Localization of the Sodium-Taurocholate cotransporting polypeptide in membrane rafts and modulation of its activity by cholesterol in vitro.
The relevance of discrete localization of hepatobiliary transporters in specific membrane microdomains is not well known. To determine whether the Na+/taurocholate cotransporting polypeptide (Ntcp), the main hepatic sinusoidal bile salt transporter, is localized in specific membrane microdomains. Presence of Ntcp in membrane rafts obtained from mouse liver was studied by immunoblotting and immunofluorescence. HEK-293 cells stably transfected with rat Ntcp were used for in vitro studies. Expression, localization and function of Ntcp in these cells were assessed by immunoblotting, immunofluorescence and biotinylation studies and Na+ -dependent taurocholate uptake assays, respectively. The effect of cholesterol depletion/repletion assays on Ntcp function was also investigated. Ntcp localized primarily to membrane rafts in in vivo studies and localized partially in membrane rafts in transfected HEK-293 cells. In these cells, membrane cholesterol depletion resulted in a shift of Ntcp localization into non-membrane rafts, which correlated with a 2.5-fold increase in taurocholate transport. Cholesterol repletion shifted back part of Ntcp into membrane rafts, and normalized taurocholate transport to values similar to control cells. Ntcp localizes in membrane rafts and its localization and function are regulated by membrane cholesterol content. This may serve as a novel regulatory mechanism of bile salt transport in liver.


EGR1 upregulation following Venezuelan equine encephalitis virus infection is regulated by ERK and PERK pathways contributing to cell death.
Venezuelan equine encephalitis virus (VEEV) is a neurotropic virus that causes significant disease in both humans and equines. Here we characterized the impact of VEEV on signaling pathways regulating cell death in human primary astrocytes. VEEV productively infected primary astrocytes and caused an upregulation of early growth response 1 (EGR1) gene expression at 9 and 18 h post infection. EGR1 induction was dependent on extracellular signal-regulated kinase1/2 (ERK1/2) and protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK), but not on p38 mitogen activated protein kinase (MAPK) or phosphoinositide 3-kinase (PI3K) signaling. Knockdown of EGR1 significantly reduced VEEV-induced apoptosis and impacted viral replication. Knockdown of ERK1/2 or PERK significantly reduced EGR1 gene expression, dramatically reduced viral replication, and increased cell survival as well as rescued cells from VEEV-induced apoptosis. These data indicate that EGR1 activation and subsequent cell death are regulated through ERK and PERK pathways in VEEV infected primary astrocytes.


Guanine nucleotide exchange factors (GEFs) have a critical but not exclusive role in organelle localization of Rab GTPases.
Membrane fusion at eukaryotic organelles is initiated by Rab GTPases and tethering factors. Rabs in their GDP-bound form are kept soluble in the cytoplasm by the GDP dissociation inhibitor (GDI) chaperone. Guanine nucleotide exchange factors (GEFs) are found at organelles and are critical for Rab function. Here, we surveyed the overall role of GEFs in Rab localization. We show that GEFs, but none of the proposed GDI displacement factors, are essential for the correct membrane localization of yeast Rabs. In the absence of the GEF, Rabs lost their primary localization to the target organelle. Several Rabs, such as vacuolar Ypt7, were found at the endoplasmic reticulum and thus were still membrane-bound. Surprisingly, a Ypt7 mutant that undergoes facilitated nucleotide exchange localized to vacuoles independently of its GEF Mon1-Ccz1 and rescued vacuole morphology. In contrast, wild-type Ypt7 required its GEF for localization and to counteract the extraction by GDI. Our data agree with the emerging model that GEFs are critical for Rab localization but raise the possibility that additional factors can contribute to this process.


Transitional cell carcinoma of the pelvicalices and ureter.
Transitional cell carcinoma accounts for about 90% of all cancers of the renal pelvis and more than 90% of all cancers of the ureter. Its clinical presentation is nonspecific. Radiology plays a critical role in detection, evaluation, and disease monitoring. We reviewed the pathologic and clinical features of transitional cell carcinoma of the upper urinary tract, with attention to its radiology appearance, staging, and treatment.


Assessment of dental malocclusion and soft-tissue features among children with special needs in the Western UP region: A cross-sectional study.
Assessment of dental malocclusion and soft-tissue features among children with special needs and their correlation with normal children. A cross-sectional study was carried out among 128 children (63 special health-care needs children and 65 normal children), between 8 and 18 years of age. Two special schools (Vatsalya and Jeevandhara) were included in the study for case group and two local schools (one government and one private) were included in the study for control group. Index of Orthodontic Treatment Need was used to measure the malocclusion. To assess and compare various facial features, extra-oral photographs were taken from two different views (frontal and side). Data were analyzed using ANOVA and Chi-square test, with keeping level of significance at P < 0.05. The result of the present study demonstrated a significant difference between the study and control group with respect to overjet, caries, stains and calculus, soft-tissue facial profile, lip competency, and Korkhaus lip step. Soft-tissue comparison demonstrated facial asymmetry; lip incompetency was more prevalent in the study group compared to the control group. Overall, it was concluded that malocclusion was more prevalent in the study group compared to their counterparts. Malocclusion was more prevalent in children with disability compared to their counterparts. On clinical examination, a significant difference in relation to overjet, caries and stains, and calculus was observed, whereas a significant difference on soft-tissue examination was observed in facial profile, lip competency, and Korkhaus lip step in the study group compared to normal children.


Solitary plasmacytoma associated with Epstein-Barr virus: a clinicopathologic, cytogenetic study and literature review.
Solitary plasmacytoma (SP) is an uncommon, indolent tumor of plasma cell neoplasms that presents as a mass lesion in extramedullary sites. Evidence of Epstein-Barr virus (EBV) infection is frequently associated with various lymphatic and hematopoietic malignancies but is relatively rare in SP. Moreover, it is essential to distinguish EBV-positive plasmacytoma from plasmablastic lymphoma. In this study, we found 4 EBV-encoded RNA (EBER)-positive patients among 46 consecutive immunocompetent patients of SP and compared the clinicopathologic features of these patients with those of the EBER-negative cohort. In the 4 EBER-positive patients, the common presenting feature was a local mass lesion without symptoms of chronic active EBV infection. Upon histologic examination, neoplastic cells demonstrated well-differentiated morphology in the absence of plasmablastic lymphoma components. Fluorescence in situ hybridization analysis showed that all cases were negative for del13q14, t(11;14)(q13;32) and MYC rearrangement but that 1 case had cytogenetic aberrations involving del17p13. Follow-up data revealed that EBER-positive patients had benign prognoses without aggressive clinical course and that there was no significant difference in the overall survival time between the 2 groups, but EBER-positive patients were more likely to have disease progression (relapse/progression to multiple myeloma) compared with EBER-negative patients. More case studies are needed to better understand the impact of EBV on disease pathogenesis and development in immunocompetent patients of SP.


Regulatory elements in aflatoxin biosynthesis.
This review provides a synopsis of factors involved in the regulation of aflatoxin inAspergillus species at the molecular level. Much of the knowledge available today on the regulation of secondary metabolite production in fungi has been gleaned from studies of the aflatoxin gene cluster inA. flavus andA. parasiticus and the sterigmatocystin gene cluster inA. nidulans. Regulation of these two gene clusters is under the control of both pathway-specific transcription factors such as AflR and AflJ and global or broad-domain transcription factors such as AreA and PacC. Study of secondary metabolite (sec-) mutants inA. parasiticus first identified an association between mycotoxin production and fungal development. This linkage has been extended at the molecular level by the characterization of a G-protein/cAMP/Protein kinase A signaling pathway that regulates sporulation via the transcription factor BrlA and aflatoxin/sterigmatocystin production via AflR. Another global regulator of mycotoxin production, VeA, mediates a developmental light-response inA. nidulans andA. flavus. Though not similar to any known fungal transcriptional regulators, VeA controls aflatoxin/sterigmatocystin production via transcriptional control of AflR and it also regulates development of sexual structures such as cleistothecia inA. nidulans and sclerotia inA. flavus.


Effects of anterior-posterior shifts in prosthetic alignment on the sit-to-stand movement in people with a unilateral transtibial amputation.
The sit-to-stand movement can be challenging for people with a transtibial amputation (TTA). The alignment of the prosthesis may influence the movement strategies people with TTA use to transfer from sit-to-stand by affecting foot placement. The purpose of this study was to determine how shifting the prosthetic foot anterior and posterior relative to the socket affects movement strategies used to transfer from sit-to-stand. To aid in interpretation, we compared movement strategies between people with and without TTA. Nine people with TTA and nine sex-, and age-matched non-amputee controls completed five self-paced sit-to-stand trials. With the posterior alignment, participants with TTA had 1) smaller braking GRF impulse on the prosthetic side and greater impulse on the intact side compared to the anterior alignment, 2) no significant differences between sides, which suggests greater braking impulse symmetry compared to anterior and prescribed alignments, and 3) smaller axial trunk range of motion compared to the prescribed alignment. There were also differences between participants with TTA and controls in braking GRF impulse, knee extension moment, anterior/posterior center of pressure position, and lateral and axial trunk range of motion. Based on these results, shifting the prosthetic foot posterior to the socket may be a useful tool to reduce braking impulse asymmetry and trunk motion in people with TTA during sit-to-stand. Thus, prosthetic alignment can have important implications for the comfort and ability of people with TTA to transfer from sit-to-stand as well as for development of secondary health conditions like low back pain, which is associated with compensatory movements.


A Resuscitated Adult With Left Main Coronary Artery Ostial Atresia and Graves' Disease: 10-Year Follow-up.
This is the first report of a resuscitated adult with left main coronary artery ostial atresia (LMCAOA), with long-term follow-up for 10 years. A 57-year-old woman with untreated Graves' disease presented with resuscitated cardiac arrest, and her computed tomography coronary angiography showed a string-like left main without significant atherosclerosis, which led to the diagnosis of LMCAOA. Noninvasive and invasive testing revealed extensive myocardial ischemia because of LMCAOA with concomitant coronary spasm. After successful revascularization with coronary artery bypass grafting, the patient has remained stable for 10 years, which highlights this treatment as being highly effective and durable in patients with LMCAOA and cardiac arrest.


Ongoing use of an affective rating scale in the treatment of a mentally retarded individual with a rapid-cycling bipolar affective disorder.
Empirically tracking cyclic variations in the behavior of mentally retarded individuals with bipolar affective disorders is difficult because disturbances in mood are difficult to operationally define and quantify. The following report presents a case study in which a moderately retarded man's mood and energy were rated by direct care staff who completed a mood rating scale two times each day. The resulting weekly summaries of the data were plotted on a graph which indicated the cyclic fluctuations in symptom areas related to his bipolar disorder. This information was of great value in assessing therapeutic interventions and in designing habilitative activities congruent with shifts in the behavioral patterns.


A modified method using TRIzol reagent and liquid nitrogen produces high-quality RNA from rat pancreas.
To establish an economical and reproducible method for the high-quality RNA extraction from pancreas, we isolated total RNA from rat pancreas with TRIzol reagent and liquid nitrogen. In the initial stage, we optimized three influential factors, the way to homogenize pancreas, the time to collect the pancreatic tissue from animals, and the weight of the pancreatic tissue in 1 ml of TRIzol reagent. The RNA quality was determined by detecting total RNA content and its absorbance at 260/280 nm wavelength, visualizing RNA in non-denatured agarose gel and performing RT-PCR of pancreas-specific genes. The A (260)/A (280) ratio of the total RNA extracted by grinding 20-30 mg of rat pancreatic tissue removed from the rats in liquid nitrogen within 1 min and then immersed in 1 ml of the TRIzol Reagent was 1.75-1.89, and the ratio of 28S/18S ribosomal RNA bands was more than 1.8. Furthermore, full length of Pdx1 open-reading frame was amplified with RNA extracted from the grinding group rather than from the conventional group. The RT-PCR products of pancreas-specific genes from both exocrine and endocrine parts of pancreas were successfully derived from the extracted RNA. The results suggested that we successfully provided an economical, fast, and reproducible method to obtain the high-quality and intact RNA from rat pancreas with TRIzol Reagent and liquid nitrogen.


Aurora-A kinase nuclear expression in chronic lymphocytic leukemia.
Aurora-A kinase is a cell-cycle-regulating kinase required for chromosomal segregation. Overexpression of Aurora-A kinase has been shown to correlate with tumor proliferation and chromosomal instability. We investigated Aurora-A kinase expression in peripheral blood and bone marrow of 47 chronic lymphocytic leukemia patients and 20 age-matched hematologically healthy subjects. Western blot analysis showed significantly higher Aurora-A levels in chronic lymphocytic leukemia (42 of 47) compared with lymphocytes of healthy subjects. However, Aurora-A mRNA expression in three chronic lymphocytic leukemia patients was similar to or lower than that of healthy control subjects. In 28 of 42 chronic lymphocytic leukemia patients with elevated Aurora-A kinase expression, one or more chromosomal abnormalities were detected, including trisomy 12 in 9 patients and deletion of the ataxia telangiectasia-mutated gene in 9 patients. Aurora-A was also detected in all (100%) chronic lymphocytic leukemia cases by immunohistochemistry, with a nuclear staining pattern. The larger prolymphocytes and paraimmunoblasts showed stronger Aurora-A kinase expression than did small lymphocytes. In contrast, normal bone marrow reactive lymphocytes were negative for Aurora-A with positive histiocytes and immature myeloid cells. Immunostaining for acetylated histone H3 showed a nuclear pattern in all 38 chronic lymphocytic leukemia cases and double labeling showed coexpression of acetylated histone H3 and Aurora-A. In summary, Aurora-A kinase is overexpressed in chronic lymphocytic leukemia cells. The expression of acetylated histone H3 suggests that Aurora-A kinase may be active (functional). Thus, Aurora-A kinase overexpression in chronic lymphocytic leukemia may be involved in the genesis of chromosomal abnormalities and is a potential target for therapeutic intervention.


Preferential expression of actin genes during oogenesis of Drosophila.
The expression of actin genes was examined during oogenesis of Drosophila. Accumulation of actin proteins was quantitated by a two-stage electrophoresis procedure. Egg chambers accumulate actins preferentially, resulting in a twofold enrichment over other nonyolk proteins. RNA gel blot hybridization experiments demonstrated a concomitant twofold selective increase of actin mRNA levels over that of other mRNAs, suggesting regulation of actin genes at the pretranslational level. Despite an abrupt arrest of actin protein accumulation near the end of oogenesis, the bulk of the actin mRNAs remains associated with polysomes of constant size. It appears that this shut-off of actin protein accumulation is due to an overall decrease in translational efficiency, rather than actin mRNA degradation or its dissociation from polysomes.


Corneal edema resolution after "descemetorhexis".
A 79-year-old woman had left eye phacoemulsification complicated by inadvertent excision of Descemet's membrane (DM). One day postoperatively, the visual acuity was counting fingers with diffuse corneal edema. The patient was treated medically, with gradual resolution of the corneal edema over a 6-month period. The torn edge of DM could be visualized as the edema cleared, and no endothelial cell count could be obtained centrally. Approximately 1 year postoperatively, the central endothelial cell count was 2114 cells/mm(2) in the right eye and 827 cells/mm(2) in the left eye. The decreased cell count, increased polymegethism, and pleomorphism suggested that endothelial cells migrated to cover the stromal surface area in the absence of DM.


Behavioral factors in development of tolerance to ethanol's effects.
Dose-effect analyses were used to monitor the development of tolerance for ethanol's effects on FR30 operant performance in rats under different conditions of chronic ethanol exposure: (a) pre-session ethanol injections (PRE) vs. post-session ethanol injections (POST) in Experiment 1; and (b) an ethanol liquid diet (ED) vs. a control diet (CD) in Experiment 2. The PRE and ED groups developed tolerance at the conclusion of the chronic regimens, which declined by six months but not to baseline levels. These data suggest that tolerance results from learned compensatory adjustments (through intoxicated practice) to ethanol's disruptive effects. The POST, but not the CD, group developed a progressively increasing degree of tolerance after several ethanol challenge tests. These results suggest that some threshold level of passive ethanol exposure in the POST group interacted with their limited intoxicated practice. Finally, the tolerance developed under intoxicated practice conditions did not appear to reflect a generalized tolerance to rate-reducing properties of drugs, changes in ethanol kinetics, or age-related changes.


Stroke patients' preferences and values about emergency research.
In the USA, the Food and Drug Administration waiver of informed consent permits certain emergency research only if community consultation occurs. However, uncertainty exists regarding how to define the community(ies) or their representatives. To collect data on the actual preferences and values of a group-those at risk for stroke-most directly affected by the waiver of informed consent for emergency research. Face to face focused interviews were conducted with 12 patients who were hospitalised with a stroke diagnosis in the previous year. The interviews were audiotaped and a transcript based method was used for their analysis. All 12 participants felt "that it was important that new treatments for stroke be developed", but they were initially confused about the distinction between "research for stroke" and "emergency research for stroke". However, after explanation, most (n = 10; 83%) expressed willingness to participate in the latter. In the absence of a surrogate to give informed consent in a stroke emergency situation, the majority (n = 11; 92%) said they would want the physician to "go ahead and enrol them in the trial". This study is the first to identify the values and concerns of individuals most directly affected by stroke emergency research. Further interviews and focus groups are needed to develop and test a validated questionnaire on the preferences and values surrounding emergency research for stroke.


Enzymes of the crotonase superfamily: Diverse assembly and diverse function.
The crotonase fold is generated by a framework of four repeats of a ββα-unit, extended by two helical regions. The active site of crotonase superfamily (CS) enzymes is located at the N-terminal end of the helix of the third repeat, typically being covered by a C-terminal helix. A major subset of CS-enzymes catalyzes acyl-CoA-dependent reactions, allowing for a diverse range of acyl-tail modifications. Most of these enzymes occur as trimers or hexamers (dimers of trimers), but monomeric forms are also observed. A common feature of the active sites of CS-enzymes is an oxyanion hole, formed by two peptide-NH hydrogen bond donors, which stabilises the negatively charged thioester oxygen atom of the reaction intermediate. Structural properties and possible use of these enzymes for biotechnological applications are discussed.


Molecular signature of excessive female aggression: study of stressed mice with genetic inactivation of neuronal serotonin synthesis.
Aggression is a complex social behavior, critically involving brain serotonin (5-HT) function. The neurobiology of female aggression remains elusive, while the incidence of its manifestations has been increasing. Yet, animal models of female aggression are scarce. We previously proposed a paradigm of female aggression in the context of gene x environment interaction where mice with partial genetic inactivation of tryptophan hydroxylase-2 (Tph2+/- mice), a key enzyme of neuronal 5-HT synthesis, are subjected to predation stress resulting in pathological aggression. Using deep sequencing and the EBSeq method, we studied the transcriptomic signature of excessive aggression in the prefrontal cortex of female Tph2+/- mice subjected to rat exposure stress and food deprivation. Challenged mutants, but not other groups, displayed marked aggressive behaviors. We found 26 genes with altered expression in the opposite direction between stressed groups of both Tph2 genotypes. We identified several molecular markers, including Dgkh, Arfgef3, Kcnh7, Grin2a, Tenm1 and Epha6, implicated in neurodevelopmental deficits and psychiatric conditions featuring impaired cognition and emotional dysregulation. Moreover, while 17 regulons, including several relevant to neural plasticity and function, were significantly altered in stressed mutants, no alteration in regulons was detected in stressed wildtype mice. An interplay of the uncovered pathways likely mediates partial Tph2 inactivation in interaction with severe stress experience, thus resulting in excessive female aggression.


Prevalence and risk factors of bluetongue in small and large ruminants maintained on Government farms in North-western Pakistan.
This study reports prevalence of antibodies against bluetongue virus (BTV) in animals kept on Government farms/research stations in North-western Pakistan and its association with different risk factors. In total, 1257 blood samples were collected, at random, from animals on 12 separate Government farms/research stations. The prevalence of antibodies against BTV was evaluated using a competitive ELISA. Mixed effects univariate and multivariate logistic regressions were applied to ascertain different risk factors associated with the prevalence of the infection using farm as random effect variable. The overall weighted seroprevalence was recorded as 52%. In univariate analysis, a significant association between sero-conversion to BTV infection and species (P < 0.0001), sex (P < 0.0001), herd size (P = 0.0295) and age of animal (P < 0.0001) was recorded. In multivariate mixed effects logistic regression analysis, prevalence of the infection was found to be 7 (95% CI =2-28) times higher in goats and buffalo than in sheep. Prevalence of the infection was found to be 2.5 (95% CI =1.7-3.3) times higher in female than male animals. However, no significant association was found between sero-conversion of BTV and herd size in multivariate mixed effects logistic regression. Age was found to be a risk factor for the sero-conversion; odds of sero-conversion to BTV increased by 1.29, 1.4, 1.32 and 1.6 times per year increase in age of sheep, goats, buffalo and cattle, respectively. Prevalence of bluetongue was found higher in animals maintained on Government owned farms than that in individual holdings, as previously reported in Pakistan.


Urodiagrams: a new method of uroflow pattern analysis.
Uroflow diagrams, obtained by plotting the mean flow rate at 1-second intervals for controls and patients with bladder outflow obstruction, have been studied in 60 healthy controls and 100 patients. Standard patterns were obtained for male and female controls in 3 different age groups and for patients with various types of lower urinary tract obstruction. Outflow diagrams in age and sex-matched controls were compared to those obtained from patients, indicating the nature and the site of obstruction.


Identification and comparative profiling of miRNAs in herbaceous peony (Paeonia lactiflora Pall.) with red/yellow bicoloured flowers.
Herbaceous peony (Paeonia lactiflora Pall.) is popular worldwide because of its gorgeous flower colour, and the yellow flower is the rarest. However, its mechanism of yellow formation is still unexplored from the post-translational level. In this study, the anatomy of the petal, cell sap pH and metal elements were investigated in bicoloured flower cultivar 'Jinhui' with red outer-petal and yellow inner-petal, and the yellow formation was influenced by the anatomy of petal, while not by the cell sap pH and metal elements. Subsequently, microRNAs sequencing (miRNA-seq) was used to identify small RNAs (sRNAs). A total of 4,172,810 and 3,565,152 specific unique sRNAs were obtained, 207 and 204 conserved miRNAs and 38 and 42 novel miRNAs were identified from red outer-petal and yellow inner-petal, respectively, which were confirmed by subcloning. Among these miRNAs, 163 conserved and 28 novel miRNAs were differentially expressed in two wheel of petals. And 5 differentially expressed miRNAs and their corresponding target genes related to yellow formation were screened, and their dynamic expression patterns confirmed that the yellow formation might be under the regulation of miR156e-3p-targeted squamosa promoter binding protein-like gene (SPL1). These results improve the understanding of miRNA regulation of the yellow formation in P. lactiflora.


Quetiapine alleviates the cuprizone-induced white matter pathology in the brain of C57BL/6 mouse.
Recent human studies employing new magnetic resonance imaging techniques and micro-array analyses feature schizophrenia as a brain disease with alterations in white matter (WM), which is mainly composed of oligodendrocytes (OLs) and their processes wrapping around neuronal axons. To examine the putative role of OLs in the pathophysiology and treatment of schizophrenia, animal studies are essential. In the present study, C57BL/6 mice were given 0.2% cuprizone (CPZ) in their diet for five weeks during which they drank distilled water without or with quetiapine (QTP, 10 mg/kg). The mice fed with normal chow were used as controls. CPZ is a copper chelator and has been reported to induce consistent demyelination in the brain of C57BL/6 mouse by specifically damaging OLs. QTP is an atypical antipsychotic widely used in the treatment of schizophrenia and other psychotic disorders. In accordance with previous studies, CPZ-exposed mice showed pervasive myelin breakdown and demyelination. The amount of myelin basic protein (MBP) in the cerebral cortex was decreased by CPZ-exposure as shown in Western-blot analysis. In addition, the demyelinated sites were teemed with activated microglia and astrocytes but a few myelin forming OLs. Moreover, the activity of copper-zinc superoxide dismutase decreased in the cerebral cortex of CPZ-exposed mice. However, all of these pathological changes in WM were either prevented or alleviated in CPZ-exposed mice co-administered with QTP. These results suggest that the CPZ-exposed C57BL/6 mouse is a potential animal model to study possible roles of OLs in the pathogenesis and treatment of schizophrenia.


Glucocorticoids and insulin but not growth hormone modulate insulin binding to adipocyte membranes from sheep.
Mechanisms by which the glucocorticoid analogue dexamethasone and growth hormone modulate insulin action in sheep adipose tissue have been investigated. Maintenance of sheep adipose tissue in culture for 48 hr in the absence of exogenous hormones resulted in a decrease in insulin binding to adipocyte membranes; this was prevented by the inclusion of 10 nM dexamethasone during culture. Tissue culture for 48 hr with insulin itself decreased insulin binding to adipocyte membranes, whereas tissue culture with growth hormone had no effect on insulin binding. Neither dexamethasone nor growth hormone altered the ability of insulin to decrease insulin binding to its receptor. The study shows that the insulin-antagonistic effects of growth hormone on sheep adipose tissue metabolism are due to an effect subsequent to insulin binding to its receptor, whereas some of the effects of dexamethasone may be due to an increase in the insulin-binding capacity of membranes.


Pulmonary Cavitation With Eosinophilia in a Young Man.
An 18-year-old man with no noted medical history from Northern India presented with history of fever for 15 days and nocturnal cough for 10 days. He denied breathlessness or wheeze. There was no medical history of asthma. He denied any current sinus-related symptoms, pruritis, skin rashes, lesions, or ulcers, abdominal pain, dysphagia, vomiting or diarrhea, numbness or tingling, joint pain, or food allergy. There was no recent exposure to a patient with TB or history of substance misuse. The patient had sought medical care 7 days before presentation for the same symptoms, and after a chest radiograph was obtained, the patient was started on an antitubercular regimen.


Loss of Slfn3 induces a sex-dependent repair vulnerability after 50% bowel resection.
Bowel resection accelerates enterocyte proliferation in the remaining gut with suboptimal absorptive and digestive capacity because of a proliferation-associated decrease in functional differentiation markers. We hypothesized that although schlafen 3 (Slfn3) is an important regulator of enterocytic differentiation, Slfn3 would have less impact on bowel resection adaptation, where accelerated proliferation takes priority over differentiation. We assessed proliferation, cell shedding, and enterocyte differentiation markers from resected and postoperative bowel of wild-type (WT) and Slfn3-knockout (Slfn3KO) mice. Villus length and crypt depth were increased in WT mice and were even longer in Slfn3KO mice. Mitotic marker, Phh3+, and the proliferation markers Lgr5, FoxL1, and platelet-derived growth factor-α (PDGFRα) were increased after resection in male WT, but this was blunted in male Slfn3KO mice. Cell-shedding regulators Villin1 and TNFα were downregulated in female mice and male WT mice only, whereas Gelsolin and EGFR increased expression in all mice. Slfn3 expression increased after resection in WT mice, whereas other Slfn family members 1, 2, 5, 8, and 9 had varied expressions that were affected also by sex difference and loss of Slfn3. Differentiation markers sucrase isomaltase, Dpp4, Glut2, and SGLT1 were all decreased, suggesting that enterocytic differentiation effort is incompatible with rapid proliferation shift in intestinal adaptation. Slfn3 absence potentiates villus length and crypt depth, suggesting that the differentiating stimulus of Slfn3 signaling may restrain mucosal mass increase through regulating Villin1, Gelsolin, EGFR, TNFα, and proliferation markers. Therefore, Slfn3 may be an important regulator not only of "normal" enterocytic differentiation but also in response to bowel resection.NEW & NOTEWORTHY The differentiating stimulus of Slfn3 signaling restrains an increase in mucosal mass after bowel resection, and there is a Slfn3-sex interaction regulating differentiation gene expression and intestinal adaptation. This current study highlights the combinatory effects of gender and Slfn3 genotype on the gene expression changes that contribute to the adaptation in intestinal cellular milleu (i.e. villus and crypt structure) which are utilized to compensate for the stress-healing response that the animals display in intestinal adaptation.


Isolation and partial characterization of three allergens of timothy pollen.
Three allergens, antigen Nos. 3, 25, and 30, were isolated from freeze-dried aqueous extract of timothy pollen by various combinations of anionic and cationic exchange and gel chromatography. The allergens were all of protein nature and contained less than 2% (w/w) immunochem;cally detectable impurities. Molecular weights and pI's were determined to less than 10 X 10(3), 15 X 10(3) and 3.9, 4.5, 9.4, respectively, and antigen 25 was determined as the major component of the earlier isolated antigen B. amino acid analyses performed an antigens 3 and 30 revealed large variation s in the amino acid composition. The allergenic activities were verified by means of RAST inhibition and pick tests and proved antigen 25 to be quantitatively the most important allergen of timothy pollen.


High-performance liquid chromatographic determination of erdosteine and its optical active metabolite utilizing a fluorescent chiral tagging reagent, R-(-)-4-(N,N-dimethylamiosulfonyl)-7-(3-aminopyrrolidin-1-yl)-2 ,1,3-benzoxadiazole.
Chiral separation of racemic M1 metabolized from erdosteine was investigated by reversed-phase chromatography. The sensitive determination of M1 and erdosteine with UV detection was difficult because of their low absorptivity in the effective wavelength region. To improve the sensitivity and separatability, one thiol and two carboxyl groups in the M1 structure were labelled with DBD-F and R-(-)-DBD-APy, respectively. Non-fluorescent DBD-F quantitatively reacted with thiol in M1 at room temperature for 30 min in borate buffer (pH 9.3) to produce the fluorescent derivative. On the other hand, the labelling of two carboxyls was carried out with a chiral fluorescent reagent, R-(-)-DBD-APy, in acetonitrile containing DPPA. The derivatives corresponding to a pair of the enantiomers were completely separated with water-acetonitrile containing 0.1% TFA as the mobile phase by an ODS column. Erdosteine with a carboxyl group was also labelled with R-(-)-DBD-APy and separated together with M1 derivatives. The detection limits (S/N=3) of erdosteine and M1 were 0.37 and 0.22 pmol, respectively. The proposed derivatization and separation methods were applied to simultaneous determination of racemic M1 and erdosteine in rat plasma after administration of erdosteine. The amounts of both enantiomers of M1 were essentially the same in oral and intravenous administrations. In contrast, total amounts (reduced-form and oxidized-form) of S-(-)-M1 in rat plasma were higher than those of R(+)-M1 in both administrations.


Avoidance of adjuvant radiotherapy in selected patients with invasive breast cancer.
Current standard therapy for invasive breast carcinoma is mastectomy or breast conservation with adjuvant radiation. Data from randomized trials suggest no advantage for radiotherapy after lumpectomy in highly selected patients. Selective radiotherapy would make contemporary breast cancer therapy more rational with decreased morbidity and expense. A total of 163 patients were treated by breast conservation without adjuvant radiation between 1978 and June 2003. They declined radiation after discussion or had medical contraindications. The great majority were postmenopausal and had lower-grade T1 tumors with resection margins > or = 1 cm and no nodal metastases. The goal was to identify patients with favorable prognostic features for omission of postsurgical irradiation without impaired local recurrence or survival. Twenty patients (12%) had local recurrences; 17 (10%) were invasive, and 3 (2%) were ductal carcinoma-in-situ. An ideal patient subgroup >50 years of age with grade 1 or 2 cancers < or =1.5 cm in diameter and with surgical margins > or = 1 cm was empirically defined. Of 80 such patients, 5 (6%) had local recurrence; 3 (3.5%) were invasive, and 2 (2.5%) were ductal carcinoma-in-situ. A defined ideal subset of older breast cancer patients with smaller, lower-grade cancers and adequate excision margins can be treated with lumpectomy without irradiation and with minimal local recurrence.


Torsion of an accessory spleen: a rare case preoperatively diagnosed and cured by single-port surgery.
We report a very rare case of acute abdomen caused by torsion of an accessory spleen that was preoperatively diagnosed and cured by single-port surgery. A 31-year-old woman was admitted to our hospital with severe left abdominal pain. Physical examination revealed a left upper quadrant abdominal tenderness with voluntary guarding. Ultrasound demonstrated a well-defined round mass isoechoic to the spleen, measuring 3.0 cm in diameter in the left upper quadrant adjacent to the spleen. A contrast-enhanced CT scan showed a normally enhanced spleen and a 3.0 × 3.0, hypodense, non-enhancing mass anterior to the spleen with a twisted funicular structure. Torsion of an accessory spleen was suspected, and emergency single-port surgery was performed. During surgery, a rounded violet mass measuring 3.0 cm in diameter, suggestive of an accessory spleen, with a 1800° torsion around a long vascular pedicle along the left side of the greater omentum was discovered. The mass was removed and post-operative recovery was uneventful. A review of the literature revealed 26 cases (including ours) of torsion of an accessory spleen in English. Even with the recent advances in radiologic imaging modalities, making a preoperative diagnosis of this is difficult and most cases are diagnosed during laparotomy. This is the first report preoperatively diagnosed and cured by single-port surgery. We decided to start the operation by using a single port, not only for cosmetic reasons for this young female patient, but also for final confirmation of our diagnosis. We believe that single-port laparoscopy is valuable as a diagnostic tool as long as safety is assured for patients with acute abdomen. Although torsion of an accessory spleen is extremely rare, it should be considered in the differential diagnosis of acute abdomen in children and young adults.


Increase in acetylcholine concentrations in the brain of 'old' rats following treatment with pyrithioxin (Encephabol).
Treatment of old rats, for two to three weeks, with pyrithioxin led to an increase in the levels of endogenous acetylcholine (ACh) in the cortex and the striatum but not in the hippocampus. Pretreatment of old rats with pyrithioxin also increased the resting release and the K+ stimulated release of radioactive ACh from brain slices in vitro.


New Scopes for Practice - Interdisciplinary Webinars for Emergency Medicine and Biomedical Informatics - Health Informatics.
This paper presents the early outcomes of the educational cooperation between two European academic associations, namely the European Federation of Medical Informatics (EFMI) and European Society of Emergency Medicine (EUSEM). Two webinars were organized in December 2019 and June 2020 to explore areas where mutual education would be beneficial for interdisciplinary cooperation to advance the digitization of emergency departments for the benefit of patients, health professionals and the health system as a whole. Preliminary findings from the analysis of these two webinars are presented and the steps for further cooperation are outlined.


Improved utilization of active sites for phosphorus adsorption in FeOOH/anion exchanger nanocomposites via a glycol-solvothermal synthesis strategy.
Metal oxide/hydroxide-based nanocomposite adsorbents with porous supporting matrices have been recognized as efficient adsorbents for phosphorus recovery. Aiming at satisfying increasingly restrictive environmental requirements involving improving metal site utilization and lowering metal leakage risk, a glycol-solvothermal confined-space synthesis strategy was proposed for the fabrication of FeOOH/anion exchanger nanocomposites (Fe/900s) with enhanced metal site utilization and reduced metal leakage risk. Compared to composites prepared using alkaline precipitation methods, Fe/900s performed comparably, with a high adsorption capacity of 19.05 mg-P/g with an initial concentration of 10 mg-P/L, a high adsorption selectivity of 8.2 mg-P/g in the presence of 500 mg-SO42-/L, and high long-term resilience (with a capacity loss of ~14% after five cycles), along with substantially lower Fe loading amount (4.11 wt.%) and Fe leakage percentage. Mechanistic investigation demonstrated that contribution of the specific FeOOH sites to phosphate adsorption increased substantially (up to 50.97% under the optimal conditions), in which Fe(III)-OH was the dominant efficient species. The side effects of an excessively long reaction time, which included quaternary ammonium decomposition, FeOOH aggregation, and Fe(III) reduction, were discussed as guidance for optimizing the synthesis strategy. The glycol-solvothermal strategy provides a facile solution to environmental problems through nanocrystal growth engineering in a confined space.


Objective Measures of Cognitive Performance in Sleep Disorder Research.
Neurocognitive tests offer objective and reliable assessment of patients' status and progress. However, there is no consensus on how to use neurocognitive assessment in sleep disorder research. An effective use of neurocognitive assessment must be based on standardized practices and have a firm theoretic basis. The aim of this review is to offer an overview of how different tests have been used in the field, mapping each test onto a corresponding cognitive domain and propose how to move forward with a suggested cognitive battery of tests covering all major cognitive domains.


Immune response in infants after universal hepatitis B vaccination: a community-based study in Malaysia.
This study aimed to assess the immune response in infants who received the three-shot hepatitis B vaccine in Malaysia. Consecutive infants born between March 2002 and April 2010 who received three doses of hepatitis B vaccine at a community clinic in Malaysia were enrolled in the study. Screening for hepatitis B surface antigen (HBsAg) and antibody against HBsAg (anti-HBs) was performed after the completion of primary immunisation, at approximately one year of age. A total of 572 infants (median age 9.3 ± 2.7 months; range 6.3-48 months) were screened for immune response to hepatitis B vaccination - 553 (96.7%) infants had adequate levels of anti-HBs (≥ 10 IU/L). Of the 440 mothers whose HBsAg status was known, 14 (3.2%) were positive for HBsAg. None of the 14 infants who were born to HBsAg-positive mothers were positive for HBsAg, and all but one infant had anti-HBs level ≥ 10 IU/L. Gender, gestational age and maternal HBsAg status were not found to significantly affect the subsequent immune response in infants following vaccination. The proportion of Malaysian mothers who are positive for HBsAg remains high. The three-shot hepatitis B vaccine, given as part of universal vaccination against hepatitis B, provides adequate anti-HBs in the vast majority of infants in a community setting in Malaysia.


A generalized framework of feature learning enhanced convolutional neural network for pathology-image-oriented cancer diagnosis.
In this paper, a feature learning enhanced convolutional neural network (FLE-CNN) is proposed for cancer detection from histopathology images. To build a highly generalized computer-aided diagnosis (CAD) system, an information refinement unit employing depth- and point-wise convolutions is meticulously designed, where a dual-domain attention mechanism is adopted to focus primarily on the important areas. By deploying a residual fusion unit, context information is further integrated to extract highly discriminative features with strong representation ability. Experimental results demonstrate the merits of the proposed FLE-CNN in terms of feature extraction, which has achieved average sensitivity, specificity, precision, accuracy and F1 score of 0.9992, 0.9998, 0.9992, 0.9997 and 0.9992 in a five-class cancer detection task, and in comparison to some other advanced deep learning models, above indicators have been improved by 1.23%, 0.31%, 1.24%, 0.5% and 1.26%, respectively. Moreover, the proposed FLE-CNN provides satisfactory results in three important diagnosis, which further validates that FLE-CNN is a competitive CAD model with high generalization ability.


Dioxin-like compounds in Australian sewage sludge--review and national survey.
An Australian survey of dioxin-like compounds in sewage sludge was conducted in two parts (a) a national survey, and (b) a time-study. All sewage sludge samples analysed as part of these studies had low overall concentrations of dioxin-like compounds. Out of 37 samples, all except one, were within the reported concentration range of soil within the Australian environment. The mean concentration of dioxin-like compounds in the Australian sewage sludge survey of 2006 was found to be 5.6 (s.d. 4.5) ng WHO(05) TEQkg(-1) (n=14) and were within the range of 1.2-15.3 ng WHO(05) TEQ kg(-1). All the Australian sewage sludge samples cited in these studies were below the Victorian EPA "investigation limit" of 50 ng WHO(98) TEQ kg(-1), and well below the European proposed guidelines of 100 ng I-TEQ kg(-1). The burden of dioxin-like compounds in Australian sewage sludge is low and its land application as biosolids is not likely to pose a problem. A general positive relationship was found between population of the town producing the waste and both dioxin-like PCDD/Fs and dioxin-like PCBs. The one exception to this trend was sludge from a town that had a history of smelting and had a relatively high burden of dioxin-like compounds. Sludge from one rural WWTP also had a higher burden of dioxin-like compounds. The treatment plant services a geographically isolated town with a low population and no known emitters of dioxin-like compounds. However, this sample also had a relatively high burden of dioxin-like PCBs, which could be the source of the dioxin-like PCDD/Fs found in this sludge. The time study analyzing sludges from three WWTP from the same city between the years 2002 and 2006 found no apparent difference between WWTPs, but a statistically significant decline of 1.49 ng WHO(05) TEQ kg(-1) per year. Also, a comprehensive review of the scientific literature, presents typical levels and sources of dioxin-like compounds in international sewage sludges.


Association between perceived organizational support and COVID-19 vaccination intention: A cross-sectional study.
We examined the association between perceived organizational support (POS) and COVID-19 vaccination intention as well as the influence of the implementation of workplace infection prevention measures. We analyzed data from an Internet survey of workers aged 20-65 years conducted in December 2020, during a period of widespread COVID-19 infection in Japan. Of the 23 846 participants in this survey, 1958 (8%) reported very high POS. In the group with very high POS, 836 (43%) workers wanted the COVID-19 vaccination; in contrast 1382 (36%) workers in the group with very low POS wanted the vaccination. POS was associated with COVID-19 vaccination intention (odds ratio [OR] = 1.11). The OR decreased after additional adjustment for the number of workplace infection control measures (OR = 1.06). In the analysis with POS as a categorical variable, very high POS was associated with COVID-19 vaccination intention (reference: very low POS) (OR = 1.34). The OR decreased after additional adjustment for the number of workplace infection control measures (OR = 1.17). High POS was associated with COVID-19 vaccination intention (OR = 1.17) but not with vaccination intention after additional adjustment for the number of workplace infection control measures (OR = 1.05). High POS during the COVID-19 pandemic increased employees' vaccination intention. The relationship between POS and vaccination intention was strongly influenced by implementation of workplace infection prevention measures. Implementing appropriate workplace infection prevention measures in the event of an emerging infectious disease outbreak may influence the vaccination behavior of employees, which may contribute to the acquisition of herd immunity in the community.


Minimally invasive plate osteosynthesis: An update of practise.
Since its conception in 1989, minimally invasive plate osteosynthesis (MIPO) has gained widespread popularity. It has been studied in over forty countries with most of the publications originating from Asia, Europe and North America. This review aims to describe the scientific path of MIPO from the very beginning to where it stands in current day times; study the pattern and contributing factors influencing its global spread. Finally, the up to date evidence is discussed with regard to several anatomical regions in which MIPO is mostly used. In the meantime, MIPO treads steadily towards accomplishing the same or better outcomes for more and more indications with the goal to leave a smaller surgical footprint to allow for undisturbed bone healing.


Gangliocytic paraganglioma arising from mature cystic teratoma of the ovary.
Gangliocytic paraganglioma is a rare neoplasm involving the small intestine, stomach, and spinal cord. Ovarian gangliocytic paraganglioma has not been reported in the medical literature. A 55-year-old caucasian woman underwent exploratory laparotomy, total abdominal hysterectomy, and bilateral salpingo-oophorectomy for evaluation of a persistent right adnexal mass. Microscopic examination of the right ovary revealed a mature cystic teratoma with a mural nodule consistent with gangliocytic paraganglioma. As there was no evidence of significant pleomorphism or neoplastic infiltration, surgical staging was not performed. Gangliocytic paraganglioma may arise from ovarian cystic teratoma. Although most cases of gangliocytic paragangliomas are benign, surgical staging and retroperitoneal lymphadenectomy may be required if histopathology is suggestive of invasive disease or if enlarged lymph nodes are noted.


Compact homogeneous Leviflat CR-manifolds.
We consider compact Leviflat homogeneous Cauchy-Riemann (CR) manifolds. In this setting, the Levi-foliation exists and we show that all its leaves are homogeneous and biholomorphic. We analyze separately the structure of orbits in complex projective spaces and parallelizable homogeneous CR-manifolds in our context and then combine the projective and parallelizable cases. In codimensions one and two, we also give a classification.


Perioperative Cardiovascular Risk of Prior Coronary Stent Implantation Among Patients Undergoing Noncardiac Surgery.
Previous studies have observed high rates of perioperative cardiovascular events in patients with coronary stents undergoing noncardiac surgery (NCS). It is uncertain whether this finding reflects an independent association. The goal of this study was to assess the independent relationship between prior coronary stent implantation and the occurrence of perioperative major adverse cardiac and cerebrovascular events (MACCE) and bleeding and its relation with time from stenting to NCS. A total of 24,313 NCS cases at the Mayo Clinic (Rochester, Minnesota) from 2006 through 2011 were included in the study; 1,120 (4.6%) cases involved patients with coronary stents. MACCE was defined as death, myocardial infarction, cardiac arrest, or stroke. Age-adjusted odds ratios (aORs) were calculated after propensity adjustment for Revised Cardiac Risk Index factors and other conventional risk factors. The 30-day MACCE rates were 3.7% and 1.5% in stented and unstented patients, respectively (p < 0.001). The risk of MACCE was largely related to the time from stent implantation to NCS, indicating substantially elevated risk in the first year after stenting (aOR: 2.59; 95% confidence interval [CI]: 1.36 to 4.94) but not thereafter (aOR: 0.89; 95% CI: 0.59 to 1.36). Bleeding displayed a similar pattern, indicating elevated risk in the first year after stenting (aOR: 2.23; 95% CI: 1.55 to 3.21) but not thereafter (aOR: 1.07; 95% CI: 0.89 to 1.28). Subgroup analysis in patients with known stent type found that the increased risk of both MACCE and bleeding >1 month after stent implantation was not limited to only those with drug-eluting stents. This study found that prior coronary stent implantation is an independent risk factor for MACCE and bleeding when time from stenting to NCS is <1 year, both in patients with bare-metal and drug-eluting stents.


Endoglin (CD105) and vascular endothelial growth factor as prognostic markers in esophageal adenocarcinoma.
Endoglin (CD105), a member of transforming growth factor beta1 receptor complex, has been shown to be a more useful marker to identify tumor angiogenesis than panendothelial markers such as CD31. We investigated endoglin and vascular endothelial growth factor (VEGF) expression as possible prognostic markers in esophageal adenocarcinoma. Surgical specimens from 75 patients with esophageal adenocarcinoma treated with esophagectomy were immunostained for endoglin, CD31, and VEGF. We also included 10 cases of Barrett's esophagus with high-grade dysplasia and 10 cases with Barrett's esophagus low-grade dysplasia. Positively stained microvessels (MVs) were counted in hot spots at magnification of x400. Results were expressed as the highest number of MV identified. For VEGF, intensity of staining was scored on 3-tiered scale. Endoglin demonstrated significantly more vessels than the CD31 (mean, 28.9 +/- 13.2 versus 19.0 +/- 9.4, P < .001). Both endoglin and CD31 MV counts showed significant correlation with stage of the disease (r = 0.59, P < .001; r = 0.52, P < .001, respectively) and patient survival (log rank P < .01). Only endoglin MV count was significantly correlated with the presence of angiolymphatic invasion (r = 0.34, P < .05) and lymph node (LN) metastases (r = 0.48, P < .001). Univariate analysis showed that endoglin MV count is an independent prognostic factor. Endoglin showed a significant increase in MV count in Barrett's esophagus with high-grade dysplasia when compared with Barrett's esophagus low-grade dysplasia (P < .01), whereas CD31 did not show any significant difference. VEGF was expressed in 48 (64%) of 75 cases of adenocarcinoma and was significantly correlated with angiolymphatic invasion, LN metastases, and survival. In conclusion, endoglin is a specific and sensitive marker for tumor angiogenesis. Endoglin staining also showed prognostic significance with positive correlation with the presence of angiolymphatic invasion, LN metastases, tumor stage, and survival.


The release of lysosomal enzymes from human polymorphonuclear leukocytes by human C3e.
C3e is a leukocytosis-inducing peptide of degraded C3 that has the electrophoretic behavior of prealbumin and a MW of 10-12,000. Using a homogeneous preparation, the ability of C3e to promote lysosomal enzyme release from human polymorphonuclear leukocytes (PMNs) was examined by incubation of various concentrations of C3e with cytochalasin B-treated (5 micrograms/ml) human PMNs for 60 min at 37 degrees C. Amounts of extracellular beta-glucuronidase, myeloperoxidase, and lysozyme were determined in the cell-free supernatants and it was found that all three enzymes were released in significant amounts without concomitant release of the cytoplasmic enzyme lactate dehydrogenase (LDH). At a concentration of 25 micrograms/ml of C3e, 25 +/- 1.1% (SD) of lysozyme, 20 +/- 0.9% beta-glucuronidase, and 24.3 +/- 0.9% myeloperoxidase were released into the supernatant while the release of LDH remained within the 4-7% range throughout these studies. Furthermore the supernatants were found to contain a substance which was capable of a generating chemotactic fragment from isolated C5. The same range of C3e concentrations (5-25 micrograms/ml) was, however, incapable of effecting histamine release from basophils. These results suggest that generation of C3e in vivo may serve as a potent stimulus for the generation of the C5-cleaving enzyme from PMNs which in turn may function to recruit more neutrophils by a positive feedback mechanism.


Lumbar Morel-Lavallee lesion after trauma: a report of 2 cases.
Morel-Lavallee syndrome is a posttraumatic soft tissue injury in which the subcutaneous tissue is broken off from the underlying fascia, creating a cavity filled with hematoma and liquefied fat. It commonly occurs over the greater trochanter and, rarely, may also occur in the lumbal region.Morel-Lavallee syndrome can be often diagnosed late because of ommitted diagnosis in emergency services. The emergency physician and radiologist must keep this syndrome in mind because early diagnosis can enable conservative management, whereas delayed diagnosis may lead to surgical exploration. In this article,we present the clinical and radiologic features of 2 cases of lumbar Morel-Lavallee syndrome detected after trauma.


G protein-coupled oestrogen receptor promotes cell growth of non-small cell lung cancer cells via YAP1/QKI/circNOTCH1/m6A methylated NOTCH1 signalling.
Results from various studies reveal that the role of G protein-coupled oestrogen receptor (GPER) is cancer-context dependent, and the function of GPER in non-small-cell lung cancer (NSCLC) is still unclear. The present study demonstrated that neoplasm lung tissues expressed higher level of GPER compared with the normal lung tissues. The clinical data also showed that GPER expression level was positively correlated with the tumour stage of NSCLC. Our experimental data confirmed that GPER played an oncogenic role to promote cell growth of NSCLC cells. Mechanistic dissection revealed that GPER could modulate the NOTCH1 pathway to regulate cell growth in NSCLC cells. Further exploration of the mechanism demonstrated that GPER could up-regulate circNOTCH1, which could compete with NOTCH1 mRNA for METTL14 binding. Because of the lack of m6A modification by METTL14 on the NOTCH1 mRNA, NOTCH1 mRNA was more stable and much easier to undergo protein translation. Subsequently, we found that GPER could prevent YAP1 phosphorylation and promote YAP1-TEAD's transcriptional regulation on QKI, a transacting RNA-binding factor involved in circRNA biogenesis, to facilitate circNOTCH1 generation. Supportively, data from preclinical mice model with implantation of H1299 cells also demonstrated that knock-down of circNOTCH1 could block GPER-induced NOTCH1 to suppress NSCLC tumour growth. Together, our data showed that GPER could promote NSCLC cell growth via regulating the YAP1/QKI/circNOTCH1/m6A methylated NOTCH1 pathway, and targeting our identified molecules may be a potentially therapeutic approach to suppress NSCLC development.


Theoretical and computational models of ion channels.
Computational studies can make meaningful contributions to our understanding of biological ion channels. A wide variety of methods, at different levels of approximation, can be used. Over the past few years, progress in the experimental determination of three-dimensional structures has given a fresh impetus to the theorists. Noteworthy progress has been made in carefully constructing realistic models of a number of complex biological channels to address important questions about their function.


A layered magnetic iron/iron oxide nanoscavenger for the analytical enrichment of ng-L(-1) concentration levels of heavy metals from water.
Magnetically driven separation techniques have received considerable attention in recent decade because of their great potential application. In this study, we investigate the application of an unmodified layered magnetic Fe/Fe(2)O(3) nanoscavenger for the analytical enrichment and determination of sub-parts per billion concentrations of Cd(II), Pb(II), Ni(II), Cr(VI) and As(V) from water samples. The synthesized nanoscavenger was characterized by BET, TGA, XRD and IR and the parameters influencing the extraction and recovery of the preconcentration process were assessed by atomic absorption spectrometry. The possible mechanism of the enrichment of heavy metals on Fe/Fe(2)O(3) was proposed, which involved the dominant adsorption and reduction. The nanoscale size offers large surface area and high reactivity of sorption and reduction reactions. The obtained limits of detection for the metals studied were in the range of 20-125 ng L(-1) and the applicability of the nanomaterial was verified using a real sample matrix. The method is environmentally friendly as only 15 mg of nanoscavenger are used, no organic solvent is required for the extraction and the experiment is performed without the need for filtration or preparation of packed preconcentration columns.


Subfoveal choroidal thickness as a predictor of treatment response to anti-vascular endothelial growth factor therapy for polypoidal choroidal vasculopathy.
To investigate whether subfoveal choroidal thickness predicted treatment response to anti-vascular endothelial growth factor (VEGF) in polypoidal choroidal vasculopathy (PCV). This retrospective observational case series included 66 eyes of 60 patients who were diagnosed with new-onset PCV and who were followed for a minimum of 6 months. Patients received three monthly intravitreal injections of 0.5 mg ranibizumab or 1.25 mg bevacizumab, at baseline, month 1, and month 2. "Good responders" were defined as those who showed complete resolution of subretinal and/or intraretinal fluid at month 3 after the loading injections, whereas "poor responders" were defined as those who showed persistent retinal fluid on optical coherence tomography (OCT) at month 3 after treatment. Differences in best-corrected visual acuity, indocyanine green angiography, and spectral domain-OCT findings at baseline were analyzed between the two groups. The mean patient age was 68.2 ± 9.7 years, and the mean follow-up period was 27 ± 21 months. The mean subfoveal choroidal thickness was 273 ± 117 μm, and choroidal vascular hyperpermeability was observed in 35 eyes (53.0 %). Thirty-three eyes (50 %) showed good response to treatment, and a thinner subfoveal choroid at baseline significantly correlated with favorable treatment response (P = 0.024). However, there was no significant relationship between treatment response and choroidal vascular hyperpermeability (P = 0.999). The subfoveal choroid was found to be significantly thinner among patients who achieved complete resolution of macular exudation after three loading injections of anti-VEGF agents.


Nightmare Disorder and Isolated Sleep Paralysis.
Nightmare disorder and recurrent isolated sleep paralysis are rapid eye movement (REM) parasomnias that cause significant distress to those who suffer from them. Nightmare disorder can cause insomnia due to fear of falling asleep through dread of nightmare occurrence. Hyperarousal and impaired fear extinction are involved in nightmare generation, as well as brain areas involved in emotion regulation. Nightmare disorder is particularly frequent in psychiatric disorders and posttraumatic stress disorder. Nonmedication treatment, in particular imagery rehearsal therapy, is especially effective. Isolated sleep paralysis is experienced at least once by up to 40% of the general population, whereas recurrence is less frequent. Isolated sleep paralysis can be accompanied by very intense and vivid hallucinations. Sleep paralysis represents a dissociated state, with persistence of REM atonia into wakefulness. Variations in circadian rhythm genes might be involved in their pathogenesis. Predisposing factors include sleep deprivation, irregular sleep-wake schedules, and jetlag. The most effective therapy consists of avoiding those factors.


Assessment of goat semen freezability according to the spermatozoa characteristics from fresh and frozen samples.
A total of 110 ejaculates were assessed in order to determine the influence of the physical parameters of goat semen on post-thaw motility and acrosome integrity. Sperm ejaculate characteristics, sperm motility, morphology and acrosome integrity were assessed in fresh and frozen samples by the sperm class analyzer (SCA) and Spermac staining technique. A decrease in acrosome integrity and sperm motility was found after thawing (P<0.01). Six semen parameters assessed before freezing were identified as predictors of sperm freezability (P<0.01). The percentage of morphological abnormalities (R=0.856) and motile sperm cells (R=0.655) in fresh semen are the best predictors to know the total post-thaw variability parameters.


First step in assessment of VipGrade®, a computerized clinical decision system to assess Vipera envenomation grading: a single-center interrater reliability study.
We conducted a retrospective review of Vipera spp. snakebite cases registered by the PCC of Bordeaux, France, between January 1, 2018, and December 31, 2020, evaluating the agreement between VipGrade® assessments, toxicologists' assessments, and current guidelines. 133 patients with Vipera aspis snakebites were included. There was 100% agreement in severity grading by PCC guidelines and VipGrade®. However, grading by toxicologists and VipGrade® diverged in 19 cases (85% agreement; κ = 0.80; 95% CI: 0.71 to 0.87). The VipGrade® tool's grading reflects current PCC guidelines, which are authoritative in France, and may allow for a more rapid and standardized determination of management and follow-up of viper-bitten patients. It should be noted, however, that the more complex and dynamic aspects of management are not included in VipGrade®. Its purpose is to supplement, not replace, the advice of the PCC's clinical toxicologists, and this advice should be sought whenever a viper bite is encountered in clinical practice.


Weaning from Mechanical Ventilation in Children: Are We Getting It Right?
How to cite this article: Baalaaji ARM. Weaning from Mechanical Ventilation in Children: Are We Getting It Right? Indian J Crit Care Med 2021;25(9):974-975.


Intersectoral problems in the Russian organisation of public health.
In spite of the ongoing transition of the Russian society, there is still a traditional view of public health, which is based to a great extent on the ideals and priorities of the Soviet period. Public health activities are regarded mainly as a responsibility of the health sector. There are, however, important public health activities going on also in other sectors of the society, for example, in the educational sector and the local communities, but also in the social insurance system. There is an important Russian tradition of prophylactic treatment in sanatoriums and health resorts, which is financed to a large extent by the social insurance. Based on three qualitative empirical studies, this article describes the organisation of public health in the Russian Federation and analyses the problems of intersectoral co-ordination and collaboration within this organisation. The analysis is focusing on the relations between the health sector and the social insurance system, which are not so well known outside the country. The results of this analysis show a fragmented organisation with a serious lack of co-ordination, but also a limited collaboration between the different sectors involved in public health. On the basis of these results, there is a discussion of how intersectoral collaboration could be improved in the Russian organisation of public health.


Plasticity in the injured spinal cord: can we use it to advantage to reestablish effective bladder voiding and continence?
Micturition is coordinated at the level of the spinal cord and the brainstem. Spinal cord injury therefore directly interrupts spinal neuronal pathways to the brainstem and results in bladder areflexia. Some time after injury, however, dyssynergic bladder and sphincter function emerges. The changes mediating the appearance of bladder function after spinal cord injury are currently unknown. Primary afferent neurons have been shown to sprout in response to spinal cord injury. Sprouting primary afferents have been linked to the pathophysiology of centrally manifested disorders, such as autonomic dysreflexia and neuropathic pain. It is proposed that sprouting of bladder primary afferents contributes to disordered bladder functioning after spinal cord injury. During development of the central nervous system, the levels of specific neuronal growth-promoting and guidance molecules are high. After spinal cord injury, some of these molecules are upregulated in the bladder and spinal cord, suggesting that axonal outgrowth is occurring. Sprouting in lumbosacral spinal cord is likely not restricted to neurons involved in the micturition reflex. Furthermore, sprouting of some afferents may be contributing to bladder function after injury, whereas sprouting of others might be hindering emergence of function. Thus selective manipulation of sprouting targeting afferents that are contributing to emergence of bladder function after injury is critical. Further research regarding the role that neuronal sprouting plays in the emergence of bladder function may contribute to improved treatment of bladder dyssynergia after spinal cord injury.


Aberrant inactivation of SCNN1G promotes the motility of head and neck squamous cell carcinoma.
The sodium channel epithelial 1 subunit gamma (SCNN1G) is mainly responsible for sodium entry and absorption. The dysfunction of SCNN1G has been widely studied in kidney-related diseases and chronic heart failure. However, its role in cancer remains unclear. Here, we found that SCNN1G was aberrantly downregulated in head and neck squamous cell cancer (HNSCC) tissues, which showed an efficifent diagnostic value according to the ROC curve analysis. The lower expression of SCNN1G was significantly correlated with lymphatic metastasis and a worse outcome of HNSCC patients. Ectopic overexpressing SCNN1G inhibited the invasive and migratory abilities of HNSCC cells, while knocking down SCNN1G showed an opposite effect. A positive correlation between SCNN1G and CDH1 expression was observed, which suggested that SCNN1G might impede HNSCC metastasis via strengthing cell-cell adherin. In addition, RAS signaling and ion channel transport signaling were enriched by SCNN1G in HNSCC using GSEA analysis, indicating that these signaling pathways might be the underlying mechanisms for SCNN1G as well. In addition, six sorts of immune infiltrate subtype cells were associated with SCNN1G expression. Our findings support that SCNN1G inactivation contributes to the metastasis of HNSCC. SCNN1G could serves as a valuable diagnostic and prognostic marker for HNSCC.


Effect of the esophageal carcinogen methylbenzylnitrosamine and of a putative potentiating factor, a trichothecene mycotoxin, on O6-methylguanine-dna methyl transferase in rat esophagus and liver.
Epidemiological evidence from China and South Africa has implicated Fusaria mycotoxins in the etiology of esophageal cancer, although treatment of animals with extracts of Fusaria cultures did not cause cancer of the esophagus. Fusaria are the major producers of trichothecenes, and animal experiments have shown that these mycotoxins can damage the esophagus but they have not been shown to cause esophageal cancer. A plausible concept is therefore that esophageal cancer is initiated by the potent environmental esophageal carcinogens, certain nitrosamines, but that the levels of exposure are too low to cause clinical cancer unless their effects are enhanced by additional risk factors. Among the most likely enhancing factors in the regions mentioned above are Fusaria mycotoxins. As trichothecenes are known to inhibit sulphydryl-dependent reactions and to inhibit protein synthesis, experiments were carried out to determine whether potentiation of cancer could be mediated via inhibition of the DNA repair protein O6-methylguanine-DNA methyl transferase (O6MG-MT). The effect of diacetoxyscirpenol (DS) on O6MG-MT was studied. Chronic or acute treatment with DS did not alter the level of O6MG-MT in esophagus, or affect the depletion which occurs after injection of methylbenzylnitrosamine, or alter the rate of reappearance of O6MG-MT. A high dose of DS induced O6MG-MT in liver. These results suggest that if trichothecenes are risk factors for esophageal cancer, the effect is unlikely to be mediated by inhibition of O6MG-MT. Induction of the repair protein in liver may be relevant in the animal toxicoses caused by consumption of trichothecenes, but is unlikely to be implicated in the etiology of liver cancer in man.


Amyloid-β40 E22K fibril in familial Alzheimer's disease is more thermostable and susceptible to seeding.
Alzheimer's disease (AD) is the most prevalent and devastating neurodegenerative disease occurred in the elderly. One of the pathogenic hallmarks is senile plaques composed of amyloid-β (Aβ) fibrils. Single mutations resided in Aβ were found in familial AD (FAD) patients that have early onset of the disease. The molecular details and properties of each FAD Aβ variants are still elusive. Here, we employed collective spectroscopic techniques to examine the properties of various Aβ40 fibrils. We generated fibrils of wild type (WT) and three FAD mutants on residue E22 including E22G, E22K, and E22Q. We monitored fibril formation by thioflavin T (ThT) assay, examined secondary structure by Fourier transform infrared and far-UV circular dichroism spectroscopy, imaged fibril morphology by transmission electron microscopy, and evaluated ThT-binding kinetics. In the thermal experiments, we found E22K fibrils resisted to high temperature and retained significant β-sheet content than the others. E22K fibril seeds after high-temperature treatment still possess the seeding property, whereas WT fibril seeds are disturbed after the treatment. Therefore, in this study we demonstrated the mutation at E22K increases the thermal stability and seeding function of amyloid fibrils.


Development of specific IgE antibodies after repeated exposure to snake venom.
A patient who had been working with snakes for many years developed urticarial lesions on contact with the venom of the poisonous rinkals (Haemachates haemachatus). More recently, the patient complained of generalized allergic reactions occurring within minutes of exposure to the venom. The patient's serum, but not control sera, contained IgE antibodies that reacted with the specific snake venom in an ELISA and was demonstrated to associate with a 66 kd component of the venom with Western blotting. With an ELISA, the patient's serum was also demonstrated to contain IgG antibodies to the specific snake venom and to venom from three other snakes with which the patient had previously been in contact. The possibility of an acute allergic reaction should be considered in individuals continuously working with snakes or in individuals who have previously been bitten by snakes.


Plexiform fibrohistiocytic tumor. Report of a case involving preoperative aspiration cytology and immunohistochemical and ultrastructural analysis of surgical specimens.
A typical case of plexiform fibrohistiocytic tumor (Enzinger and Zhang) occurring in the skin and subcutis of the abdominal wall in a 7-year-old girl is reported. Preoperative fine-needle aspiration cytology revealed a benign lesion with fibroblastic-histiocytic features which also contained bi- and multinucleated giant cells. The surgical specimen showed a tumor with multiple small nodules within fibrous septa; these nodules were composed of spindle cells and epithelioid cells and contained scattered multinucleated osteoclast-like cells. The tumor cells showed ultrastructural and immunohistochemical features of myofibroblasts and histiocyte-like cells. Thus, there was an abundance of lysosomes, prominent filopodia and bundles of thin cytofilaments along the cytoplasmic border, as well as immunoreactivity for alpha-smooth-muscle-specific actin, alpha-1-antitrypsin and alpha-1-antichymotrypsin. Ultrastructurally there were tumor cells exhibiting features of histiocytes which also contained bundles of actin of smooth muscle type. The presented case of plexiform fibrohistiocytic tumor appears to be composed of a rather peculiar cell form, somewhere between myofibroblasts and histiocytes.


Difficult iatrogenic bile duct injuries following different types of upper abdominal surgery: report of three cases and review of literature.
Iatrogenic bile duct injuries (BDIs) are mostly associated with laparoscopic cholecystectomy but may also occur following gastroduodenal surgery or liver resection. Delayed diagnosis of type of injury with an ongoing biliary leak as well as the management in a non-specialized general surgical units are still the main factors affecting the outcome. Herein we present three types of BDIs (Bismuth type I, IV and V) following three different types of upper abdominal surgery, ie. Billroth II gastric resection, laparoscopic cholecystectomy and left hepatectomy. All of them were complex injuries with complete bile duct transections necessitating surgical treatment. All were also very difficult to treat mainly because of a delayed diagnosis of type of injury, associated biliary leak and as a consequence severe inflammatory changes within the liver hilum. The treatment was carried out in our specialist hepatobiliary unit and first focused on infection and inflammation control with adequate biliary drainage. This was followed by a delayed surgical repair with the technique which had to be tailored to the type of injury in each case. We emphasize that staged and individualized treatment strategy is often necessary in case of a delayed diagnosis of complex BDIs presenting with a biliary leak, inflammatory intraabdominal changes and infection. Referral of such patients to expert hepatobiliary centres is crucial for the outcome.


How is intolerance of uncertainty related to negative affect in individuals with substance use disorders? The role of the inability to control behaviors when experiencing emotional distress.
We used structural equation modeling to assess the role of impaired emotional awareness and clarity (Impaired Awareness/Clarity) and inability to control behaviors when experiencing emotional distress (Inability to Control Behaviors) as an account for the relationship between intolerance of uncertainty (IU) and negative affect (NA) in individuals with Substance Use Disorders (SUDs) and healthy controls (HCs) used for comparison. One-hundred and thirty-one individuals with SUDs (42.75% female; mean age = 39.74 ± 11.83) and 131 sex-matched HCs (mean age = 40.02 ± 12.34) entered the study. Participants completed questionnaires assessing the constructs of interest. Single-group analyses aimed to identify a baseline model for each group and test the hypothesized direct/indirect relations' overall significance. Then, a multigroup analysis tested the invariance of model parameters between SUD and HC groups. The model in which IU had both direct and indirect relationships with NA through Impaired Awareness/Clarity and Inability to Control Behaviors was a good fit to the data. The indirect relationship of IU with NA through Inability to Control Behaviors was significant and moderate-sized. The relationship involving Impaired Awareness/Clarity and Inability to Control Behaviors was small-sized and significant in single group analysis only. The multigroup analysis supported the association of IU with NA through Inability to Control Behaviors in the SUD group. Overall, our study highlights the crucial role of the Inability to Control Behaviors in SUDs and suggests that its association with IU might fuel NA in this population.


Color information encoded by the spatiotemporal patterns of light response in ganglion cells of chick retina.
In the present study, the light responses of ganglion cells to chromatic stimulus were recorded from isolated retina of neonatal chick. It was found that for some non-color-opponent ganglion cells, the spatiotemporal patterns of the cells' light responses were related to the chromatic information that they received. When stimulus with some chromatic component was applied, some ganglion cells would generate distinguishable temporal patterns of light responses although these cells can be classified as non-color-opponent according to their light responses. The results suggest that in chick retina, the color information might be encoded not only by the color opponent ganglion cells, but also the spatiotemporal patterns of some ganglion cells that are traditionally classified as non-color-opponent subtype.


Advances in modification and delivery of nucleic acid drugs.
Nucleic acid-based drugs, such as RNA and DNA drugs, exert their effects at the genetic level. Currently, widely utilized nucleic acid-based drugs include nucleic acid aptamers, antisense oligonucleotides, mRNA, miRNA, siRNA and saRNA. However, these drugs frequently encounter challenges during clinical application, such as poor stability, weak targeting specificity, and difficulties in traversing physiological barriers. By employing chemical modifications of nucleic acid structures, it is possible to enhance the stability and targeting specificity of certain nucleic acid drugs within the body, thereby improving delivery efficiency and reducing immunogenicity. Moreover, utilizing nucleic acid drug carriers can facilitate the transportation of drugs to lesion sites, thereby aiding efficient intracellular escape and promoting drug efficacy within the body. Currently, commonly employed delivery carriers include virus vectors, lipid nanoparticles, polymer nanoparticles, inorganic nanoparticles, protein carriers and extracellular vesicles. Nevertheless, individual modifications or delivery carriers alone are insufficient to overcome numerous obstacles. The integration of nucleic acid chemical modifications with drug delivery systems holds promise for achieving enhanced therapeutic effects. However, this approach also presents increased technical complexity and clinical translation costs. Therefore, the development of nucleic acid drug carriers and nucleic acid chemical modifications that are both practical and simple, while maintaining high efficacy, low toxicity, and precise nucleic acid delivery, has become a prominent research focus in the field of nucleic acid drug development. This review comprehensively summarizes the advancements in nucleic acid-based drug modifica-tions and delivery systems. Additionally, strategies to enhance nucleic acid drug delivery efficiency are discussed, with the aim of providing valuable insights for the translational application of nucleic acid drugs.


[Calcium salts retention in the skeletal muscles of patients on hemodialysis].
Deposition of amorphous calcium salts in muscle tissue is not only of pathogenic but also of compensatory adaptive character. This occurs in response to bone exclusion from the system of regulation of calcium homeostasis (aluminum or severe uremic intoxication). Apparently, amorphous depositions of calcium salts may buffer fluctuations in ion concentration. Their accumulation is a marker of the weakening of the cellular mechanisms and enhancement of the physicochemical ones by which calcium homeostasis is maintained.


Synthesis, DNA-damaging and cytotoxic properties of novel topoisomerase II-directed bisantrene analogues.
New bisantrene analogues were synthesized, bearing one or two 4,5-dihydro-1H-imidazol-2-yl hydrazone side chains at positions 1,4 or 9 of the anthracene ring system. A 10-azabioisostere was also prepared. The position of substituents in structurally isomeric drugs modulates topoisomerase II poisoning and specificity, along with cytotoxicity.


Early Holocene human skeletal remains from Santana do Riacho, Brazil: implications for the settlement of the New World.
In this study we compare the cranial morphology of several late Paleoindian skeletons uncovered at Santana do Riacho, Central Brazil, with worldwide human cranial variation. Mahalanobis Distance and Principal Component Analysis are used to explore the extra-continental morphological affinities of the Brazilian Paleoindian sample. Santana do Riacho is a late Paleoindian burial site where approximately 40 individuals were recovered in varying states of preservation. The site is located at Lagoa Santa/Serra do Cipó, State of Minas Gerais. The first human activities in this rockshelter date back to the terminal Pleistocene, but the burials are bracketed between circa 8200 and 9500BP. The collection contains only six skulls well-enough preserved to be measured. The Santana do Riacho late Paleoindians present a cranial morphology characterized by long and narrow neurocrania, low and narrow faces, with low nasal apertures and orbits. The multivariate analyses show that they exhibit strong morphological affinities with present day Australians and Africans, showing no resemblance to recent Northern Asians and Native Americans. These findings confirm our long held opinion that the settlement of the Americas was more complicated in terms of biological input than has been widely assumed. The working hypothesis is that two very distinct populations entered the New World by the end of the Pleistocene, and that the transition between the cranial morphology of the Paleoindians and the morphology of later Native Americans, which occurred around 8-9ka, was abrupt. This, in our opinion, is a more parsimonious explanation for the diversity detected than a long, local microevolutionary process mediated by selection and drift. The similarities of the first South Americans with sub-Saharan Africans may result from the fact that the non-Mongoloid Southeast Asian ancestral population came, ultimately, from Africa, with no major modification in the original cranial bau plan of the first modern humans.


Hydrolyzed Yeast Supplementation in Calf Starter Promotes Innate Immune Responses in Holstein Calves under Weaning Stress Condition.
Weaned calves are susceptible to infectious diseases because of the stress and malnutrition that occurs during weaning. Therefore, the dairy industry requires effective feed additives to ameliorate stress responses and promote immunity. This study aimed to investigate the effects of hydrolyzed yeast (HY) supplementation on the growth performance, immune and stress parameters, and health status of calves after weaning. Eighteen Holstein calves were randomly assigned to two groups, either receiving a control calf starter or 0.2% HY calf starter from one week of age. All calves were weaned at six weeks of age as a stress challenge. The HY-fed calves had a significantly-higher body weight gain during the post-weaning period (kg/week) compared to the control. Cortisol levels at three days post-weaning (DPW) were significantly lower in the HY group than the control group. Calves fed HY had significantly-higher serum levels of tumor necrosis factor-α and interleukin-1β at one DPW. The HY-fed calves also had higher concentrations of the acute-phase proteins, haptoglobin, serum amyloid A, and transferrin at one DPW. In addition, the diarrhea severity in HY-fed calves was milder after weaning compared to the control group. Our results indicate that HY supplementation reduces stress responses and may promote innate immunity in newly-weaned calves.


microRNA-145 modulates epithelial-mesenchymal transition and suppresses proliferation, migration and invasion by targeting SIP1 in human cervical cancer cells.
Previously, it has been reported that microRNA-145 (miR-145) is lowly expressed in human cervical cancers and that its putative tumour suppressive role may be attributed to epithelial-mesenchymal transition (EMT) regulation. Here, we aimed to assess whether miR-145 may affect EMT-associated markers/genes and suppress cervical cancer growth and motility, and to provide a mechanistic basis for these phenomena. The identification of the SMAD-interacting protein 1 (SIP1) mRNA as putative miR-145 target was investigated using a 3' untranslated region (3'UTR) luciferase assay and Western blotting, respectively. The functional effects of exogenous miR-145 expression, miR-145 suppression or siRNA-mediated SIP1 expression down-regulation in cervical cancer-derived C33A and SiHa cells were analysed using Western blotting, BrdU incorporation (proliferation), transwell migration and invasion assays. In addition, the expression levels of miR-145 and SIP1 were determined in primary human cervical cancer and non-cancer tissue samples using qRT-PCR. We found that miR-145 binds to the wild-type 3'UTR of SIP1, but not to its mutant counterpart, and that, through this binding, miR-145 can effectively down-regulate SIP1 expression. In addition, we found that exogenous miR-145 expression or siRNA-mediated down-regulation of SIP1 expression attenuates the proliferation, migration and invasion of C33A and SiHa cells and alters the expression of the EMT-associated markers CDH1, VIM and SNAI1, whereas inhibition of endogenous miR-145 expression elicited the opposite effects. The expression of miR-145 in cervical cancer tissue samples was found to be low, while that of SIP1 was found to be high compared to non-cancerous cervical tissues. An inverse expression correlation between the two was substantiated through the anlaysis of data deposited in the TCGA database. Our data indicate that low miR-145 expression levels in conjunction with elevated SIP1 expression levels may contribute to cervical cancer development. MiR-145-mediated regulation of SIP1 provides a novel mechanistic basis for its tumour suppressive mode of action in human cervical cancer cells.


Neurosurgical stimulation, impedance monitoring and data acquisition system.
We describe the design of a programmable neurosurgical stimulator with impedance monitoring facilities. The computer is used both to control a stimulator and for the storage of various parameters employed in the process. The stimulator is designed to minimize tissue damage by injecting net zero charge; its output is a current, independent of load resistance. By measuring electrode voltage, the load impedance can be calculated. Software is provided in order to log patient data, and trajectory details with reference to coordinates calculated from other imaging systems such as CAT scanners.


Short-term REM deprivation does not affect acquisition or reversal of a spatial learning task.
Although there is a general belief that rapid eye movement sleep (REM) is essential for spatial memory tasks such as the Morris water maze (MWM), there is conflicting evidence for this assertion. This study investigated the effects of short-term REM deprivation on acquisition and reversal of the MWM by varying the timing of REM deprivation and the degree of task acquisition in three separate experiments. There was no evidence for a detrimental effect of REM deprivation on acquisition, retention, or reversal in the MWM. These data add to a growing body of evidence that although REM is important for certain types of learning and memory, spatial memory, as assessed by the MWM, is not among them.


Rapid, Dose-Dependent Enhancement of Cerebral Blood Flow by transcranial AC Stimulation in Mouse.
Transcranial electrical stimulation at an appropriate dose may demonstrate intracranial effects, including neuronal stimulation and cerebral blood flow responses. We performed in vivo experiments on mouse cortex using transcranial alternating current [AC] stimulation to assess whether cerebral blood flow can be reliably altered by extracranial stimulation. We performed transcranial AC electrical stimulation transversely across the closed skull in anesthetized mice, measuring transcranial cerebral blood flow with a laser Doppler probe and intracranial electrical responses as endpoint biomarkers. We calculated a stimulation dose-response function between intracranial electric field and cerebral blood flow. Stimulation at electric field amplitudes of 5-20 mV/mm at 10-20 Hz rapidly increased cerebral blood flow (within 100 ms), which then quickly decreased with no residual effects. The time to peak and blood flow shape varied with stimulation intensity and duration, showing a linear correlation between stimulation dose and peak blood flow increase. Neither afterdischarges nor spreading depression occurred from this level of stimulation. Extracranial stimulation amplitudes sufficient to evoke reliable blood flow changes require electric field strengths higher than what is tolerable in unanesthetized humans (<1 mV/mm), but less than electroconvulsive therapy levels (>40 mV/mm). However, anesthesia effects, spontaneous blood flow fluctuations, and sampling error may accentuate the apparent field strength needed for enhanced blood flow. The translation to a human dose-response function to augment cerebral blood flow (i.e., in stroke recovery) will require significant modification, potentially to pericranial, focused, multi-electrode application or intracranial stimulation.


Ecstasy use in South Africa: findings from the South African Community Epidemiology Network on Drug Use (SACENDU) project (January 1997-December 2001).
This article provides descriptive surveillance information about the extent and consequences of Ecstasy use for five sentinel sites in South Africa. From January 1997 to December 2001, data were gathered on a biannual basis from multiple sources, including specialist treatment centers, trauma units, school students, rave party attendees, and from police and arrestees. Indicators point to relatively low levels of Ecstasy use in South Africa. Demographic characteristics of Ecstasy consumers in South Africa were identified. Ecstasy is predominantly used among White South African youth of both genders, with the age of users decreasing over recent years. The use of Ecstasy is, however, increasing among other population groups. Some emerging health risks associated with club drug use were identified, including the use of Ecstasy in combination with other substances. On the basis of this information, a number of policy recommendations are made. These are targeted at both Ecstasy demand reduction and harm minimization. The study points to the need for continued monitoring of Ecstasy use and its associated consequences in this country.


[Sex chromatin and cytohormone smear in premature and dystrophic newborn during the first week of life].
In newborn females parallel investigations on: a) oestrogenisation symptoms, b) vaginal epithelium smears stained modo Shorr, c) sex chromatin positive nuclei in buccal epithelium smears, have been performed. Low frequency of sex chromatin in the day after birth suggested a relationship between hormone level and Barr bodies' appearance.


Calcium metabolism in the Jansen type of metaphyseal dysplasia.
The Jansen type of metaphyseal dysplasia (JMD) is a rare disorder characterized by growth disturbance and progressive metaphyseal changes initially reminiscent of rickets or primary hyperparathyroidism. Seven of the 16 patients described until now presented with hypercalcaemia of unknown origin. We report studies of calcium metabolism in a hypercalcaemic girl with JMD during the first 3 years of life. The patient presented with hypercalcaemia, hypercalciuria, elevated urinary phosphate and cyclic adenosine monophosphate (AMP) excretion as well as increased 1,25-dihydroxyvitamin D concentrations in serum despite suppressed or low normal values of circulating intact parathyroid hormone (PTH) and PTH related peptide (PTHrP). Measurements of biochemical indices of bone turnover indicated increased bone resorption without sufficient compensatory bone formation. The study suggests that the hypercalcaemia in our patient was caused by an unknown factor, which is not PTH or PTHrP, with osteolytic activity and stimulatory effect on the proximal kidney tubule.


Human action recognition method based on Motion Excitation and Temporal Aggregation module.
Aiming at the problem of low modeling efficiency and feature loss of temporal modeling in human action recognition, we propose a human action recognition method based on Motion Excitation and Temporal Aggregation module (META). The method can capture multi-state and multi-scale temporal information to achieve effective motion excitation. Firstly, temporal relational sampling is performed on video frames; Secondly, META is proposed to capture multi-state and multi-scale temporal information. META is composed of Multi-scale Motion Excitation module (MME) and Squeeze and Excitation Temporal Aggregation module (SETA). MME captures the feature level temporal difference by transforming the features into the temporal channel, which directly establishes the relationship between features and temporal channel, and solves the problem of low modeling efficiency. SETA transforms the local convolution into a set of sub-convolutions. Multiple sub-convolutions form hierarchies to extract features together and share the results of the upper convolutional layer, which increases the final temporal receptive field and solves the problem of feature loss. Moreover, the optical flow features are extracted through Cross modality pre-training to improve the utilization of temporal information. Finally, the result of human action recognition is carried out by combining spatiotemporal two stream features. Experimental results show that the accuracy of this method in UCF101 and HMDB-51 is 96.0% and 71.2% respectively, which is higher than other studies in the same period.