study based on large cohort demonstrated that no significant survival difference was observed between LAEC patients treated with neo-CRT versus neo-CT. However, the results needed to be confirmed in well-designed prospective trials.


Predicting Sex in White Rhinoceroses: A Statistical Model for Conservation Management.
Ensuring the effective management of every rhinoceros population is crucial for securing a future for the species, especially considering the escalating global threat of poaching and the challenges faced in captive breeding programs for this endangered species. Steroid hormones play pivotal roles in regulating diverse biological processes, making fecal hormonal determinations a valuable non-invasive tool for monitoring adrenal and gonadal endocrinologies and assessing reproductive status, particularly in endangered species. The purpose of this study was to develop a statistical model for predicting the sex of white rhinoceroses using hormonal determinations obtained from a single fecal sample. To achieve this, 562 fecal samples from 15 individuals of the Ceratotherium simum species were collected, and enzyme immunoassays were conducted to determine the concentrations of fecal cortisol, progesterone, estrone, and testosterone metabolites. The biological validation of the method provided an impressive accuracy rate of nearly 80% in predicting the sex of hypothetically unknown white rhinoceroses. Implementing this statistical model for sex identification in white rhinoceroses would yield significant benefits, including a better understanding of the structure and dynamics of wild populations. Additionally, it would enhance conservation management efforts aimed at protecting this endangered species. By utilizing this innovative approach, we can contribute to the preservation and long-term survival of white rhinoceros populations.


Fibroblast responses to cyclic mechanical stretching depend on cell orientation to the stretching direction.
Fibroblasts in intact tendons align with stretching direction, but they tend to orient randomly in healing tendons. Therefore, a question arises: Do fibroblast responses to mechanical stretching depend on their orientation? To address this question, human patellar tendon fibroblasts were grown in custom-made silicone dishes that possess microgrooved culture surfaces. The direction of the microgrooves was either parallel or normal to the direction of cyclic uniaxial stretching. Fibroblasts grown in these microgrooves had a polar morphology and oriented along the direction of the microgrooves regardless of the stretching conditions. Tendon fibroblasts expressed higher levels of alpha-smooth muscle actin when they were oriented parallel to the stretching direction than when they were oriented normal to the stretching direction. Also, cyclic stretching of the fibroblasts perpendicular to their orientation induced a higher activity level of secretory phospholipase A(2) compared with stretching of the cells parallel to their orientation. Thus, these results show that fibroblast responses to mechanical stretching depend on cell orientation to the stretching direction.


Use of a reflectance spectrophotometer in evaluating shade change resulting from tooth-whitening products.
Historically, shade change assessment associated with vital bleaching treatment regimens has been visually evaluated through the use of shade guide tabs. Innovations in the industry of dentistry have brought forth new technologies capable of measuring such changes via the capture and analysis of reflected wavelengths of light. This article introduces the use of a 45/0 reflectance spectrophotometer and identifies the advantages and limitations associated with such a technology in the assessment of shade change owing to vital bleaching.


A novel ING2 isoform, ING2b, synergizes with ING2a to prevent cell cycle arrest and apoptosis.
We identified a novel inhibitor of growth family member 2 (ING2) isoform, ING2b, which shares exon 2 with ING2a, but lacks the N-terminal p53 binding region. Contrary to ING2a, ING2b's promoter has no p53 binding sites. Consistently, activation of p53 led to suppression of ING2a, leaving ING2b unaffected. Through isoform-specific targeting, we showed that ING2a knockdown suppressed cell growth only in the presence of p53, ING2b knockdown had no effect on cell growth, and knockdown of both induced cell cycle arrest and apoptosis independently of p53. ING2a and ING2b have compensatory roles that protect cells from cell cycle arrest and apoptosis and may be involved in development of chemotherapeutic resistance.


Natural cryoprotectants combinations of l-proline and trehalose for red blood cells cryopreservation.
Cryopreservation of red blood cells (RBCs) holds great potential benefits for supplying transfusion timely in emergencies. Currently, glycerol is the main cryoprotectant permitted in clinical therapy for RBCs cryopreservation, but its broad application is limited by the toxicity and complex deglycerolization process. Successful cryopreservation of RBCs using more effective materials should be studied to reduce freezing damage, increase biocompatibility, and save processing time. Herein, a simple protocol using natural cryoprotectants combinations of l-proline and trehalose attains a low degree of hemolysis (11.2 ± 2.73%) after thawing compared to glycerol. Furthermore, the morphology of RBCs and the activities of Na+/K+-ATPase and Ca2+/Mg2+-ATPase maintain well. Further mechanism study shows that l-proline plays an important role in decreasing the freezing points and inhibiting the growth of ice crystal by permeating into cells during the freezing process. While trehalose works as an inhibitor of ice growth in the freezing process and ice recrystallization in the thawing process. This simple l-proline & trehalose combinations protocol is a promising method to replace current time-consuming and labor-intensive cryopreservation methods of RBCs.


Baseline data of facial parameters in the population of Haryana: An anthropometric study.
Anthropometry plays an important role in the assessment of ethnicity and identification of an individual. There is paucity of literature on various facial parameters in Haryanvi population. Thus, the present study was an initiation to collect this database in Haryanvi population. The aim of the present study was to create a database of craniofacial parameters of Haryanvi population. The study was conducted on 300 individuals of Haryanvi ethnicity. A digital vernier caliper was used for the measurement of facial parameters. Chi-square test, t-test, and Pearson's correlation test were used for finding the difference between the measurements for various parameters. In the present study, mesoprosopic was the predominant facial phenotype in both males and females. A significant sexual dimorphism was found between all the facial parameters measured in the study. However, upper facial height and facial index did not follow the same pattern in relation to gender determination. Based on the present study findings, we conclude that craniofacial parameters could be used as an important tool to assess the ethnicity and gender of an individual. In addition, our data could be used as a baseline for further studies in the identification of a Haryanvi individual.


Coupling Adsorption-Photocatalytic Degradation of Methylene Blue and Maxilon Red.
The MB and MR removal process by two mechanisms of adsorption using rice straw (absence of UV light) and photodegradation on TiO2 surfaces was investigated. MB and MR removal efficiency were further intensified upon the sequential operation of adsorption followed by photocatalytic degradation over TiO2 under visible light irradiation. The TiO2 was used to remove methylene blue (MB) and Maxilon Red (MR) dye from aqueous media by continuous mode at 25 ± 2 °C, at pH 6.8 ± 0.2. Photo-illumination study revealed 75.81 and 65.51% MB and MR removal with the dose of 1 g/L TiO2 with an initial concentration of 5 mg/L within 120 min. This study can be deemed of potential applications for the removal of MB and MR dyes on an industrial level using the synergistic adsorption-photocatalytic oxidation approach. A probable photodegradation mechanism was proposed.


Coeliac disease in primary care: case finding study.
To provide evidence of underdiagnosis of coeliac disease and to describe the main presenting symptoms of coeliac disease in primary care. Case finding in a primary care setting by testing for coeliac disease by using the endomysial antibody test. Nine surgeries in and around a market town in central England, serving a population of 70 000. First 1000 patients screened from October 1996 to October 1997. Determination of endomysial antibody titre of patients fulfilling the study criteria, followed by small intestine biopsy of those with positive results. The 30 patients (out of 1000 samples) with positive results on the endomysial antibody test all had histological confirmation on small intestine biopsy. The commonest mode of presentation (15/30) was anaemia of varying severity. Most patients (25/30) presented with non-gastrointestinal symptoms. Specificity of the endomysial antibody test was 30/30. Underdiagnosis and misdiagnosis of coeliac disease are common in general practice and often result in protracted and unnecessary morbidity. Serological screening in primary care will uncover a large proportion of patients with this condition and should be made widely available and publicised. Coeliac disease should be considered in patients who have anaemia or are tired all the time, especially when there is a family history of the disease.


Exosomal HMGA2 protein from EBV-positive NPC cells destroys vascular endothelial barriers and induces endothelial-to-mesenchymal transition to promote metastasis.
Increased vascular permeability facilitates metastasis. Cancer-secreted exosomes are emerging mediators of cancer-host crosstalk. Epstein-Barr virus (EBV), identified as the first human tumor-associated virus, plays a crucial role in metastatic tumors, especially in nasopharyngeal carcinoma (NPC). To date, whether and how exosomes from EBV-infected NPC cells affect vascular permeability remains unclear. Here, we show that exosomes from EBV-positive NPC cells, but not exosomes from EBV-negative NPC cells, destroy endothelial cell tight junction (TJ) proteins, which are natural barriers against metastasis, and promote endothelial-to-mesenchymal transition (EndMT) in endothelial cells. Proteomic analysis revealed that the level of HMGA2 protein was higher in exosomes derived from EBV-positive NPC cells compared with that in exosomes derived from EBV-negative NPC cells. Depletion of HMGA2 in exosomes derived from EBV-positive NPC cells attenuates endothelial cell dysfunction and tumor cell metastasis. In contrast, exosomes from HMGA2 overexpressing EBV-negative NPC cells promoted these processes. Furthermore, we showed that HMGA2 upregulates the expression of Snail, which contributes to TJ proteins reduction and EndMT in endothelial cells. Moreover, the level of HMGA2 in circulating exosomes is significantly higher in NPC patients with metastasis than in those without metastasis and healthy negative controls, and the level of HMGA2 in tumor cells is associated with TJ and EndMT protein expression in endothelial cells. Collectively, our findings suggest exosomal HMGA2 from EBV-positive NPC cells promotes tumor metastasis by targeting multiple endothelial TJ and promoting EndMT, which highlights secreted HMGA2 as a potential therapeutic target and a predictive marker for NPC metastasis.


Paediatric day-case surgery: an audit of unplanned hospital admission Royal Hospital for Sick Children, Glasgow.
Audit of unplanned hospital admission provides information to guide quality improvement measures and is a crude indicator of quality of care in ambulatory surgery. Our objectives were to re-audit factors relating to this outcome. Previous audit conducted in this unit revealed an unplanned admission rate of 3.7%. Data were collected between April 2000-March 2004. Of 13 592 day surgery patients, 238 (1.8%) unplanned admissions occurred. The admission rate displayed a falling trend and represented a significant improvement over the previous audit (p < 0.001). Unplanned admissions were most commonly caused by nausea/vomiting 23.5% (n = 56), postoperative bleeding 13.9% (n = 34), and unexpected extent/difficulty of procedure 11.8% (n = 28). Of all admissions, 18.5% (n = 44) were following orchidopexy, 16.4% (n = 39) following circumcision, and 12.6% (n = 30) following dental extraction. This audit shows that the unplanned admission rate is low and falling, and compares favourably with other units. Measures have been implemented targeting patients at high risk of admission.


High In-hospital mortality after percutaneous endoscopic gastrostomy: results of a nationwide population-based study.
It is important to carefully select patients who undergo endoscopic procedures, to optimize health care. Percutaneous endoscopic gastrostomy (PEG) is a frequently performed invasive endoscopic procedure that has been associated with high short-term mortality. We used a national database to determine the incidence of, and factors associated with, in-hospital mortality among patients undergoing PEG. We conducted a nested, case-control, retrospective study using the US Nationwide Inpatient Sample (NIS) to analyze data from all hospitalizations in 2006 with an International Classification of Diseases, 9th revision, procedure code for PEG. Bivariate and multivariate logistic regression analyses were performed using demographic and clinical variables to identify predictors of in-hospital mortality after the procedure. A separate analysis using a propensity score matching technique was conducted to compare mortality with a control cohort. Results were validated in an independent analysis of 2007 NIS data. In-hospital mortality was 10.8% among 181,196 patients who underwent PEG in 2006 (95% confidence interval, 10.3%-11.3%). Odds of death increased with age (1%/y), congestive heart failure, renal failure, chronic pulmonary disease, coagulopathy, pulmonary circulation disorders, metastatic cancer, and liver disease. The indication for PEG was associated strongly with mortality. Women and patients with diabetes mellitus or paralysis had a lower risk of death. PEG was associated with slightly higher odds of in-hospital mortality compared with patients who did not undergo PEG. Qualitatively and quantitatively similar results were obtained when 2007 NIS data were analyzed. The mortality rate is almost 11% among hospital inpatients after PEG. We have identified factors that increase and decrease the risk of death after PEG; these factors could improve patient selection for those most likely to benefit from this procedure.