A phase I trial of oxaliplatin and topotecan in recurrent ovarian carcinoma.
Oxaliplatin and topotecan have demonstrated activity as single agents against recurrent platinum-sensitive and -resistant ovarian cancer, as well as synergy in vitro. This was a dose-finding study of combination therapy with weekly topotecan and alternating-week oxaliplatin in patients with recurrent epithelial ovarian cancer. Eligible patients had a diagnosis of recurrent ovarian or primary peritoneal carcinoma, a performance status of 0-2, and normal bone marrow, renal, and hepatic function. On days 1 and 15 of a 28-day cycle, patients received a fixed dose of oxaliplatin (85 mg/m2) via intravenous infusion. On days 1, 8, and 15, patients received an escalating dose of intravenous topotecan (2.0-4.0 mg/m2). Five dose levels were planned with a minimum cohort of 3 patients at each level. Thirteen patients were enrolled and received a total of 50 cycles of chemotherapy. The maximum tolerated dose was 85 mg/m2 of oxaliplatin and 3.0 mg/m2 of topotecan, and grade 3 neutropenia was the dose-limiting toxicity. Four of nine (44%) evaluable patients had stable disease or a partial response to the drug combination as assessed by cancer antigen-125 levels. A 28-day schedule of oxaliplatin and topotecan is safe and well tolerated. Because of the in vitro synergy observed between topoisomerase I inhibitors and platinum derivatives and the tolerability reported in the current study, this regimen warrants further investigation.


Characteristics of thirst and sodium appetite in mice (Mus musculus).
The intakes of water and sodium chloride (NaCl) solution were examined in mice following treatment with agents that either stimulate or mimic various components of the renin-angiotensin-aldosterone system. Injections of either angiotensin II (Ang II) or isoproterenol produced very little water intake compared with the robust responses to either intracellular dehydration or to extracellular dehydration induced by treatment with polyethylene glycol (PEG). In studies on appetite for NaCl solution, mice exhibited no spontaneous preference for 0.15 M NaCl solution over water and did not change this preference during treatment with deoxycorticosterone acetate (DOCA), a sodium-deficient diet, or after adrenalectomy. Plasma concentrations of aldosterone were increased in intact mice fed a sodium-deficient diet but were not eliminated by adrenalectomy. However, acute treatment with furosemide in combination with a sodium-deficient diet stimulated an appetite for NaCl solution. Chronic oral administration of an angiotensin I (Ang I) converting enzyme inhibitor failed to induce a NaCl appetite. These findings show that mice are refractory to the induction of either water or NaCl intake by stimuli of the renin-angiotensin-aldosterone system, stimulation that is highly effective in rats; this suggests that there may be major differences among rodents in the hormonal determinants of behaviors related to hydromineral homeostasis.


Inhibitory role of acyl homoserine lactones in hemolytic activity and viability of Streptococcus pyogenes M6 S165.
Streptococcus pyogenes an adapted human pathogen asymptomatically colonizes the nasopharynx, among other polymicrobial communities. However, information on the events leading to the colonization and expression of virulence markers subject to interspecies and host-bacteria interactions are limited. The interference of acyl homoserine lactones (AHLs) with the hemolytic activity and viability of S. pyogenes M6 S165 was examined. AHLs, with fatty acid side chains ≥12 carbon atoms, inhibited hemolytic activity by downregulating the expression of the sag operon involved in the production of streptolysin S. Inhibitory AHLs upregulated the expression of transcriptional regulator LuxR. Electrophoretic mobility shift assays revealed the interaction of LuxR with the region upstream of sagA. AHL-mediated bactericidal activity observed at higher concentrations (mM range) was an energy-dependent process, constrained by the requirement of glucose and iron. Ferrichrome transporter FtsABCD facilitated transport of AHLs across the streptococcal membrane. The study demonstrates a previously unreported role for AHLs in S. pyogenes virulence.


[Research on the negative immune regulation of NK cells in patients with primary immune thrombocytopenia].
Objective: To investigate the levels of NK cells and their relevant cytokines (IL-10, TGF-β and IFN-γ) in patients with primary immune thrombocytopenia (ITP) . Methods: All samples were obtained from 42 patients (22 newly diagnosed and 20 in remission) and 20 healthy volunteers. The levels of IL-10 and IFN-γ in blood serum were detected by enzyme-linked immunosorbent assay (ELISA) . The percentage of CD3(-) CD56(+) NK cell, CD3(-) CD56(bright) CD16(-) NK cell, CD3(-) CD56(dim) CD16(+) NK cell in peripheral blood lymphocyte were detected by flow cytometry. The NK cells were isolated by immunomagnetic microbeads. The mRNA expression levels of IL-10, TGF-β, and IFN-γ in NK cells were detected by real-time fluorescent quantitative PCR. Correlation between the above measured results was analyzed. Results: ① The blood serum level of IFN-γ in newly diagnosed ITP patients [ (653.0±221.6) ng/L] was higher than that in remission ITP patients [ (484.4±219.5) ng/L] and healthy control [ (390.9±253.5) ng/L] (P=0.022, P=0.001) . The blood serum level of IL-10 in newly diagnosed ITP patients was lower than that in healthy control [ (52.09±26.66) ng/L vs (79.44±38.43) ng/L, P=0.007]. ②The percentage of NK cell in newly diagnosed and remission ITP patients [ (9.53±3.93) %, (9.03±3.78) %] were significantly lower than that in healthy control [ (13.72±7.42) %] (P=0.013, P=0.007) . The ratio of CD3(-) CD56(bright) CD16(-) NK cell/total NK cells in newly diagnosed ITP patients was higher than that in healthy control [ (6.85±4.43) % vs (4.05±2.81) %, P=0.032]. The ratio of CD3(-)CD56(dim) CD16(-) NK cell/total NK cells in newly diagnosed ITP patients was lower than that in healthy control [ (93.14±4.43) % vs (95.94±2.81) %, P=0.032]. ③ There was no significant difference in the mRNA expression level of IFN-γ in NK cells of ITP patients and healthy control (all P>0.05) . The mRNA expression levels of IL-10 and TGF-β in NK cells in newly diagnosed ITP patients were significantly higher than that in healthy control (1.82±1.32 vs 1.02±1.03, P=0.023; 2.80±2.31 vs 1.46±1.37, P=0.028) . The ratio of CD3(-)CD56(bright) CD16(-) NK cell/total NK cells was positively correlated with the mRNA expression levels of IL-10, TGF-β in NK cells (r=0.424, P=0.001; r=0.432, P<0.001) . Conclusion: NK cells may compensate for the deficiency of the number by enhancing the secretion of negative regulation cytokines, acting as "protective" roles in the disease.


A Novel Glucose-Sensitive Scaffold Accelerates Osteogenesis in Diabetic Conditions.
Mandibular bone regeneration is still a big challenge in those diabetic patients with poorly controlled blood glucose. In this study, we prepared a novel glucose-sensitive controlled-release fiber scaffold (PVA-HTCC/PEO-rhBMP2-glucose oxidase (PHPB-G)), which contained the recombinant human bone morphogenetic protein 2 (rhBMP2) by coaxial cospinning and grafted with glucose oxidase (GOD). We presented evidence that PHPB-G could undergo a series of structural changes with the blood glucose and promoted bone regeneration in diabetic rat. PHPB-G expanded the voids in nanofibers when blood glucose levels elevated. More importantly, its slow-release rhBMP2 effectively promoted the healing of bone defects. These data suggested that the PHPB-G delivery system may provide a potential treatment strategy for patients with severe diabetic alveolar bone defects.


A highly specific method for the characterization of glycation and glyco-oxidation products of globins.
A new method, based on matrix-assisted laser desorption/ionization (MALDI) measurements, has been developed for the evaluation of the glycation level of globins, a relevant parameter for diabetes control. It shows high levels of reproducibility and specificity, allowing the different glycated and glyco-oxidized products of both alpha- and beta-globins to be distinguished. Such specificity is reflected in its possible diagnostic use not only for the control of diabetes, but also for the occurrence of 'oxidative stress'. The comparison, for the same samples, of the obtained MALDI data with the related HbA1c values, determined by a high performance liquid chromatographic method, allowed it to be established that HbA1c percentages are not, as usually retained, related to the simply glycated beta-globin, but to the whole pool of glycated and glyco-oxidized alpha- and beta-globins.


Ruptured aneurysm of major aortopulmonary collateral artery: management using amplatzer vascular plug.
Aneurysm of a major aortopulmonary collateral artery (MAPCA) is quite rare. Aneurysmally dilated MAPCA may be complicated with rupture and massive hemoptysis leading to sudden death. Possible pathophysiology for aneurysm formation is persistent high pressure state in collateral circulation. High index of suspicion is necessary to avoid catastrophic complications as the amount of hemoptysis does not correlate with disease severity and etiology. We present a case of large ruptured aneurysm of a MAPCA presenting with massive haemoptysis in a patient of cyanotic congenital heart disease which was salvaged by endovascular deployment of vascular plug.


[Accomplishments of tumor surgery in tumors of soft tissues].
Surgery of sarcomas includes treatment of the primary tumor and recurrences or metastases. The surgical intervention is in most cases part of a multimodal treatment approach. The surgical technique used depends on the size, localization and extension of the tumor. By selecting the appropriate surgical technique, such as compartment resection or plastic surgical procedures, as well as additional radiation or chemotherapy, amputation of an extremity can often be avoided or at least reduced in extensiveness (stump distalisation). Of course there can be no compromise on sufficient tumor-free resection margins. Through preoperative radiation therapy or regional chemotherapy, e.g. isolated hyperthermal extremity perfusion, it is possible to improve the final results of extremity conserving therapy. A mono-bloc resection of sarcomas of localisations other than the extremities is problematical and often impossible. In the context of multimodal treatment approaches the surgical reduction of the tumor is highly significant. Even if the tumor has metastasized, the prognosis can be significantly improved by surgical procedures. This is especially true if the metastases are in the lung, in which case the disease-free interval and the tumor-doubling time are significant prognostic factors. These should be considered in the treatment of metastatic disease.


BaTiO3 supercages: unusual oriented nanoparticle aggregation and continuous ordering transition in morphology.
Here we report the organic-free mesocrystalline superstructured cages of BaTiO3, i.e., the BaTiO3 supercages, which are synthesized by a one-step templateless and additive-free route using molten hydrated salt as the reaction medium. An unusual three-dimensional oriented aggregation of primary BaTiO3 nanoparticles in the medium of high ionic strength, which normally favors random aggregation, is identified to take place at the early stage of the synthesis. The spherical BaTiO3 aggregates further experience a remarkable continuous ordering transition in morphology, consisting of nanoparticle faceting and nanosheet formation steps. This ordering transition in conjunction with Ostwald ripening-induced solid evacuation leads to the formation of unique supercage structure of BaTiO3. Benefiting from their structure, the BaTiO3 supercages exhibit improved microwave absorption property.


Deciphering the onychophoran 'segmentation gene cascade': Gene expression reveals limited involvement of pair rule gene orthologs in segmentation, but a highly conserved segment polarity gene network.
The hallmark of the arthropods is their segmented body, although origin of segmentation, however, is unresolved. In order to shed light on the origin of segmentation we investigated orthologs of pair rule genes (PRGs) and segment polarity genes (SPGs) in a member of the closest related sister-group to the arthropods, the onychophorans. Our gene expression data analysis suggests that most of the onychophoran PRGs do not play a role in segmentation. One possible exception is the even-skipped (eve) gene that is expressed in the posterior end of the onychophoran where new segments are likely patterned, and is also expressed in segmentation-gene typical transverse stripes in at least a number of newly formed segments. Other onychophoran PRGs such as runt (run), hairy/Hes (h/Hes) and odd-skipped (odd) do not appear to have a function in segmentation at all. Onychophoran PRGs that act low in the segmentation gene cascade in insects, however, are potentially involved in segment-patterning. Most obvious is that from the expression of the pairberry (pby) gene ortholog that is expressed in a typical SPG-pattern. Since this result suggested possible conservation of the SPG-network we further investigated SPGs (and associated factors) such as Notum in the onychophoran. We find that the expression patterns of SPGs in arthropods and the onychophoran are highly conserved, suggesting a conserved SPG-network in these two clades, and indeed also in an annelid. This may suggest that the common ancestor of lophotrochozoans and ecdysozoans was already segmented utilising the same SPG-network, or that the SPG-network was recruited independently in annelids and onychophorans/arthropods.


Ivermectin as an antiparasitic agent in horses.
Ivermectin, described as 22,23-dihydroavermectin B1, was the compound chosen from the avermectin group of compounds for development as an antiparasitic agent in horses. A review of the literature indicates that parenteral administration in horses at 200 microgram/kg body mass is highly effective against the strongyles Strongylus vulgaris, Strongylus edentatus and triodontophorus spp., and adult and immature cyathostomes, including strains resistant to benzimidazole anthelmintics. Other nematodes controlled in horses include Oxyuris equi, Parascaris equorum, Trichostrongylus axei, and Habronema spp. Ivermectin is also highly effective against stomach bots (Gastrophilus spp.).


The effects of plasmid content, transcription efficiency, and translation efficiency on the productivity of a cloned gene protein in Escherichia coli.
In order to investigate how plasmid content, transcription efficiency, and translation efficiency affect the productivity of a cloned gene protein, a new vector (pPLc-RP4.5) was constructed. The vector has PL promoter and lacZ as a structure gene 4.5S RNA gene between PL promoter and lacZ gene. We took advantage of the characteristic that the 4.5S RNA is accumulated inside E. coli cells and can be quantitatively measured. A two-stage continuous culture system in combination with a temperature-sensitive gene switching system was used to study the performance of the recombinant fermentation. It was found that the plasmid content as varied by the dilution rate in the production stage showed a different pattern from that in the growth stage. The result showed that promoter strength had a greater influence on the overall gene expression efficiency of a cloned gene than the plasmid content, and the overall gene expression efficiency was largely dependent upon translation efficiency when a multicopy plasmid (pBR322 derivative and rop-) and a strong promoter (PL) were used to express a heterologous protein in E. coli.


Phosphorylation-dependent migration of retinoblastoma protein into the nucleolus triggered by binding to nucleophosmin/B23.
Underphosphorylated retinoblastoma (Rb) protein inhibits progression around the cell cycle by binding to transcription factors like E2F; subsequent hyperphosphorylation of Rb protein releases E2F from the complex so that it can then drive the cell into S phase. We immunolocalized Rb protein in human cells during the cell cycle. Rb protein translocated into nucleoli after DNA replication completed, and the nucleolar Rb was shown to be in the hyperphosphorylated form by immunoblotting. This form, but not its underphosphorylated counterpart, interacted with the nucleolar protein nucleophosmin/B23. The two formed a salt-resistant complex in vitro, and the two could be immunoprecipitated together from nucleolar extracts. These results suggest that hyperphosphorylated Rb protein is imported into nucleoli late in S or G2 phase with nucleophosmin/B23. Analysis of the nucleolar location of Rb protein using various deletion mutants tagged with the green fluorescent protein implicated pocket A of Rb protein as the region responsible for nucleolar targeting; this region also interacted with nucleophosmin/B23. Nucleolar translocation of Rb mutant was inhibited by introducing nucleophosmin/B23 antisense oligomer. These results suggest that nucleolar translocation of Rb protein is promoted by the binding with nucleophosmin/B23 via the pocket A region.


Selective removal of Cu(II) ions by using cation-exchange resin-supported polyethyleneimine (PEI) nanoclusters.
A novel hybrid adsorbent D001-PEI was fabricated for selective Cu(II) removal by immobilizing soluble polyethyleneimine (PEI) nanoclusters within a macroporous cation exchange resin D001. Negligible release of PEI nanoclusters unexpectedly observed during operation may result from the porous cross-linking nature of D-001 as well as the electrostatic attraction between PEI and D001. Increasing solution pH from 1 to 6 results in more favorable Cu(II) retention by D001-PEI, and Cu(II) adsorption onto D001-PEI follows the Langmuir model and the pseudosecond-order kinetic model well. Compared to the host cation exchanger D001, D001-PEI displays more preferable adsorption toward Cu(II) in the presence of competing Mg(2+), Ca(2+), Sr(2+) at greater levels in solution. Fixed-bed adsorption runs showed that Cu(II) sequestration on D001-PEI could result in its conspicuous decrease from 5 mg/L to below 0.01 mg/L. Also, the spent hybrid adsorbent can be readily regenerated by 6-8 BV HCl (0.2 mol/L)-NaCl (0.5 mol/L) binary solution for repeated use with negligible capacity loss. The results reported herein validate that D001-PEI is a promising adsorbent for enhanced removal of Cu(II) and other heavy metals from waste effluents.


Quadratus Lumborum Block Reduces Postoperative Pain Scores and Opioids Consumption in Total Hip Arthroplasty: A Meta-Analysis.
Quadratus lumborum block (QL) is a relatively new regional anesthesia technique that has been used in different surgeries for improved outcomes. There are few case reports and studies about its role in total hip arthroplasty with variable effects. This study aimed to evaluate the effect of QL block on postoperative pain control, opioid consumption, and the incidence of postoperative adverse events in total hip arthroplasty surgeries. A systematic review of the scientific literature addressing the use of QL block in hip arthroplasty was performed following the PRISMA guidelines and using the online database databases, Medline and Science Direct. We registered this review with the PROSPERO database in May 2021 (reference number-CRD42021247055). Two authors performed the literature searches in June 2021 and repeated them in July 2021 to ensure accuracy. Review Manager software (RevMan for Mac, version 5.4; Cochrane Collaboration, Oxford, United Kingdom) was used to perform a meta-analysis of studies included in our review. Five randomized controlled trials were identified for inclusion (n=394) in our meta-analysis. The results demonstrated a beneficial effect of QL block in pain control at 6, 12, and 24 hours postoperatively after hip arthroplasty (p <0.05). Opioid consumption for 24 hours was significantly reduced in the QL group (p=0.010). Our study also demonstrated that QL block is associated with a significant reduction in postoperative nausea and vomiting (PONV) (p=0.04). In conclusion, QL block can provide significantly better pain control after total hip arthroplasty at 6, 12, and 24 hours postoperatively. It also results in significantly reduced 24 hour-opioid consumption. This block is also associated with a lesser incidence of PONV and a better satisfaction level postoperatively.


Regular paracetamol in severe dengue: a lethal combination?
An eight-month-old female infant with severe dengue disease, who was repeatedly given therapeutic paracetamol for severe dengue, developed fulminant liver failure with encephalopathy, gastrointestinal haemorrhage and severe coagulopathy. She responded to supportive measures and N-acetylcysteine infusion. This case highlights the potential danger of administering repeated therapeutic doses of paracetamol in childhood severe dengue disease with hepatitis.


Laparoscopic inguinal herniorrhaphy.
Currently accepted laparoscopic inguinal herniorrhaphies are of three types: Trans-Abdominal Pre-Peritoneal (TAPP), Intra-Peritoneal Onlay Mesh (IPOM), and Totally Extra-peritoneal (EXTRA). The TAPP procedure is the most commonly performed operation. The peritoneum is opened transversely above the hernia defect and a radical dissection of the pre-peritoneal space accomplished. The hernia defect is widely covered with a large prosthesis, and the mesh is secured with staples. The peritoneum is then closed over the prosthesis. The IPOM technique has become the second most common laparoscopic inguinal herniorrhaphy. A prosthesis is placed on the intra-abdominal side of the peritoneum and stapled in place using the same landmarks as for the TAPP. This avoids an extensive dissection of the pre-peritoneal space. However, it must be considered as an experimental procedure because of the possibility of complications caused by adhesions to the intra-abdominally placed prosthesis. The third type of laparoscopic inguinal herniorrhaphy is the EXTRA. The hernia is repaired using laparoscopic instrumentation without violating the peritoneum by dissecting the space between the peritoneum and the transversalis fascia, beginning at the umbilicus. Once the inguinal region is entered, the procedure is similar to the TAPP. However, it is more difficult than the TAPP because of the small working space, especially for the inexperienced. Early results suggest that laparoscopic inguinal herniorrhaphy is an effective method for correcting an inguinal hernia. It can be performed with a reasonably low morbidity. Indications remain to be determined. A randomized prospective study comparing laparoscopic inguinal herniorrhaphy with conventional is warranted.


Association of genetic variants with diabetic nephropathy.
Diabetic nephropathy accounts for the most serious microvascular complication of diabetes mellitus. It is suggested that the prevalence of diabetic nephropathy will continue to increase in future posing a major challenge to the healthcare system resulting in increased morbidity and mortality. It occurs as a result of interaction between both genetic and environmental factors in individuals with both type 1 and type 2 diabetes. Genetic susceptibility has been proposed as an important factor for the development and progression of diabetic nephropathy, and various research efforts are being executed worldwide to identify the susceptibility gene for diabetic nephropathy. Numerous single nucleotide polymorphisms have been found in various genes giving rise to various gene variants which have been found to play a major role in genetic susceptibility to diabetic nephropathy. The risk of developing diabetic nephropathy is increased several times by inheriting risk alleles at susceptibility loci of various genes like ACE, IL, TNF-α, COL4A1, eNOS, SOD2, APOE, GLUT, etc. The identification of these genetic variants at a biomarker level could thus, allow the detection of those individuals at high risk for diabetic nephropathy which could thus help in the treatment, diagnosis and early prevention of the disease. The present review discusses about the various gene variants found till date to be associated with diabetic nephropathy.


FimH confers mannose-targeting ability to Bacillus Calmette-Guerin for improved immunotherapy in bladder cancer.
Bladder cancer is a common disease worldwide with most patients presenting with the non-muscle-invasive form (NMIBC) at initial diagnosis. Postoperational intravesical instillation of BCG is carried out for patients with high-risk disease to reduce tumor recurrence and progression to muscle invasive disease. However, BCG can also have side effects or be ineffective in some patients because it cannot enter the cancer cells. Thus, to improve the efficacy of BCG immunotherapy is the long-term pursuit of the bladder cancer field. To increase the adhesion of BCG to the urothelium we overexpressed FimH, a mannose binding protein naturally used by uropathogenic Escherichia coli to adhere to human urothelium, onto the surface of BCG. The adhesion/internalization ability of rBCG-S.FimH was examined in mouse bladder by fluorescence microscopy. Preclinical evaluation of antitumor efficacy was carried out in orthotopic mouse models of bladder cancer and in human peripheral blood mononuclear cells. Mechanistic studies were carried out using toll-like receptor 4 (TLR4) knockout mice. Immune cells and cytokines in the serum, tumor and lymph nodes were analyzed by flow cytometry, PCR, ELISA and ELISPOT. rBCG-S.FimH exhibited markedly improved adhesion and more rapid internalization into urothelial cells than wild-type BCG, resulting in more potent antitumor activity in orthotopic murine models of bladder cancer. To our surprise, rBCG-S.FimH elicited a much more prominent Th1-biased immune response known to be positively correlated with BCG efficacy. Mechanistic studies using TLR4 knockout mouse showed that rBCG-S.FimH could induce enhanced dendritic cell activation and tumor antigen-specific immune response in a TLR4-dependent manner. Furthermore, human peripheral blood mononuclear cells stimulated by rBCG-S.FimH also showed better tumoricidal effects than those using wild-type BCG. rBCG-S.FimH is a novel BCG strain with significantly improved efficacy against bladder cancer. Since intravesical BCG immunotherapy is the first-line treatment for NMIBC, which accounts for more than 70% of all bladder cancer cases, our results provide a compelling rationale for clinical development.


Thermodynamic analysis of calcium and magnesium binding to calmodulin.
To elucidate some aspects still debated concerning the interaction of Ca2+ and Mg2+ with CaM, the thermodynamic binding parameters of Ca2+-CaM and Mg2+-CaM complexes were characterized by flow dialysis and isothermal microcalorimetry under different experimental conditions. In particular, the enthalpy and entropy changes associated with Ca2+ and Mg2+ binding to their sites were determined, allowing a better understanding of the mechanism underlying cation-CaM interactions. Ca2+-CaM interaction follows an enthalpy-entropy compensation relationship, suggesting that CaM explores a subspace of isoenergetical conformations which is modified by Ca2+ binding. This Ca2+-induced change in CaM dynamics is proposed to play a key role in CaM function, i.e. in its interaction with and/or activation of target proteins. Furthermore, data show that Mg2+ does not act as a direct competitor for Ca2+ binding on the four main Ca2+ binding sites, but rather as an allosteric effector. This implies that the four main Mg2+ binding sites are distinct from the EF-hand Ca2+ binding sites. Finally, Ca2+ is shown to interact with auxiliary binding sites on CaM. These weak affinity sites were thermodynamically characterized. The results presented here challenge the current accepted view of CaM ion binding.


Combination of valproate and paroxetine in mice exposed to picrotoxin.
The frequent coexistence of depression in epileptic patients raises the issue of simultaneous use of antidepressants along with antiepileptic drugs in the management of such cases. However, it is necessary to evaluate the safety of these antiepileptic/antidepressant drug combinations. The present study investigates the effect of the antidepressant paroxetine (a selective serotonin reuptake inhibitor) administered alone or in combination with the antiepileptic drug sodium valproate on chemoconvulsions induced by picrotoxin (PTX). Seizure score was recorded in vivo, and the levels of thiobarbituric acid-reactive substances and gamma aminobutyric acid (GABA) were measured in the nucleus accumbens of the tested groups of mice. The results show enhancement of seizure severity with significant reduction in GABA levels upon PTX treatment that were reversed by its combination with sodium valproate. On the other hand, paroxetine administered in combination with sodium valproate provided significant protection against PTX-induced convulsions as well as a significant increase in GABA levels in selected brain areas. These results favor their application in management of epilepsy-depression comorbidities.


Effects of reduced terrestrial LiDAR point density on high-resolution grain crop surface models in precision agriculture.
3D geodata play an increasingly important role in precision agriculture, e.g., for modeling in-field variations of grain crop features such as height or biomass. A common data capturing method is LiDAR, which often requires expensive equipment and produces large datasets. This study contributes to the improvement of 3D geodata capturing efficiency by assessing the effect of reduced scanning resolution on crop surface models (CSMs). The analysis is based on high-end LiDAR point clouds of grain crop fields of different varieties (rye and wheat) and nitrogen fertilization stages (100%, 50%, 10%). Lower scanning resolutions are simulated by keeping every n-th laser beam with increasing step widths n. For each iteration step, high-resolution CSMs (0.01 m2 cells) are derived and assessed regarding their coverage relative to a seamless CSM derived from the original point cloud, standard deviation of elevation and mean elevation. Reducing the resolution to, e.g., 25% still leads to a coverage of >90% and a mean CSM elevation of >96% of measured crop height. CSM types (maximum elevation or 90th-percentile elevation) react differently to reduced scanning resolutions in different crops (variety, density). The results can help to assess the trade-off between CSM quality and minimum requirements regarding equipment and capturing set-up.


The effect of functional movement ability on the quality of life after total hip replacement.
To analyse in detail the relationship between the movement and generic health-related quality of life (HRQoL) indicators and the subjective feeling of health of the patients, as well as the objective movement parameters measured by the surgeon and the patient's opinion about the success of the total hip replacement (THR). We have only limited information about the effect of mobility function improvement on the HRQoL several years after THR. We have recently found that after THR postoperative health awareness is influenced mainly by cardiovascular diseases, but the effects of the movement parameters on the subsequent feelings of well-being were not examined. Retrospective longitudinal study. This study involved 109 patients who had had THR. The patients' health status and objective and subjective mobility function at the time of operation and five years later were evaluated using questionnaires (including EQ-5D and WOMAC scores) and the hospital database. All components of EQ-5D and WOMAC had significantly improved by Year 5 in patients who experienced a complete recovery after the operation, but not the mobility and pain components of EQ-5D for those patients who felt an improvement only in their subjective mobility function. The surgeon-assessed parameters and use of walking aids showed a similar distribution in patients who considered themselves to be healthy or only moderately sick five years after THR. Successful THR significantly improves the feeling of well-being and the mobility function of patients even five years after the operation. In individual cases, however, other subjective and objective factors, but not the mobility function, have a major influence on the HRQoL. Five years after successful THR, nursing care has to focus not only on the further improvement of the mobility but on strengthening the subjective feeling of the patient's well-being and health.


[Surgical treatment of the non suppurated sacrococcygeal cyst. Technical improvements].
Some justified technical improvements have been made to the method of treatment for non-infected and sacro-coccygienally located "pilo-nidal". The absence of tension due to the use of a rotational autoplasty and the drying of the residual cavity by an efficient aspirative drainage are the means essentially employed.


[Two cases of dichlorvos poisoning complicated with gastric perforation].
Severe acute dichlorvos poisoning is characterized by rapid onset, swift disease progression and serious complications. It frequently involves multiple organ failure (central, respiratory and circulatory systems), severe acidosis, and rare occurrences of gastric perforation. When secondary gastric perforation occurs, treatment becomes difficult and the prognosis of patients is poor. Thus, early and sufficient gastrointestinal decontamination is crucial. This article presented two cases of gastric perforation secondary to dichlorvos poisoning and discussed the causes of gastric perforation, as well is clinical diagnostic and treatment methods.


Emergency cricothyrotomy: temporary measure or definitive airway? A systematic review.
Being a fast and safe method in the hands of well trained professionals in both prehospital and intrahospital care, Cricothyrotomy has been broadly recommended as the initial surgical airway in the scenario "can't intubate, can't ventilate", and is particularly useful when the obstruction level is above or at the glottis. Its prolonged permanence, however, is an endless source of controversy. In this review we evaluate the complications of cricothyrotomy and the need of its routine conversion to tracheotomy through a search on PubMed, LILACS and SciELO electronic databases with no restriction to the year or language of the publication. In total, we identified 791 references, retrieved 20 full text articles, and included nine studies in our review. The incidence of short-term complications ranged from zero to 31.6%, and the long-term complications, from zero to 7.86%. Subglotic stenosis was the main long-term reported complication, even though it was quite infrequent, occurring only in 2.9 to 5%. The frequency of conversion to tracheostomy varied from zero to 100%. Although a small frequency of long-term complications was found for emergency cricothyrotomy, the studies' low level of evidence does not allow the recommendation of routine use of cricothyrotomy as a secure definitive airway.


Distinguishing Dependent-Stage Secondary Epileptogenesis in a Complex Case of Giant Hypothalamic Hamartoma With Assistance of a Computational Method.
Besides gelastic seizures, hypothalamic hamartoma (HH) is also noted for its susceptibility to remote secondary epileptogenesis. Although clinical observations have demonstrated its existence, and a three-stage theory has been proposed, how to determine whether a remote symptom is spontaneous or dependent on epileptic activities of HH is difficult in some cases. Herein, we report a case of new non-gelastic seizures in a 9-year-old female associated with a postoperatively remaining HH. Electrophysiological examinations and stereo-electroencephalography (SEEG) demonstrated seizure onsets with slow-wave and fast activities on the outside of the HH. By using computational methodologies to calculate the network dynamic effective connectivities, the importance of HH in the epileptic network was revealed. After SEEG-guided thermal coagulation of the remaining HH, the patient finally was seizure-free at the 2-year follow-up. This case showed the ability of computational methods to reveal information underlying complex SEEG signals, and further demonstrated the dependent-stage secondary epileptogenesis, which has been rarely reported.


INSULIN-INDUCED GLOMERULOSCLEROSIS IN THE RABBIT.
An attempt has been made to induce intercapillary glomerulosclerosis in rabbits by immunization with insulin incorporated in Freund's adjuvant and followed by repeated challenges with subcutaneously given insulin. It was observed that lesions resembling human diabetic glomerulosclerosis with occasional nodule-like formation could be produced and that the challenge insulin injections produced proteinuria. The presence of a delayed type of hypersensitivity seemed necessary for the lesions to occur as did the dissemination of the immunizing material to the kidneys. The experiment also disclosed that intravenously given DIS-tagged insulin localizes in a subtly different kind of glomerular lesion with different staining properties. The significance of these findings and the possible role of insulin treatment in the pathogenesis of human diabetic glomerulosclerosis is discussed.


Physiotherapy and pharmacy students perception of educational environment in a medical university from Pakistan.
To assess and compare the perceptions of the educational environment between physiotherapy and pharmacy students in a public-sector medical university. This cross-sectional study was conducted at the Peoples University of Medical and Health Sciences for Women, Nawabshah, Pakistan, and comprised undergraduate physiotherapy and pharmacy students. The Dundee Ready Educational Environment Measure questionnaire was used to assess the perceptions of students about their educational environment. Global and subscale scores were computed and compared between the respondents. P<0.05 was considered statistically significant. Of the 300 questionnaires, 281(93.66%) were returned duly filled in. The overall mean global score was 127.2±16.0. For physiotherapy students, the mean global score was 124.9±14.0 while it was 131.7±18.9 for pharmacy students (p=0.16). The domain scores were comparable for both specialties (p>0.05). There was no significance difference in the global and domain scores for preclinical and clinical years in the students (p>0.05). However, in the physiotherapy students, the global and domain scores for Dundee Ready Educational Environment Measure were significantly lower in clinical than preclinical students (p<0.05) except for students' social self-perception (p>0.05). Students were overall positive about their educational environment.


Three-dimensional visualisation of soft biological structures by X-ray computed micro-tomography.
Whereas the two-dimensional (2D) visualisation of biological samples is routine, three-dimensional (3D) imaging remains a time-consuming and relatively specialised pursuit. Current commonly adopted techniques for characterising the 3D structure of non-calcified tissues and biomaterials include optical and electron microscopy of serial sections and sectioned block faces, and the visualisation of intact samples by confocal microscopy or electron tomography. As an alternative to these approaches, X-ray computed micro-tomography (microCT) can both rapidly image the internal 3D structure of macroscopic volumes at sub-micron resolutions and visualise dynamic changes in living tissues at a microsecond scale. In this Commentary, we discuss the history and current capabilities of microCT. To that end, we present four case studies to illustrate the ability of microCT to visualise and quantify: (1) pressure-induced changes in the internal structure of unstained rat arteries, (2) the differential morphology of stained collagen fascicles in tendon and ligament, (3) the development of Vanessa cardui chrysalises, and (4) the distribution of cells within a tissue-engineering construct. Future developments in detector design and the use of synchrotron X-ray sources might enable real-time 3D imaging of dynamically remodelling biological samples.


In vitro production of IgE by human peripheral blood lymphocytes: effect of cholera toxin and beta adrenergic stimulation.
Peripheral blood lymphocytes from two human donors with elevated serum IgE concentrations were maintained in short term tissue culture preparations. Repeated culture preparations demonstrated that IgE was produced in vitro in amounts that could be measured by the double antibody radioimmunoassay technique. The amount of IgE produced by replicate cultures of cells from a single bleeding of the donor was similar when the cultures were simultaneously prepared. In contrast, IgE production by the same donor's lymphocytes varied when the culture preparations were initiated from separate bleedings. The results of simultaneous cultures of a single bleeding were sufficiently consistent to provide a means of testing the effect of pharmacologic agents on the in vitro production of IgE. Cholera toxin effected a marked reduction in production of IgE by lymphocytes of both cell donors. Isoproterenol showed marked inhibition of IgE production at 10(-3) M but cell viability studies suggested that this may have been due to decreased cell viability. At lower, nontoxic concentrations of isoproterenol (10(-4) M-10(-6) M) slight but definite inhibition of in vitro IgE production was evident. This inhibition was more pronounced subsequent to the first 24 hr of exposure of the cells to isoproterenol.


High-Throughput Patch Clamp Screening in Human α6-Containing Nicotinic Acetylcholine Receptors.
Nicotine, the addictive component of tobacco products, is an agonist at nicotinic acetylcholine receptors (nAChRs) in the brain. The subtypes of nAChR are defined by their α- and β-subunit composition. The α6β2β3 nAChR subtype is expressed in terminals of dopaminergic neurons that project to the nucleus accumbens and striatum and modulate dopamine release in brain regions involved in nicotine addiction. Although subtype-dependent selectivity of nicotine is well documented, subtype-selective profiles of other tobacco product constituents are largely unknown and could be essential for understanding the addiction-related neurological effects of tobacco products. We describe the development and validation of a recombinant cell line expressing human α6/3β2β3V273S nAChR for screening and profiling assays in an automated patch clamp platform (IonWorks Barracuda). The cell line was pharmacologically characterized by subtype-selective and nonselective reference agonists, pore blockers, and competitive antagonists. Agonist and antagonist effects detected by the automated patch clamp approach were comparable to those obtained by conventional electrophysiological assays. A pilot screen of a library of Food and Drug Administration-approved drugs identified compounds, previously not known to modulate nAChRs, which selectively inhibited the α6/3β2β3V273S subtype. These assays provide new tools for screening and subtype-selective profiling of compounds that act at α6β2β3 nicotinic receptors.


Dose response studies: how do we make them conclusive?
In this paper we discuss how to make meaningful use of a dose response study. It is argued that concepts like the minimal effective dose are not clinically meaningful and that the purpose of a dose response study should be to identify the drug potency in relation to a known active control. We also discuss various ways of carrying out the analysis.


Spleen immunomorphologic behaviour in primary and secondary acute bronchopulmonary inflammations of children. Comparative analysis of the lung and hilar-tracheobronchial lymph nodes' reactions.
The spleens sampled at necropsy of 221 children with acute primary and secondary bronchopulmonary inflammations were characterized by the hyperplasia of lymphoid follicles and plasma cells in 37 per cent of the cases, only a few of them with a multilayered organization of follicles, and by lymphoid depletion in 19 per cent of the cases. The remainder presented small unorganized lymphoid follicles of the primary type, some cases being remarkable by their nodules with a "core" of "epithelioid pattern". The pyroninophilic reactions of high intensity were preponderant in bronchopneumonia of the primary type, but unlike the lung and hilar-tracheobronchial lymph nodes, in spleen there were no differences concerning the two value groups of reactions between the primary pneumonia cases with or without associated extrapulmonary inflammations. Immunofluorescence evidenced, in decreasing order, all the three classes of immunoglobulins: IgM, IgG and IgA.


Biliary Dyskinesia in Children: A Systematic Review.
Cholecystectomy rates for biliary dyskinesia in children are rising in the United States, but not in other countries. Biliary dyskinesia is a validated functional gallbladder disorder in adults, requiring biliary colic in the diagnosis. In contrast, most studies in children require upper abdominal pain, absent gallstones on ultrasound, and an abnormal gallbladder ejection fraction (GBEF) on cholecystokinin-stimulated cholescintigraphy for diagnosis. We aimed to systematically review existing literature in biliary dyskinesia in children, determine the validity and reliability of diagnostic criteria, GBEF, and to assess outcomes following cholecystectomy. We performed a systematic review following the PRISMA checklist and searched 7 databases including PubMed, Scopus, Embase, Ovid, MEDLINE, ProQuest, Web of Science, and the Cochrane library. Bibliographies of articles were screened for additional studies. Our search terms yielded 916 articles of which 28 were included. Three articles were manually added from searched references. We reviewed 31 peer-reviewed publications, all retrospective chart reviews. There was heterogeneity in diagnostic criteria and GBEF values. Outcomes after laparoscopic cholecystectomy varied from 34% to 100% success, and there was no consensus concerning factors influencing outcomes. The observational, retrospective study designs that comprised our review limited interpretation of safety and efficacy of the investigations and treatment in biliary dyskinesia in children. Symptoms of biliary dyskinesia overlapped with functional dyspepsia. There is a need for consensus on symptoms defining biliary dyskinesia, validation of testing required for diagnosis of biliary dyskinesia, and randomized controlled trials comparing medical versus surgical management in children with upper abdominal pain.


[Relationship between cranial nerve involvement in nasopharyngeal carcinoma and the prognosis].
To analyze the feature of cranial nerve involvement in nasopharyngeal carcinoma (NPC) and its relationship with the prognosis. A total of 1892 patients who were diagnosed as NPC in our hospital from January 2002 to December 2003, of which the cranial nerve involvement was 183 (9.6%) patients, were analyzed the effect of cranial nerve involvement on the prognosis. The percentage of cranial nerve involvement was 9.4%. The 5 year overall survival rate was 61.0%, disease free survival rate was 55.3%, local relapse free survival rate was 75.2% and distant metastasis free survival rate was 73.4%. Periods of cranial nerve involvement, clinical stage, the diameter of the lymph nodes, involvement of cavernous sinus, and the level of the recovery of cranial nerve involvement were significantly associated with prognosis in univariate analysis(P < 0.05). With multivariate analysis, the recovery level of cranial nerve involvement was the independent factor that affected the 5-year overall survival (RR = 2.087). The diameter of the lymph nodes and involvement of cavernous sinus were the independent factors that affected the 5-year distant metastasis-free survival (RR = 1.954 and 2.136, respectively). Periods of cranial nerve involvement and the level of the recovery of cranial nerve involvement were significantly correlated with prognosis. Involvement of cavernous sinus could increase the rate of distant metastasis.


Pilot programs in newborn screening.
The term "pilot study" has been used over the years to describe the evaluation of the many elements involved in deciding whether a proposed condition should be added to a newborn screening (NBS) panel, and until recently, was unilaterally used to describe the evaluation of the assay to be used before the condition was officially adopted by a state for its newborn screening panel. Since Guthrie's introduction of screening for PKU, each time a new condition was added to the panel, the screening assay itself was validated through a population-based trial, in which the test was performed with de-identified samples to avoid association between the test result and the infant. This is considered by the laboratory as the "pilot phase" of adding a new condition. To advance the science of NBS, especially to accommodate new technologies that may provide new types of information (genetic versus physiological) for each new condition, pilot programs are essential. Involvement of the clinical community serves to improve these evaluations and provides the needed clinical validation of decisions made as a result of it. This paper describes the historical context of pilot programs in population-based NBS that utilize laboratory-based markers as indicators of concern; specifically, three applications that demonstrate different approaches to the use of pilots in adding conditions to a NBS panel are described.


The effect of stem growth habit on single seed weight and seed uniformity in soybean (Glycine max (L.) Merrill).
The timing of flower formation and length of the seed-filling period of indeterminate growth soybean varieties vary more than those of determinate varieties (Glycine max (L.) Merrill). These variations have been hypothesized to affect single seed weight and its uniformity which determine the processing quality of soybean used in foods. We derived near isogenic lines (NILs) with different growth characteristics from an indeterminate line (donor parent) and three determinate lines with heavy seeds (recurrent parents), and evaluated the effects of growth habit on seed weight and its uniformity. Each NIL population consisting of five indeterminate and five determinate BC4F4 lines tested at two locations in two different years with two replications. Split-plot analysis of variance, with main-plot and sub-plot being cross combination and growth habit, respectively, showed that indeterminate varieties had slightly heavier seeds than determinate varieties and that there was no significant difference in uniformity of single seed weights. The effects of growth habit on seed uniformity was related to genetic background, but differences between the two growth characteristics were less than the differences among genetic background. This indicates that indeterminate growth habit did not much influence seed weight or its uniformity.


Pseudo Prune Belly Syndrome: Diagnosis Revealed by Imaging - A Case Report and Brief Review.
Prune Belly Syndrome (PBS) is a rare entity, usually found in male neonates. It comprises complex urinary tract anomalies, bilateral undescended testis and absence of anterior abdominal wall muscles. Patients with unilateral abdominal wall deficiency, unilateral undescended testis and female neonates with abdominal wall laxity are classified as Pseudo Prune Belly syndrome (PPBS). Reports on PPBS do not highlight the radiological and imaging characteristics of this syndrome and the current literature on the role of newer imaging modalities, such as Magnetic Resonance Imaging (MRI), remains relatively sparse. We describe a new case of PPBS and emphasize the role of imaging, especially ultrasound and MRI in the process of diagnosis and briefly review the subject. A male infant of four months of age was referred for evaluation of left-sided cryptorchidism. Clinical examination revealed laxity of the left abdominal wall. Ultrasound examination of the abdomen, pelvis and scrotum was performed together with routine laboratory tests. Ultrasound examination was followed by intravenous urography, voiding cysto-urethrography and MRI of the abdomen. On ultrasound, the left testis was located in the inguinal canal, the right kidney was slightly enlarged and the left kidney could not be localized. Ultrasound appearances suggested chronic obstruction in the urinary bladder. Intravenous urography, voiding cysto-urethrography and MRI confirmed the ultrasound diagnosis and also revealed a left dysplastic kidney with a dilated, tortuous ureter. Clinical and imaging features were consistent with pseudo prune belly syndrome (PPBS). We report a new occurrence of PPBS, a rare entity. The imaging approach for a comprehensive evaluation of the renal system in PPBS, especially with MRI, is emphasized.


Live-donor liver transplantation for hepatocellular carcinoma.
Live-donor liver transplantation (LDLT) is a valuable option for patients with hepatocellular carcinoma (HCC) because compared with deceased-donor liver transplantation (DDLT), the tumor could be eradicated early. However, a higher incidence of recurrence is observed when the result is compared with DDLT. The difference is explained by the timing of transplant because only patients with slow HCC growth (and probably less aggressive tumors) can wait for DDLT. Nevertheless, arecent survey of results of LDLT for HCC in Asia indicated that the 3-year survival rate is approximately 60-80%, which is better than that of any treatment modalities for inoperable HCC associated with poor liver function. LDLT for HCC is still worthwhile to pursue and deserves further evaluation.


Automated diagnosis of prostate cancer in multi-parametric MRI based on multimodal convolutional neural networks.
Automated methods for prostate cancer (PCa) diagnosis in multi-parametric magnetic resonance imaging (MP-MRIs) are critical for alleviating requirements for interpretation of radiographs while helping to improve diagnostic accuracy (Artan et al 2010 IEEE Trans. Image Process. 19 2444-55, Litjens et al 2014 IEEE Trans. Med. Imaging 33 1083-92, Liu et al 2013 SPIE Medical Imaging (International Society for Optics and Photonics) p 86701G, Moradi et al 2012 J. Magn. Reson. Imaging 35 1403-13, Niaf et al 2014 IEEE Trans. Image Process. 23 979-91, Niaf et al 2012 Phys. Med. Biol. 57 3833, Peng et al 2013a SPIE Medical Imaging (International Society for Optics and Photonics) p 86701H, Peng et al 2013b Radiology 267 787-96, Wang et al 2014 BioMed. Res. Int. 2014). This paper presents an automated method based on multimodal convolutional neural networks (CNNs) for two PCa diagnostic tasks: (1) distinguishing between cancerous and noncancerous tissues and (2) distinguishing between clinically significant (CS) and indolent PCa. Specifically, our multimodal CNNs effectively fuse apparent diffusion coefficients (ADCs) and T2-weighted MP-MRI images (T2WIs). To effectively fuse ADCs and T2WIs we design a new similarity loss function to enforce consistent features being extracted from both ADCs and T2WIs. The similarity loss is combined with the conventional classification loss functions and integrated into the back-propagation procedure of CNN training. The similarity loss enables better fusion results than existing methods as the feature learning processes of both modalities are mutually guided, jointly facilitating CNN to 'see' the true visual patterns of PCa. The classification results of multimodal CNNs are further combined with the results based on handcrafted features using a support vector machine classifier. To achieve a satisfactory accuracy for clinical use, we comprehensively investigate three critical factors which could greatly affect the performance of our multimodal CNNs but have not been carefully studied previously. (1) Given limited training data, how can these be augmented in sufficient numbers and variety for fine-tuning deep CNN networks for PCa diagnosis? (2) How can multimodal MP-MRI information be effectively combined in CNNs? (3) What is the impact of different CNN architectures on the accuracy of PCa diagnosis? Experimental results on extensive clinical data from 364 patients with a total of 463 PCa lesions and 450 identified noncancerous image patches demonstrate that our system can achieve a sensitivity of 89.85% and a specificity of 95.83% for distinguishing cancer from noncancerous tissues and a sensitivity of 100% and a specificity of 76.92% for distinguishing indolent PCa from CS PCa. This result is significantly superior to the state-of-the-art method relying on handcrafted features.


Inhibition of Wntless/GPR177 suppresses gastric tumorigenesis.
Wntless/GPR177 functions as WNT ligand carrier protein and activator of WNT/β-catenin signaling, however, its molecular role in gastric cancer (GC) has remained elusive. We investigated the role of GPR177 in gastric tumorigenesis and provided the therapeutic potential of a clinical development of anti-GPR177 monoclonal antibodies. GPR177 mRNA expression was assessed in GC transcriptome data sets (GSE15459, n = 184; GSE66229, n = 300); protein expression was assessed in independent patient tumor tissues (Yonsei TMA, n = 909). GPR177 expression were associated with unfavorable prognosis [log-rank test, GSE15459 (P = 0.00736), GSE66229 (P = 0.0142), and Yonsei TMA (P = 0.0334)] and identified as an independent risk predictor of clinical outcomes: GSE15459 [hazard ratio (HR) 1.731 (95% confidence interval; CI; 1.103- 2.715), P = 0.017], GSE66229 [HR 1.54 (95% CI, 1.10-2.151), P = 0.011], and Yonsei TMA [HR 1.254 (95% CI, 1.049- 1.500), P = 0.013]. Either antibody treatment or GPR177 knockdown suppressed proliferation of GC cells and sensitized cells to apoptosis. And also inhibition of GPR177 suppresses in vitro and in vivo tumorogenesis in GC cells and inhibits WNT/β-catenin signaling. Finally, targeting and inhibition of GPR177 with antibody suppressed tumorigenesis in PDX model. Together, these results suggest GPR177 as a novel candidate for prognostic marker as well as a promising target for treatment of GC patients. [BMB Reports 2018; 51(5): 255-260].


Analysis of protrusion dynamics in amoeboid cell motility by means of regularized contour flows.
Amoeboid cell motility is essential for a wide range of biological processes including wound healing, embryonic morphogenesis, and cancer metastasis. It relies on complex dynamical patterns of cell shape changes that pose long-standing challenges to mathematical modeling and raise a need for automated and reproducible approaches to extract quantitative morphological features from image sequences. Here, we introduce a theoretical framework and a computational method for obtaining smooth representations of the spatiotemporal contour dynamics from stacks of segmented microscopy images. Based on a Gaussian process regression we propose a one-parameter family of regularized contour flows that allows us to continuously track reference points (virtual markers) between successive cell contours. We use this approach to define a coordinate system on the moving cell boundary and to represent different local geometric quantities in this frame of reference. In particular, we introduce the local marker dispersion as a measure to identify localized membrane expansions and provide a fully automated way to extract the properties of such expansions, including their area and growth time. The methods are available as an open-source software package called AmoePy, a Python-based toolbox for analyzing amoeboid cell motility (based on time-lapse microscopy data), including a graphical user interface and detailed documentation. Due to the mathematical rigor of our framework, we envision it to be of use for the development of novel cell motility models. We mainly use experimental data of the social amoeba Dictyostelium discoideum to illustrate and validate our approach.


Midazolam sedation for upper gastrointestinal endoscopy: comparison between the states of patients in partial and complete amnesia.
The amnesia produced by anesthesia is advantageous for unpleasant procedures like gastroscopy, and midazolam is one of the most commonly used anesthesias for endoscopy. However the proper use of midazolam from the viewpoint of complete amnesia has been discussed very little. One hundred and thirty-three unselected patients about to undergo upper gastrointestinal endoscopy were premedicated with sufficient intravenous midazolam to cause enough sedation so that no response was evoked when calling their name. Pulse, arterial pressure, arterial oxygen saturation and the physical signs of patients were recorded continuously during the procedures. After the study, patients were given 0.25 mg of flumazenil and asked if they could recall the procedures. Those who could recall even part of the procedure were not regarded as achieving complete amnesia. The efficacy of the sedative was judged by the appearance of complete amnesia. From our regression analysis complete amnesia was achieved in 75.9% of the total patients. The differences of the blood pressure fall, pulse rate increase and arterial oxygen saturation fall between the patients with complete and partial amnesia were minute and did not cause serious complications. Regression analysis revealed the most important factors for the complete amnesia to be midazolam dose per body weight and habitual hypnotic use. There are no obvious disadvantages to producing complete amnesia with midazolam for upper gastrointestinal endoscopy. Habitual hypnotic use along with midazolam dose per body weight is the most influencing factor for that purpose.


Perioperative latex hypersensitivity reactions: an integrative literature review.
This article characterizes hypersensitivity reactions during anesthetic-surgical procedures. This integrative literature review was conducted in the LILACS, CINAHL, COCHRANE and MEDLINE databases including papers published from 1966 to September 2011. A total of 17 case reports, two prevalence studies and one cohort study were identified. Latex reactions were mainly type III and the primary source of intraoperative reaction was latex gloves. The average time for clinical manifestation was 59.8 minutes after anesthetic induction; 44.4% of patients reported a reaction to latex at the pre-anesthetic evaluation. It was determined that the history of allergic reactions to latex obtained in the pre-anesthetic evaluation does not ensure the safety of patients if the staff is inattentive to the severity of the issue. There is also a tendency to initially attribute the anaphylactic event to the anesthetic drugs.


Pathophysiological concepts and screening of cardiovascular disease in dialysis patients.
Dialysis patients experience 10-20 times higher cardiovascular mortality than the general population. The high burden of both conventional and nontraditional risk factors attributable to loss of renal function can explain higher rates of cardiovascular disease (CVD) morbidity and death among dialysis patients. As renal function declines, uremic toxins accumulate in the blood and disrupt cell function, causing cardiovascular damage. Hemodialysis patients have many cardiovascular complications, including sudden cardiac death. Peritoneal dialysis puts dialysis patients with end-stage renal disease at increased risk of CVD complications and emergency hospitalization. The current standard of care in this population is based on observational data, which has a high potential for bias due to the paucity of dedicated randomized clinical trials. Furthermore, guidelines lack specific guidelines for these patients, often inferring them from non-dialysis patient trials. A crucial step in the prevention and treatment of CVD would be to gain better knowledge of the influence of these predisposing risk factors. This review highlights the current evidence regarding the influence of advanced chronic disease on the cardiovascular system in patients undergoing renal dialysis.


Cystathionine excretion in relation to vitamin B-6 nutriture of rats: strain differences and effects of DL- or L-methionine supplementation.
Wistar and Long-Evans rats excreted significantly more cystathionine during days 27 to 31 of a vitamin B-6 deficiency than did Spague-Dawley rats. Wistar rats were therefore chosen for experiments designed to test the effects of dietary DL- and L-methionine supplementation upon cystathionine excretion of vitamin B-6-deficient and control rats. Methionine supplementation did not significantly affect mean daily food consumption or weight gain of the control animals. L-Methionine-supplemented, deficient rats gained significantly more during the first 15 days of the experiment and less during the last 11 days than did the other deficient groups. No cystathionine was detected in the urine of methionine-supplemented or unsupplemented control rats between days 8 and 26 of the experiment; but measurable quantities of cystathionine were present in the urine of all deficient groups by days 8 to 12. Deficient animals fed DL-methionine excreted up to 2.33 mg more cystahionine per 4-day period than did the unsupplemented deficient rats, whereas rats fed L-methionine excreted up to 7.44 mg more per 4-day period than did the unsupplemented ones. This difference in cystathionine response was highly significant and indicates that the L supplement stressed the vitamin B-6-deficient rats more than did the DL supplement. An explanation for this may be that the D isomer in the DL supplement was not as efficiently absorbed and/or metabolized as the L form.


Vinblastine plus bleomycin continuous infusion chemotherapy of stage III testicular carcinomas.
Thirty-four consecutive patients with stage III testicular carcinomas were treated with vinblastine, 8 mg/m2 given in 2 fractions on day 1 and 2, followed by continuous intravenous administration of bleomycin, 15 mg/m2 in 1000 cc of 5% glucose and distilled water over a 24-hour period for 5 successive days beginning on day 2. This cycle was repeated every 28-35 days as toxicity permitted. Complete remission occurred in 18% and complete plus partial remission in 79%. Only 2 of 22 patients with advanced abdominal disease achieved a complete remission. After cytoreductive surgery the complete remission rate was increased to 39%. Median survival of complete responders at 3 years has not been reached, and it has been shown to be significantly superior to that of partial (p less than 0.01) and nonresponders (p less than 0.01). Toxic effects consisted mainly in severe leukopenia, stomatitis, adynamic ileum and osteoarticular pain. One drug-related death due to sepsis with agranulocytopenic fever was observed. Probably because of different patient selection, this report could not reproduce the results reported by Samuels et al. with equivalent drug dosage, but it was confirmed that this regimen is able to achieve a high overall response rate and a prolonged median survival in complete responders. The consistent success of this aggressive combination in inducing a high percentage of partial responses has opened the way for a better definition of the role of surgery for the treatment of advanced testicular carcinoma at out Institute.


Limbic neurogenesis/plasticity in the R6/2 mouse model of Huntington's disease.
Huntington's disease is an inherited neurodegenerative condition characterized by movement disorders, and mood and cognitive disturbance. Mammalian neurogenesis persists into adulthood in the subventricular zone and dentate gyrus of the hippocampus. Neurogenesis is abnormal in the dentate gyrus in the R6/2 transgenic mouse model of Huntington's disease. We have now found that the number of immature neurons (doublecortin-positive cells) is markedly reduced in the piriform and insular cortex but not in the temporal germinal layer or caudal subventricular zone of R6/2 mice. Furthermore, numbers of such cells were unaltered in response to seizures in both wild-type and R6/2 mice. These results support the possibility that impaired neurogenesis and/or plasticity could contribute to cognitive and psychiatric impairments in Huntington's disease.


Estrogen receptor-based multi-residue screening of bisphenol compounds in urine.
Human exposure to bisphenol compounds (BPs) has been implicated in the development of several chronic diseases. Instead of exploiting the traditional methods for determination of BPs, this work confirms that the human estrogen receptor α ligand binding domain (hERα-LBD) is a powerful recognition element that can be used to monitor multi-residue of BPs in urine samples by fluorescence polarization (FP) assay. Test parameters were optimized for the best performance. Under the optimal conditions, the IC50 values of BPs are in the range of 0.04-1.61 μg mL-1 . Recovery experiments were then performed to assess the accuracy and precision of the established method. The results detected by FP assay show good agreements with that of liquid chromatography-tandem mass spectrometry method with a fit of R2 = 0.9372 and 0.9640 for BPE and BPAP, respectively. A computational methodology, ligand-based pharmacophore model, was also employed to further explore the broad-specific of tested compounds. It was found that the two hydrogen bond acceptor features and one hydrophobic aliphatic feature were essential for the corresponding cross-reactivity results from the FP assay. All these results suggest that the established method can be successfully applied to monitor the occurrence of BPs in urine.


[Analysis of the statistical significance of the difference in patient setup error caused by the current staff and new staff in the radiotherapy].
We verified the setup error (SE) in two persons' radiation therapist's team, which consist of staff and new face. We performed the significance test for SE by the staff group and the new face group. One group consists of four staff therapists with at least 5 to 30 years of experience. The other group consists of new face radiation therapists that have 1 to 1.5 years of experience. Analyzed were 53 patients diagnosed with pelvic cancer (seven patients who underwent 3 dimensional conformal radiation therapy (3DCRT) and 46 patients who underwent intensity modulated radiation therapy (IMRT). Image verification was 1460 times. It was performed through setup verification by cone beam computed tomography (CBCT), and we measured SE of four directions (lateral, long, vertical, 3D). We performed the student's t-test to get the difference of the average error between the staff group and the new face group. The results of significance tests show that there is no difference between SE in the staff group and the new face group in radiotherapy.


Obesity, inflammation, and depression in adolescents.
The prevalence of depression and obesity among adolescents has markedly increased over the last few decades. A bidirectional relationship has been proposed between depression and obesity in adolescence, but it remains poorly understood. Inflammation is a phenomenon that has been implicated in both disorders. Thus, a cross-sectional study was designed to investigate inflammation as a factor in the association between obesity and depression. The goal of this study is to better understand the interplay between these two disorders. The study sample consisted of female and male, black and white adolescents aged 15-18 years. Participants were diagnosed with major depressive disorder (MDD) according to the Diagnostic and Statistical Manual of Mental Disorders-5. Depression severity was determined using the Quick Inventory of Depressive Symptomatology (QIDS). Participants completed the Childhood Trust Events Survey (CTES) and received an Early Life Stress (ELS) score based on the survey results. Those with a score of ≥4 were placed in the ELS group and those with a score ≤ 3 were placed in the non-ELS group. Anthropometric measures and a Dual Energy X-ray Absorptiometry (DEXA) scan were performed for body composition. Blood samples were collected to measure inflammatory factors. Adolescents with MDD (n = 47) had significantly elevated body mass index (BMI) percentiles compared to the controls (n = 47) (77.11 ± 3.58 vs. 59.63 ± 4.40), and increased adiposity measures, including total fat (p = 0.016), trunk fat (p = 0.016), and trunk/total fat ratio (p = 0.021). Levels of C-reactive protein, tumor necrosis factor-alpha, interleukin-6, leptin, and adiponectin varied significantly between the MDD and control groups, however, significance was not retained when BMI percentile and ELS score were controlled. There was a significant and positive relationship between QIDS and multiple measures of adiposity such as BMI percentile, visceral abdominal tissue, and trunk/total ratio. Depression severity was best predicted by ELS score, visceral adipose tissue, and adiponectin level. Adolescents with MDD had increased levels of inflammatory factors and many measures of adiposity. Thus, the treatment of adolescent depression should include a focus on managing body composition and reducing chronic inflammation to potentially improve treatment outcomes.


Neonatal BCG vaccination has no effect on recurrent wheeze in the first year of life: A randomized clinical trial.
Recurrent wheeze (RW) is frequent in childhood. Studies have suggested that BCG vaccination can have nonspecific effects, reducing general nontuberculosis morbidity, including respiratory tract infections and atopic diseases. The mechanisms behind these nonspecific effects of BCG are not fully understood, but a shift from a TH2 to a TH1 response has been suggested as a possible explanation. We hypothesized that BCG at birth would reduce the cumulative incidence of RW during the first year of life. The Danish Calmette Study is a multicenter randomized trial conducted from 2012-2015 at 3 Danish hospitals. The 4262 newborns of 4184 included mothers were randomized 1:1 to BCG (SSI strain 1331) or to a no-intervention control group within 7 days of birth; siblings were randomized together as one randomization unit. Exclusion criteria were gestational age of less than 32 weeks, birth weight of less than 1000 g, known immunodeficiency, or no Danish-speaking parent. Information was collected through telephone interviews and clinical examinations at 3 and 13 months of age; data collectors were blind to randomization group. RW was defined in several ways, with the main definition being physician-diagnosed and medically treated RW up to 13 months of age. By 13 months, 211 (10.0%) of 2100 children in the BCG group and 195 (9.4%) of 2071 children in the control group had received a diagnosis of RW from a medical doctor and received antiasthma treatment (relative risk, 1.07; 95% CI, 0.89-1.28). Supplementary analyses were made, including an analysis of baseline risk factors for development of RW. Neonatal BCG had no effect on the development of RW before 13 months of age.


Retrieval of Trichostrongylus colubriformis infective larvae from grass contaminated in winter and in spring.
The survival of infective larvae (L3) of Trichostrongylus colubriformis was evaluated on Brachiaria, Coast-cross and Aruana forage grasses. Feces of sheep parasitized exclusively by T. colubriformis were deposited in winter and spring on experimental plots whose grasses were cut at two heights: 5 cm and 30 cm. One, two, four, eight, 12 and 16 weeks after depositing the feces, fecal and forage samples were collected for the retrieval and quantification of L3. Retrieval of L3 from feces and forage was negligible in winter due to the dry weather, although a few larvae were retrieved in the last larval collections. However, L3 retrieval from fecal samples was greater in spring, especially two weeks after feces were deposited on 30 cm high grasses. At this time, the L3 retrieval rate from the three forage grasses differed significantly (P <0.05), with Aruana grass showing the highest average L3 retrieval rate, followed by Coast-cross and Brachiaria. In conclusion, the winter drought proved very unfavorable for the presence of L3 in the environment, and the microclimate of Aruana pastureland was generally the most favorable for the retrieval of infective larvae.


Synthesis and Photocatalytic Application of Stable Lead-Free Cs2 AgBiBr6 Perovskite Nanocrystals.
Lead halide perovskite nanocrystals (NCs) have demonstrated great potential as appealing candidates for advanced optoelectronic applications. However, the toxicity of lead and the intrinsic instability toward moisture hinder their mass production and commercialization. Herein, to solve such thorny problems, novel lead-free Cs2 AgBiBr6 double perovskite NCs fabricated via a simple hot-injection method are reported, which exhibit impressive stability in moisture, light, and temperature. Such materials are then applied into photocatalytic CO2 reduction, achieving a total electron consumption of 105 µmol g-1 under AM 1.5G illumination for 6 h. This study offers a reliable avenue for Cs2 AgBiBr6 perovskite nanocrystals preparation, which holds a great potential in the further photochemical applications.


[Comparison between the mammographic extent of microcalcifications and the virtual extent of breast carcinoma, and observation of changes in mammographic features with time].
In 26 nonpalpable breast carcinoma cases showing microcalcifications not accompanied by any associated mass on mammograms, the maximum diameter of the area of microcalcifications was measured and then compared with the histological extent of carcinoma. The extent of carcinoma was larger than the diameter of the area of microcalcifications in 14 cases (53.8%) and almost equal in five cases. When the maximum diameter of the area of microcalcifications was less than 2.5cm, carcinoma extended no more than 1.5cm beyond the diameter of the microcalcifications. Employing 24 cases subjected to excision biopsy, the extent of carcinoma was compared with the diameter of the area of microcalcifications on sectioned material containing microcalcifications, and it was found that carcinoma tended to extend further than the extent of calcifications (62.5%). Mammographic microcalcifications obtained from 37 breast cancer cases not accompanied by any associated mass were analyzed in contrast to their previous survey films. Twelve cases were found to have shown several extremely faint calcifications on the previous survey films. Follow-up study that focused on such faint calcifications had been performed in 43 cases from 1990 to 1992, resulting in the successful detection of four cases of breast cancer.


Intestinal calcium-binding protein 3 months after massive small bowel resection in the piglet.
Changes in intestinal calcium-binding protein and calcium binding activity were studied at resection and 3 months after 90% small bowel resection in piglets and one adult pig. A calcium-binding protein (MW congruent to 11.000) with calcium-dependent eletrophoretic mobility was partially purified from mucosal extract of proximal jejunum, mid-gut, and ileum. The concentration of calcium-binding protein and the calcium-binding activity of the intact animals were found highest in the proximal jejunal segment, lowest in the ileal segment. After resection in the four surviving animals out of nine, a significant increase in calcium-binding activity was observed in the proximal jejunum and in the distal ileal segment. The change in calcium-binding activity was much more marked in the ileum than the jejunum. These data demonstrate that pig intestinal mucosa possesses an adaptive capacity to increase the synthesis of calcium-binding protein after massive small bowel resection.


Traditional cardiovascular risk factors and coronary artery calcification in adults with polymyositis and dermatomyositis: a Danish multicenter study.
To determine the occurrence of traditional cardiovascular (CV) risk factors and coronary artery calcification (CAC) in adults with polymyositis (PM) or dermatomyositis (DM) compared to healthy controls and to assess the association between CV risk factors, PM/DM, and CAC score. Traditional CV risk factors were assessed in a cross-sectional, observational study of 76 patients with PM/DM and in 48 sex- and age-matched healthy controls. CAC was quantified by means of cardiac computed tomography scan and expressed in Agatston units. The associations between CV risk factors, PM/DM, and CAC were studied by multivariate analyses. Thirty-three percent of the patients were obese compared to 11% of the controls (P = 0.005). Hypertension and diabetes mellitus were more frequent in patients (71% versus 42%; P = 0.002, and 13% versus 0%; P = 0.007), and patients had higher levels of triglycerides (P = 0.0009). High CAC score occurred more frequently in patients (20% versus 4%; P = 0.04). In multivariate analysis of patient factors associated with CAC were age (P = 0.02) and smoking (P = 0.02). In this study, traditional CV risk factors and severe CAC were commonly found in patients with PM/DM. However, severe CAC was not associated with PM/DM per se, but rather with age and smoking in these patients.


Cooperativity and frustration in protein-mediated parallel actin bundles.
We examine the mechanism of bundling of cytoskeletal actin filaments by two representative bundling proteins, fascin and espin. Small-angle x-ray studies show that increased binding from linkers drives a systematic overtwist of actin filaments from their native state, which occurs in a linker-dependent fashion. Fascin bundles actin into a continuous spectrum of intermediate twist states, while espin only allows for untwisted actin filaments and fully overtwisted bundles. Based on a coarse-grained, statistical model of protein binding, we show that the interplay between binding geometry and the intrinsic flexibility of linkers mediates cooperative binding in the bundle. We attribute the respective continuous (discontinuous) bundling mechanisms of fascin (espin) to difference in the stiffness of linker bonds themselves.


Total intravenous anesthesia with etomidate. II. Evaluation of a practical technique for children.
A practical technique for the administration of anesthesia to children is described, using only intravenous agents. Anesthesia was induced using etomidate 0.3 mg/kg, analgesia being provided by fentanyl or pentazocine, and muscle relaxation by suxamethonium or pancuronium. Unconsciousness was maintained by infusion of a 1% solution of etomidate given at a pre-determined rate of 30 microgram/kg/min. Paralysis was maintained throughout the period of surgical stimulation, in the majority of patients by continuous infusion of suxamethonium 0.1 mg/kg/min. The chosen rate of infusion of etomidate appears to be adequate to reliably maintain sleep in children, yet allow rapid recovery of consciousness when the infusion is stopped, thereby relieving the anesthetist of concern about these points. The maintenance of complete paralysis throughout operation removes the possibility of movement, the major cause of unsatisfactory anesthesia using only intravenous agents.


Triplet sensitization in an anionic poly(phenyleneethynylene) conjugated polyelectrolyte by cationic iridium complexes.
We describe a systematic study of triplet sensitization in a poly(phenyleneethynylene) conjugated polyelectrolyte (CPE) in methanol solution by using a series of three cationic iridium complexes with varying triplet energy. The cationic iridium complexes bind to the anionic CPE by ion-pairing, leading to singlet state quenching of the polymer, and allowing for efficient back-transfer of triplet excitation energy to the polymer. Efficient (amplified quenching) of the polymer's fluorescence is observed for each iridium complex, with Stern-Volmer quenching constants in excess of 10(5) M(-1). Triplet sensitization is confirmed for two of the iridium complexes by monitoring the relative yield of the CPE triplet state by transient absorption spectroscopy. One of the iridium complexes does not sensitize the CPE triplet, and consideration of the energies of the three complexes allows us to bracket the triplet energy of the CPE within the range 1.95-2.26 eV.


Quantum-mechanical evaluation of π-π versus substituent-π interactions in π stacking: direct evidence for the Wheeler-Houk picture.
The influence of substituents on π-stacking interactions has previously been explained by two competing hypotheses: a nonlocal effect in which tuning of the π density by the substituent alters the interaction (the Hunter-Sanders picture) or a local effect in which the direct interaction of the added substituent and changed polarity of the phenyl-substituent σ bond alter the interaction (the Wheeler-Houk picture). In this work, we applied the recently developed functional-group partition of symmetry-adapted perturbation theory (F-SAPT) to directly quantify these two effects in situ. The results show that both pictures contribute to the change in interaction energy but that the Wheeler-Houk picture is usually dominant.


Osteogenic effect of fluvastatin combined with biodegradable gelatin-hydrogel.
The aim was to investigate the local osteogenic effect of fluvastatin incorporated into a biodegradable gelatin-hydrogel (GH) scaffold. The GH scaffolds were prepared through crosslinking by ultraviolet irradiation followed by freeze-drying. Two circular defects were surgically created on fifteen-week-old male rats calvaria. All defects of each rat were randomly filled with two of three treatments, specifically: fluvastatin incorporated into a GH disk (Flu-GH), distilled water incorporated into a GH disk, and no treatment. New bone formation was quantitatively analyzed after 7, 14, and 28 days using a micro-computed tomography (micro-CT) system, and histologically observed. Evaluation by micro-CT revealed a significant difference in new bone formation among the three kinds of defect. A highly osteogenic effect was observed in the Flu-GH group. The results showed that the fluvastatin incorporated into a biodegradable GH scaffold promoted osteogenesis in rat calvarial bone, indicating its potential for bone regeneration.


The use of milk Fourier-Transform Infrared spectra for predicting cheese-making traits in Grana Padano PDO.
The prediction of the cheese yield (%CY) traits for curd, solids, and retained water and the amount of fat, protein, solids and energy recovered from the milk into the curd (%REC) by Bayesian models, using Fourier-transform infrared spectroscopy (FTIR), can be of significant economic interest to the dairy industry and can contribute to the improvement of the cheese process efficiency. The yields give a quantitative measure of the ratio between weights of the input and output of the process, whereas the nutrient recovery allows to assess the quantitative transfer of a component from milk to cheese (expressed in % of the initial weight). The aims of this study were to: i) investigate the feasibility of using bulk milk spectra to predict %CY and %REC traits, ii) quantify the effect of the dairy industry and the contribution of single spectrum wavelengths on the prediction accuracy of these traits using vat milk samples destined to the production of Grana Padano Protected Designation of Origin (PDO) cheese. Information from 72 cheese-making days (in total 216 vats) from 3 dairy industries were collected. For each vat, the milk was weighed and analyzed for composition (total solids, lactose, protein, and fat). After 48h from cheese making, each cheese was weighted, and the resulting whey was sampled for composition as well (total solids, lactose, protein and fat). Two spectra from each milk sample were collected in the range between 5,011 and 925 cm-1 and averaged before the data analysis. The calibration models were developed via a Bayesian approach by using the BGLR (Bayesian Generalized Linear Regression) package of R software. The performance of the models was assessed by the coefficient of determination (R2VAL) and the root mean squared error (RMSEVAL) of validation. Random cross-validation (CV) was applied [80% calibration (CAL) and 20% validation (VAL) set] with 10 replicates. Then, a Stratified Cross Validation (SCV) was performed to assess the effect of the dairy industry on prediction accuracy. The study was repeated using a selection of informative wavelengths to assess the necessity of using whole spectra to optimize prediction accuracy. Results showed the feasibility of using FTIR spectra and Bayesian models to predict cheese-making traits. The R2VAL values obtained with the CV procedure were promising in particular for the CY and %REC for protein, ranging from 0.44 to 0.66 with very low RMSEVAL (from 0.16 to 0.53). Prediction accuracy obtained with the SCV was strongly influenced by the dairy factory industry. The general low values gained with the SCV do not permit a practical application of this approach, but they highlight the importance of building calibration models with a data set covering the largest possible sample variability. This study also demonstrated that the use of the full FTIR spectra may be redundant for the prediction of the cheese-making traits and that a specific selection of the most informative wavelengths led to improved prediction accuracy. This could lead to the development of dedicated spectrometers using selected wavelengths with built-in calibrations for the on-line prediction of these innovative traits.


Effects of different types of contingent tactile stimulation on crying, smiling, and sleep in newborns: an observational study.
Sleep, the brain and the ability to interact with the environment change a great deal over the first year of life; however, there are no studies on the possible influence of different environmental stimulations on the organization of subsequent sleep-wake cycles in infants. The hypothesis of this study was that greater continuity of contingent tactile stimulation decreases crying behavior, subsequent active sleep (AS) and its fragmentation, and increases smiling behavior and subsequent quiet sleep in newborns. Forty out of the 82 newborns (15- to 30-hr old) of the initial sample satisfied the inclusion criteria and completed the first cycle of sleep during the period between two feedings. The 40 newborns were randomly assigned to four groups after 2' of baseline observation: continuous stimulation (CS, n = 10); discontinuous nonperiodic stimulation (DnPS, n = 10); discontinuous periodic stimulation (DPS, n = 10); absent stimulation (AbS, n = 10). During baseline measurements, there were no significant differences in crying and smiling behaviors between the four groups, while during the subsequent stimulated wake, the CS group compared to the DnPS group showed more smiling (p < .05) and less crying (p < .05), longer poststimulation wake before sleep (p < .01) as well as AS with a lower percentage of grouped-rapid eye movements [grouped REM (GREM); p < .001]. The number of GREM during AS was negatively correlated to the number of smiles (p < .05) and positively to the number of cries (p < .05) of the previous stimulated wake. These findings suggest that, after birth, different continuity levels of contingent tactile stimulations may affect crying and smiling behaviors and the organization of behavioral states. AS could have an important role in processing affective states.


[Key technologies of functional fascicular groups three dimensional visualization of long segmented peripheral nerve based on two-time imaging technique and automatic registration].
To explore and solve the key technologies of the three dimensional (3D) visualization reconstruction of functional fascicular groups inside long segmented peripheral nerve. A 20 cm ulnar nerve from upper arm of fresh adult dead body was embedded by OCT with four pieces of woman's hair which was used as locating material, then the samples were serially horizontally sliced into 400 slices with 15 microm thickness and 0.5 mm interval. All slices were stained with acetylcholinesterase (AchE) histochemical staining. After that, the 2D panorama images of the same slice were obtained with Olympus stereomicroscope and MSHOT MD90 micro figure image device before and after AchE staining. Using the layer processing technique of Photoshop image processing software, the decomposition images including complete 4 location pots were obtained, based on which the algorithm of optimized least square support vector machine (Optimized LS-SVM) and space transformation method was used to fulfill automatic registration. Finally, with artificial assistant outline obtaining, the 3D visualization reconstruction model of functional fascicular groups of 20 cm ulnar nerve was made using Amira 4.1, and the effects of reverse reduction and the suitability of 3D reconstruction software were evaluated. The two-time imaging technique based on the layer process of Photoshop image processing software had the advantages: the image outline had high goodness of fit; the locating pots of merging image was accurate; and the whole procedure was simple and fast. The algorithm of Optimized LS-SVM had high degree of accuracy, and the error rate was only 8.250%. The 3D reconstruction could display the changes of the chiastopic fusion of different nerve functional fascicular groups directly. It could extract alone, merge and combine arbitrarily, and revolve at any angles. Furthermore, the reverse reduction on arbitrarily level dissection of the 3D model was very accurately. Based on the two-time imaging technique and computer image layer processing technology, the compute algorithm of auto-registration can be developed and applied to 3D visualization reconstruction of long segmented peripheral nerve. The technological processes is fast, and the reconstruction effect is good.


Isotope dilution-mass spectrometry determination of blood cyanide by headspace gas chromatography.
A direct and sensitive method for the determination of blood cyanide by isotope dilution was developed. The blood is placed in a headspace vial, and K13C15N is added as internal standard. Addition of phosphoric acid liberates the cyanide as HCN. The detection is accomplished by mass spectrometry after a fine mass calibration tuning. The detection limit obtained is 0.3 micromol/L. The within- and inter-run coefficients of variation are 4.4% (for a concentration of 2.5 micromol/L) and 3.9% (for a concentration of 4.7 micromol/L), respectively. The observed recovery is 98%. A round-robin exercise was carried out to compare the performance of this method with others currently in use in other clinical laboratories.


Three E2F target-related genes signature for predicting prognosis, immune features, and drug sensitivity in hepatocellular carcinoma.
Background: Hepatocellular carcinoma (HCC) is extremely malignant and difficult to treat. The adenoviral early region 2 binding factors (E2Fs) target pathway is thought to have a major role in tumor growth. This study aimed to identify a predictive E2F target signature and facilitate individualized treatment for HCC patients. Methods: We constructed an E2F target-related gene profile using univariate COX and LASSO regression models and proved its predictive efficacy in external cohorts. Furthermore, we characterized the role of the E2F target pathway in pathway enrichment, immune cell infiltration, and drug sensitivity of HCC. Results: Lasso Cox regression created an E2F target-related gene signature of GHR, TRIP13, and CDCA8. HCC patients with high risk were correlated with shorter survival time, immune evasion, tumor stem cell characteristics and high sensitivity to Tipifarnib and Camptothecin drugs. Conclusion: Hepatocellular carcinoma prognosis was predicted by an E2F target signature. This finding establishes the theoretical usefulness of the E2F target route in customized identification and treatment for future research.


[The effect of exclusion of thyroid hormones on cardiac adaptation to increased work load in rabbits].
The authors studied, in experiments in rabbits (26), the effect of exclusion of thyroid hormones on the formation and evolution of cardiac hypertrophy in animals with artificial insufficiency of the aortic valves. Lack of thyroid hormones due to thyroidectomy, according to the observation of the authors, led to slowing down of the growth of the mass of the heart muscle and to increased concentrations of ribonucleic acid, i. e. to changes usually observed during increased work loads of the heart. Thyroidectomy also prevented the occurrence of certain changes in the concentration of proteins in the subcellular structures of the heart muscle, which usually accompany the formation and evolution of hypertrophy. The authors present the hypothesis that the hormones of the thyroid gland play an important role in adaptation of the heart to increased work loads, but they are not indispensable for the onset and evolution of cardiac hypertrophy.


From Protein Corona to Colloidal Self-Assembly: The Importance of Protein Size in Protein-Nanoparticle Interactions.
Protein adsorption on nanoparticles is an important field of study, particularly with regard to nanomedicine and nanotoxicology. Many factors can influence the composition and structure of the layer(s) of adsorbed proteins, the so-called protein corona. However, the role of protein size has not been specifically investigated, although some evidence has indicated its potential important role in corona composition and structure. To assess the role of protein size, we studied the interactions of hemoproteins (spanning a large size range) with monodisperse silica nanoparticles. We combined various techniques-adsorption isotherms, isothermal titration calorimetry, circular dichroism, and transmission electron cryomicroscopy-to address this issue. Overall, the results show that small proteins behaved as typical model proteins, forming homogeneous monolayers on the nanoparticle surface (protein corona). Their adsorption is purely enthalpy-driven, with subtle structural changes. In contrast, large proteins interact with nanoparticles via entropy-driven mechanisms. Their structure is completely preserved during adsorption, and any given protein can directly bind to several nanoparticles, forming bridges in these newly formed protein-nanoparticle assemblies. Protein size is clearly an overlooked factor that should be integrated into proteomics and toxicological studies.


[Duodenal polyps of gastric origin].
Recently, thanks to the collected knowledge and increased diagnostic abilities we more often meet the diseases that have been considered very seldom. Beside that, we form the new assumptions that must be proved. Today, more often we meet gastric mucosa in duodenum. That according to some researchers, introduces a real possibility for appearance of the polyps, ulcers or cancer on gastric substratum. In the subject patient the two polyps of the gastric origin were found in a duodenum. That could support the assumption that ectopic gastric mucosa presents one of the real possibilities for appearance of polyps, ulcers and cancer.