A Comprehensive Voice Analysis in Benign Vocal Fold Lesions Treated by Cold Knife Endolaryngeal Surgery Using Subjective, Objective and Video-Stroboscopic Parameters.
In the era of globalisation, numerous technical methods have emerged in the management of benign laryngeal lesions. Still cold knife endolaryngeal surgery holds the basic and effective position in providing excellent voice outcome. The aim of this study is to assess the cold knife as a tool for excision of benign laryngeal lesions by protocol of voice assessment. Fifty-five patients with benign vocal fold lesions were included (26 women and 29 men), with age ranging from 22 to 56 years. Each patient was subjected to endoscopic microlaryngeal surgery with cold instruments. Voice assessment was done preoperatively and 3 weeks postoperatively and 3 month post-operatively. The patients were assessed subjectively by Voice Problem Self-Assessment Scale and objectively by laryngoscopy, stroboscopy, and acoustic analysis. Outcome was measured by comparing preoperative and postoperative groups. Significant improvement (< 0.05) was observed in the voice handicap index, acoustic parameters and video stroboscopy parameters between the preoperative and the postoperative groups. The cold knife endo-laryngoscopic surgery still stands out to be a simple, cost effective yet efficient way in treating majority of benign vocal fold lesions causing hoarseness of voice.


High prevalence of small dense LDL in diabetic nephropathy is not directly associated with kidney damage: a possible role of postprandial lipemia.
To determine whether high prevalence of small dense low-density lipoprotein (LDL) in non-insulin-dependent diabetes (NIDDM) with nephropathy is directly associated with kidney damage, we measured LDL particle size by non-denaturing 2-16% gradient polyacrylamide gel electrophoresis in non-diabetic patients with primary renal disease and compared the results to particle size in NIDDM patients with diabetic nephropathy. The average LDL particle diameter was significantly smaller in patients with diabetic nephropathy (245+/-3 A mean +/- SEM) compared to the controls (263+/-1 A), diabetics without nephropathy (257+/-2 A), patients with primary renal disease (254+/-2 A) or non-diabetic patients treated with hemodialysis (HD) (260+/-1 A). The incidence of small LDL (mean diameter is < or =255 A) was remarkably increased in diabetic nephropathy (67%) compared to diabetes without nephropathy (27%), patients with renal disease (24%), HD patients (15%) and controls (10%). LDL size in patients with primary renal disease was significantly smaller than those in controls. However, because there was an excellent correlation between LDL size and plasma triglyceride (TG) levels, when hypertriglyceridemic subjects (TG >1.7 mM) were excluded, no difference of LDL size was observed between the renal disease group (260+/-2 A) and the control group (264+/-1 A). On the other hand, even when hypertriglyceridemic subjects were excluded, LDL size was still smaller in diabetic nephropathy (250+/-4 A). We performed an oral fat load test in normotriglyceridemic subjects (fasting TG <1.7 mM) of control, diabetes with and without nephropathy and primary renal disease. The TG responses in plasma and TG-rich-lipoprotein (TRL) (d <1.006) after the oral fat load were significantly greater in NIDDMs with nephropathy compared to controls or NIDDMs without nephropathy, while such a marked postprandial lipemia was not observed in patients with primary renal disease. In these fasting normotriglyceridemic subjects, LDL size was significantly inversely correlated with postprandial TG responses, which is totally independent from fasting TG levels. These results suggest that high prevalence of small dense LDL in NIDDM patients with nephropathy is not directly associated with kidney damage. Postprandial lipemia may play an important role in reducing LDL particle size in these patients.


Characterization of natural gums via elemental and chemometric analyses, synthesis of silver nanoparticles, and biological and catalytic applications.
Gums; composed of polysaccharides, carbohydrates, proteins, and minerals, are high molecular weight hydrophilic compounds with several biological applications. This study describes the nutritional and toxic elements content, chemical composition, synthesis of silver nanoparticles (G-AgNPs), and pharmacological and catalytic properties of Prunus armeniaca (apricot), Prunus domestica (plums), Prunus persica (peaches), Acacia modesta (phulai), Acacia arabica (kikar), and Salmalia malabarica (silk cotton tree) gums. The elemental contents were analyzed by inductively coupled plasma-optical emission spectroscopy (ICP-OES) and ICP-mass spectrometry (ICP-MS). NMR spectroscopy was used for the identification of class of compounds in the mixture, their functional groups were determined through FTIR techniques, and plasmon resonance and size of G-AgNPs through UV-Vis spectroscopic technique and transmission electron microscopy (TEM). From the results, nutritional elements were present at appreciable concentrations, whereas toxic elements showed content below the maximum permissible ranges. Using the elemental data, linear discriminant and principal component analyses classified the gums to 99.9% variability index. Furthermore, G-AgNPs exhibited significant antioxidant, antibacterial, and redox catalytic potential. Hence, the subject G-AgNPs could have promising nutritional, therapeutic and environmental remediation applications.


Synthesis and antimicrobial activities of 5-fluoro-1,2,6-trisubstituted benzimidazole carboxamide and acetamide derivatives.
Some 5-fluoro-6-substitute-1 H-benzimidazole-2-carbamates (12a-e), 5-fluoro-6-substituted 1H-benzimidazole-2-acetate (13a-e) and 2-acetamide (14a-f) derivatives, 2-acetamido-5-fluoro-6-(morpholin-4-yl)-1-propyl-1H-benzimidazole (15), and 1-cyclopropyl-2-ethyl-5-fluoro-6-(4-methylpiperazin-1-yl)- 1H-benzimidazole (16) were synthesized, and their antimicrobial and antifungal activities evaluated. Compound 12c exhibited the best activity against Candida albicans.


Histological scoring system for subchondral bone changes in murine models of joint aging and osteoarthritis.
To establish a histopathological scoring system for changes in subchondral bone in murine models of knee osteoarthritis (OA), three key parameters, subchondral bone plate (Subcho.BP) consisting of the combination of Subcho.BP.thickness (Subcho.BP.Th) and angiogenesis, bone volume (BV/TV) and osteophytes, were selected. The new grading system was tested in two mouse OA models, (1) senescence accelerated mouse (SAM)-prone 8 (SAMP8) as spontaneous OA model with SAM-resistant 1 (SAMR1) as control; (2) destabilization of the medial meniscus in C57BL/6 mice as surgical OA model. Results of the spontaneous OA model showed that Subcho.BP.Th was significantly wider, angiogenesis was greater, and BV/TV was higher in SAMP8 than SAMR1. Notably, subchondral bone score was dramatically higher in SAMP8 at 6 weeks than SAMR1, while OARSI cartilage scores became higher only at 14 weeks. In the surgical OA model, the results were similar to the spontaneous OA model, but osteophytes appeared earlier. There were strong correlations both in Subcho.BP.Th and BV/TV between this scoring system and µCT (r = 0.89, 0.84, respectively). Inter-rater reliabilities for each parameter using this system were more than 0.943. We conclude that this new histopathological scoring system is readily applicable for evaluating the early changes in aging and OA-affected murine subchondral bone.


α1,3Galactosyltransferase knockout pigs produce the natural anti-Gal antibody and simulate the evolutionary appearance of this antibody in primates.
Anti-Gal is the most abundant natural antibody in humans and Old World primates (apes and Old World monkeys). Its ligand, the α-gal epitope (Galα1-3Galβ1-4GlcNAc-R), is abundant in nonprimate mammals, prosimians and New World monkeys whereas it is absent in humans and Old World primates as a result of inactivation of the α1,3galactosyltransferase (α1,3GT) gene in ancestral Old World primates, as recent as 20-28 million years ago. Since anti-Gal has been a "forbidden" autoantibody for >140 million years of evolution in mammals producing α-gal epitopes it was of interest to determine whether ancestral Old World primates could produce anti-Gal once α-gal epitopes were eliminated, i.e. did they carry anti-Gal encoding immunoglobulin genes, or did evolutionary selection eliminate these genes that may be detrimental in mammals synthesizing α-gal epitopes. This question was studied by evaluating anti-Gal prodution in α1,3GT knockout (GT-KO) pigs recently generated from wild-type pigs in which the α-gal epitope is a major self-antigen. Anti-Gal antibody activity in pig sera was assessed by ELISA, flow cytometry and complement mediated cytolysis and compared to that in human sera. The study demonstrates abundant production of the natural anti-Gal antibody in GT-KO pigs at titers even higher than in humans. The fine specificity of GT-KO pig anti-Gal is identical to that of human anti-Gal. Pigs and probably other mammals producing α-gal epitopes carry immunoglobulin genes encoding anti-Gal as an autoantibody. Once the α-gal epitope is eliminated in GT-KO pigs, they produce anti-Gal. These findings strongly suggest that similar to GT-KO pigs, inactivation of the α1,3GT gene in ancestral Old World primates enabled the immediate production of anti-Gal, possibly as a protective antibody against detrimental microbial agents carrying α-gal epitopes.


Depression in mentally retarded children.
Thirty-one mentally retarded emotionally disturbed children, hospitalized within a university medical school's psychiatric intensive care program, were matched on age and sex and compared to 31 children from a normal school setting on depression. Measures included the Child Depression Inventory (CDI) and the Child Behavior Profile (CBP), with children being compared on total and subfactor scores for both measures. Depression and its various subcomponents were more prevalent in the mentally retarded group. There were no significant sex or age differences. Degree of overall psychopathology and depression were highly related. The relationship between criteria for depression on the CDI and CBC were also made. Correlational data showed a strong relationship between the cut-off scores for both measures, an important finding because they were based on norms established with children of normal intelligence. These data suggest that similarities exist between depression in mentally retarded children and those without such cognitive handicaps. The relationship of depression to other forms of psychopathology in the group of 31 emotionally disturbed mentally retarded children was also examined. A wide range of disorders including schizophrenia, aggression, withdrawal, and hyperactivity were evaluated. These are the first empirical data with mentally retarded children in the United States that are aimed specifically at evaluating depression, and should be useful to the clinicians in better understanding the phenomenon.


Quantitative proteomics revealed energy metabolism pathway alterations in human epithelial ovarian carcinoma and their regulation by the antiparasite drug ivermectin: data interpretation in the context of 3P medicine.
Energy metabolism abnormality is the hallmark in epithelial ovarian carcinoma (EOC). This study aimed to investigate energy metabolism pathway alterations and their regulation by the antiparasite drug ivermectin in EOC for the discovery of energy metabolism pathway-based molecular biomarker pattern and therapeutic targets in the context of predictive, preventive, and personalized medicine (PPPM) in EOC. iTRAQ-based quantitative proteomics was used to identify mitochondrial differentially expressed proteins (mtDEPs) between human EOC and control mitochondrial samples isolated from 8 EOC and 11 control ovary tissues from gynecologic surgery of Chinese patients, respectively. Stable isotope labeling with amino acids in cell culture (SILAC)-based quantitative proteomics was used to analyze the protein expressions of energy metabolic pathways in EOC cells treated with and without ivermectin. Cell proliferation, cell cycle, apoptosis, and important molecules in energy metabolism pathway were examined before and after ivermectin treatment of different EOC cells. In total, 1198 mtDEPs were identified, and various mtDEPs were related to energy metabolism changes in EOC, with an interesting result that EOC tissues had enhanced abilities in oxidative phosphorylation (OXPHOS), Kreb's cycle, and aerobic glycolysis, for ATP generation, with experiment-confirmed upregulations of UQCRH in OXPHOS; IDH2, CS, and OGDHL in Kreb's cycle; and PKM2 in glycolysis pathways. Importantly, PDHB that links glycolysis with Kreb's cycle was upregulated in EOC. SILAC-based quantitative proteomics found that the protein expression levels of energy metabolic pathways were regulated by ivermectin in EOC cells. Furthermore, ivermectin demonstrated its strong abilities to inhibit proliferation and cell cycle and promote apoptosis in EOC cells, through molecular networks to target PFKP in glycolysis; IDH2 and IDH3B in Kreb's cycle; ND2, ND5, CYTB, and UQCRH in OXPHOS; and MCT1 and MCT4 in lactate shuttle to inhibit EOC growth. Our findings revealed that the Warburg and reverse Warburg effects coexisted in human ovarian cancer tissues, provided the first multiomics-based molecular alteration spectrum of ovarian cancer energy metabolism pathways (aerobic glycolysis, Kreb's cycle, oxidative phosphorylation, and lactate shuttle), and demonstrated that the antiparasite drug ivermectin effectively regulated these changed molecules in energy metabolism pathways and had strong capability to inhibit cell proliferation and cell cycle progression and promote cell apoptosis in ovarian cancer cells. The observed molecular changes in energy metabolism pathways bring benefits for an in-depth understanding of the molecular mechanisms of energy metabolism heterogeneity and the discovery of effective biomarkers for individualized patient stratification and predictive/prognostic assessment and therapeutic targets/drugs for personalized therapy of ovarian cancer patients.


Peripheral nervous system of shiverer mutant mice: developmental change of myelin components and immunohistochemical demonstration of the absence of MBP and presence of P2 protein.
Peripheral nerves of the shiverer mouse, which are characterized by the absence of major dense lines and myelin basic proteins in CNS myelin, were analyzed. From subcellular fractionation of sciatic nerves, it was found from the SDS-polyacrylamide gel electrophoresis that the Pl and Pr proteins equivalent to myelin basic protein of CNS and PM protein were missing in the shiverer in both P2A and P3A fractions in which PNS myelin is recovered. No extra bands were observed in any other fractions of the shiverer in place of the absence of the proteins. The activities of 2',3'-cyclic nucleotide 3'-phosphohydrolase (CNPase) of P2A and P3A fractions were high, but that of the P3X fraction which floated over 0.32 M sucrose was the highest among the fractions examined in both the shiverer and the control. Developmental analysis of the protein profiles revealed that PO, Pl, Pr and PM proteins increased rapidly from the sixth day postnatally up to the twentieth day after birth in the control. No differences were observed between the shiverer and the control as for PO protein, but Pl, Pr and PM proteins were absent in the shiverer throughout the development. The CNPase activity of total homogenate of sciatic nerve fibers at birth in the control showed high activity comparable to that of the adult value, but there was no significant difference in activity between the control and the shiverer at any stage of development. Immunohistochemical reaction using peroxidase anti-peroxidase method showed that the myelin from the shiverer did not react with the MBP antiserum, while that of the control reacted positively. On the contrary, the myelin from both shiverer and the control reacted positively against P2 antibody.


Fast growth can counteract antibiotic susceptibility in shaping microbial community resilience to antibiotics.
Microbial communities often face external perturbations that can induce lasting changes in their composition and functions. Our understanding of how multispecies communities respond to perturbations such as antibiotics is limited, with susceptibility assays performed on individual, isolated species our primary guide in predicting community transitions. Here, we studied how bacterial growth dynamics can overcome differences in antibiotic susceptibility in determining community resilience: the recovery of the original community state following antibiotic exposure. We used an experimental community containing Corynebacterium ammoniagenes and Lactobacillus plantarum that displays two alternative stable states as a result of mutual inhibition. Although C. ammoniagenes was more susceptible to chloramphenicol in monocultures, we found that chloramphenicol exposure nonetheless led to a transition from the L. plantarum-dominated to the C. ammoniagenes-dominated community state. Combining theory and experiments, we demonstrated that growth rate differences between the two species made the L. plantarum-dominated community less resilient to several antibiotics with different mechanisms of action. Taking advantage of an observed cooperativity—a dependence on population abundance—in the growth of C. ammoniagenes, we next analyzed in silico scenarios that could compromise the high resilience of the C. ammoniagenes-dominated state. The model predicted that lowering the dispersal rate, through interacting with the growth at low population densities, could make the C. ammoniagenes state fragile against virtually any kind of antibiotic, a prediction that we confirmed experimentally. Our results highlight that species susceptibility to antibiotics is often uninformative of community resilience, as growth dynamics in the wake of antibiotic exposure can play a dominant role.


Utility of semiautomatic clinic and 24-h ambulatory blood pressure measurements to evaluate combination therapy: the Ramipril-Hydrochlorothiazide Hypertension trial.
Angiotensin-converting enzyme inhibitors combined with higher doses of hydrochlorothiazide (HCT), that is, 25 mg daily, have been recognized as an effective form of antihypertensive therapy. To evaluate the coadministration of 20 mg ramipril with 25 mg HCT, we carried out a randomized, double-blind, controlled trial with two dose schedules of ramipril (20 mg q.d. and 10 mg b.i.d.) and HCT monotherapy arms as comparators in 354 patients with stage 2 hypertension. The clinic blood pressure (BP) was assessed using a semiautomatic digital device and 24-h BP was measured using ambulatory BP recordings at baseline and after 8 weeks of therapy. At baseline, the demographics and baseline BP values were similar in the four treatment groups (age: 51-53 years, 52-58% male, 64-68% non-black, clinic BP: 155-158/103-104 mm Hg). Ramipril-HCT induced significantly greater reductions in both the clinic and ambulatory BP than the HCT and ramipril monotherapy treatments (for example, additional reductions in ambulatory BP on ramipril-HCT ranged from -7.3/-5.2 to -10.3/-7.4 mm Hg compared to the monotherapies, all P<0.001). Reductions from baseline were still numerically greater for the clinic BPs derived from device measurements than those for the BP values derived from 24-h ambulatory BP measurements (changes in clinic diastolic BP ranged from -8.5 to -15.5 mm Hg across treatment groups, whereas changes in ambulatory diastolic BP were -4.7 to -12.0 mm Hg for the same groups). Thus, these data support the use of ambulatory BP monitoring even when automated BP devices are used for the assessment of clinical BP in trials that attempt to differentiate BP responses among active comparator groups. In conclusion, based on its efficacy and tolerability profile the combination of ramipril and HCT was shown to be effective therapy for the treatment of stage 2 hypertension.


High-performance alkaline water electrolyzers based on Ru-perturbed Cu nanoplatelets cathode.
Alkaline electrolyzers generally produce hydrogen at current densities below 0.5 A/cm2. Here, we design a cost-effective and robust cathode, consisting of electrodeposited Ru nanoparticles (mass loading ~ 53 µg/cm2) on vertically oriented Cu nanoplatelet arrays grown on metallic meshes. Such cathode is coupled with an anode based on stacked stainless steel meshes, which outperform NiFe hydroxide catalysts. Our electrolyzers exhibit current densities as high as 1 A/cm2 at 1.69 V and 3.6 A/cm2 at 2 V, reaching the performances of proton-exchange membrane electrolyzers. Also, our electrolyzers stably operate in continuous (1 A/cm2 for over 300 h) and intermittent modes. A total production cost of US$2.09/kgH2 is foreseen for a 1 MW plant (30-year lifetime) based on the proposed electrode technology, meeting the worldwide targets (US$2-2.5/kgH2). Hence, the use of a small amount of Ru in cathodes (~0.04 gRu per kW) is a promising strategy to solve the dichotomy between the capital and operational expenditures of conventional alkaline electrolyzers for high-throughput operation, while facing the scarcity issues of Pt-group metals.


A monoclonal antibody-based time-resolved fluoroimmunoassay for chloramphenicol in shrimp and chicken muscle.
A time-resolved fluoroimmunoassay (TR-FIA) for determination of chloramphenicol (CAP) in shrimp and chicken muscle was developed. The method was based on a direct competitive immunoassay using europium-labeled anti-CAP monoclonal antibody (MAb) and CAP-ovalbumin as coated antigen. The limit of detection was 0.05 ng g(-1) and limit of quantification was 0.1 ng g(-1). Recoveries ranged from 101.2 to 112.5% for shrimp and 104.9 to 115.3% for chicken muscle at spiked levels of 0.1-5 ng g(-1), with intra-assay and inter-assay variations 8.7-14.6 and 9.6-17.8%, respectively. The results obtained by the TR-FIA and ELISA correlated well. The established TR-FIA was validated for the determination of incurred shrimp samples and confirmed by gas chromatography with microcell electron capture detector (GC-microECD).


Quantification of microporosity in fruit by MRI at various magnetic fields: comparison with X-ray microtomography.
Microstructure determines the mechanical and transport properties of fruit tissues. One important characteristic of the microstructure is the relative volume fraction of gas-filled intercellular spaces, i.e., the tissue microporosity. Quantification of this microporosity is fundamental for investigating the relationship between gas transfer and various disorders in fruit. We present a new method for quantifying the apparent microporosity using magnetic resonance imaging (MRI). The method is based on the differences in magnetic susceptibility between gas-filled intercellular spaces and their environment inside fruit tissues. It was tested at two different magnetic fields (1.5 and 0.2 T) on apple and tomato fruit. The method was validated by comparing the MRI results with estimation of local tissue porosity using X-ray microtomography experiments. MRI was shown to be effective in determining the distribution of apparent microporosity in fruit.


Endothelin in hypertension: a role for receptor antagonists?
The rapid development of endothelin-receptor antagonists has made the endothelin pathway a new therapeutic target in the treatment of cardiovascular diseases, only ten years after the report of its discovery. While the first clinical trials will help to position this new family of compounds in our therapeutic armament for the treatment of essential or secondary forms of hypertension, several preclinical chronic studies already provide a picture of what we can expect from these drugs. Endothelin-receptor antagonists are not effective in all experimental models of hypertension, but those that respond present hypertrophy of small arteries, secondary to a local overexpression of the peptide. Although angiotensin II seems to represent a stimulus for endothelin overexpression in some models, other, as yet undetermined, stimuli are likely in others. Besides their narrow spectrum of antihypertensive activity, endothelin-receptor antagonists may also protect from complications of hypertension by improving end-organ function in a pressure-independent manner. This seems to be the case for the structure and reactivity of resistance arteries, as well as for renal damage. However, it is not clear at this point if cardiac structure and function are improved beyond the benefits produced by blood pressure reduction. The first results in essential hypertensive subjects suggest some degree of efficacy of endothelin-receptor antagonists. Other clinical trials will help to determine if secondary forms of the disease benefit equally or more from this new class of drugs, and if end-organ damage can be reduced beyond blood-pressure reduction.


Iron requirements of broiler chickens as affected by supplemental phytase.
Iron is routinely supplemented in broiler feeds intending to prevent dietary deficiencies. The present research was conducted with the objective of assessing Fe requirements of broilers when fed supplemental phytase. A total of 1,280 1-d-old male Cobb × Cobb 500 were distributed in a 2 × 5 factorial arrangement (phytase-supplemented feeds × 5 graded increases of supplemental Fe) in 80 battery cages, eight replications of eight chicks each. The trial was replicated once. Chicks were fed a Fe-deficient diet without phytase (Fe analyzed at 31.30 ± 3.79 mg/kg) from placement to 7 d and then randomly distributed into battery cages with corresponding dieting treatments with or without phytase and graded increases of supplemental Fe. Feeds were formulated with corn and soybean meal (SBM), laboratory-grade calcium carbonate, and phosphoric acid; therefore, the vast majority of dietary Fe originated from corn and SBM (analyzed diet had 53.3 ± 1.41 mg/kg Fe). Phytase was added in excess to the producer recommendation of 1,000 FYT (4,452 ± 487 FYT/kg analyzed) such that phytate degradation was expected to be maximized. Supplemental Fe was from laboratory-grade ferrous sulfate heptahydrate (FeSO47H2O) which was increasingly added to the feeds (analyzed Fe in the supplemented feeds were: 53.3 ± 1.41, 65.5 ± 0.59, 77.2 ± 1.97, 87.6 ± 1.72, 97.7 ± 1.33 mg/kg). There were no interactions between phytase and dietary Fe for any response throughout the study (P > 0.05). Supplementing phytase had no effects on Fe intake or Fe excretion, as well as on hematocrit (Ht), hemoglobin (Hb), ferritin, Fe contents in the liver or thigh muscle color (P > 0.05). However, phytase-supplemented feeds produced better live performance as well as higher ileal digestible energy and Fe digestibility (P < 0.05). No effects were found for dietary Fe in live performance at day 28 (P > 0.05). On the other hand, increasing dietary Fe led to linear increases in Fe retention and excretion, Fe contents in livers, as well as Ht and Hb at 14 d (P < 0.05). Quadratic responses (P < 0.05) were observed for Hb at 21 d, serum ferritin on days 14, 21, and 28 (maximum responses were 83.3, 104.0, 91.9, and 88.3 mg/kg Fe, respectively). In conclusion, supplementing Fe adding to a total of 97.7 mg/kg dietary Fe did not affect live performance traits. However, the average of Fe-related blood parameters was maximized at 91.9 mg/kg dietary Fe. Supplementing phytase provided a significant increase in Fe digestibility.


Differential expression and in vivo secretion of the antimicrobial peptides psoriasin (S100A7), RNase 7, human beta-defensin-2 and -3 in healthy human skin.
Antimicrobial peptides (AMP) are key players in the skin's defense system. Previous observations suggest a site- and age-dependent expression of individual AMP. We investigated the expression and secretion patterns of four important AMP in a representative collective of healthy human skin samples. Levels of psoriasin, RNase 7 and hBD-3 expression - assessed by immunohistochemistry - varied between different body localisations. Older individuals expressed hBD-2 more frequently. No gender-related expression was observed. The in vivo secretion of psoriasin, measured in skin washing fluids using ELISA, was related to body localisation and age, whereas RNase 7 secretion showed no significant differences regarding these variables. HBD-2 and -3 secretion could not be detected. Our findings suggest the usage of control samples matching localisation and approximate age (in the case of hBD-2) for comparative immunohistochemical analysis. To avoid bias through great interindividual differences, sufficient large collectives should be used for in vivo secretion analyses.


Computerized tomography in the evaluation of localized renal cortical hypertrophy.
The value of computerized tomography in the diagnosis of localized renal cortical hypertrophy is discussed. This modality can replace angiography in patients in whom ultrasonography is inconclusive in the investigation of renal masses.


Imaging and Spectroscopic-Based Methods to Understand Cancer Metabolism and Biology.
The results of publications in PubMed with the MeSH terms "cancer", "biology", "imaging and cancer", "metabolism" and "spectroscopy" are shown in Figure 1 in the form of a Venn diagram [...].


Development and validation of a deep learning radiomics nomogram for preoperatively differentiating thymic epithelial tumor histologic subtypes.
Using contrast-enhanced computed tomography (CECT) and deep learning technology to develop a deep learning radiomics nomogram (DLRN) to preoperative predict risk status of patients with thymic epithelial tumors (TETs). Between October 2008 and May 2020, 257 consecutive patients with surgically and pathologically confirmed TETs were enrolled from three medical centers. We extracted deep learning features from all lesions using a transformer-based convolutional neural network and created a deep learning signature (DLS) using selector operator regression and least absolute shrinkage. The predictive capability of a DLRN incorporating clinical characteristics, subjective CT findings and DLS was evaluated by the area under the curve (AUC) of a receiver operating characteristic curve. To construct a DLS, 25 deep learning features with non-zero coefficients were selected from 116 low-risk TETs (subtypes A, AB, and B1) and 141 high-risk TETs (subtypes B2, B3, and C). The combination of subjective CT features such as infiltration and DLS demonstrated the best performance in differentiating TETs risk status. The AUCs in the training, internal validation, external validation 1 and 2 cohorts were 0.959 (95% confidence interval [CI]: 0.924-0.993), 0.868 (95% CI: 0.765-0.970), 0.846 (95% CI: 0.750-0.942), and 0.846 (95% CI: 0.735-0.957), respectively. The DeLong test and decision in curve analysis revealed that the DLRN was the most predictive and clinically useful model. The DLRN comprised of CECT-derived DLS and subjective CT findings showed a high performance in predicting risk status of patients with TETs. Accurate risk status assessment of thymic epithelial tumors (TETs) may aid in determining whether preoperative neoadjuvant treatment is necessary. A deep learning radiomics nomogram incorporating enhancement CT-based deep learning features, clinical characteristics, and subjective CT findings has the potential to predict the histologic subtypes of TETs, which can facilitate decision-making and personalized therapy in clinical practice. • A non-invasive diagnostic method that can predict the pathological risk status may be useful for pretreatment stratification and prognostic evaluation in TET patients. • DLRN demonstrated superior performance in differentiating the risk status of TETs when compared to the deep learning signature, radiomics signature, or clinical model. • The DeLong test and decision in curve analysis revealed that the DLRN was the most predictive and clinically useful in differentiating the risk status of TETs.


Effect of intravenously infused porcine GIP on serum insulin in obese and lean subjects studied with the hyperglycemic clamp technique.
To ascertain whether an altered sensitivity to gastric inhibitory polypeptide (GIP) in morbidly obese subjects can play a role in the postprandial hyperinsulinemia seen in this condition, eight obese and eight control subjects were studied with an intravenous infusion of porcine GIP. The blood glucose was maintained at 4 mmol/l above the basal level by a hyperglycemic clamp technique. Although the mean serum insulin level was higher in the obese group throughout the study, the shapes of the serum insulin curves were almost identical in the two groups after the GIP infusion. This together with the normal GIP secretion found in obese subjects question the existence of a causal relationship between an overactive entero-insular axis and the hyperinsulinemia found in these subjects.


Spectral and fractal analysis of cerebellar activity after single and repeated brain injury.
The cerebellum, even when not directly damaged, is potentially interesting for understanding the adaptive responses to brain injury. Cerebellar electrocortical activity (ECoG) in rats was studied using spectral and fractal analysis after single and repeated unilateral injury of the parietal cortex. Local field potentials of cerebellar paravermal cortex were recorded before brain injury, in the acute phase (up to 2.5 hours) after a first injury of anesthetized rats, and then before and after second, third, and, in some cases, fourth injury. Relative gamma power (32.1-128.0 Hz) and fractal dimension of ECoGs were temporarily increased after the first injury. However, there was a permanent mild increase in gamma activity and a mild increase in the fractal dimension of cerebellar activity as a chronic change after repeated remote brain injury. There was a negative linear correlation between the normalized difference in fractal dimensions and normalized difference in gamma powers of cerebellar activity only in the case of repeated brain injury. This is the first study showing that correlation between the parameters of spectral and fractal analyses of cerebellar activity can discriminate between single and repeated brain injuries, and is, therefore, a promising approach for identifying specific pathophysiological states.


The macaque inferior parietal lobule: cytoarchitecture and distribution pattern of serotonin 5-HT1A binding sites.
The inferior parietal lobule (IPL) of the macaque monkey integrates sensory information as a prerequisite for reaching and grasping movements. Electrophysiological data suggest that the convexity of the IPL is heterogeneous along its rostro-caudal axis. Cytoarchitecture reflects this functional diversity. However, various parcellations have been proposed so far, ranging from one homogeneous region to four areas. In order to obtain a more valid anatomical map of the IPL, we studied the distribution pattern of serotonin 5-HT1A binding sites (i.e., the domain of synaptic transmission and cortical information processing) and cytoarchitecture with an observer-independent technique (thus avoiding the subjectivity inherent in visually guided microstructural parcellations). We cut with a cryostat microtome four unfixed macaque hemispheres and processed sections for 5-HT1A binding sites with [3H]8-OH-DPAT receptor autoradiography or for cell bodies with a modified silver stain. We digitized the autoradiographs and the histological sections and extracted from the cortex of the IPL equidistant density profiles oriented vertically to the cortical layers. We then compared groups of neighboring profiles with multivariate statistics expecting to see a significant difference in profile shape at the interface between two cortical areas. These positions were compared between 5-HT1A autoradiographs (neurochemical borders) and adjacent histological sections (cytoarchitectonic borders). Neurochemical and cytoarchitectonic borders showed a good topographical correspondence and revealed three areas arranged in a rostro-caudal sequence along the convexity of the IPL. Dorsally, the areas extend approximately 1 mm into the depth of the lateral bank of the intraparietal sulcus. Their ventral border lies on the convexity of the IPL close to the shoulder of the lateral sulcus. The three areas are in close agreement with areas PF, PFG, and PG as defined by Pandya and Seltzer (J Comp Neurol 204:196-210, 1982) and Gregoriou et al. (Program No. 919.5, Abstract Viewer/Itinerary Planner, Washington, Society for Neuroscience, 2003). The neurochemical and cytoarchitectonic data show that a complex structural framework underlies the functional heterogeneity along the rostro-caudal axis of the IPL, e.g., the representation of different types of arm and hand actions in different sectors of the monkey's workspace.


Cytogenetics of uveal melanoma: a 7-year clinical experience.
Chromosome 3 loss and chromosome 8 gains in uveal melanoma are associated with metastatic death. Since 1999, we have offered cytogenetic analysis to patients treated by local resection or enucleation. This study correlated our cytogenetic results with clinical and histologic predictors and disease-specific mortality. Nonrandomized case series. Three hundred fifty-six patients with uveal melanoma with data on chromosome 3 and chromosome 8. Tumor diameter was measured by echography. Cell type, presence of closed connective tissue loops, and mitotic rate were determined histopathologically. Fluorescence in-situ hybridization was performed using centromeric probes for chromosomes 3 and 8 and for c-myc. Patients were flagged at the National Health Service Cancer Registry, which notified us of any deaths. Statistics included Cox multivariate analysis and Kaplan-Meier analysis. Disease-specific mortality, according to clinical, histologic and cytogenetic features as well as correlation between cytogenetic variables and other mortality predictors, including a predictive index. The patients had a mean age of 61.9 years. The tumors showed no cytogenetic abnormalities of chromosomes 3 or 8 in 42%, chromosome 8 gains in 11%, monosomy 3 in 21%, and both abnormalities in 27%. These correlated with ciliary body involvement (P<0.001), extraocular spread (P = 0.007), large basal tumor diameter (P<0.001), epithelioid cellularity (P<0.001), closed connective tissue loops (P<0.001), and mitotic rate exceeding 4/40 high power fields (P<0.001). By the study close, 76 patients had died (67 from metastasis). Cox multivariate analysis showed the most significant factors to be basal tumor diameter (P<0.001), monosomy 3 (P<0.001), and epithelioid cellularity (P = 0.004). A predictive index (PI) was derived from these variables. Kaplan-Meier analysis showed that 5-year metastatic death rates ranged from 0% in 84 patients with low-grade melanoma (PI<19) to 66% in 100 patients with high-grade tumor (PI>26; 95% confidence interval, 53%-80%). Cytogenetic analysis of chromosomes 3 and 8 enhances prediction of disease-specific mortality after treatment of uveal melanoma but must be interpreted together with tumor diameter and cell type.


Hemostasis control after femoral percutaneous approach: A systematic review and meta-analysis.
Hemostasis control after percutaneous endovascular procedures through the femoral approach remains challenging for catheterization laboratory nurses, given method variability. To summarize the available evidence on vascular devices efficacy dedicated to hemostasis control compared to the extrinsic compression after percutaneous procedures in the femoral vein or artery. A systematic review with meta-analysis of randomized clinical trials was conducted. We compared different hemostasis methods in adult patients who underwent diagnostic and/or therapeutic procedures through femoral access. The databases searched were PubMed, Embase, CINAHL and Cochrane CENTRAL, and updated on 03/2022. The outcomes included hematoma, pseudoaneurysm, bleeding, minor and major vascular complication, time to hemostasis, device failure, and manual compression repetition. The risk of bias was assessed using the Cochrane Risk of Bias Tool 1.0. Pooled effect sizes on continuous, categorical and proportion variables were estimated with the random effects model. The continuous variables were summarized as the difference between means weighted by the inverse of variance (WMD), and the categorical ones by the summary of relative risks (RR), estimated by the DerSimonian and Laird method. The Freeman-Tukey method was used to estimate the summary effect of proportions. Fifty articles were included in the systematic review. When compared to extrinsic compression, vascular closure devices resulted in a relative risk reduction (RRR) for hematoma: RR 0.82 [95%CI 0.72 to 0.94] and in shorter time to hemostasis WMD -15.06 min [95%CI -17.56 to -12.56]; no association was observed between interventions with vascular closure devices and extrinsic compression for pseudoaneurysm, bleeding, minor and major vascular complications. Compared to extrinsic compression, sealant or gel type devices were compatible with a RRR for hematoma: RR 0.73 [95%CI 0.59 to 0.90]; and metal clip or staple type devices for pseudoaneurysm: RR 0.48 [95%CI 0.25 to 0.90]; and major vascular complication: RR 0.33 [95%CI 0.17 to 0.64]. For each 100 observations, the device failure rate for metal clip or staple was 3.28% [95%CI 1.69 to 6.27]; for suture 6.84% [95%CI 4.93 to 9.41]; for collagen 3.15% [95%CI 2.24 to 4.41]; and for sealant or gel 7.22% [95% CI 5.49 to 9.45]. Vascular closure devices performed better in hemostasis control. The certainty of the evidence was rated as very low to moderate. PROSPERO CRD42019140794.


X-ray tomography of whole cells.
X-ray tomography has been shown to provide insights into the internal structure of whole cells that can't be obtained by any other means. With recent advances in instrumentation and the advent of automated cryogenic sample stages, it has become possible to collect isotropic tomographic data from radiation-sensitive cells and to compute reconstructions with a high degree of fidelity to a resolution of 50 nm. The new generation of X-ray optics will extend this resolution limit to 15 nm or better. The development of X-ray tomography of whole cells generates opportunities to study cells, and cellular processes, in a completely new way.


Usage of shape memory alloy actuators for large force active disassembly applications.
Shape memory alloys (SMAs) possess inherent superior properties that make their applications in active disassembly an emerging and interesting field of research. This is because extremely large forces can be generated repeatedly using a small compact-sized element, such as an SMA actuator. To ensure the ability of the SMA actuator to generate a repeated large force or withstand repeated load, several factors should be considered. These include factors that affect the value of the generated recovery forces, such as the amount of strain used, activation temperature, activation time, and cross-sectional area of the SMA element. In general, the compressive strain can be considered as the most influential factor that affects the value of the generated recovery force. The present research investigates the possible use of the SMA actuator in large-force active disassembly applications. To the best of the authors' knowledge, all the studies conducted in this field are concerned with implementing active disassembly in applications requiring small disassembly forces. The present research was conducted in three phases. First, the behaviour of the SMA element upon exposure to different repetitive compressive strains was studied, and the generated recovery force and strain hardening induced in the material were considered to ensure the continuous generation of large recovery forces with the least amount of residual strain induced in the material. Second, the optimum value of the compressive strain required to generate the maximum force with the least amount of residual strain induced in the material was estimated. Third, a practical case study was presented to validate the possible implementation of SMA actuators in large force active disassembly applications. The study successfully estimated the optimum compressive strain value that generated the required recovery force to disassemble the conducted case study using active disassembly technique.


Effect of atrial natriuretic factor on the water permeability of endothelial cells.
Atrial natriuretic factor increases the water permeability of the whole endothelium. This study investigates how it would affect the transcellular osmotic water permeability of bovine artery endothelial cells. The cyclic-GMP production by the isolated cells was maximal for 10(-6)M atrial natriuretic factor within 30 minutes at 37 degrees C. The cyclic-GMP protein kinase cell concentration was 1.87 +/- 0.15 ng/mg protein. The control apparent water permeability of the cells measured by light scattering was 195 +/- 11 microns/sec (n = 5). Membrane folding revealed by light and scanning electron microscopy indicated that their true water permeability values would be close to 20-40 microns/sec, similar to the values for lipid membranes. The energy activation calculated from the temperature dependence of water permeability between 15 degrees C and 37 degrees C was 9.3 kcal/mol. This value suggests water movement through the lipid bilayer and not through water channels. Atrial natriuretic factor 10(-6)M did not significantly increase the water permeability of the cells. Hence, atrial natriuretic factor-stimulated increase in water permeability of the endothelium is more related to changes in paracellular water pathways than in transcellular water flux.


Plasma beta-thromboglobulin in normal pregnancy and pregnancy-induced hypertension.
Plasma beta-thromboglobulin (BTG) was measured in 25 patients with pregnancy-induced hypertension (PIH), 7 of whom had severe PIH, and in 23 healthy gravidae. Also platelet counts, spontaneous platelet aggregation in vitro, and coagulation studies such as fibrinogen, fibrinogen degradation products and antithrombin III (AT III) were carried out: fetal outcome was judged by birthweight, placental weight and venous umbilical pH. Plasma BTG values of the PIH and severe PIH patients were significantly higher than those of the controls (P less than 0.05), suggesting enhanced platelet activation in the former. Compared with the controls, the entire PIH group was found to have significantly lower AT III values (P less than 0.05), more positive protamine sulphate tests (P less than 0.025), and higher plasma urate concentrations (P less than 0.01), but increased BTG values were more often observed than abnormal coagulation tests. No relationship could be demonstrated between the BTG level and fetal outcome. The significant increase in plasma BTG in PIH indicates enhanced platelet activation in these patients.


CT-guided percutaneous microwave ablation of liver metastases from nasopharyngeal carcinoma.
To access efficacy of percutaneous microwave ablation (MWA) of liver metastases from nasopharyngeal carcinoma (NPC). From March 2007 to June 2012, 18 consecutive patients with NPC and liver metastases (15 men and three women; average age, 45.7 y; age range, 31-61 y) received computed tomography (CT)-guided percutaneous MWA treatment. A total of 27 ablations were performed involving 24 liver metastatic lesions in 18 patients with NPC. Average patient follow-up after ablation was 22.4 months (range, 2-52 mo). The average number of liver metastases per patient was 1.3 (range, 1-4 lesions), with lesion diameters ranging from 1.9 cm to 4.2 cm. Evaluation was then performed to assess percentage of complete necrosis, local tumor progression, and safety. Technical success was achieved in all 27 MWA procedures performed. During follow-up, new metastatic lesions developed in four of 18 patients. Of these, two were liver metastases, and were successfully treated with repeat WMA. Only two major complications were observed: pneumothorax in a patient with an ablation pathway involving the thorax and postprocedural pain in two other patients. A median overall survival time of 41.4 months was observed (range, 2-50 mo); three of 18 patients died during follow-up. CT-guided MWA is safe and offers an effective treatment alternative for local tumor control in selected patients with liver metastases from NPC.


Epigenetic Dysregulation in Autoimmune and Inflammatory Skin Diseases.
Epigenetics is the study of heritable, reversible gene expression patterns that do not originate from alterations in the DNA sequence. Epigenetic modifications influence gene expression patterns and include DNA methylation, histone modifications, and gene regulation via non-coding RNAs. While the study of epigenetics has been most broadly applied to neoplastic diseases, the role of the epigenome in a wide range of disease processes including autoimmune, allergic, and inflammatory processes is increasingly being recognized. Recent advances in the study of the epigenome have led to novel insights into the pathogenesis and potential therapeutic targets of various pathologic entities including inflammatory diseases. In this review, we examine the nature of epigenetic modifications in several well-studied autoimmune, allergic, and/or inflammatory disorders of the skin including systemic lupus erythematosus, vitiligo, systemic sclerosis, alopecia areata, pemphigus, psoriasis, atopic dermatitis, keloidal scarring, and hidradenitis suppurativa with the aim to determine how such epigenetic changes may be targeted for therapeutic benefit.


ORP5 and ORP8 bind phosphatidylinositol-4, 5-biphosphate (PtdIns(4,5)P 2) and regulate its level at the plasma membrane.
ORP5 and ORP8, members of the oxysterol-binding protein (OSBP)-related proteins (ORP) family, are endoplasmic reticulum membrane proteins implicated in lipid trafficking. ORP5 and ORP8 are reported to localize to endoplasmic reticulum-plasma membrane junctions via binding to phosphatidylinositol-4-phosphate (PtdIns(4)P), and act as a PtdIns(4)P/phosphatidylserine counter exchanger between the endoplasmic reticulum and plasma membrane. Here we provide evidence that the pleckstrin homology domain of ORP5/8 via PtdIns(4,5)P 2, and not PtdIns(4)P binding mediates the recruitment of ORP5/8 to endoplasmic reticulum-plasma membrane contact sites. The OSBP-related domain of ORP8 can extract and transport multiple phosphoinositides in vitro, and knocking down both ORP5 and ORP8 in cells increases the plasma membrane level of PtdIns(4,5)P 2 with little effect on PtdIns(4)P. Overall, our data show, for the first time, that phosphoinositides other than PtdIns(4)P can also serve as co-exchangers for the transport of cargo lipids by ORPs.ORP5/8 are endoplasmic reticulum (ER) membrane proteins implicated in lipid trafficking that localize to ER-plasma membrane (PM) contacts and maintain membrane homeostasis. Here the authors show that PtdIns(4,5)P 2 plays a critical role in the targeting and function of ORP5/8 at the PM.


Measurement of a solid-state triple point at the metal-insulator transition in VO2.
First-order phase transitions in solids are notoriously challenging to study. The combination of change in unit cell shape, long range of elastic distortion and flow of latent heat leads to large energy barriers resulting in domain structure, hysteresis and cracking. The situation is worse near a triple point, where more than two phases are involved. The well-known metal-insulator transition in vanadium dioxide, a popular candidate for ultrafast optical and electrical switching applications, is a case in point. Even though VO2 is one of the simplest strongly correlated materials, experimental difficulties posed by the first-order nature of the metal-insulator transition as well as the involvement of at least two competing insulating phases have led to persistent controversy about its nature. Here we show that studying single-crystal VO2 nanobeams in a purpose-built nanomechanical strain apparatus allows investigation of this prototypical phase transition with unprecedented control and precision. Our results include the striking finding that the triple point of the metallic phase and two insulating phases is at the transition temperature, Ttr = Tc, which we determine to be 65.0 ± 0.1 °C. The findings have profound implications for the mechanism of the metal-insulator transition in VO2, but they also demonstrate the importance of this approach for mastering phase transitions in many other strongly correlated materials, such as manganites and iron-based superconductors.


A case of macrocystic-type serous cystic neoplasm with repeated pancreatitis within a short period of time.
The patient was a 39-year-old woman in whom computed tomography (CT) in 201X had revealed a pancreatic cystic neoplasm (PCN) of 4.3 cm in diameter in the pancreatic body. In June 201X + 3, the patient consulted our hospital regarding severe acute pancreatitis. The condition improved through treatment with large-volume fluid replacement and continuous regional arterial infusion therapy. Thereafter, acute pancreatitis recurred twice, in November 201X + 3 and in January 201X + 4. During an 8-month period, acute pancreatitis occurred three times. The PCN was examined by endoscopic ultrasound, thin-slice contrast-enhanced CT, and T2-weighted magnetic resonance imaging, which led to the diagnosis of macrocystic-type serous cystic neoplasm (SCN). The SCN was found to be 5.8 cm in diameter with dilatation of the main pancreatic duct (MPD) caudal to the SCN for 3 years. We suspected that the repeated pancreatitis had been obstructive pancreatitis resulting from displacement of the MPD caused by the SCN, and therefore recommended that the patient undergo surgery for the SCN. In March 201X + 4, distal pancreatectomy was performed. In the resected specimen, a macrocystic-type SCN was diagnosed. No recurrence of acute pancreatitis has been observed postoperatively. A macrocystic-type SCN with repeated pancreatitis within a short period of time is rare.


Phytochelatin synthase is required for tolerating metal toxicity in a basidiomycete yeast and is a conserved factor involved in metal homeostasis in fungi.
Phytochelatin synthase (PCS) is an enzyme that catalyzes the biosynthesis of phytochelatin from glutathione. Phytochelatins protect cells against the toxic effects of non-essential heavy metals, such as cadmium, and hence growth is restricted in the presence of these metals in mutants in PCS-encoding genes. PCS genes from fungi have been characterized in only two species in the Ascomycota, and these genes are considered sparsely distributed in the fungal kingdom. A gene encoding a putative PCS was identified in Sporobolomyces sp. strain IAM 13481, a fungus that is a member of the Pucciniomycotina subphylum of the Basidiomycota. The function of this PCS1 gene was assessed by heterologous expression in the Ascomycota yeasts Saccharomyces cerevisiae and Schizosaccharomyces pombe, and by mutating the gene in Sporobolomyces. The gene is required for tolerance to toxic concentrations of non-essential cadmium as well as the essential metal copper. Pcs1 homologs in fungi and other eukaryotes have putative targeting sequences for mitochondrial localization: the S. pombe homolog was fused to green fluorescent protein and it co-localized with a mitochondrial dye. Evaluation of the presence or absence of PCS and PCS-like homologs in the genome sequences of fungi indicates that they have a wide distribution, and the absence in most Ascomycota and Basidiomycota (the Dikarya) species can be explained by a small number of gene losses. The ecology of the species within the fungi carrying putative PCS genes, the phenotypes of phytochelatin synthase mutants in two major fungal lineages, and the presence of homologs in many non-Dikarya lineages parallel what is seen in the plant and animal kingdoms. That is, PCS is a protein present early during the evolution of the fungi and whose role is not solely dedicated to combating toxic concentrations of non-essential metals.


A survey of radionuclide contents and radon emanation rates in building materials used in the U.S.
Building materials commonly used in the U.S. were surveyed for both radionuclide content and radon emanation rate. Particular emphasis was placed on concrete, for which samples from ten major metropolitan areas were measured. Gamma-ray spectroscopy techniques, as well as direct radon emanation measurements, were employed in this study. The results of this survey suggest that these materials are not the primary source of radon in typical U.S. houses.


Gene Therapy of the Peripheral Nervous System: Celiac Ganglia.
Gene therapy has played an integral role in advancing our understanding of the central nervous system. However, gene therapy techniques have yet to be widely utilized in the peripheral nervous system. Critical targets for gene therapy within the PNS are the neurons in sympathetic ganglia, which are the final pathway to end organs. Thus they are the most specific targets for organ-specific neuron modification. This presents challenges because neurons are not viscerotopically organized within the ganglia and therefore cannot be targeted by their location. However, organ-specific neurons have been identified in sympathetic ganglia of some species and this offers an opportunity for targeting and transducing neurons by way of their target. In fact, alterations in sympathetic neurons have had pathological effects, and transducing organ-specific sympathetic neurons offer an exciting opportunity to selectively modify sympathetic pathology. In this chapter, we describe a method to virally transduce the celiac ganglion (CG), a prevertebral sympathetic ganglion that innervates abdominal organs, with AAV serotypes 1 and 6; thereby, providing a potential avenue to modulate specific subsets of neurons within the celiac ganglion.


Competition between abiogenic and biogenic metal cations in biological systems: Mechanisms of gallium's anticancer and antibacterial effect.
Metal cations are key players in a plethora of essential biological processes. Over the course of evolution specific biological functions have been bestowed upon two dozen of (biogenic) metal species, some of the most frequently found being sodium, potassium, magnesium, calcium, zinc, manganese, iron, and copper. On the other hand, there is a group of less studied abiogenic metals like lithium, strontium and gallium that possess not known functions in living organisms, but, by mimicking the native ions and/or competing with them for binding to key metalloenzymes, may exert beneficial effect on humans in particular medical conditions. This review summarizes and critically examines the mechanisms of gallium's therapeutic action in anticancer and antibacterial therapies by exploiting the tools of molecular modeling and experimental biochemistry. These approaches allow for identifying key factors for Ga3+ beneficial effect such as the electrostatic interactions with the protein ligands, substrates or bacterial siderophores, intramolecular hydrogen bond formation, and pH and dielectric properties of the medium. Several intriguing questions concerning the gallium competition with the native ferric ion have found their answers.


Unplanned Reoperation After Trapeziometacarpal Arthroplasty: Rate, Reasons, and Risk Factors.
Trapeziometacarpal (TMC) arthritis is an expected part of ageing to which most patients adapt well. Patients who do not adapt to TMC arthritis may be offered operative treatment. The factors associated with reoperation after TMC arthroplasty are incompletely understood. The purpose of this study was to determine the rate of, the underlying reasons for, and the factors associated with unplanned reoperation after TMC arthroplasty. In this retrospective study, we included all adult patients who had TMC arthroplasty for TMC arthritis at 1 of 3 large urban area hospitals between January 2000 and December 2009. Variables were inserted into a multivariable Cox proportional hazards model to determine factors associated with unplanned reoperation, and the Kaplan-Meier curve was used to estimate and describe the probability of unplanned reoperation over time. Among 458 TMC arthroplasties, 19 (4%) had an unplanned reoperation; 16 of 19 (84%) for persistent pain and two-thirds within the first year. The multivariate Cox regression analysis showed that unplanned reoperation was independently associated with younger age, surgeon inexperience, and index procedure type. Surgeons should be aware as well as patients should be informed that as many as 4% are offered or request a second surgery, usually for persistent pain and often within the 1-year window when additional improvement is anticipated.


Soil macrofauna and nitrogen on a sub-Antarctic island.
The densities, diets and habitat preferences of the soil macrofaunal species on sub-Antarctic Marion Island (47°S, 38°E) are described. Their role in N cycling on the island is assessed, using a mire-grassland community as an example. Primary production on the island is high and this leads to a substantial annual requirement of nutrients by the vegetation. This requirement must almost wholly be met by mineralization of nutrient reserves in the organic matter. Rates of peat nitrogen mineralization mediated by microorganisms alone are much too low to account for rates of N uptake by the vegetation. Although soil macroinvertebrates, and bacteria represent a very small fraction of the total N pool, their interaction accounts for most of the peat N mineralization, as indicated by the amounts of inorganic N released into solution in microcosms. Extrapolation of the microcosm results shows that the soil macrofauna (mainly earthworms) stimulate the release of enough N from the mire-grassland peat to account for maximum N mineralization rates calculated from temporal changes in peat inorganic N levels and plant uptake during the most active part of the growing season. Considering that large numbers of mesoand microinvertebrates occur and must also contribute to nutrient mineralization, the soil faunal component is clearly of crucial importance to nutrient cycling on Marion Island. This is probably true of all sub-Antarctic islands.


Impact of formal family planning residency training on clinical competence in uterine evacuation techniques.
The goal of this study was to assess the impact of formal opt-out family planning training on clinical competence in uterine evacuation. Residents who participated in newly established, routine opt-out family planning training completed surveys before and after their rotations. The surveys asked residents to report clinical experience and competence in family planning. One hundred ninety-six pre- and postrotation questionnaires were collected for a total response rate of 63%. After completing the rotation, residents reported higher competence in medical abortion, manual uterine aspiration, electric uterine aspiration and dilation and evacuation (p<.001). Residents also reported increased clinical experience with methods of termination, postabortion contraception, including intrauterine contraception, ultrasound and perioperative pain management. Participation in a formal opt-out family planning rotation results in increased clinical exposure to family planning and in reported competence in pregnancy termination.


On Sanders, Trump, and rhinoceroses: Quantifying subjective construals helps predict political attitudes.
People with different worldviews may have different interpretations for the same object. Freedom fighters for some are terrorists for others; immigrants can be seen as a threat or being threatened. To incorporate differences in interpretations into quantitative models, I propose the construct of value-instantiating beliefs, or perceived consequences of actions for basic human values. I hypothesize that these beliefs moderate the relationship between personal values and attitudes. In a preregistered mixed-methods study (N = 2038) I assess personal value priorities, attitudes, and perceived consequences of four political behaviours. Beliefs about consequences of the behaviours differed with political affiliation: for example, liberals saw voting for Trump in light of negative consequences for universalistic values, while conservatives stressed positive consequences for self-direction and security. The moderation hypothesis was confirmed. Including value-instantiating beliefs in the models significantly improved the predictions of attitudes towards and intentions to perform the behaviours.


Accelerated removal of deferoxamine mesylate-chelated aluminum by charcoal hemoperfusion in hemodialysis patients.
Although deferoxamine mesylate (DFO) is effective in removing aluminum (Al) in hemodialysis patients, treatment with this drug is associated with a number of adverse effects. In order to limit the exposure of patients to DFO-Al complexes, the efficacy of colloidin-coated microencapsulated charcoal cartridges added in series to conventional dialyzers was investigated. The clearances of Al by the sorbent system were initially 116 +/- 4.7 mL/min, but decreased to 42.5 +/- 6.6 mL/min after 120 minutes of treatment. Thereafter, the Al clearances remained constant. In contrast, the Al clearances of the dialyzer were 29.5 +/- 1.8 mL/min initially and did not change during the treatment period. Both the percent and absolute decrease in Al levels after four hours of dialysis were greater with the dialyzers plus carbon cartridges than with the dialyzers alone. This resulted in an increase in the minimum net Al removal from 1,862 +/- 174 micrograms/treatment to 3,007 +/- 43 micrograms/treatment (P less than 0.05). Treatment with sorbent hemoperfusion should be considered in selected hemodialysis patients being treated with DFO for Al overload.


[Treatment of pharyngeal disease in general and pediatric practice].
Based on 1351 reports by 180 physicians, it was found that pediatricians and younger physicians conducted more diagnostic tests and judged a tonsillectomy as necessary less frequently than GP's, especially those without board certification, and older physicians.


Muscarinic pharmacology of the spinal cord of the neonatal rat in vitro.
The pharmacology of two muscarinic responses, recorded from the ventral roots of the spinal cord in the neonatal rat, have been compared: the depolarising response and the inhibition of the monosynaptic compound action potential (CAP). Pirenzepine was more potent than AF-DX 116 in antagonising the depolarising response. However, the potencies of these compounds indicated that this response may be mediated by neither M1 nor M2 (cardiac-like) receptors. The drug AF-DX 116 (1 microM), but not pirenzepine, selectively reduced the inhibitory effect. It is concluded that the receptors mediating these two responses are different.


Implementation of an outbreak response vaccination campaign with typhoid conjugate vaccine - Harare, Zimbabwe, 2019.
Typhoid fever is a public-health problem in Harare, the capital city of Zimbabwe, with seasonal outbreaks occurring annually since 2010. In 2019, the Ministry of Health and Child Care (MOHCC) organized the first typhoid conjugate vaccination campaign in Africa in response to a recurring typhoid outbreak in a large urban setting. As part of a larger public health response to a typhoid fever outbreak in Harare, Gavi approved in September 2018 a MOHCC request for 340,000 doses of recently prequalified Typbar-TCV to implement a mass vaccination campaign. To select areas for the campaign, typhoid fever surveillance data from January 2016 until June 2018 was reviewed. We collected and analyzed information from the MOHCC and its partners to describe the vaccination campaign planning, implementation, feasibility, administrative coverage and financial costs. The campaign was conducted in nine high-density suburbs of Harare over eight days in February-March 2019 and targeted all children aged 6 months-15 years; however, the target age range was extended up to 45 years in one suburb due to the past high attack rate among adults. A total of 318,698 people were vaccinated, resulting in overall administrative coverage of 85.4 percent. More than 750 community volunteers and personnel from the MOHCC and the Ministry of Education were trained and involved in social mobilization and vaccination activities. The MOHCC used a combination of vaccination strategies (i.e., fixed and mobile immunization sites, a creche and school-based strategy, and door-to-door activities). Financial costs were estimated at US$ 2.39 per dose, including the vaccine and vaccination supplies (US$ 0.79 operational costs per dose excluding vaccine and vaccination supplies). A mass targeted campaign in densely populated urban areas in Harare, using the recently prequalified typhoid conjugate vaccine, was feasible and achieved a high overall coverage in a short period of time.


Environmental control for fungal allergen exposure.
With our limited knowledge of the mold allergens, we must rely on common sense to reduce environmental exposure for patients who are allergic to mold. We understand that the first step is moisture control. Appropriate building design, keeping rainwater and ground water away from the interior, accomplishes this. In addition, the heating ventilation and air conditioning system must be appropriately designed and maintained. Functional maintenance of inside water sources such as free water from plumbing, appliances, and showers can prevent damaging leaks. Indoor humidity or water vapor must be controlled and maintained to prevent condensation on walls or in microenvironments, such as attics, bedrooms, basements, and beneath wall-to-wall carpeting. Few abatement trials have been published, but several suggest that such measures can reduce mold exposure.


Oxygen free radical scavengers decrease reperfusion injury in lung transplantation.
An in vivo canine model was used to assess the ability of an oxygen free radical scavenger to decrease reperfusion injury in lung transplantation. In 12 dogs, the left lungs were transplanted after they had been preserved for 24 hours at 4 degrees C after pulmonary artery flushing with modified Eurocollins solution. In 6 dogs, dimethylthiourea, a potent oxygen free radical scavenger, was added to the flush solution and was also given to the recipients just before reperfusion. In all animals, the contralateral pulmonary artery and bronchus were ligated and lung function was assessed for 12 hours or until death. Three dogs died prematurely in the control group, whereas only 1 dog died prematurely in the dimethylthiourea group. This resulted in a statistically significant difference in the average length of survival (p less than 0.05). Pulmonary artery and right atrial pressures were significantly lower in the dimethylthiourea group during the first 6 hours (p less than 0.05). Treatment with dimethylthiourea resulted in a significantly higher arterial oxygen tension at 4 hours, and intrapulmonary shunt tended to be lower. Thus, it would appear that dimethylthiourea has a protective effect on lungs preserved for 24 hours before transplantation in dogs.


Sarcopenia in Elderly Diabetic Patients: Role of Dipeptidyl Peptidase 4 Inhibitors.
Our study aimed to investigate the effect of dipeptidyl peptidase 4 inhibitors (DPP4-I) on sarcopenic parameters in elderly type 2 diabetic patients. All elderly diabetic patients were invited to present themselves at our outpatient Geriatric Centre to undergo to evaluation of glycemic, inflammatory, and sarcopenic parameters and to perform a meal test for glucagon-like peptide-1 analogue (GLP-1) activity evaluation. According to European Working Group on Sarcopenia in Older People (EWGSOP) criteria, sarcopenic parameters were assessed by bioelectrical impedance analysis (BIA) and Kern dynamometer and 4-m gait speed tests. All patients received standardized meals for the assessment of postprandial levels of GLP-1 activity. Data of 80 elderly diabetic patients treated with oral glucose-lowering drugs (DPP4-I or Sulfonylureas Group) for at least 24 months before enrollment were analyzed. The DPP4-I Group showed appropriate glycemic control, lower levels of inflammatory parameters, a significant and greater increase, during interprandial periods, of GLP-1 activity, and better sarcopenic parameters (fat-free mass, skeletal muscle mass, and related indices, muscle strength, and gait speed) compared with the Sulfonylureas Group. Univariate analysis showed that sarcopenic parameters correlated with glycemic control and with GLP-1 area under the curve values. Multivariate analysis confirms these relationships. The results are consistent with the hypothesis that DPP4-I use might have a positive effect on the loss of muscle mass and its function.


Fluctuations in Pharmacokinetics Profiles of Monoclonal Antibodies.
Monoclonal antibodies (mAbs) are a group of drugs with predicted slow linear and target-mediated distribution and elimination. Visual inspection of published pharmacokinetic profiles of mAbs frequently reveals plateaus in the distribution phase or an increasing concentration many days after a single intravenous dose. A question which has been left unanswered until now is whether mAbs undergo recirculation mechanisms. If so, then which mechanisms are crucial for the fluctuation in their pharmacokinetics profiles? What is the impact of such mechanisms on mAb absorption, distribution and elimination? Current commentary accounts for the fluctuation of mAbs concentrations based on different mechanisms, as well in different phases of their in vivo disposition. Current knowledge shows significant impact of mAbs lymphatic recirculation on characteristics of their pharmacokinetics profiles. Fluctuating or plateau phases in pharmacokinetic profiles of mAbs are a consequence of multiple simultaneously occurring recirculatory as well as adsorption/desorption processes rather than only slow, continuous elimination. Lymphatic recirculation as well as other mechanisms appears to be an obvious element of the mAbs disposition. Periodic changes in the key factors affecting mAbs disposition can be responsible for the unpredictable concentration peaks in absorption, distribution and the elimination phase.


Nutritional jejunostomy in esophagectomy for cancer, a national register-based cohort study of associations with postoperative outcomes and survival.
Insertion of a nutritional jejunostomy in conjunction with esophagectomy is performed with the intention to decrease the risk for postoperative malnutrition and improve recovery without adding significant catheter-related complications. However, previous research has shown no clear benefit and there is currently no consensus of practice. All patients treated with esophagectomy due to cancer during the period 2006-2017 reported in the Swedish National Register for Esophageal and Gastric Cancer were included in this register-based cohort study from a national database. Patients were stratified into two groups: esophagectomy alone and esophagectomy with jejunostomy. A total of 847 patients (45.27%) had no jejunostomy inserted while 1024 patients (54.73%) were treated with jejunostomy. The groups were comparable, but some differences were seen in histological tumor type and tumor stage between the groups. No significant differences in length of hospital stay, postoperative surgical complications, Clavien-Dindo score, or 90-day mortality rate were seen. There was no evidence of increased risk for significant jejunostomy-related complications. Patients in the jejunostomy group with anastomotic leaks had a statistically significant lower risk for severe morbidity defined as Clavien-Dindo score ≥ IIIb (adjusted odds ratio 0.19, 95% CI: 0.04-0.94, P = 0.041) compared to patients with anastomotic leaks and no jejunostomy. A nutritional jejunostomy is a safe method for early postoperative enteral nutrition which might decrease the risk for severe outcomes in patients with anastomotic leaks. Nutritional jejunostomy should be considered for patients undergoing curative intended surgery for esophageal and gastro-esophageal junction cancer.


Chest CT examinations in patients presenting with acute chest pain: a pictorial review.
Acute chest pain (ACP) is one of the most common presenting symptoms at the emergency department. The differential diagnosis is vast. To exclude life-threatening causes, radiologists encounter an increasing amount of thoracic computed tomography (CT) examinations including CT angiography of the heart and great vessels. The dual- and triple-rule CT examinations are currently implemented in clinical practice. We retrospectively identified chest CT examinations in the setting of acute chest pain in our hospitals and collected a variety of common and uncommon cases. In this pictorial essay, we present the most educative cases from patients who presented with acute chest pain in the emergency department of our hospitals and for whom a thoracic CT was ordered. When aortic emergencies, acute coronary syndrome, and pulmonary embolism are excluded, these cases may help the radiologist to suggest alternative diagnoses in the diagnostic challenge of acute chest pain. Teaching Points • The number of chest CT examinations for ACP is increasing.• Chest CT examinations may help suggesting alternative diagnosis in ACP.• Radiologists should be aware of the differential diagnosis of ACP.


Syphilitic coronary artery ostial stenosis resulting in acute myocardial infarction and death.
Cardiovascular abnormalities are well-known manifestations of tertiary syphilis infections. Most notable in this regard is syphilitic aortitis, which tends to result in aortic root dilatation and its associated complications. A less common manifestation of syphilitic aortitis is coronary artery ostial narrowing related to aortic wall thickening. Herein, we present the case of a 32-year-old female who died of a myocardial infarct due to coronary artery ostial stenosis secondary to syphilitic aortitis.


Influence of seasonal differences on semen quality and subsequent embryo development of Belgian Blue bulls.
Belgian Blue bulls are more susceptible to high temperature and humidity index (THI) than most other cattle breeds. Here, we investigated whether high ambient temperature during summer affected semen quality and subsequent embryo development in Belgian Blue cattle. For this purpose, semen samples were collected from six healthy mature Belgian Blue bulls in March (Low THI group; THI between 30.6 and 56.4) and August 2016 (High THI group; maximum THI of 83.7 during meiotic and spermiogenic stages of spermatogenesis; 14-28 days prior to semen collection) respectively. Motility, morphology, acrosome integrity, chromatin condensation, viability, and reactive oxygen species production were assessed for frozen-thawed semen. Moreover, the efficiency of blastocyst production from the frozen-thawed semen samples of the two groups was determined in vitro. Blastocyst quality was determined by assessing inner cell mass ratio and apoptotic cell ratio. Fresh ejaculates showed a higher sperm concentration in low THI when compared to the high THI group (P ≤ 0.05), whereas semen volume, subjective motility, and total sperm output were not affected (P > 0.05). In frozen-thawed semen, total and progressive motility, viability, and straight-line velocity were lower in high THI compared to the low THI group (P < 0.05), while H2O2 concentration, aberrant chromatin condensation, and abnormal spermatozoa were higher in the high THI group (P < 0.05). Blastocyst rates were significantly higher when low THI samples were used (P < 0.05). Moreover, the total cell number and trophectoderm cells were significantly higher (P < 0.05) in blastocysts derived from low THI samples, whereas the apoptotic cell ratio was significantly higher (P < 0.01) in blastocysts derived from high THI spermatozoa. In summary, our data show that elevated ambient temperature and humidity during summer can decrease the quality of frozen-thawed spermatozoa in Belgian Blue bulls and also affect subsequent embryo development.


Serum oestriol, oestrone and oestradiol concentrations during oral oestriol succinate treatment in ovariectomized women.
Serum oestriol, oestrone and 17 beta-oestradiol concentrations during oral oestriol succinate treatment were investigated in ovariectomized women. Either a single dose of 8 mg or two doses of 4 mg were given daily. With the second divided dosage the serum oestriol levels remained uniform. The oestriol concentrations were clearly higher than in the beginning or in the middle of the normal menstrual cycle in the fertile woman. With both treatment schemes the ratio E3/(E2 + E1) was clearly higher than before treatment and during the normal menstrual cycle. Oestriol succinate treatment lowered the ratio E1/(E2 + E3), which was rather similar to the one during normal menstrual cycle.


Impact of brown adipose tissue vascular density on body adiposity in healthy Japanese infants and children.
The importance of brown adipose tissue (BAT) is well recognized in healthy infants and children. However, information regarding age-related changes in BAT vascular density (BAT-d) and the impact of BAT-d on body adiposity are lacking. This study aimed to evaluate the normal values of BAT-d, factors influencing BAT-d, and the impact of BAT-d on body adiposity in healthy infants and children. This study included 240 participants (127 girls and 113 boys) aged 1 month to 5 years. The tissue total hemoglobin concentration in the supraclavicular region adjusted according to the subcutaneous adipose tissue thickness (SAT) ([total-Hb-Adj]sup) as BAT-d. SAT in the deltoid and interscapular regions (SATdel+int), the Kaup index (body weight [g]/height or length [cm]/height or length [cm] × 10) as body adiposity, and fertilization season were also measured. The [total-Hb-Adj]sup of boys was higher than that of girls (r = 0.277, p = 0.009). Younger children had a significantly higher Kaup index (r = 0.495, p < 0.001) and SATdel+int (r = 0.614, p < 0.001) than older children. Children who had higher [total-Hb-Adj]sup had a significantly lower Kaup index (r = 0.495, p = 0.037) and SATdel+int (r = 0.614, p < 0.001). The [total-Hb-Adj]sup, as a parameter of BAT-d, is negatively correlated with body adiposity in children aged 1 month to 5 years, and BAT might affect human obesity to a much greater extent than expected. To prevent or treat obesity in early childhood, the level of BAT-d should be considered when using a dietary intervention.


Separation of epithelial and immune cells from biopsy samples.
Celiac disease (CD) is a chronic and autoimmune disease that develops in genetically predisposed individuals upon exposure to dietary gluten. The availability of the target tissue for research has made it possible to identify alterations in the transcriptome and methylome in the celiac gut. However, gene expression and methylation is highly variable among different cell types, and separation of cellular populations in target tissue must be considered for the understanding of the specific cellular and immune responses to gluten. In this context, a few studies have demonstrated that focusing on an isolated cell population, novel candidate genes involved in the pathogenesis of the disease can be identified. Here, we describe a method to separate epithelial and immune cells from biopsy samples for DNA and RNA isolation. With minor variations, the same technique can be applied to other tissues and cell types.


Synthesis of fluorinated triphenylphosphonium analogs that improve cancer cell selectivity and in vivo detection.
Triphenylphosphonium (TPP+) compounds like mito-metformin (MMe) target cancer cells by exploiting their hyperpolarized mitochondrial membrane potential. Here, we present a protocol for synthesizing TPP+ analogs with selectivity for mammalian cancer cells, reduced toxicity, and quantifiability using fluorine-19 nuclear magnetic resonance (19F-NMR). We describe steps for treating mammalian cells with mitochondria-targeted compounds, treating and preparing mouse tissue with these compounds, and 19F-NMR detection of MMe analogs in cells and tissue. TPP+-conjugated metformin analogs include para-methoxy (pMeO-MMe) and para-trifluoromethyl MMe (pCF3-MMe) and meta-trifluoromethyl MMe (mCF3-MMe).


The narcissism and death of Yukio Mishima--from the object relational point of view.
The author discussed the life and work of Yukio Mishima from the object relational point of view. First, he described his brief life history, pointing out the four big identity crises in his life as his fierce struggles against the suicidal wishes were likely to enlarge within himself. Then, he suggested that Mishima had been in the state of part object relationship throughout his life. Thirdly, the important role of the body or bodies in his fantastic and real life was discussed as a manifestation of not merely autoerotic activities but also disturbances of the core of identity. Finally, the fragility of the intermediate area of experience which was thought to have eventually led him to the last action, the seppuku, was examined.


A rule-based seizure prediction method for focal neocortical epilepsy.
In the present study, we have developed a novel patient-specific rule-based seizure prediction system for focal neocortical epilepsy. Five univariate measures including correlation dimension, correlation entropy, noise level, Lempel-Ziv complexity, and largest Lyapunov exponent as well as one bivariate measure, nonlinear interdependence, were extracted from non-overlapping 10-s segments of intracranial electroencephalogram (iEEG) data recorded using electrodes implanted deep in the brain and/or placed on the cortical surface. The spatio-temporal information was then integrated by using rules established based on patient-specific changes observed in the period prior to a seizure sample for each patient. The system was tested on 316 h of iEEG data containing 49 seizures recorded in 11 patients with medically intractable focal neocortical epilepsy. For seizure occurrence periods of 30 and 50 min our method showed an average sensitivity of 79.9% and 90.2% with an average false prediction rate of 0.17 and 0.11/h, respectively. In terms of sensitivity and false prediction rate, the system showed superiority to random and periodical predictors. The nonlinear analysis of iEEG in the period prior to seizures revealed patient-specific spatio-temporal changes that were significantly different from those observed within baselines in the majority of the seizures analyzed in this study. The present results suggest that the patient specific rule-based approach may become a potentially useful approach for predicting seizures prior to onset.


Correlative study of sensory cell density and cochlear length in humans.
In the group of 50 cochlea from 28 men aged 38-73 years a great variability in the length of the cochlear duct was found ranging from 28.0 to 40.1 mm. The variability in the number of inner and outer hair cells is not so prominent and the same holds for the variability in density. Average densities of the inner and outer hair cells decrease with increasing cochlear length. However, the long cochleae have a greater number of hair cells which indicates that long cochleae have more sensory cells in a given frequency region.


[Age-related macular degeneration (AMD)--primary results "Bus-Tour'2011" action].
The aim of article is to sum up "Bus-Tour'2011" action concerning age-related macular degeneration (AMD). Between March 29 to May 28.2011 in 10 polish cities 7292 persons were examined. The ophthalmological examination were done in special bus with diagnostic equipment (Bausch & Lomb owner). In almost 19% (1355 persons), changes in eye fundus as age-related macular degeneration were found. Additionally in 324 persons (4,4%), ophthalmologists found some high suspicious AMD changes. Knowledge about AMD in polish population is very poor.


Phase I dose-escalation study of the thioxanthone SR271425 administered intravenously once every 3 weeks in patients with advanced malignancies.
This study was performed to determine the dose limiting toxicity (DLT), the recommended phase II dose and the pharmacokinetic profile for SR271425, given over 1 h every 3 weeks. The initial starting dose of SR271425 was 17 mg/m(2). Patient selection was based on common phase I criteria as well as additional cardiac criteria. Thirty-eight patients were accrued to 16 dose levels from 17 to 1,320 mg/m(2). Patient characteristics included 24 males and 14 females ages 35-78 with an Eastern Cooperative Oncology Group performance status of 0 (ten patients), 1 (27) and 2 (1). Tumor types were typical for a phase I study. The maximum administered dose was 1,320 mg/m(2) with two DLTs, both QTc grade 3 prolongation. No drug related hematological toxicity was noted. Grade 1 toxicities included rash, flushing, pruritus, weight loss, diarrhea, hypertension and fatigue. Grade 2 toxicities included yellow discoloration of the skin, nausea and vomiting. QTc prolongation and hyperbilirubinemia were the only grade 3 toxicities noted. No confirmed tumor response was observed; however, two patients had prolonged stable disease. Both C(end) and area under the plasma concentration-time curve increased in a dose related manner. Plasma drug concentrations declined in a biphasic manner with a mean terminal elimination half-life (t (1/2)) of 7.1 h (+/-1.3). There was no change in clearance or volume of distribution over the dose range studied. Due to cardiac toxicity occurring with both the parent compound, SR233377, as well as this analog, this series of agents was abandoned from further clinical development.


A steep dependence of inward-rectifying potassium channels on cytosolic free calcium concentration increase evoked by hyperpolarization in guard cells
Inactivation of inward-rectifying K+ channels (IK,in) by a rise in cytosolic free [Ca2+] ([Ca2+]i) is a key event leading to solute loss from guard cells and stomatal closure. However, [Ca2+]i action on IK,in has never been quantified, nor are its origins well understood. We used membrane voltage to manipulate [Ca2+]i (A. Grabov and M.R. Blatt [1998] Proc Natl Acad Sci USA 95: 4778-4783) while recording IK,in under a voltage clamp and [Ca2+]i by Fura-2 fluorescence ratiophotometry. IK,in inactivation correlated positively with [Ca2+]i and indicated a Ki of 329 +/- 31 nM with cooperative binding of four Ca2+ ions per channel. IK,in was promoted by the Ca2+ channel antagonists Gd3+ and calcicludine, both of which suppressed the [Ca2+]i rise, but the [Ca2+]i rise was unaffected by the K+ channel blocker Cs+. We also found that ryanodine, an antagonist of intracellular Ca2+ channels that mediate Ca2+-induced Ca2+ release, blocked the [Ca2+]i rise, and Mn2+ quenching of Fura-2 fluorescence showed that membrane hyperpolarization triggered divalent release from intracellular stores. These and additional results point to a high signal gain in [Ca2+]i control of IK,in and to roles for discrete Ca2+ flux pathways in feedback control of the K+ channels by membrane voltage.


Stimulatory effect of lactic acid bacteria from commercially available Nozawana-zuke pickle on cytokine expression by mouse spleen cells.
We investigated the effect of lactic acid bacteria (LAB) isolated from eight samples of commercially available Nozawana-zuke, a traditional Japanese pickle, on cytokine expression by mouse spleen cell cultures. The 12 isolated strains of LAB (Nz1-Nz12), which were identified as genus Lactobacillus or Leuconostoc by the API50CHL test, enhanced the expression of interferon (IFN)-gamma with 6 h of culture. Ten of these 12 LAB, particularly Nz8, enhanced interleukin (IL)-12 p40 expression. The actinase E- and Benzonase-treated or untreated cell wall fraction of Nz8 enhanced both IFN-gamma and IL-12 p40 expression, while the cell plasma fraction had little effect. In the presence of anti-toll like receptor 4 antibody, the effect of the cell wall fraction of Nz8 was significantly abrogated. These results suggest that some LAB from Nozawana-zuke have a T helper 1-type immunoenhancing effect.


Omega-3 fatty acids and individual variability in plasma triglyceride response: A mini-review.
Cardiovascular disease (CVD) is a leading cause of death worldwide. Supplementation with the marine omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is associated with lower CVD risk. However, results from randomized controlled trials that examine the effect of omega-3 supplementation on CVD risk are inconsistent. This risk-reducing effect may be mediated by reducing inflammation, oxidative stress and serum triglyceride (TG) levels. However, not all individuals respond by reducing TG levels after omega-3 supplementation. This inter-individual variability in TG response to omega-3 supplementation is not fully understood. Hence, we aim to review the evidence for how interactions between omega-3 fatty acid supplementation and genetic variants, epigenetic and gene expression profiling, gut microbiota and habitual intake of omega-3 fatty acids can explain why the TG response differs between individuals. This may contribute to understanding the current controversies and play a role in defining future personalized guidelines to prevent CVD.


Stimulators of megakaryocyte development and platelet production.
The range of known purified and cloned growth factors and their target cells within the megakaryocytic lineage is described. Data are reviewed outlining that megakaryocytopoiesis appears to be controlled at two levels: (i) by feedback control via circulating factors, and (ii) by factors within the marrow itself. Hypotheses are presented about the nature of thrombopoietin, its relationship to known growth factors, especially Interleukin-6 (IL-6), and the specificity of a thrombopoietic response following change in the circulating platelet mass.


Maternal behavior of primiparous females in inbred strains of mice: a detailed descriptive analysis.
In the present study, we compared the maternal and non-maternal behaviors of primiparous females in both the light and dark phases during 3 weeks postpartum in five inbred strains of mice (BALB/c, CBA/Ca, C3H/He, C57BL/6, and DBA/2) to examine the strain differences in the behaviors in detail. Generally, nursing postures (arched-back, blanket, and supine) and pup lickings (anogenital and body) occurred more frequently in the light phase, whereas nest building occurred more frequently in the dark phase. As pups grew, arched-back and blanket nursing, anogenital and body licking, and nest building decreased, but supine nursing slightly increased. The present results revealed strain-specific variations in maternal behavior. In general, BALB did not engage in maternal behavior very vigorously, but the other four strains actively did. The patterns of strain differences were not parallel between the subcomponents of nursing posture or pup licking. CBA showed more arched-back and supine nursing, and DBA showed more blanket nursing. C57 and CBA showed more anogenital licking, while C3H and DBA showed more body licking. Strain differences were also found for the changes across postpartum days in almost all behaviors. These findings provide information to examine the effects of genetic and environmental factors on the development of maternal behavior in mice.


Nd:YAG/Er:YAG dual laser vs. topical steroid to treat vulvar lichen sclerosus: study protocol of a randomized controlled trial.
Vulvar lichen sclerosus (LS) is a chronic debilitating inflammatory skin disease. Today, the gold standard is a life-long topical steroid treatment. Alternative options are highly desired. We present a study protocol of a prospective, randomized, active-controlled, investigator-initiated clinical trial comparing a novel non-invasive dual Nd:YAG/Er:YAG laser therapy with the gold standard for the management of LS. We recruited 66 patients, 44 in the laser arm and 22 in the steroid arm. Patients with a physician-administered clinical LS score ≥ 4 were included. Participants received either four laser treatments 1-2 months apart, or 6 months of topical steroid application. Follow-ups were planned at 6, 12, and 24 months. The primary outcome looks at the efficacy of the laser treatment at the 6-month follow-up. Secondary outcomes look at comparisons between baseline and follow-ups within the laser or the steroid arm, and comparisons between laser vs. steroid arm. Objective (LS score, histopathology, photo documentation) and subjective (Vulvovaginal Symptoms Questionnaire, symptom VAS score, patient satisfaction) measurements, tolerability, and adverse events are evaluated. The findings of this trial have the potential to offer a novel treatment option for LS. The standardized Nd:YAG/Er:YAG laser settings and the treatment regime are presented in this paper. NCT03926299.


Adult forensic age estimation using mandibular first molar radiographs: A novel technique.
To develop an independent procedure for estimating age for Indian individuals using radiographs of multi-rooted posterior teeth with accuracy needed in forensic age prediction. Orthopantomography (OPG) was obtained for 88 subjects. The subjects were divided into two sub sets; study subset (n = 60) which were used to find regression formula to calculate the age from pulp chamber height and test subset (n = 28) which were used to test the accuracy of this formula. There was a statistically significant strong correlation between chronological age and pulp chamber crown root trunk height ratio (r = -0.56; P = 0.000). The regression equation for estimating the age, derived from the study subset was estimated age = -100.920 (PCTHR) +55.415. (PCTHR is the pulp chamber crown root trunk height ratio). This equation was applied on the test subset and there was no significant difference between estimated ages and chronological ages (P = 0.639). The mean absolute error (MAE) was 6.96 years, which was within acceptable error limits for forensic age estimation (<±10 years). The procedure developed to estimate the age using height reduction in pulp chamber was found to be fairly accurate to perform forensic age prediction in Indian individuals.