Differential diagnosis of primary nasopharyngeal lymphoma and nasopharyngeal carcinoma focusing on CT, MRI, and PET/CT.
No study has done a comparative analysis of radiologic imaging findings between primary nasopharyngeal lymphoma (PNL) and nasopharyngeal carcinoma (NPC). The purpose of this study was to analyze computed tomography (CT) and magnetic resonance (MR) images and to evaluate the maximum standardized uptake value (SUV max) of positron emission tomography (PET)/CT between PNL and NPC, knowing the imaging features that distinguish PNL from NPC. Cross-sectional study. University tertiary care facility. The authors analyzed the features on CT, MR imaging, and PET/CT of 16 patients diagnosed with PNL and 32 patients diagnosed with NPC histopathologically. Patients with PNL had a larger tumor volume and showed symmetry of tumor shape than did patients with NPC. Patients with PNL also had higher tumor homogeneity than NPC patients on CT, T2-weighted, and postcontrast MR images. All PNL patients showed a high degree of enhancement without invasion to the adjacent deep structure. The involvement of the Waldeyer ring was significantly higher in PNL patients. Cervical and retropharyngeal lymphadenopathy and PET/CT SUV max showed no significant difference between PNL and NPC. If the images present a bulky, symmetric nasopharyngeal mass with marked homogeneity, a high degree of enhancement, and a higher Waldeyer ring involvement combined with no invasion into the deep structure, PNL should be considered over NPC.


N-Oleoyldopamine promotes the differentiation of mouse trophoblast stem cells into parietal trophoblast giant cells.
The placenta plays various roles in a healthy pregnancy, and abnormalities in the placenta result in adverse outcomes. Adequate differentiation of trophoblast subtypes is necessary for placental function, but the molecular mechanisms that determine trophoblast cell fate remain unclear. Here, we screened small molecular compound (SMC) libraries (1904 SMCs) to identify particular SMCs which regulate trophoblast differentiation in mouse trophoblast stem cells (mTSCs) to understand the molecular mechanisms underlying cell fate decision in trophoblast cells. The two-step screening revealed a novel effect of N-oleoyldopamine (OLDA), an endogenic vanilloid, to promote differentiation into parietal trophoblast giant cells (P-TGCs) and repress them into spongiotrophoblast cells in mTSCs. Analyses by gene deletion and inhibitor treatments indicated that transient receptor potential cation channel subfamily V member 3 (Trpv3), one of the candidates for targeting by OLDA, was involved in maintaining stem status and P-TGC differentiation in mTSCs. Finally, transcriptome analysis revealed that Fosl1, a key regulatory factor in differentiation into P-TGCs, was upregulated by OLDA treatment, suggesting that OLDA promoted the differentiation of mTSCs into P-TGCs via regulation of Fosl1 expression.


Endoscopists performance in optical diagnosis of colorectal polyps in artificial intelligence studies.
Widespread adoption of optical diagnosis of colorectal neoplasia is prevented by suboptimal endoscopist performance and lack of standardized training and competence evaluation. We aimed to assess diagnostic accuracy of endoscopists in optical diagnosis of colorectal neoplasia in the framework of artificial intelligence (AI) validation studies. Literature searches of databases (PubMed/MEDLINE, EMBASE, Scopus) up to April 2022 were performed to identify articles evaluating accuracy of individual endoscopists in performing optical diagnosis of colorectal neoplasia within studies validating AI against a histologically verified ground-truth. The main outcomes were endoscopists' pooled sensitivity, specificity, positive and negative predictive value (PPV/NPV), positive and negative likelihood ratio (LR) and area under the curve (AUC for sROC) for predicting adenomas versus non-adenomas. Six studies with 67 endoscopists and 2085 (IQR: 115-243,5) patients were evaluated. Pooled sensitivity and specificity for adenomatous histology was respectively 84.5% (95% CI 80.3%-88%) and 83% (95% CI 79.6%-85.9%), corresponding to a PPV, NPV, LR+, LR- of 89.5% (95% CI 87.1%-91.5%), 75.7% (95% CI 70.1%-80.7%), 5 (95% CI 3.9%-6.2%) and 0.19 (95% CI 0.14%-0.25%). The AUC was 0.82 (CI 0.76-0.90). Expert endoscopists showed a higher sensitivity than non-experts (90.5%, [95% CI 87.6%-92.7%] vs. 75.5%, [95% CI 66.5%-82.7%], p < 0.001), and Eastern endoscopists showed a higher sensitivity than Western (85%, [95% CI 80.5%-88.6%] vs. 75.8%, [95% CI 70.2%-80.6%]). Quality was graded high for 3 studies and low for 3 studies. We show that human accuracy for diagnosis of colorectal neoplasia in the setting of AI studies is suboptimal. Educational interventions could benefit by AI validation settings which seem a feasible framework for competence assessment.


MIP-3alpha, MIP-3beta and fractalkine induce the locomotion and the mobilization of intracellular calcium, and activate the heterotrimeric G proteins in human natural killer cells.
We demonstrate here that the CC chemokines macrophage inflammatory protein-3alpha (MIP-3alpha), macrophage inflammatory protein-3beta (MIP-3beta) and the CX3C chemokine fractalkine induce the chemotaxis of interleukin-2 (IL-2)-activated natural killer (IANK) cells. In addition, these chemokines enhance the binding of [gamma-35S]guanine triphosphate ([gamma-35S]GTP) to IANK cell membranes, suggesting that receptors for these chemokines are G protein-coupled. Our results show that MIP-3alpha receptors are coupled to Go, Gq and Gz, MIP-3beta receptors are coupled to Gi, Gq and Gs, whereas fractalkine receptors are coupled to Gi, and Gz. All three chemokines induced a robust calcium response flux in IANK cells. Cross-desensitization experiments show that MIP-3alpha, MIP-3beta or fractalkine use receptors not shared by each other or by the CC chemokine regulated on activation, normal, T-cell expressed, and secreted (RANTES), the CXC chemokines stromal-derived factor-1alpha (SDF-1alpha) and interferon-inducible protein-10 (IP-10), or the C chemokine lymphotactin.


Functional and structural properties of cardiotoxin isomers produced by blocking negatively charged groups.
In this study, we investigated the functional roles of Asp40, Asp57, and C-terminal Asn60 in Naja atra cardiotoxin 3 (CTX3) structure and function by modifying these three carboxyl groups with semicarbazide. The conjugation of the carboxyl groups with semicarbazide produced two conformational isomers whose gross and fine structures were different from those of CTX3. The blocking of the carboxyl groups increased the structural flexibility of CTX3 in response to trifluoroethanol-induced effect. Despite presenting modest to no effect on decreasing the induction of permeability in zwitterionic phospholipid vesicles, the carboxyl group-modified CTX3 showed a marked reduction in its permeabilizing effect on anionic phospholipid vesicles in comparison to that of the native protein. Compared with native CTX3, carboxyl group-modified CTX3 exhibited lower activity in inducing membrane leakage in U937 cells. The CD spectra of lipid-bound toxins and the color transition of polydiacetylene/lipid assay showed that the membrane interaction mode of CTX3 was distinctly changed by the modification in the carboxyl groups. Given that the selective modification of Asp40 does not cause the conformational isomerization of CTX3, our data indicate that the carboxyl groups in Asp57 and Asn60 are essential in maintaining the structural topology of CTX3. Furthermore, modification of carboxyl groups changes the interdependence between the infrastructure and the global conformation of CTX3 in modulating membrane permeabilizing activity.


Rearrangements of the short arm of chromosome No. 6 in T-cell lymphomas.
Cytogenetic studies on four patients with T-cell lymphomas are reported. In all four the short arm of chromosome No. 6 (6p) was abnormal. In three cases it was involved in a translocation, and in one there was a deletion of the terminal part: del(6)(p23-24). One of the translocations could be identified as a t(2:6)(q24;p24). Identification was not possible in the others. These 6p anomalies were associated with complex structural and numerical abnormalities of other chromosomes in three out of four cases. In three patients chemo- and/or radiotherapy administration preceded cytogenetic investigations.


Multiple-spike waves in a one-dimensional integrate-and-fire neural network.
This paper builds on the past study of single-spike waves in one-dimensional integrate-and-fire networks to provide a framework for the study of waves with arbitrary (finite or countably infinite) collections of spike times. Based on this framework, we prove an existence theorem for single-spike traveling waves, and we combine analysis and numerics to study two-spike traveling waves, periodic traveling waves, and general infinite spike trains. For a fixed wave speed, finite-spike waves, periodic waves, and other infinite-spike waves may all occur, and we discuss the relationships among them. We also relate the waves considered analytically to waves generated in numerical simulations by the transient application of localized excitation.


Activation and proliferation signals in mouse B cells. I. A comparison of the capacity of anti-Ig antibodies or phorbol myristic acetate to activate B cells from CBA/N or normal mice into G1.
B lymphocytes from the CBA/N mouse do not synthesize DNA when cultured with anti-Ig antibodies. However, these cells like normal B cells, do manifest increased Ia antigen expression and RNA synthesis (i.e. enter G1) when stimulated by anti-Ig, even at doses which are nonmitogenic for normal B cells. Pretreatment of both normal and CBA/N B cells with anti-Ig also primes them to give an enhanced proliferative response to lipopolysaccharide (LPS). The tumor promoter phorbol myristic acetate (PMA) also enhances RNA synthesis and Ia antigen expression in B cells from both normal and CBA/N mice. However, PMA only primes CBA/N B cells to respond to LPS: pretreatment of normal B cells with PMA causes a modest suppression of LPS-induced, and a marked suppression of anti-Ig induced, DNA synthesis. These results therefore confirm and extend earlier data showing that there are distinct activating (G0 to G1) vs. proliferative (G1 to S) signals discernible in B cells. They also suggest that the activation mechanism of CBA/N B cells is subtly different from that of any known subpopulation of normal B cells.


Dual stresses of flooding and agricultural land use reduce earthworm populations more than the individual stressors.
Global climate change is leading to a significant increase in flooding events in many countries. Current practices to prevent damage to downstream urban areas include allowing the flooding of upstream agricultural land. Earthworms are ecosystem engineers, but their abundances in arable land are already reduced due to pressure from farming practices. If flooding increases on agricultural land, it is important to understand how earthworms will respond to the dual stresses of flooding and agricultural land use. The earthworm populations under three land uses (pasture, field margin, and crops), across two UK fields, were sampled seasonally over an 18-month period in areas of the fields which flood frequently and areas which flood only rarely. Earthworm abundance in the crop and pasture soils and total earthworm biomass in the crop soils was significantly lower in the frequently flooded areas than in the rarely flooded areas. The relative percentage difference in the populations between the rarely and frequently flooded areas was greater in the crop soils (-59.18% abundance, -63.49% biomass) than the pasture soils (-13.39% abundance, -9.66% biomass). In the margin soils, earthworm abundance was significantly greater in the frequently flooded areas (+140.56%), likely due to higher soil organic matter content and lower bulk density resulting in soil conditions more amenable to earthworms. The findings of this study show that earthworm populations already stressed by the activities associated with arable land use are more susceptible to flooding than populations in pasture fields, suggesting that arable earthworm populations are likely to be increasingly at risk with increased flooding.


What predicts drug-free type 2 diabetes remission? Insights from an 8-year general practice service evaluation of a lower carbohydrate diet with weight loss.
Type 2 diabetes (T2D) is often regarded as a progressive, lifelong disease requiring an increasing number of drugs. Sustained remission of T2D is now well established, but is not yet routinely practised. Norwood surgery has used a low-carbohydrate programme aiming to achieve remission since 2013. Advice on a lower carbohydrate diet and weight loss was offered routinely to people with T2D between 2013 and 2021, in a suburban practice with 9800 patients. Conventional 'one-to-one' GP consultations were used, supplemented by group consultations and personal phone calls as necessary. Those interested in participating were computer coded for ongoing audit to compare 'baseline' with 'latest follow-up' for relevant parameters. The cohort who chose the low-carbohydrate approach (n=186) equalled 39% of the practice T2D register. After an average of 33 months median (IQR) weight fell from 97 (84-109) to 86 (76-99) kg, giving a mean (SD) weight loss of -10 (8.9)kg. Median (IQR) HbA1c fell from 63 (54-80) to 46 (42-53) mmol/mol. Remission of diabetes was achieved in 77% with T2D duration less than 1 year, falling to 20% for duration greater than 15 years. Overall, remission was achieved in 51% of the cohort. Mean LDL cholesterol decreased by 0.5 mmol/L, mean triglyceride by 0.9 mmol/L and mean systolic blood pressure by 12 mm Hg. There were major prescribing savings; average Norwood surgery spend was £4.94 per patient per year on drugs for diabetes compared with £11.30 for local practices. In the year ending January 2022, Norwood surgery spent £68 353 per year less than the area average. A practical primary care-based method to achieve remission of T2D is described. A low-carbohydrate diet-based approach was able to achieve major weight loss with substantial health and financial benefit. It resulted in 20% of the entire practice T2D population achieving remission. It appears that T2D duration <1 year represents an important window of opportunity for achieving drug-free remission of diabetes. The approach can also give hope to those with poorly controlled T2D who may not achieve remission, this group had the greatest improvements in diabetic control as represented by HbA1c.


CERES-Maize model for simulating genotype-by-environment interaction of maize and its stability in the dry and wet savannas of Nigeria.
When properly calibrated and evaluated, dynamic crop simulation models can provide insights into the different components of genotype by environment interactions (GEIs). Modelled outputs could be used to complement data from multi-environment trials. Field experiments were conducted in the rainy and dry seasons of 2015 and 2016 across four locations in maize growing regions of Northern Nigeria using 16 maize varieties planted under near-optimal conditions of moisture and soil nitrogen. The CERES-Maize model was calibrated using data from three locations and two seasons (rainy and dry) and evaluated using data from one location and two seasons all in 2015. Observed data from the four locations and two seasons in 2016 was used to create eight different environments. Two profile pits were dug in each location and were used separately in the simulations for each environment to provide replicated data for stability analysis in a combined ANOVA. The effects of the environment, genotype and GEI were highly significant (p = 0.001) for both observed and simulated grain yields. The environment explained 67 % and 64 % of the variations in observed and simulated grain yields respectively. The variance component of GEI (13 % for observed and 15 % for simulated) were lower but still considerable when compared to that of genotypes (19 % for observed and 21 % for simulated). From the stability analysis of the observed and simulated grain yields using six different stability models, three models (ASV, Ecovalence, and Sigma) ranked Ife Hybrid as the most stable variety. The slope of the regression (bi) model ranked Sammaz 11 as the most stable variety, while the Shukla model ranked Sammaz 28 as the most stable variety. Long-term seasonal analysis with the CERES-Maize model revealed that early and intermediate maturing varieties produce high yields in both wet and dry savannas, early and extra-early varieties produce high yields only in the dry savannas, while late maturing varieties produce high yields only in the wet savannas. When properly calibrated and evaluated, the CERES-Maize model can be used to generate data for GEI and stability studies of maize genotype in the absence of observed field data.


The efficacy of a leukotriene receptor antagonist in the treatment of human rectal aberrant crypt foci: a nonrandomized, open-label, controlled trial.
Leukotriene receptor antagonists (LTRAs) are broadly used for the management of allergic asthma and have recently been indicated to inhibit carcinogenesis and cancer cell growth. In colorectal cancer (CRC) chemoprevention studies, the occurrence of adenoma or CRC itself is generally set as the trial endpoint. Although the occurrence rate of CRC is the most confident endpoint, it is inappropriate for chemoprevention studies because CRC incidence rate is low in the general population and needed for long-term monitoring. Aberrant crypt foci (ACF), defined as lesions containing crypts that are larger in diameter and darker in methylene blue staining than normal crypts, are regarded to be a fine surrogate biomarker of CRC. Therefore, this prospective study was designed to explore the chemopreventive effect of LTRA on colonic ACF formation and the safety of the medicine in patients scheduled for a poly resection as a pilot trial leading the CRC chemoprevention trial. This study is a nonrandomized, open-label, controlled trial in patients with colorectal ACF and polyps scheduled for a polypectomy. Participants meet the inclusion criteria will be recruited, and the number of ACF in the rectum will be counted at the baseline colonoscopic examination. Next, the participants will be assigned to the LTRA or no treatment group. Participants in the LTRA group will continue 10 mg of oral montelukast for 8 weeks, and those in the no treatment group will be observed without the administration of any additional drugs. At the end of the 8-week LTRA intervention period, a polypectomy will be conducted to evaluate the changes in the number of ACF, and cell proliferation in the normal colorectal epithelium will be analyzed. This will be the first study to investigate the effect of LTRAs on colorectal ACF formation in humans. This trial has been registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry as UMIN000029926 . Registered 10 November 2017.


Chiral resolution of diastereomeric di- and tripeptides on a teicoplanin aglycone phase by capillary electrochromatography.
The chiral separation ability of a capillary packed with teicoplanin aglycone as a chiral stationary phase was investigated. This stationary phase was used successfully for chiral resolution of both diastereomeric dipeptides and tripeptides possessing one or two chiral centers. The composition of the mobile phase was shown to be crucial for separation. The use of reversed-phase mode was clearly superior to the polar-organic mode. The nature of the organic modifier was found to have a marked influence on separation. After optimizing conditions, all diasteromeric dipeptides and tripeptides investigated were baseline-resolved, however, it was not possible to find a uniform mobile phase showing optimal results for all peptides investigated.


The T1796A mutation of the BRAF gene is absent in Spitz nevi.
BRAF, a serine/threonine kinase, is a component of the retrovirus-associated sequence (RAS)-RAF-extracellular-regulated protein kinase (ERK)-MAP kinase signal transduction pathway mediating signals from RAS to ERK. The T1796A single point mutation in exon 15 of the BRAF gene has recently been reported in a high percentage of malignant melanomas and benign melanocytic lesions such as congenital nevi, compound nevi, intradermal nevi and dysplastic nevi. The T1796A mutation has been shown to promote cell proliferation. We screened 21 Spitz nevi and six spitzoid malignant melanomas for the presence of the T1796A BRAF mutation. The T1796A BRAF mutation could not be detected in any of the 21 Spitz nevi but was present in two of the six spitzoid malignant melanomas. Our results, in conjunction with data from a previous investigation, suggest that the melanocytic proliferation of Spitz nevi might be induced by components of the RAS-RAF-ERK-MAP kinase pathway different from BRAF, possibly combined with other genetic aberrations. The lack of the T1796A BRAF mutation might be of practical importance in distinguishing Spitz nevi from other melanocytic lesions simulating Spitz nevi as a part of a future complex diagnostic assay.


Genetic studies of water buffalo blood markers. I. Red cell acid phosphatase, albumin, catalase, red cell alpha-esterase-3, group-specific component, and protease inhibitor.
We have developed the methodologies for typing and family studies to establish the modes of inheritance of water buffalo red cell acid phosphatase (Acp), protease inhibitor (Pi), and group-specific component (Gc) on isoelectric focusing and albumin (Alb), red cell alpha-esterase-3 (Est-3), and catalase (Cat) on polyacrylamide gel electrophoresis. Family studies showed that Pi, Gc, Alb, and Cat are coded by autosomal genes with two codominant alleles, while Est-3 is autosomal with two codominant alleles and a recessive null allele and Acp exhibits three codominant alleles.


Chemical profile, antiproliferative and antioxidant activities of rhizome oil of Zingiber anamalayanum from Western Ghats in India.
Volatile oil from fresh rhizomes of Zingiber anamalayanum was isolated by hydrodistillation and characterised by GC-FID and GC-MS. Twenty-one out of 24 constituents comprising 99.47% of the oil were identified. Major components in Z. anamalayanum rhizome oil were δ-2-carene (52.83%), camphene (9.83%), endo-fenchol (9.42%), iso-dihydrocarveol (6.44%) and cis-p-mentha-2,8-dien-1-ol (5.19%). Monoterpene hydrocarbons in the rhizome oil were 65.81%, followed by oxygenated monoterpenes (23.78%) and sesquiterpene hydrocarbons (9.87%). Physical parameters of rhizome oil were [Formula: see text] 1.4031, [Formula: see text] - 16.097(o) (c = 1, CHCl3) and [Formula: see text] 0.9202. Z. anamalayanum rhizome oil showed significant anti-Dalton's Lymphoma Ascitic activity.


Colorimetric Detection of ATP by a Chlorophosphonazo III -based Mg2+ Complex in Aqueous Solution via Indicator Displacement Approach.
A simple and effective colorimetric detection of adenosine 5-triphosphate (ATP) in 100% aqueous media was developed based on an indicator displacement approach (IDA). A commercially available dye, Chlorophosphonazo III (CPA), was utilized as the indicator and the ATP detection was achieved using the complex of CPA with Mg2+ in a 2:1 stoichiometric ratio (CPA2-Mg2+) through the regeneration of CPA by the binding of ATP to Mg2+. Upon addition of a series of anions to the CPA2-Mg2+ complex, only the appearance of the solution of the complex with ATP exhibited a color change from blue to purple which can be detected by the naked eye. Moreover, the ATP recognition was not hampered by the presence of other anions. Hence, CPA2-Mg2+ is efficient in ATP highly selective and sensitive colorimetric detection in 100% aqueous media.


Possible Involvement of Palmitate in Pathogenesis of Periodontitis.
Type 2 diabetes (T2D) is characterized by decreased insulin sensitivity and higher concentrations of free fatty acids (FFAs) in plasma. Among FFAs, saturated fatty acids (SFAs), such as palmitate, have been suggested to promote inflammatory responses. Although many epidemiological studies have shown a link between periodontitis and T2D, little is known about the clinical significance of SFAs in periodontitis. In this study, we showed that gingival fibroblasts have cell-surface expression of CD36, which is also known as FAT/fatty acid translocase. Moreover, CD36 expression was increased in gingival fibroblasts of high-fat diet-induced T2D model mice, compared with gingival fibroblasts of mice fed a normal diet. DNA microarray analysis revealed that palmitate increased mRNA expression of pro-inflammatory cytokines and chemokines in human gingival fibroblasts (HGF). Consistent with these results, we confirmed that palmitate-induced interleukin (IL)-6, IL-8, and CXCL1 secretion in HGF, using a cytokine array and ELISA. SFAs, but not an unsaturated fatty acid, oleate, induced IL-8 production. Docosahexaenoic acid (DHA), which is one of the omega-3 polyunsaturated fatty acids, significantly suppressed palmitate-induced IL-6 and IL-8 production. Treatment of HGF with a CD36 inhibitor also inhibited palmitate-induced pro-inflammatory responses. Finally, we demonstrated that Porphyromonas gingivalis (P.g.) lipopolysaccharide and heat-killed P.g. augmented palmitate-induced chemokine secretion in HGF. These results suggest a potential link between SFAs in plasma and the pathogenesis of periodontitis.


Evolution of altruistic punishment in heterogeneous populations.
Evolutionary models for altruistic behavior typically make the assumption of homogeneity: each individual has the same costs and benefits associated with cooperating with each other and punishing for selfish behavior. In this paper, we relax this assumption by separating the population into heterogeneous classes, such that individuals from different classes differ in their ability to punish for selfishness. We compare the effects of introducing heterogeneity this way across two population models, that each represents a different type of population: the infinite and well-mixed population describes the way workers of social insects such as ants are organized, while a spatially structured population is more related to the way social norms evolve and are maintained in a social network. We find that heterogeneity in the effectiveness of punishment by itself has little to no effect on whether or not altruistic behavior will stabilize in a population. In contrast, heterogeneity in the cost that individuals pay to punish for selfish behavior allows altruistic behavior to be maintained more easily. Fewer punishers are needed to deter selfish behavior, and the individuals that punish will mostly belong to the class that pays a lower cost to do so. This effect is amplified when individuals that pay a lower cost for punishing inflict a higher punishment. The two population models differ when individuals that pay a low cost for punishing also inflict a lower punishment. In this situation, altruistic behavior becomes harder to maintain in an infinite and well-mixed population. However, this effect does not occur when the population is spatially structured.


Visually evoked changes of blood flow velocity and pulsatility index in the posterior cerebral arteries: a transcranial Doppler study.
Transcranial Doppler sonography (TCD) can detect visual evoked blood flow responses non-invasively and continuously with high temporal resolution. While the mean flow velocity response to visual stimuli is well documented, the response of the pulsatile characteristics of the waveform is less well known. We examined the changes of blood flow velocity and pulsatility index (PI) in the posterior cerebral artery (PCA) in 50 healthy volunteers. TCD responses were measured in response to metabolic activation of the visual cortex by visual stimulation. A specific, stimulus-related increase of the mean flow velocity (MFV) in the PCA was found. The intensity of the blood flow response was significantly influenced by the complexity of the stimulus. During complex visual stimulation we found a mean flow velocity (MFV) increase of 29.4 % from the baseline in the subjects. However, a stimulus-related decrease was observed in the pulsatility index (PI); although the mean PI with closed eyes during baseline measurement was 1.18 (SD 0.27), on average, it fell significantly to 0.95 (SD 0.23) with the alternating chessboard and 0.82 (SD 0.22) during the complex stimulus condition. The relative decrement of the pulsatility index with increasing complexity of the visual stimulus is highly significant, with values of -19.5 % and -30.5 % compared to the baseline. These findings demonstrate the inverse correlation between MFV response and pulsatility index in the PCA. We assume that this decrease of the PI in the PCA may reflect the reduced regional vascular resistance in the visual cortex during visual stimulation.


Vacuum Sealing Drainage Treatment Combined with Antibiotic-Impregnated Bone Cement for Treatment of Soft Tissue Defects and Infection.
BACKGROUND This study aimed to evaluate the combined effect of vacuum sealing drainage (VSD) and antibiotic-loaded bone cement on soft tissue defects and infection. MATERIAL AND METHODS This prospective non-blinded study recruited 46 patients with soft tissue defects and infection from January 2010 to May 2014 and randomly divided them into experimental and control groups (n=23). Patients in the experimental group were treated with VSD and antibiotic-loaded bone cement, while the patients in the control group were treated with VSD only. RESULTS In the experimental group, the wound was healed in 23 cases at 4 weeks postoperatively, of which direct suture was performed in 12 cases, and additional free flap transplantation or skin grafting was performed in 6 cases and 5 cases, respectively. No infection reoccurred in 1-year follow-up. In the control group, the wound was healed in 15 cases at 6 weeks postoperatively, of which direct suture was performed in 8 cases, and additional free flap transplantation or skin grafting was performed in 3 cases and 4 cases, respectively. In the other 8 cases the wound was healed at 8 weeks postoperatively. Infection reoccurred in 3 cases during the follow-up. The experimental group had significantly fewer VSD dressing renewals, shorter time needed until the wound was ready for surgery, shorter duration of antibiotic administration, faster wound healing, and shorter hospital stay than the control group (p<0.01). CONCLUSIONS The combination of VSD and antibiotic bone cement might be a better method for treatment of soft tissue defects and infection.


γ-Heptalactone is an endogenously produced quorum-sensing molecule regulating growth and secondary metabolite production by Aspergillus nidulans.
Microbes monitor their population density through a mechanism termed quorum sensing. It is believed that quorum-sensing molecules diffuse from the microbial cells and circulate in the surrounding environment as a function of cell density. When these molecules reach a threshold concentration, the gene expression of the entire population is altered in a coordinated manner. This work provides evidence that Aspergillus nidulans produces at least one small diffusible molecule during its growth cycle which accumulates at high cell density and alters the organism's behaviour. When added to low-density cell cultures, ethyl acetate extracts from stationary phase culture supernatants of A. nidulans resulted in the abolition of the lag phase, induced an earlier deceleration phase with 16.3 % decrease in the final cell dry weight and resulted in a 37.8 % increase in the expression of ipnA::lacZ reporter gene construct, which was used as a marker for penicillin production compared to non-treated controls. The bioactive molecule present in the stationary phase extract was purified to homogeneity and was identified by liquid chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy to be γ-heptalactone. This study provides the first evidence that A. nidulans produces γ-heptalactone at a high cell density and it can alter the organism's behaviour at a low cell density. γ-Heptalactone hence acts as a quorum-sensing molecule in the producing strain.


Meningococcal purpura fulminans in children. II: Late orthopedic sequelae management.
Purpura fulminans is a rare and extremely severe infection, mostly due to Neisseria meningitidis. Nineteen patients were followed up immediately after the initial multivisceral failure in order to diagnose late-onset orthopedic sequelae. We report our experience with these 19 patients, in light of our medical follow-up protocol and surgical management. Nineteen patients were referred for acute purpura fulminans between 1987 and 2005 to our institution and followed up prospectively until the present. We collected information on all diagnosed orthopedic sequelae, all surgical procedures performed, and the actual orthopedic outcome. Fourteen patients developed at least one orthopedic sequel after a mean of 2 years delay, with a mean of 8.65 years follow-up (range 3-22 years). The most common presentation was lower limb physeal growth plate arrest in eight patients involving 18 growth plates, leading to five limb length discrepancies and 12 significant knee and/or ankle deviations. Patients were treated by completing epiphysiodesis in addition to limb lengthening and/or reaxation osteotomies, except for two patients, in which epiphysiolysis was performed. All outcomes are, to date, satisfactory, with both knee and ankle axes within the physiological range. Among the seven patients who underwent below-knee amputation, six needed stump revision because of skin conflict (4) or prosthetics misadaptation due to upper tibial varus (2). Regarding the upper limb, three patients presented with four cicatricial scar bands, one located on a ring finger, two at the first commissure, and one at the wrist (all were successfully treated by enlargement Z-plasties). Two patients developed hip avascular necrosis. It is important for children diagnosed with meningococcal purpura fulminans to be followed up closely starting from the very beginning by a pediatric orthopedic surgeon. It ensures that late-onset orthopedic sequelae will be diagnosed early. In accordance to the literature, this study highlights the high rate of lower limb epiphysiodesis, above all other types of sequelae. This study reports a possible link between purpura fulminans and avascular necrosis of the hip.


Mutagenic effects of restriction enzymes in Chinese hamster cells: evidence for high mutagenicity of Sau3AI at the hprt locus.
CHO cells were exposed to seven different restriction endonucleases by electroporation and their cytotoxicity and mutagenicity measured. Cell killing as determined by a colony formation assay occurred in a concentration-dependent manner for each enzyme. The D0 of the survival curves were: MspI = 24U; AluI = 31U; Sau3AI = 106U; HaeIII = 46U; HinfI = 30U; PvuII = 35U; BamHI = 163U. BamHI and Sau3AI were particularly ineffective in cell killing. For the 6-base recognition sequence enzymes, PvuII (a blunt-ended cutter) was much more cytotoxic per unit electroporated than BamHI (a sticky-ended cutter). Among the 4-base cutters, Sau3AI and HaeIII were generally less cytotoxic than HinfI or PvuII. Cell killing appeared to depend on the nature of the recognition sequence and cutting sites rather than on the cutting frequency. The mutagenic effects of these restriction endonucleases were investigated by measuring the induced frequencies of hprt gene mutations. The mutagenicity of Sau3AI was dramatically higher than the other enzymes, increasing linearly with dose up to 35U. When normalized for survival, the mutagenicity of Sau3AI relative to the other enzymes was even greater. The mutagenic effect of BamHI, which has the same 5' protruding site as Sau3AI, was much lower at similar dose and survival levels. MspI, BamHI, and PvuII which have no recognition sites within the hprt coding sequence were marginally- or non-mutagenic. Based on these results and the distribution of cutting sites within the hprt cDNA for the enzymes studied, the hypothesis is discussed that a region in exon 4 is highly sensitive to the induction of mutants by DNA double-strand breaks.


Cannabis use is a better indicator of poor mental health in women than in men: a cross-sectional study in young adults from the general population.
Cannabis use is a known risk factor for a range of mental health problems, but less is known on the association with general mental health. We aim to explore the relationship between cannabis use and general mental health. We did a cross-sectional online survey of 1,929 young adults aged 18-30 years. Participants reported socio-demographic data, substance use and the Symptom Checklist-90 (SCL-90). Monthly cannabis use was associated with a higher total score on the SCL-90, both in a crude (OR 1.94, 95% CI 1.57-2.38) and fully adjusted model (OR 1.48, 95% CI 1.07-2.03). The association between cannabis and mental health was stronger in women and weekly users, and was independent of age at first use of cannabis. We conclude that moderate cannabis use is associated with general mental health problems in young adulthood. This relationship is independent of age at first use and of other risk factors, and is strongest in women.


Availability of lobe-selective bronchial blockade for video-assisted thoracic surgery: an initial experience with three cases.
Stable oxygenation and sufficient collapse of the lung are essential for video-assisted thoracic surgery (VATS). We performed the lobe-selective lung collapse technique with VATS for patients who had deteriorated lung function. CASE 1: A 75-year-old man who had undergone thoracoplasty showed spontaneous pneumothoraces in the contralateral side. Bullae were stapled successfully under complete isolation and collapse of diseased lobe. CASE 2: A 57-year-old woman who had undergone left lower lobectomy for lung cancer presented with another lung cancer in the right lower lobe. The right lower lobe bronchus was closed selectively, and basal segmentectomy was performed. CASE 3: A 60-year-old woman who had lost left lung function presented with right-side spontaneous pneumothoraces. The right upper lobe was collapsed selectively, and bullectomy was performed. Lobe-selective bronchial blockade may be beneficial when VATS is performed for selected patients with deteriorated lung function.


Sulfated vizantin causes detachment of biofilms composed mainly of the genus Streptococcus without affecting bacterial growth and viability.
Sulfated vizantin, a recently developed immunostimulant, has also been found to exert antibiofilm properties. It acts not as a bactericide, but as a detachment-promoting agent by reducing the biofilm structural stability. This study aimed to investigate the mechanism underlying this activity and its species specificity using two distinct ex vivo oral biofilm models derived from human saliva. The biofilm, composed mainly of the genus Streptococcus and containing 50 μM of sulfated vizantin, detached significantly from its basal surface with rotation at 500 rpm for only 15 s, even when 0.2% sucrose was supplied. Expression analyses for genes associated with biofilm formation and bacterial adhesion following identification of the Streptococcus species, revealed that a variety of Streptococcus species in a cariogenic biofilm showed downregulation of genes encoding glucosyltransferases involved in the biosynthesis of water-soluble glucan. The expression of some genes encoding surface proteins was also downregulated. Of the two quorum sensing systems involved in the genus Streptococcus, the expression of luxS in three species, Streptococcus oralis, Streptococcus gordonii, and Streptococcus mutans, was significantly downregulated in the presence of 50 μM sulfated vizantin. Biofilm detachment may be facilitated by the reduced structural stability due to these modulations. As a non-specific reaction, 50 μM sulfated vizantin decreased cell surface hydrophobicity by binding to the cell surface, resulting in reduced bacterial adherence. Sulfated vizantin may be a candidate for a new antibiofilm strategy targeting the biofilm matrix while preserving the resident microflora.


Structural characterization of cyclosporin A, C and microbial bio-transformed cyclosporin A analog AM6 using HPLC-ESI-ion trap-mass spectrometry.
Cyclosporin A (CyA), a cyclic undecapeptide produced by a number of fungi, contains 11 unusual amino acids, and has been one of the most commonly prescribed immunosuppressive drugs. To date, there are over sixty different analogs reported as congeners and analogs resulting from precursor-directed biosynthesis, human CYP-mediated metabolites, or microbial bio-transformed analogs. However, there is still a need for more structurally diverse CyA analogs in order to discover new biological potentials and/or improve the physicochemical properties of the existing cyclosporins. As a result of the complexity of the resulting mass spectrometric (MS) data caused by its unusual amino acid composition and its cyclic nature, structural characterization of these cyclic peptides based on fragmentation patterns using multiple tandem MS analyses is challenging task. Here, we describe, an efficient HPLC-ESI-ion trap MS(n) (up to MS(8)) was developed for the identification of CyA and CyC, a (Thr(2))CyA congener in which L-aminobutyric acid (Abu) is replaced by L-threonine (Thr). In addition, we examined the fragmentation patterns of a CyA analog obtained from the cultivation of a recombinant Streptomyces venezuelae strain fed with CyA, assigning this analog as (γ-hydroxy-MeLeu(6))CyA (otherwise, known as an human CYP metabolite AM6). This is the first report on both the MS(n)-aided identification of CyC and the structural characterization of a CyA analog by employing HPLC-ESI-ion trap MS(n) analysis.


Incidence of and Risk Factors for Tuberculosis (TB) in Gastric Cancer Patients in an Area Endemic for TB: A Nationwide Population-based Matched Cohort Study.
To date, there have been few reports investigating the relationship between tuberculosis (TB) and gastric cancer.We conducted a nationwide population-based matched cohort study using data retrieved from Taiwan's National Health Insurance Research Database to determine the incidence of and risk factors for TB in patients diagnosed with gastric cancer. From 2000 to 2011, we identified 36,972 gastric cancer patients and normal subjects from the general population matched for age, sex, and comorbidities at a 1:1 ratio. The data were analyzed using Cox proportional hazards models.Compared with the matched cohort, gastric cancer patients exhibited a higher risk for TB (adjusted hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.65-3.05, P < 0.001), and those with TB exhibited higher mortality (adjusted HR 1.59, 95% CI 1.41-1.79, P < 0.001). Old age (adjusted HR 2.40, 95% CI 1.92-2.99, P < 0.001), male sex (adjusted HR 2.13, 95% CI 1.76-2.57, P < 0.001), diabetes mellitus (adjusted HR 1.28, 95% CI 1.05-1.56, P = 0.013), and chronic obstructive pulmonary disease (COPD) (adjusted HR 1.44, 95% CI 1.19-1.75, P < 0.001) were identified as independent risk factors for TB in gastric cancer patients. Dyslipidemia was an independent protective factor for both TB (adjusted HR 2.13, 95% CI 1.73-2.62, P < 0.001) and mortality (adjusted HR 1.11, 95% CI 1.08-1.15, P < 0.001) in gastric cancer patients.Old age, male sex, diabetes mellitus, and COPD were independent risk factors for TB in gastric cancer. High-risk gastric cancer patients, especially those in TB-endemic areas, should be regularly screened for TB.


Prognostic significance of CA 125, CD44, and epithelial membrane antigen in renal cell carcinoma.
To study retrospectively CA 125, CD44, and epithelial membrane antigen (EMA) expression in renal cell carcinoma and their role as prognostic factors. CD44 is a cell adhesion molecule, and CA 125 and EMA are tumor-associated antigens used in the diagnosis and monitoring of the outcome and response to treatment of various human malignancies. Their expression and prognostic significance after resection of renal cell carcinoma have not been adequately studied. The expression of CA 125, CD44, and EMA were studied immunohistochemically and correlated with the outcome of 92 patients who underwent nephrectomy for renal cell carcinoma. Positive staining was found for CA 125 in 28 patients (30.43%), CD44 in 48 patients (52.17%), and EMA in 74 patients (80.43%). CA 125 expression was increased in those with higher T stage (P <0.001) and histologic grade (P = 0.007). An inverse relationship was found between EMA expression and grade (P <0.001). The median follow-up was 41.5 months (range 30 to 65). The median survival for positive and negative patients was 34.6 versus 54.3 months for CA 125 (P = 0.0044), 48.3 versus 51.5 months for CD44 (P = 0.4677), and 53.2 versus 34 months for EMA (P = 0.0046). Multivariate analysis showed that CA 125 and EMA expression were independent prognostic factors (P = 0.021 and P = 0.018, respectively). Subgroup analysis showed that CA 125 expression predicted a significantly higher probability of death (28.6% versus 8%, P =0.0413) in patients with T1 or T2 tumors. CA 125 and EMA appear to be useful prognostic markers in renal cell carcinoma. Additional studies are needed to determine the value of these markers as a means of selection for postoperative management.


Rapidly Learning Generalizable and Robot-Agnostic Tool-Use Skills for a Wide Range of Tasks.
Many real-world applications require robots to use tools. However, robots lack the skills necessary to learn and perform many essential tool-use tasks. To this end, we present the TRansferrIng Skilled Tool Use Acquired Rapidly (TRI-STAR) framework for task-general robot tool use. TRI-STAR has three primary components: 1) the ability to learn and apply tool-use skills to a wide variety of tasks from a minimal number of training demonstrations, 2) the ability to generalize learned skills to other tools and manipulated objects, and 3) the ability to transfer learned skills to other robots. These capabilities are enabled by TRI-STAR's task-oriented approach, which identifies and leverages structural task knowledge through the use of our goal-based task taxonomy. We demonstrate this framework with seven tasks that impose distinct requirements on the usages of the tools, six of which were each performed on three physical robots with varying kinematic configurations. Our results demonstrate that TRI-STAR can learn effective tool-use skills from only 20 training demonstrations. In addition, our framework generalizes tool-use skills to morphologically distinct objects and transfers them to new platforms, with minor performance degradation.


Retracted: Application of Wireless Sensor Network Technology in Multipoint Control in Music Performance Management System.
[This retracts the article DOI: 10.1155/2022/2783944.].


Magnetic nanoparticles coated with polyphenols for spatio-temporally controlled cancer photothermal/immunotherapy.
As the combination of photothermal therapy (PTT) with immunotherapy provides an effective strategy in cancer treatment, a magnetic nanoparticle delivery system was constructed to load indocyanine green (ICG) and immunostimulator R837 hydrochloride (R837) for spatio-temporally PTT/immunotherapy synergism in cancer. This delivery system is composed of Fe3O4 magnetic nanoparticles (MPs) as the core to load ICG and polyethylene glycol polyphenols (DPA-PEG) as the coating layer to load R837, which formed R837 loaded polyphenols coating ICG loaded magnetic nanoparticles (MIRDs). After intravenous injection, the formed MIRDs resulted in long circulation, magnetic resonance imaging (MRI) guides, and magnetic targeting. Once targeting to the tumor, the MIRDs with the near-infrared (NIR) irradiation caused tumor ablation and resulted in tumor-associated antigens releasing to induce the body's immunological response, which was markedly improved it to attack the tumors with the R837 releasing from the outer DPA-PEG. In this case, the synergism of the PTT and immunotherapy inhibited tumor growth, metastasis and recurrence, which resulted in potent anticancer therapeutic effects with few side effect.


Chronic haloperidol treatment with low doses may enhance the increase of homovanillic acid in rat brain.
Homovanillic acid (HVA) levels were determined by high performance liquid chromatography with electrochemical detection in the striatum and prefrontal cortex of rats that had received single or repeated injections of various doses of haloperidol. Haloperidol increased the HVA concentrations in both brain regions after both acute and chronic treatment with doses of 0.01-1 mg/kg. The increase in the HVA concentrations in the striatum was blunted after repeated haloperidol injections with doses of 0.5-1 mg/kg, suggesting that haloperidol pretreatment results in a decreased responsiveness to the drug at high doses (tolerance). Tolerance also developed to the effect of long-term haloperidol treatment on the HVA concentrations in the prefrontal cortex at the highest dose used (1 mg/kg). This suggests that the differences in the development of tolerance between the striatum and prefrontal cortex are not qualitative but quantitative. However, repeated haloperidol injections at doses of 0.01-0.05 mg/kg enhanced the increase in HVA concentrations. This suggests that tolerance does not develop after chronic haloperidol treatment with low doses. Decreased HVA concentrations were also found after withdrawal from chronic haloperidol treatment (rebound decrease). However, this rebound decrease was much smaller than the decrease in response of the HVA concentrations to repeated haloperidol injections, suggesting that different mechanisms are involved.


Quinolone pharmacokinetics in the elderly.
As a class, quinolones undergo both renal excretion and hepatic metabolism. The dominant elimination pathway is usually renal, where secretion by the proximal tubule results in renal clearances 1.5-4 times greater than creatinine clearance. The benefit of this two-pathway elimination is protection from excessive accumulation in patients with single-organ dysfunction. A number of investigations have been performed to assess how the changes in renal and hepatic function that occur in the elderly influence quinolone pharmacokinetics. For example, lomefloxacin serum concentrations are slightly higher in elderly subjects, whereas total clearance, renal clearance, and nonrenal clearance are reduced, in comparison with younger subjects. The decline in renal clearance can be explained, in part, by the parallel decline in creatinine clearance in the elderly. Dosage adjustments should not be necessary in elderly patients with only minor changes in renal function caused by age-related changes in physiology. Although the relationship between nonrenal clearance of lomefloxacin and age is slightly less precise than the relationship between total clearance and age, this may be explained by the age-related decline in hepatic function and perhaps by changes in metabolic function. Quinolones show little evidence of altered absorption or altered pharmacodynamics in the elderly. These age-related alterations in drug elimination due to normal physiologic changes are generally not significant enough to warrant changes in dosage regimens; however, disease effects, particularly alterations of renal function, appear to be more important than gradual changes in physiology characteristic of the aging population.


Lapicque's 1907 paper: from frogs to integrate-and-fire.
Exactly 100 years ago, Louis Lapicque published a paper on the excitability of nerves that is often cited in the context of integrate-and-fire neurons. We discuss Lapicque's contributions along with a translation of the original publication.


Vertebral injuries: detection and implications.
Vertebral injuries occur in a predictable and reproducible manner that is dependent upon the mechanism of injury. Each mechanism of injury leaves distinct imaging 'fingerprints' regardless of the location in the spine. This chapter will discuss four areas: the mechanisms of injury and their imaging 'fingerprints'; abnormalities of alignment and anatomy, bony integrity, cartilage or joint space, and soft tissues-the ABCS of injury; the imaging features that will indicate stability of the spine following injury; and the classification of spine injuries into two categories-'major' or 'minor'. The imaging features described in this chapter apply to both radiography as well as to computed tomography (CT). Although helical CT is being used more commonly for the evaluation of suspected cervical injuries, radiography of the entire spine remains the standard.


Some introductory concepts of human growth: an overview.
Growth study methodology is described with emphasis upon cross-sectional versus longitudinal methods. The uses and advantages of velocity growth data are presented. Catch-up growth is defined and measurement ratios-indices discussed. The methodology necessary for the measurement of key indicators of human growth is described. These are body weight, recumbent length, head circumference.


Synthesis of novel thiazolidinic-phthalimide derivatives evaluated as new multi-target antiepileptic agents.
Epilepsy is a disease that affects millions of people around the globe and has a multifactorial cause. Inflammation is a process that can be involved in the development of seizures. Thus, the present study proposed the design and synthesis of new candidates for antiepileptic drugs that would also control the inflammatory process. Nine new derivatives of the substituted thiazophthalimide hybrid core were obtained with satisfactory purity ≥99% and yields between 27% and 87%. All compounds showed cell viability values greater than 90% in the culture of PBMC cells from healthy volunteers and, therefore, were not considered cytotoxic. These compounds modulated proinflammatory cytokines IFN-y and IL-17A and can mitigate inflammation. Acute toxicity studies of compound 7i in an animal model indicated that the compound has low toxicity and an LD50 greater than 2 g/kg in healthy adult rats. The same compound did not show positive results for anticonvulsant activity through the PTZ test. However, 7i demonstrates the interaction with the target GABA-A receptor in silico, indicating a possible activity as an agonist of that receptor. Thus, further studies are needed to investigate the anticonvulsant activity, in particular, using models in which the inflammatory process triggers epileptic seizures.


Eukaryotic elongation factor 2 loses its non-specific affinity for RNA and leaves polyribosomes as a result of ADP-ribosylation.
ADP-ribosylation of rabbit reticulocyte elongation factor 2 (EF-2) catalyzed by the A fragment of diphtheria toxin leads to a loss of its non-specific affinity for RNA. The removal of the ADP-ribose residue from EF-2 in the reverse reaction with nicotinamide restores its affinity for RNA. ADP-ribosylation of EF-2 is accompanied by its dissociation from the complexes with mono- and polyribosomes detected in the rabbit reticulocyte lysate at low ionic strength. The loss of the non-specific affinity of EF-2 for RNA as a result of ADP-ribosylation and, as a consequence, its decompartmentation from polyribosomes is assumed to be a reason for the diphtheria toxin-induced inactivation of the factor in eukaryotic cells.


The Activity of Small Urea-γ-AApeptides Toward Gram-Positive Bacteria.
Host Defense Peptides (HDPs) have gained considerable interest due to the omnipresent threat of bacterial infection as a serious public health concern. However, development of HDPs is impeded by several drawbacks, such as poor selectivity, susceptibility to proteolytic degradation, low-to-moderate activity and requiring complex syntheses. Herein we report a class of lipo-linear α/urea-γ-AApeptides with a hybrid backbone and low molecular weight. The heterogeneous backbone not only enhances chemodiversity, but also shows effective antimicrobial activity against Gram-positive bacteria and is capable of disrupting bacterial membranes and killing bacteria rapidly. Given their low molecular weight and ease of access via facile synthesis, they could be practical antibiotic agents.


Interaction and functional association of protein disulfide isomerase with alphaVbeta3 integrin on endothelial cells.
Adhesive properties of endothelial cells are influenced by the thioldisulfide balance. However, the molecular mechanism of this effect is unclear, although recent observations indicate that integrin receptors may be direct targets for redox modulation. The purpose of this study was to examine whether protein disulfide isomerase (PDI) is directly involved in this process. As manganese ions are known to affect the thioldisulfide balance and activate integrins to maximal affinity, we searched for PDI interactions with integrins, particularly with alpha(V)beta(3), in Mn(2+)-treated endothelial cells. By employing confocal microscopy, flow cytometry and coimmunoprecipitation experiments, we showed that exposure of endothelial cells to Mn(2+) resulted in: (a) the appearance of surface protein thiol groups, which can be found in PDI and alpha(V)beta(3), and both proteins colocalizing on the cellular surface; and (b) the formation of the PDI-alpha(V)beta(3) complex, which dissociates upon reduction. In addition, PDI in a complex with alpha(V)beta(3) induces conversion of the integrin to the ligand-competent high-affinity state, as evidenced by increased binding of vitronectin. The membrane-impermeable sulfhydryl blockers 3-N-maleimidylpropionyl biocytin 3-N-maleimidylpropionyl biocytin and p-chloromercuriphenyl sulfonate, as well as the PDI inhibitors bacitracin, MA3 018, and MA3 019, abolished the binding of vitronectin and LM609 to endothelial cells that is activated by Mn(2+). Consistently, LM609 almost completely blocked binding of vitronectin to such cells. The formation of the PDI-alpha(V)beta(3) stoichiometric complex was further demonstrated by surface plasmon resonance analysis, which showed that the initial reversible binding of PDI becomes irreversible in the presence of Mn(2+), probably mediated by disulfide bonds. Thus, we show that Mn(2+) simultaneously modulates the thiol isomerase activity of PDI that is bound to alpha(V)beta(3) and induces its transition to the ligand-competent state, suggesting an alternative mechanism of integrin regulation.


Redlining and Neighborhood Walking in Older Adults: The 2017 National Household Travel Survey.
In the 1930s, Black, working-class, and immigrant neighborhoods were color coded on maps (i.e., redlining) indicating investment risk, which negatively impacted mortgage attainment/homeownership for these groups and led to long-standing segregation by race/ethnicity and socioeconomic status. Limited studies have investigated the health impacts of redlining, particularly among older adults who tend to stay closer to their residences. This study examines whether older adults in historically redlined neighborhoods report less neighborhood walking and whether associations vary by race/ethnicity and income. The sample included 4,651 individuals aged ≥65 years from the 2017 U.S. National Household Travel Survey. U.S. Census tract‒based redlining scores were 1=best, 2=still desirable, 3=definitely declining, and 4=hazardous. Multivariable negative binomial regression tested the associations between redlining and neighborhood walking/day in the overall sample and with stratification by poverty status (analyzed in 2022). Participants were on average aged 73 years, and 11% were African/American Black, 75% were White, 8% were Hispanic/Latinx, and 6% were of other race/ethnicity. Participants reported a mean of 7.1 neighborhood walking minutes/day (SD=20.6), and 60% lived in definitely declining or hazardous neighborhoods. Individuals in hazardous neighborhoods (versus those in best neighborhoods) reported less neighborhood walking (prevalence ratio=0.64; 95% CI=0.43, 0.97). Among those living in poverty, living in definitely declining and hazardous neighborhoods was associated with less neighborhood walking (prevalence ratio=0.39 [95% CI=0.20, 0.79] and 0.39 [95% CI=0.18, 0.82], respectively). Less neighborhood walking was reported among individuals living in neighborhoods with a historic redlining score of definitely declining or hazardous. Future studies using larger, more diverse cohorts may elucidate whether associations differ by race/ethnicity and geographic location/city.


Pulse amplitude and volume-pressure relationships in experimental hydrocephalus.
The bolus injection test was used to study the intracranial volume pressure relationships in an experimental population of normal and hydrocephalic dogs. Hydrocephalus was developed by means of an intracisternal injection of a kaolin powder solution. Hydrocephalic animals were tested a mean of 15 days after kaolin injection. The intraventricular pressure (ICPo) and amplitude of intraventricular pulse wave (AMPo) were measured at baseline steady-state. Pressure-volume index (PVI) and intracranial compliance (C) were calculated from bolus injection tests. The ICPo (p less than 0.01) and AMPo (p less than 0.001) were much higher in hydrocephalic animals and C decreased significantly (p less than 0.001). There were no statistical differences regarding PVI. A direct linear correlation was found between AMPo and ICPo (p less than 0.001) and between PVI and ICPo (p less than 0.05) but no correlations were found between PVI and AMPo. The regression analysis showed a non-linear correlation between C and ICPo (p less than 0.01) and between C and AMPo (p less than 0.001). The results of our experimental study suggest that: 1) pulse amplitude relates to the intracranial compliance, and 2) the intracranial compliance is a better parameter of the volume-pressure response than PVI.


Vertebral hemi-resection for bone tumor with wide invasion of the vertebral canal: modified surgical method.
The authors describe a variation in the method of vertebral hemi-resection used for the treatment of neoplasms that present a wide invasion of the vertebral canal. This is followed by a review of the literature on the subject.


Neurogenic cardiopulmonary complications associated with spontaneous cerebellar hemorrhage.
Neurogenic cardiopulmonary complications associated with acute brain injury other then subarachnoid hemorrhage were seldom reported, especially in the pediatric population. We report a child who developed cardiac arrhythmia, severe myocardial injury and neurogenic pulmonary edema after cerebellar hemorrhage. An 11-year-old girl had abrupt onset of spontaneous cerebellar hemorrhage presented with a fulminant picture of hypertension, supraventricular tachyarrhythmia, markedly elevated cardiac enzyme (troponin-I > 50 ng/ml), and acute pulmonary edema. The cardiopulmonary complications were deemed neurogenic because of their rapid onset after brain injury and exclusion of external blunt chest injury, resuscitative injury, and risks for underlying cardiac disease. In addition to SAH, severe neurogenic cardiopulmonary complications could develop in pediatric patients with cerebellar hemorrhage. Supraventricular tachycardia may be an uncommon presenting rhythm that warrants considering cerebral etiology in patients without apparent cardiac risk.


Cordycepin buffers anisomycin-induced fear memory deficit by restoring hippocampal BDNF.
The process of memory consolidation involves the synthesis of new proteins, and interfering with protein synthesis through anisomycin can impair memory. Memory deficits due to aging and sleep disorders may also result from a reduction in protein synthesis. Rescuing memory deficits caused by protein synthesis deficiency is therefore an important issue that needs to be addressed. Our study focused on the effects of cordycepin on fear memory deficits induced by anisomycin using contextual fear conditioning. We observed that cordycepin was able to attenuate these deficits and restore BDNF levels in the hippocampus. The behavioral effects of cordycepin were dependent on the BDNF/TrkB pathway, as demonstrated by the use of ANA-12. Cordycepin had no significant impact on locomotor activity, anxiety or fear memory. Our findings provide the first evidence that cordycepin can prevent anisomycin-induced memory deficits by regulating BDNF expression in the hippocampus.


Evaluation and management of biliary complications after pediatric liver transplantation: pearls and pitfalls for percutaneous techniques.
In pediatric liver transplantation, bile duct complications occur with a greater incidence than vascular anastomotic dysfunction and represent a major source of morbidity and mortality. While surgical re-anastomosis can reduce the need for retransplantation, interventional radiology offers minimally invasive and graft-saving therapies. The combination of small patient size and prevailing Roux-en-Y biliary enteric anastomotic techniques makes endoscopic retrograde cholangiopancreatography difficult if not impossible. Expertise in percutaneous management is therefore imperative. This article describes post-surgical anatomy, pathophysiology and noninvasive imaging of biliary complications. We review percutaneous techniques, focusing heavily on biliary access and interventions for reduced liver grafts. Subsequently we review the results and adverse events of these procedures and describe conditions that masquerade as biliary obstruction.


Heteroarylation of unactivated C-H bonds suitable for late-stage functionalization.
The late-stage introduction of diverse heterocycles onto complex small molecules enables efficient access to new medicinally relevant compounds. An attractive approach to such a transformation would utilize the ubiquitous aliphatic C-H bonds of a complex substrate. Herein, we report a system that enables direct C-H heteroarylation using a stable, commercially available O-alkenylhydroxamate with heterocyclic sulfone partners. The C-H heteroarylation proceeds efficiently with a range of aliphatic substrates and common heterocycles, and is a rare example of heteroarylation of strong C-H bonds. Importantly, the present approach is amenable to late-stage functionalization as the substrate is the limiting reagent in all cases.


Infantile small cell gliomas.
Fourteen juvenile patients with small cell gliomas were studied at two institutes. These tumors are believed to form a distinct entity. They arise mostly in the diencephalon or the brain stem and are composed of a poorly differentiated small cell component having a pronounced tendency to differentiate into a glioma. Signs of neuroblastic differentiation were also found with the electron microscope. Small cell gliomas disseminate early and profusely throughout the ventricular walls and the subarachnoid spaces including the spinal meninges. Prognosis is grave, most patients dying within 1 year of diagnosis or surgical intervention. The designation "infantile small cell glioma" overlaps with both the "metastasising gliomas in young subjects" of Eade and Urich (1971) and with the primitive neuroectodermal tumor of infancy of Hart and Earle (1973).


Rhinoplasty in the African American Patient: Anatomic Considerations and Technical Pearls.
There are several anatomic considerations as well as variations in patients of African heritage. The goal of improvement in aesthetics and functionality must be in balance with racial preservation. Preoperative counseling must discuss patient expectations and surgical limitations based on patients' skin and cartilage. Dorsal augmentation, increased tip projection, and rotation are often needed. Understanding the thick, sebaceous skin often seen in African Americans assists in postoperative management of swelling.


Elevated atmospheric CO2 concentrations alter grapevine (Vitis vinifera) systemic transcriptional response to European grapevine moth (Lobesia botrana) herbivory.
Atmospheric carbon dioxide (CO2) concentrations are among the chief factors shaping the mode and magnitude of interactions between plants and herbivorous insects. Here, we describe the first global analysis of systemic transcriptomic responses of grapevine Vitis vinifera plants to feeding of European grapevine moth Lobesia botrana larvae at future elevated CO2 concentrations. The study was conducted on mature, fruit-bearing grapevine plants under ambient and elevated CO2 concentrations in a grapevine free-air carbon dioxide enrichment (FACE) facility. Grapevine transcriptional response to herbivory was clearly dependent on phenological stage, with a higher number of differentially expressed genes identified at fruit development compared to berry ripening. At fruit development, more transcripts were differentially expressed as a response to herbivory under elevated compared to ambient CO2 concentrations. Classification of the respective transcripts revealed that in particular genes involved in metabolic pathways, biosynthesis of secondary metabolites and plant-pathogen interactions were significantly enriched. Most of these genes had similar expression patterns under both CO2 concentrations, with a higher fold-change under elevated CO2 concentrations. Differences in expression levels of a subset of herbivory responsive genes were further validated by RT-qPCR. Our study indicates that future elevated CO2 concentrations will affect interactions between grapevine plants and one of its key insect pests, with consequences for future relevance of L. botrana in worldwide viticulture.


Low dose aspirin increases 15-epi-lipoxin A4 levels in diabetic chronic kidney disease patients.
Resolution of inflammation is regulated by endogenous lipid mediators, such as lipoxins and their epimers, including 15-epi-lipoxin A4 (15-epi-LXA4). However, there is no information on 15-epi-LXA4 and its in vivo regulation in chronic kidney disease (CKD) patients. Open label randomized clinical trial. 50 participants with chronic kidney disease (CKD) stage 3 and 4 without prior cardiovascular disease (25 in the aspirin group and 25 in the standard group) followed for 46 months. Aspirin (100mg/day) or standard treatment. To analyze the effect of aspirin on plasma 15-epi-LXA4 levels and inflammatory markers in CKD patients. Baseline plasma15-epi-LXA4 levels were lower in diabetic (1.22 ± 0.99ng/ml) than in non-diabetic CKD patients (2.05 ± 1.06ng/ml, p < 0.001) and inversely correlated with glycosylated hemoglobin levels (r = -0.303, p = 0.006). In multivariate analysis, diabetes was associated with lower 15-epi-LXA4 levels, adjusted for age, inflammatory markers and renal function (p = 0.005). In the whole study population, 15-epi-LXA4 levels tended to increase, but not significantly (p = 0.45), after twelve months on aspirin (from mean ± SD 1.84 ± 1.06 to 2.04 ± 0.75ng/ml) and decreased in the standard care group (1.60 ± 1.15 to 1.52 ± 0.68ng/ml, p = 0.04). The aspirin effect on 15-epi-LXA4 levels was more striking in diabetic patients, increasing from 0.94 ± 0.70 to 1.93 ± 0.74ng/ml, p = 0.017. Diabetic patients with CKD have lower circulating 15-epi-LXA4 levels than non-diabetic CKD patients. Low dose aspirin for 12 months increased 15-epi-LXA4 levels in diabetic patients. Given its anti-inflammatory properties, this increase in 15-epi-LXA4 levels may contribute to the beneficial effects of low dose aspirin.


Benefits and challenges of a nursing service-learning partnership with a community of internally-displaced persons in Colombia.
Service-learning partnerships between nursing programs and health care settings in vulnerable communities may be challenging to initiate, but can offer multiple benefits for students, faculty, and the community served. The aim of this qualitative descriptive study was to explore the benefits and challenges of establishing a service-learning partnership between a university nursing program and an isolated community of internally-displaced persons in Medellin, Colombia. Semi-structured, in-depth interviews were conducted with 10 nursing professors and nine students who participated in the service-learning partnership. Interviews were audio-recorded, transcribed and analyzed using qualitative content analysis. Main benefits identified were: learning about the social determinants of health, development of compassion, appreciation for the community nursing role, professional growth and development, community engagement and increased access to care for community members. Challenges related to the service-learning experience included feelings of moral distress, lack of value for community nursing, and conflict with traditional biomedical approaches to care. Several threats to program sustainability were also identified. Professors and students offered several recommendations for program improvement, including interdisciplinary collaboration, documentation and dissemination of the service-learning experience, increased community autonomy and capacity for self-care, and curricular changes to enhance recognition of the importance of community nursing.


Activation of carbonic anhydrase II by active-site incorporation of histidine analogs.
The hydration of CO2 catalyzed by human carbonic anhydrase II (HCA II) is accompanied by proton transfer from the zinc-bound water of the enzyme to solution. We have replaced the proton shuttling residue His 64 with Ala and placed cysteine residues within the active-site cavity by mutating sites Trp 5, Asn 62, Ile 91, and Phe 131. These mutants were modified at the single inserted cysteine with imidazole analogs to introduce new potential shuttle groups. Catalysis by these modified mutants was determined by stopped-flow and 18O-exchange methods. Specificity in proton transfer was demonstrated; only modifications of the Cys 131-containing mutant showed enhancement in the proton transfer step of catalysis compared with unmodified Cys 131-containing mutant. Modifications at other sites resulted in up to 3-fold enhancement in rates of CO2 hydration, with apparent second-order rate constants near 350 microM(-1) s(-1). These are among the largest values of kcat/Km observed for a carbonic anhydrase.


The effect of nifedipine, a calcium channel blocker, on human spermatozoal functions.
In vitro addition of 0.1-100 microns of a calcium channel blocker, Nifedipine, resulted in a significant non-competitive inhibition in the uptake of Ca++. The activity of Ca(++)-dependent ATPase enzyme was also decreased. Motility of the spermatozoa was significantly arrested following incubation with different doses of the drug at 37 degrees C for different durations. The pattern of motility changed within two hours from rapid and linear progression to slow or sluggish linear or non-linear movement and finally to non-progressive motility or even immotility. Scanning electron microscopic studies revealed disruptive changes in the head as well as tail region and coiling of spermatozoa after Nifedipine treatment. An increase in the formation and release of malonyldialdehyde was observed following Nifedipine addition in a dose-dependent fashion. The membrane cholesterol and phospholipid contents were considerably lowered in the treated samples. The potential of such calcium channel blocking agent in the designing of male contraceptive programme is discussed.


Terminal endbuds and acini as the respective major targets for chemical and sporadic carcinogenesis in the mammary glands of human c-Ha-ras protooncogene transgenic rats.
A rat strain carrying the human c-Ha-ras protooncogene, established by our laboratory, is highly susceptible to mammary chemical carcinogens. The transgenic rats exhibit increased number of terminal endbuds (TEBs) at the tips of developing ducts in the mammary gland compared to non-transgenic littermates. Confocal microscopy revealed the level of active mitogen-activated protein kinase to be elevated in these TEBs, and a close correlation between their numbers and tumorigenic response initiated by 7,12-dimethylbenz[a]anthracene was confirmed. Single injections of N-methyl-N-nitrosourea into the transgenic rats caused mutations in codon 12 of human c-Ha-ras transgene in TEBs before tumor development, supporting the conclusion that these structures are the major targets of chemical carcinogens. In contrast, with spontaneous development of lesions, alveolar hyperplasia with elevated expression levels of rat and human c-Ha-ras protooncogenes is the first morphological alteration which becomes apparent. Some but not all hyperplastic alveolar nodules were found to harbor mutations in the transgene. The results indicate that elevated expression of c-Ha-ras protooncogene is sufficient in itself to cause a highly proliferative phenotype of mammary alveoli. Our data suggest that TEBs and acini are the major targets for chemical and sporadic carcinogenesis, respectively, in the mammary glands of human c-Ha-ras protooncogene transgenic rats.


Monophyly of primary photosynthetic eukaryotes: green plants, red algae, and glaucophytes.
Between 1 and 1.5 billion years ago, eukaryotic organisms acquired the ability to convert light into chemical energy through endosymbiosis with a Cyanobacterium (e.g.,). This event gave rise to "primary" plastids, which are present in green plants, red algae, and glaucophytes ("Plantae" sensu Cavalier-Smith). The widely accepted view that primary plastids arose only once implies two predictions: (1) all plastids form a monophyletic group, as do (2) primary photosynthetic eukaryotes. Nonetheless, unequivocal support for both predictions is lacking (e.g.,). In this report, we present two phylogenomic analyses, with 50 genes from 16 plastid and 15 cyanobacterial genomes and with 143 nuclear genes from 34 eukaryotic species, respectively. The nuclear dataset includes new sequences from glaucophytes, the less-studied group of primary photosynthetic eukaryotes. We find significant support for both predictions. Taken together, our analyses provide the first strong support for a single endosymbiotic event that gave rise to primary photosynthetic eukaryotes, the Plantae. Because our dataset does not cover the entire eukaryotic diversity (but only four of six major groups in), further testing of the monophyly of Plantae should include representatives from eukaryotic lineages for which currently insufficient sequence information is available.


A META-ANALYSIS OF COGNITIVE BEHAVIOR THERAPY AND MEDICATION FOR CHILD OBSESSIVE-COMPULSIVE DISORDER: MODERATORS OF TREATMENT EFFICACY, RESPONSE, AND REMISSION.
Individual randomized controlled trials (RCTs) have demonstrated the efficacy of cognitive behavioral therapy (CBT) and serotonin reuptake inhibitors (SRIs) for the treatment of youth with obsessive-compulsive disorder (OCD). Although meta-analyses have confirmed these results, there has been minimal examination of treatment moderators or an examination of treatment response and symptom/diagnostic remission for these two treatment types. The present report examined the treatment efficacy, treatment response, and symptom/diagnostic remission for youth with OCD receiving either CBT or SRIs relative to comparison conditions, and examined treatment moderators. A comprehensive literature search identified 20 RCTs that met inclusion criteria, and produced a sample size of 507 CBT participants and 789 SRI participants. Random effects meta-analyses of CBT trials found large treatment effects for treatment efficacy (g = 1.21), treatment response (relative risk [RR] = 3.93), and symptom/diagnostic remission (RR = 5.40). Greater co-occurring anxiety disorders, therapeutic contact, and lower treatment attrition were associated with greater CBT effects. The number needed to treat (NNT) was three for treatment response and symptom/diagnostic remission. Random effects meta-analyses of SRI trials found a moderate treatment effect for treatment efficacy (g = 0.50), treatment response (RR = 1.80), and symptom/diagnostic remission (RR = 2.06). Greater methodological quality was associated with a lower treatment response for SRI trials. The NNT was five for treatment response and symptom/diagnostic remission. Findings demonstrate the treatment effects for CBT and SRIs across three important outcome metrics, and provide evidence for moderators of CBT across trials.


What is the impact of age on reoperation rates for femoral neck fractures treated with internal fixation and hemiarthroplasty? A comparison of hip fracture outcomes in the very elderly population.
A retrospective comparative study was performed at a level 1 trauma center at which electronic medical records and digital radiographs were reviewed for 949 femoral neck fractures. For the primary outcome of reoperation based on age, Kaplan-Meier models were built and analysis applied. A total of 334 fractures were nondisplaced treated with closed reduction and percutaneous pinning (CRPP), and 615 were displaced managed with hemiarthroplasty (HA). Overall, 98 patients (10.33%) required reoperation. Increasing reoperation rates for CRPP was seen with each subsequent age group. The opposite was seen with HA in which increasing age groups showed lower reoperation rates.


Seeking drugs or seeking help? Escalating "doctor shopping" by young heroin users before fatal overdose.
To identify prescription drug-seeking behaviour patterns among young people who subsequently died of heroin-related overdose. Linkage of Medicare and Pharmaceutical Benefits Scheme and Coroner's Court records from Victoria. Two hundred and two 15-24-year-olds who died of heroin-related overdose between 6 January 1994 and 6 October 1999. Patterns of use of medical services and prescription drugs listed on the Pharmaceutical Benefits Scheme in the years before death, and use of all drugs just before death. Polydrug use was reported in 90% of toxicology reports, and prescription drugs were present in 80% of subjects. Subjects accessed medical services six times more frequently than the general population aged 14-24 years, and more than half of all prescribed drugs were those prone to misuse, such as benzodiazepines and opioid analgesics. A pattern of increasing drug-seeking behaviour in the years before death was identified, with doctor-visitation rates, number of different doctors seen and rates of prescriptions peaking in the year before death. An apparent increase in "doctor shopping" in the years before heroin-related death may reflect the increasing misuse of prescription drugs, but also an increasing need for help. Identification of a pattern of escalating doctor shopping could be an opportunity for intervention, and potentially, reduction in mortality.


In vitro proliferation of primary human head and neck squamous cell carcinomas evaluated by flow cytometry.
In vitro proliferation of primary human head and neck squamous cell carcinomas was investigated using single cell suspensions and tissue explants of primary specimens and xenografts from 20 tumor specimens. The evaluations of the cells emerging in culture were performed with flow cytometry. Epithelial-like cells proliferated in serum-free medium, while no fibroblast-like cells were observed in culture. The epithelial-like cells could be subcultured several passages before senescence occurred. Conditioned medium or serum supplementation was necessary for a sustained outgrowth of malignant squamous cells as documented by flow cytometry. From a tumor line established in nude mice slowly proliferating tumor cells emerged. After 4-5 months in culture tumor cells seemed to be adapted to the culture conditions used. This resulted in a more consistent tumor cell proliferation. Early passage cultures from primary human head and neck squamous cell carcinomas are clearly difficult to obtain either from primary human specimens or from tumor lines established in nude mice.


Failure patterns according to molecular subtype in patients with invasive breast cancer following postoperative adjuvant radiotherapy: long-term outcomes in contemporary clinical practice.
Although gene expression profiling provides critical information, knowledge remains limited regarding the differential effects of molecular subtype on clinical course. This study evaluated the impact of molecular status on long-term patterns of failure in patients with non-metastatic breast cancer. We analyzed data from 1181 individuals with invasive breast cancer undergoing surgery plus PORT from 2003 to 2011. Molecular subtypes were defined as luminal A (LA), luminal B (LB)-HER2(-), LB-HER2(+), HER2, and triple-negative (TN) based on the 2013 St. Gallen Consensus criteria. Competing risks analysis and baseline hazard rate function plots were used to explore subtype-specific recurrence patterns. The 10-year overall survival rates of LA, LB-HER2(-), LB-HER2(+), HER2, and TN groups were 96, 93, 94, 84, and 85%, respectively (P < 0.001). Distant metastatic events differed significantly according to molecular subtype (P < 0.001). In competing risks regression analysis, initial development of distant metastasis was the highest with TN tumors, followed by HER2, LB-HER2(-), and LB-HER2(+) subtypes (P = 0.005). Regarding preferential sites of distant metastasis, the risk of initial brain metastasis was significantly higher with HER2 tumors, followed by TN tumors (P = 0.001). A low-level but sustained metastatic risk increment was observed in luminal tumors, whereas TN and HER2 subtypes showed a short-term risk surge within 5 years. From the significant impact of molecular profile on distant metastasis, subtype-specific individualization of systemic treatment and close surveillance are suggested. The preferential and long-term risk of brain metastasis in the HER2 subtype underlines the importance of alternative anti-HER2 therapies.


The serum osmole gap.
Estimation and measurement of serum osmolality can be of value in the clinical management of certain forms of critical illness. Osmolality is a measure of the concentration of osmotically active particles, or solutes, in a solution. Only low-formula weight ions and uncharged molecules that are present in relatively high concentrations contribute significantly to serum osmolality. Serum osmolality can be easily estimated from the three major osmotic constituents of normal serum (sodium, urea, and glucose) by a simple formula. An understanding of serum osmolality, its laboratory measurement, its bedside estimation, and the concept of the osmole gap, is crucial in making a preliminary diagnosis of methanol and ethylene glycol intoxication, as well as a few other related compounds. There are important caveats to this use of the osmole gap, because under certain circumstances both false-positive and false-negative interpretations may occur. The osmole gap may also be helpful for confirming pseudohyponatremia, as a gauge for dosing mannitol and glycerol when used to treat intracranial hypertension, and as a prognostic indicator in circulatory shock.


Expression of the Insulin Receptor Substrate 1 in primary tumors and lymph node metastases in breast cancer: correlations with Bcl-xL and Bax proteins.
In our previous investigation Insulin Receptor Substrate 1 (IRS-1) correlated with proliferation marker Ki-67 in human breast cancer. The aim of the present study was to assess relationships between IRS-1 expression and anti-apoptotic Bcl-xL as well as proapoptotic Bax proteins, assessed by immunohistochemistry, in primary tumors and lymph node metastases of breast cancer. IRS-1 is positively associated with both Bcl-xL and Bax in primary and metastatic tumors. Thus, our results could suggest that IRS-1 might affect turnover of cancer cells and breast cancer progression through activation of mitogenesis and participation in the regulation of the balance between anti- and proapoptotic pathways.


Sustained function of alginate-encapsulated human islet cell implants in the peritoneal cavity of mice leading to a pilot study in a type 1 diabetic patient.
Alginate-encapsulated human islet cell grafts have not been able to correct diabetes in humans, whereas free grafts have. This study examined in immunodeficient mice whether alginate-encapsulated graft function was inferior to that of free grafts of the same size and composition. Cultured human islet cells were equally distributed over free and alginate-encapsulated grafts before implantation in, respectively, the kidney capsule and the peritoneal cavity of non-obese diabetic mice with severe combined immunodeficiency and alloxan-induced diabetes. Implants were followed for in vivo function and retrieved for analysis of cellular composition (all) and insulin secretory responsiveness (capsules). Free implants with low beta cell purity (19 ± 1%) were non-functional and underwent 90% beta cell loss. At medium purity (50 ± 1%), they were functional at post-transplant week 1, evolving to normoglycaemia (4/8) or to C-peptide negativity (4/8) depending on the degree of beta cell-specific losses. Encapsulated implants immediately and sustainably corrected diabetes, irrespective of beta cell purity (16/16). Most capsules were retrievable as single units, enriched in endocrine cells that exhibited rapid secretory responses to glucose and glucagon. Single capsules with similar properties were also retrieved from a type 1 diabetic recipient at post-transplant month 3. However, the vast majority were clustered and contained debris, explaining the poor rise in plasma C-peptide. In immunodeficient mice, i.p. implanted alginate-encapsulated human islet cells exhibited a better outcome than free implants under the kidney capsule. They did not show primary non-function at low beta cell purity and avoided beta cell-specific losses by rapidly establishing normoglycaemia. Retrieved capsules presented secretory responses to glucose, which was also observed in a type 1 diabetic recipient.


Role of oceanic fronts in enhancing phytoplankton biomass in the eastern Arabian Sea during an oligotrophic period.
In the present study, using in-situ and satellite observations, we investigate the influence of physical processes on the enhancement of phytoplankton biomass in the eastern Arabian Sea (EAS). Water column measurements were carried out from 9⁰N to 21⁰N (stations II-2 to II-14) along 68⁰E transect in the EAS during the beginning of fall intermonsoon (FIM) of 2014. Both in-situ and satellite-derived chlorophyll a (Chl a) showed higher biomass at 15⁰N (station II-8) compared to northern and southern stations. We explored the possible physical processes which can lead to high biological productivity at this station. Our study shows that nearly two times enhancement in Chl a at station II-8 was contributed by an open-ocean front, which occurred two days before the measurement. Based on phytoplankton marker pigments, it was evident that haptophytes were abundant at II-8 with a minor contribution from diatoms and dinoflagellates. This condition also led to a high concentration (4.9 nM) of dimethylsulphide (DMS), an anti-green house gas with a net flux of 3.76 μmol m-2d-1 at this site. Among the picophytoplankton, Synechococcus were abundant at this station, however Prochlorococcus were absent as confirmed by both marker pigment and flow cytometric counts. The case study presented here demonstrates the dynamic nature of open ocean fronts and their overall contribution to the productivity of the eastern Arabian Sea during the oligotrophic inter-monsoon period.


Structural brain characteristics and gene co-expression analysis: A study with outcome label from normal cognition to mild cognitive impairment.
Longitudinal studies reported that some elderly people with normal cognition (NC) converted to mild cognitive impairment (MCI), and some remained normal state (NC_S). The underlying factor for this difference conversion of NC is worthy of exploration METHODS: Eighty-three NC participants were tracked for eight years. Thirty participants transitioned from NC to MCI (NC_MCI). The remaining 53 participants retained an NC_S. The structural brain features and genetic expression of the 83 NC participants were obtained. We applied weighted gene co-expression network analysis (WGCNA) to inquire into the co-expression network of those. Mediator effect analysis of regulatory roles was conducted to inquire into the associations between brain measures, expression values, and clinical scores. The main results are: 1) 20 brain features and 740 gene expression had significant differences between the two groups, 2) one module including 187 genes had the most correlation with cortical thickness of left superior temporal sulcus (L.STS), 3) NFKBIA and RARA genes were the top two genes that made the greatest contribution to L.STS thickness, and 4) mediating effect was found between the L.STS thickness, the NFKBIA and RARA expression levels, and clinical scores. Our results provide a theoretical foundation based on gene expression and brain imaging for the factors of NC with different outcomes.


Applicability and validation of the Reaction to Tests Scale (RTT) in a sample of Portuguese medical students.
Test anxiety is a crucial factor in determining academic outcomes, and it may lead to poor cognitive performance, academic underachievement, and psychological distress, interfering specifically with their ability to think and perform during tests. The main objective of this study was to explore the applicability and psychometric properties of a Portuguese version of the Reactions to Tests scale (RTT) in a sample of medical students. A sample of 672 medical students completed the RTT. The sample was randomly split in half to allow for independent Exploratory Factor Analysis (EFA) and to test the best fit model-Confirmatory Factor Analysis (CFA). CFA was used to test both the first-order factor structure (four subscales) and second-order factor structure, in which the four subscales relate to a general factor, Test Anxiety. The internal consistency of the RTT was assessed through Cronbach's alpha, Composite reliability (CR) and Average Variance Extracted (AVE) for the total scale and each of the four subscales. Convergent validity was evaluated through the correlation between RTT and the State-Trait Anxiety Inventory (STAI-Y).To explore the comparability of measured attributes across subgroups of respondents, measurement invariance was also studied. Results from exploratory and confirmatory factor analyses showed acceptable fits for the Portuguese RTT version. Concerning internal consistency, results indicate that RTT was found to be reliable to measure test anxiety in this sample. Convergent validity of the RTT with both state and trait anxiety STAI-Y's subscales was also shown. Moreover, multigroup analyses showed metric invariance across gender and curriculum phase. Our results suggest that the RTT scale is a valid and reliable instrument for the measurement of test anxiety among Portuguese Medical Students.


Successful antibiotic eradication of Streptococcus pneumoniae infection of a ventriculoatrial shunt.
A case of Streptococcus pneumoniae meningitis in a possibly immune-compromised child with a ventriculoatrial shunt is described. The infection was successfully eradicated by treatment with intravenous ceftriaxone and rifampicin, without removal of the shunt.


Recycling of bottom ash derived from combustion of cattle manure and its adsorption behaviors for Cd(II), Cu(II), Pb(II), and Ni(II).
Bottom ash generated by the combustion of cattle manure (BA-CCM) was investigated as an adsorbent for the removal of heavy metals such as Cd(II), Cu(II), Pb(II), and Ni(II) from aqueous solutions. When cattle manure was used as fuel, the thermal efficiency of the boiler was 88.7%, and the CO and CO2 concentrations in the exhaust gas were 2.3 ppm and 12.1%, respectively. The percentage of remaining solids was 31 wt.% after combustion at 900 °C. X-ray fluorescence analyses showed that the elemental composition of the BA-CCM was mainly CaO (43.3%), SiO2 (15.8%), CO2 (13.0%), and P2O5 (10.3%). The kinetic adsorption of Cd(II), Cu(II), Pb(II), and Ni(II) by BA-CCM reached equilibrium after 12 h, and the pseudo-second-order model fitted the experimental data well. The maximum amount of Cd(II), Cu(II), Pb(II), and Ni(II) adsorbed by the bottom ash was 5.4, 72.6, 88.2, and 24.6 mg/g, respectively. The equilibrium adsorption of metals onto BA-CCM was well-described by the Freundlich model. Thermodynamic analysis showed that the adsorption onto the bottom ash was endothermic and that the Gibbs free energy decreased as the temperature increased. The presence of cations such as Na+, Ca2+, and Al3+ was found to reduce the amount of metals adsorbed onto the BA-CCM, and Cd(II) adsorption was found to be more dependent on ionic strength than adsorption of Cu(II), Pb(II), and Ni(II). This study demonstrates the feasibility of producing heat energy by burning cattle manure and removing heavy metals from aqueous solutions using the generated bottom ash as an adsorbent.


Novel mutation in SLC9A6 gene in a patient with Christianson syndrome and retinitis pigmentosum.
Mutations in the SLC9A6 gene cause Christianson syndrome in boys. This X-linked syndrome is characterized by profound mental retardation with autistic behavior, microcephaly, epilepsy, ophthalmoplegia, and ataxia. Progressive cerebellar atrophy with motor regression is a remarkable feature in some patients. We report on a 22year-old male patient with Christianson syndrome carrying the novel p.Gln306X mutation. The infantile phenotype suggested pervasive developmental disorder, then profound mental retardation ensued. In later childhood, progressive cerebellar atrophy was diagnosed on serial brain MRIs and motor regression occurred. Furthermore, ophthalmological evaluations showed a retinitis pigmentosum previously unreported in this condition. We conclude that the natural history of the disease in this patient tends to confirm the degenerative nature of Christianson syndrome, and that retinal degeneration may be part of the condition. Before the onset of degeneration, the syndromic association of severe mental retardation, autistic behavior, external ophthalmoplegia, and facial dysmorphism in male patients is a clue to the diagnosis.