Evaluating Paenibacillus odorifer for its potential to reduce shelf life in reworked high-temperature, short-time fluid milk products.
Rework is a common practice used in the dairy industry as a strategy to help minimize waste from processing steps or errors that might otherwise render the product unsaleable. Dairy processors may rework their high-temperature, short-time (HTST) fluid milk products up to code date (21 d) at a typical dilution rate of ≤20% rework into ≥80% fresh raw milk. Bacterial spores present in raw milk that can survive pasteurization and grow at refrigeration temperatures are often responsible for milk spoilage. However, the potential impact of growth and thermal resistance of organisms in reworked product has not been investigated. Our objective was to characterize growth, sporulation, and thermal resistance of Paenibacillus odorifer under conditions representative of extreme storage conditions (time and temperature) of reduced fat (2%) and chocolate milk to evaluate whether product containing rework would have a reduced shelf life. Commercial UHT-pasteurized 2% milk and chocolate milk were independently inoculated with 4 strains of P. odorifer at 1 to 2 log cfu/mL and stored at 4°C and 7°C for 30 d. Changes in P. odorifer cell densities were determined by standard serial dilution with spread plating on tryptic soy agar with yeast extract and incubation at 25°C for 48 h. Spore counts were determined following thermal treatment at 80°C for 12 min. Thermal resistance of a cocktail of P. odorifer in milk was determined after treatments at 63°C for 30 min and 72°C for 15 s. Strains of P. odorifer grew rapidly at 7°C and reached a maximum cell density of ~8 log cfu/g in both 2% and chocolate milk within 12 d. All strains grew more slowly at 4°C and had not reached maximum cell density by 21 d. With extreme temperature abuse (25°C, 24 h), P. odorifer will sporulate in milk; however, thermally resistant subpopulations, including spores, did not develop in milk at 4°C until after stationary phase was achieved (>24 d). Vegetative cells of P. odorifer were verified to be sensitive to pasteurization (>7 log reduction); therefore, P. odorifer would not be expected to contribute to reduced shelf life of fluid milk products containing rework, even with extended storage before rework.


Hand involvement in paraneoplastic syndrome: a case report.
Cutaneous paraneoplastic syndromes are skin and mucous membrane changes that are associated with cancer. We report a previously healthy 76-year-old man who developed marked finger and thumb contracture, pain, and hypersensitivity of both hands who was diagnosed subsequently as having gastric carcinoma with colonic metastasis. After the gastrointestinal tumors were resected the finger and thumb contracture lessened and the pain eased. Both the temporal relationship between the changes in the hand and the neoplasm and the improvement after resection suggest a paraneoplastic syndrome.


Evaluation of the serum virome in calves persistently infected with Pestivirus A, presenting or not presenting mucosal disease.
Bovine viral diarrhea virus 1, reclassified as Pestivirus A, causes an economically important cattle disease that is distributed worldwide. Pestivirus A may cause persistent infection in that calves excrete the virus throughout their lives, spreading the infection in the herd. Many persistently infected (PI) calves die in the first 2 years of life from mucosal disease (MD) or secondary infections, probably as a consequence of virus-induced immune depression. Here, high-throughput sequencing (HTS) was applied for evaluation of the total virome in sera of (i) PI calves displaying clinically apparent MD (n = 8); (ii) PI calves with no signs of MD (n = 8); and (iii) control, Pestivirus A-free calves (n = 8). All the groups were collected at the same time and from the same herd. Serum samples from calves in each of the groups were pooled, submitted to viral RNA/DNA enrichment, and sequenced by HTS. Viral genomes of Pestivirus A, Ungulate erythroparvovirus 1, bosavirus (BosV), and hypothetical circular Rep-encoding single-stranded DNA (CRESS-DNA) viruses were identified. Specific real-time PCR assays were developed to determine the frequency of occurrence of such viruses in each of the groups. The absolute number of distinct viral genomes detected in both PI calf groups was higher than in the control group, as revealed by higher number of reads, contigs, and genomes, representing a wider range of taxons. Genomes representing members of the family Parvoviridae, such as U. erythroparvovirus 1 and BosV, were most frequently detected in all the three groups of calves. Only in MD-affected PI calves, we found two previously unreported Hypothetical single-stranded DNA genomes clustered along with CRESS-DNA viruses. These findings reveal that parvoviruses were the most frequently detected viral genomes in cattle serum; its frequency of detection bears no statistical correlation with the status of calves in relation to Pestivirus A infection, since clinically normal or MD-affected/non-affected PI calves were infected with similar U. erythroparvovirus 1 genome loads. Moreover, MD-affected PI calves were shown to support viremia of CRESS-DNA viral genomes; however, the meaning of such correlation remains to be established.


Utility of stone volume estimated by software algorithm in predicting success of medical expulsive therapy.
We sought to assess the accuracy of using stone volume (SV) estimated with a software algorithm as a predictor for stone passage in a trial of medical expulsive therapy (MET). We identified patients with ureteral stones discharged from the emergency department on MET. Patients with infection, non-ureteral stones, or needing immediate surgical intervention were excluded. For each stone, longest dimension (LD) was recorded, and SV was estimated by a computed tomography (CT)-based region-growing (RG) algorithm and standard ellipsoid formula (EF). Stone passage within 30 days was assessed via electronic chart and followup phone call. Fifty-one patients were included for analysis (53±16.7 years, 24% female). The mean LD was 4.85±2.02 mm. The mean SV was similar by EF and RG (0.051±0.057cm3 vs. 0.049±0.052 cm3, p=0.28). Thirty-three (65%) patients passed their stone, while 18 (35%) did not. The mean LD for passed stones vs. failed passage was 4.1±1.7 mm vs. 6.2±1.8 mm (p=0.0002); the mean EF volume was 0.028±0.035 cm3 vs. 0.093±0.066 cm3 (p=0.00007); and the mean volume by RG was 0.028±0.027 cm3 vs. 0.088±0.063 cm3 (p=0.00005). The clinical utility of SV estimated by software algorithm as a predictor for success of MET has not previously been examined. We demonstrated that spontaneously passed stones had a significantly smaller volume than those requiring intervention. Further prospective studies are needed to validate these findings and establish volume thresholds for probability of stone passage.


Single center preliminary experience with hand-assisted laparoscopic resection of isolated renal cell carcinoma fossa recurrences.
Solitary metastasis to the renal fossa after radical nephrectomy for renal cell carcinoma is uncommon. We report the first series on hand-assisted laparoscopic excision for renal cell carcinoma fossa recurrences. We performed a retrospective review of patients who underwent hand-assisted laparoscopic excision of renal cell carcinoma fossa recurrence. Patients with distant metastasis or local lymph node or adrenal metastasis were excluded from analysis. We collected data on patient and tumor characteristics, nephrectomy and fossa mass excision procedures, and postoperative outcomes. Between 2001 and 2007, 5 patients underwent laparoscopic resection of a renal fossa recurrence. Mean time to recurrence after radical nephrectomy was 23 months (range, 5 to 46 months) and mean size of the renal fossa mass was 6 cm (range, 4.2 to 9.5 cm). The average operative time was 232 minutes (range, 150 to 300 minutes) and average estimated blood loss was 175 mL (range, 25 to 400 mL). One patient required conversion to open surgery. There were no postoperative complications and mean hospital stay was 4 days. With mean follow-up of 43 months, the cancer-specific and disease-free survival rates were 60% and 20%, respectively. Of the 4 patients who underwent complete resection, 2 died from metastatic disease at 13 and 56 months, 1 continues to have progressive metastatic disease at 69 months, and 1 remains free of any clinical evidence of metastatic disease or recurrence at 37 months. One patient who underwent incomplete resection as a result of inferior vena cava invasion continues to have progressive local and distant metastatic disease at 40-month follow-up. Hand-assisted laparoscopic excision of renal fossa recurrence after radical nephrectomy appears to be safe and effective for carefully selected patients.


Benign cystic nephroblastoma.
A benign cystic nephroblastoma in a 6-month-old boy is presented. Erroneous interpretation as malignant nephroblastoma led to unnecessarily aggressive therapy. There is no evidence of recurrence or metastatic disease 12 years after the initial resection. As shown in our case and in the others previously reported in the literature, benign cystic nephroblastoma represents a distinct clinicopathological entity which does not show malignant behavior.


Chronic Intranasal Insulin Does Not Affect Hepatic Lipids but Lowers Circulating BCAAs in Healthy Male Subjects.
Nonalcoholic fatty liver disease and elevated circulating branched-chain amino acids (BCAAs) are common characteristics of obesity and type 2 diabetes. In rodents, brain insulin signaling controls both hepatic triglyceride secretion and BCAA catabolism. Whether brain insulin signaling controls similar metabolic pathways in humans is unknown. Here we assessed if intranasal insulin, a method to preferentially deliver insulin to the central nervous system, is able to modulate hepatic lipid content and plasma BCAAs in humans. We conducted a randomized, double-blind, placebo-controlled trial at the Medical University of Vienna. We assessed if a chronic 4-week intranasal insulin treatment (40 IU, 4 times daily) reduces hepatic triglyceride content and circulating BCAAs in 20 healthy male volunteers. Hepatic lipid content was assessed noninvasively by 1H-magnetic resonance spectroscopy, and BCAAs were measured by gas chromatography mass spectrometry at defined time points during the study. Chronic intranasal insulin treatment did not alter body weight, body mass index, and hepatic lipid content but reduced circulating BCAA levels. These findings support the notion that brain insulin controls BCAA metabolism in humans. Thus, brain insulin resistance could account at least in part for the elevated BCAA levels observed in the insulin-resistant state.


Sono-electrolysis performance based on indirect continuous sonication and membraneless alkaline electrolysis: Experiment, modelling and analysis.
In the present study, experiments of membraneless alkaline sono-electrolysis are combined to a mathematical model describing the performance of a sono-electrolyzer based on the electrochemical resistances and overpotentials (activation, Ohmic and concentration) and the oscillation of the acoustic cavitation bubble, and its related sono-physical and sonochemical effects, as a single unit and within population. The study aims to elucidate the mechanism of action of acoustic cavitation when coupled to alkaline electrolysis, using a membraneless H-cell configuration and indirect continuous sonication (40 kHz, 60 We). The calorimetric characterization constituted the bridge between experimental results and the numerical and simulation approach, while the quantification of the rate of produced hydrogen both experimentally and numerically highlighted the absence of the contribution of sonochemistry, and explained the role of ultrasounds by the action of shockwaves and microjets. Finally, the energetic sono-physical approach allowed an estimation of the predominance of the shockwaves and microjets effects according to the bubble size distribution within the population corresponding to the acoustic conditions of the study. The resulting macroscopic effect in sono-electrolysis process has been assessed considering the induced degassing. A reduction in the fraction of electrodes' coverage by bubbles from 76% to 42% has been recorded, corresponding to a decrease of 7.2% in Ohmic resistance and 62.35% in bubble resistance.


Acute myocardial infarction due to an unruptured sinus of Valsalva aneurysm in a patient with Behçet's syndrome.
This report describes the case of a 45-year-old Korean female who had suffered from Behçet's syndrome for two years with a huge, unruptured aneurysm originating from the left coronary sinus. The aneurysm had caused myocardial and aortic insufficiency by compressing the proximal left anterior descending coronary artery. The orifice of the aneurysm was at the left coronary sinus, about 5 mm from the left main coronary ostium, and it was filled with organized thrombi. Surgical repair was performed by closing the entrance of the aneurysm with a Dacron patch and by implementing aortic valve repair and coronary artery bypass grafting. The patient's coronary flow was restored postoperatively, and all anginal symptoms disappeared.


Charge-based and charge-free molecular assemblies comprising π-extended derivatives of anion-responsive acyclic oligopyrroles.
Assemblies comprising anion complexes of π-extended oligopyrrole derivatives and counter cations, as well as those of anion-free receptor molecules, exhibited the formation of mesophases based on columnar structures using electrostatic and π-π interactions.


Unique characteristics of superoxide production by human eosinophils in eosinophilic states.
Eosinophils from patients with peripheral blood eosinophilia and human neutrophils from normal subjects and patients with neutrophilia produced superoxide anion (O2-) in vitro at similar rates in the absence of stimulation and exhibited comparably increased rates of O2- production during the initial 1 h of incubation with opsonized zymosan. In the presence of opsonized zymosan, the rate of O2- production by eosinophils was constantly high for 3 h, whereas the rate of production by neutrophils fell by more than 65% after 1 h. Consequently, the amount of superoxide produced by phagocytizing leukocytes was twofold higher for eosinophils than for neutrophils at 3 h. O2- production by cell-free sonicates of zymosan-stimulated eosinophils and neutrophils exhibited the same preference for NADPH over NADH. One mM sodium azide significantly decreased the generation of O2- by phagocytizing eosinophils, but lacked an effect on neutrophils. the prolonged release of O2- by eosinophils engaged in phagocytosis may contribute both to their unique microbicidal profile and to the capacity of eosinophils to injure host tissues in some eosinophilic syndromes.


[Intravenous midazolam-ketamine anaesthesia for closed reduction of forearm fractures in children: impact of additional axillary plexus anaesthesia].
The aim of this study was to compare ketamine requirements in children undergoing closed reduction of forearm fractures under midazolam-ketamine anaesthesia with or without axillary plexus anaesthesia. With hospital ethical committee approval, we retrospectively analyzed the records of children who received midazolam-ketamine anaesthesia in the years 2000-2001 (group A) and midazolam-ketamine anaesthesia combined with axillary plexus anaesthesia in the years 2002-2004 (group B) for closed reduction of forearm fractures. Requirements for ketamine and postoperative analgesics were noted. Groups were compared with the Mann-Whitney U-test or T-test and the chi2-test (p<0.05). A total of 455 children (group A 225/group B 230) were included in this study. The total amounts of ketamine were not statistically different between the two groups (p=0.154). However, ketamine requirements became less if the time interval between start of axillary plexus anaesthesia and start of intervention became more than 15 min (p<0.05). Patients in group B requested fewer analgesics in the postoperative period (p<0.01). In the clinical routine of an emergency department the combination of midazolam-ketamine anaesthesia with axillary plexus anesthesia for closed reduction of forearm fractures in children did not result in lower requirements of ketamine.


Interferon-alpha/beta receptor-mediated selective induction of a gene cluster by CpG oligodeoxynucleotide 2006.
Oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODN) are known to exert a strong adjuvant effect on Th1 immune responses. Although several genes have been reported, no comprehensive study of the gene expression profiles in human cells after stimulation with CpG ODN has been reported. This study was designed to identify a CpG-inducible gene cluster that potentially predicts for the molecular mechanisms of clinical efficacy of CpG ODN, by determining mRNA expression in human PBMC after stimulation with CpG ODN. PBMCs were obtained from the peripheral blood of healthy volunteers and cultured in the presence or absence of CpG ODN 2006 for up to 24 hours. The mRNA expression profile was evaluated using a high-density oligonucleotide probe array, GeneChip. Using hierarchical clustering-analysis, out of a total of 10,000 genes we identified a cluster containing 77 genes as having been up-regulated by CpG ODN. This cluster was further divided into two sub-clusters by means of time-kinetics. (1) Inflammatory cytokines such as IL-6 and GM-CSF were up-regulated predominantly 3 to 6 hours after stimulation with CpG ODN, presumably through activation of a transcription factor, NF-kappaB. (2) Interferon (IFN)-inducible anti-viral proteins, including IFIT1, OAS1 and Mx1, and Th1 chemoattractant IP-10, were up-regulated predominantly 6 to 24 hours after stimulation. Blocking with mAb against IFN-alpha/beta receptor strongly inhibited the induction of these IFN-inducible genes by CpG ODN. This study provides new information regarding the possible immunomodulatory effects of CpG ODN in vivo via an IFN-alpha/beta receptor-mediated paracrine pathway.


A genome-scale dynamic constraint-based modelling (gDCBM) framework predicts growth dynamics, medium composition and intracellular flux distributions in CHO clonal variations.
Optimizing mammalian cell growth and bioproduction is a tedious task. However, due to the inherent complexity of eukaryotic cells, heuristic experimental approaches such as, metabolic engineering and bioprocess design, are frequently integrated with mathematical models of cell culture to improve biological process efficiency and find paths for improvement. Constraint-based metabolic models have evolved over the last two decades to be used for dynamic modelling in addition to providing a linear description of steady-state metabolic systems. Formulation and implementation of the underlying optimization problems require special attention to the model's performance and feasibility, lack of defects in the definition of system components, and consideration of optimal alternate solutions, in addition to processing power limitations. Here, the time-resolved dynamics of a genome-scale metabolic network of Chinese hamster ovary (CHO) cell metabolism are shown using a genome-scale dynamic constraint-based modelling framework (gDCBM). The metabolic network was adapted from a reference model of CHO genome-scale metabolic model (GSMM), iCHO_DG44_v1, and dynamic restrictions were imposed to its exchange fluxes based on experimental results. We used this framework for predicting physiological changes in CHO clonal variants. Because of the methodical creation of the components for the flux balance analysis optimization problem and the integration of a switch time, this model can generate sequential predictions of intracellular fluxes during growth and non-growth phases (per hour of culture time) and transparently reveal the shortcomings in such practice. As a result of the differences exploited by various clones, we can understand the relevance of changes in intracellular flux distribution and exometabolomics. The integration of various omics data into the given gDCBM framework, as well as the reductionist analysis of the model, can further help bioprocess optimization.


Monocyte chemotactic protein-1, RANTES and macrophage migration inhibitory factor levels in gingival crevicular fluid of metabolic syndrome patients with gingivitis.
The aim of the present study was to determine gingival crevicular fluid (GCF) levels of monocyte chemotactic protein-1 (MCP-1), regulated on activation, normal T-cell expressed and secreted protein (RANTES) and macrophage migration inhibitory factor (MIF) in metabolic syndrome patients with gingivitis. Twenty metabolic syndrome patients with gingivitis (MSG), 20 MetS patients with clinically healthy periodontium (MSH), 20 systemically healthy subjects with gingivitis and 20 subjects who were both systemically and periodontally healthy were included. Periodontal and systemical parameters were recorded. GCF MCP-1, RANTES and MIF levels were assayed by enzyme-linked immunosorbent assay method. MSG and MSH groups had elevated blood pressure, triglyceride, waist circumference and fasting glucose values in comparison to gingivitis and healthy groups (P<0.0001). Clinical periodontal parameters were higher in MSG and gingivitis groups when compared to those of the MSH and healthy groups (P<0.0001). MCP-1 and RANTES levels (ng/mg total protein) of MSG group were higher than those of the MSH groups (P=0.005, P=0.0001, respectively). Also gingivitis group had higher MCP-1, RANTES and MIF levels compared to the healthy group (P=0.011, P=0.0001, P=0.011 respectively). The RANTES level of MSG group was significantly higher than those of the gingivitis group (P=0.01), but MCP-1 and MIF levels were similar in the MSG and gingivitis groups (P>0.05). Elevated levels of GCF RANTES in MetS patients with gingivitis might associate with the presence of increased gingival inflammation by MetS. Low-grade systemic inflammation associated with MetS and adipose tissue-derived RANTES might lead to altered GCF RANTES levels in the presence of gingival inflammation.


Error propagation in E. coli protein synthesis.
A new approach to the error catastrophe theory, proposed by Leslie Orgel, is presented here. Our model is a development of previous models, but differs in several respects: the overall activity is assumed to be dependent on the error level, the effect of errors in the translating system, giving rise to additional errors in the succeeding generation of products, is explicitly included as a special term in our model, and scavenging enzymes are assumed to break down and eliminate products with a loose structure. Their efficiency is dependent on the error level. The model also takes into account the dilution of incorrect ribosomes and enzymes, and is described by a time-dependence in terms of ribosome/enzyme generations. The model and the contribution to the time development are discussed in the light of experiments on E. coli treated with streptomycin.


Superoxide dismutases from larvae of the camel tick Hyalomma dromedarii.
Three superoxide dismutases (EC 126.96.36.199) (TLSOD1, TLSOD2 and TLSOD3) were purified from larvae of the camel tick Hyalomma dromedarii by ammonium sulfate precipitation, ion exchange and gel filtration columns. SDS-PAGE revealed that the subunit molecular masses of the SODs are 40±2 kDa, 67±1.5 kDa and 45±2.6 kDa for TLSOD1, TLSOD2 and TLSOD3, respectively. TLSOD1 and TLSOD2 are monomeric proteins, while TLSOD3 isoenzyme exhibits dimeric structure with native molecular mass of 90 kDa. The pI values are estimated at pH 8.0, pH 7.2 and pH 6.6 for the three SODs which displayed pH optima at 7.6, 8.0 and 7.8, respectively. CuCl(2) and ZnCl(2) increase the activity of TLSOD2 and TLSOD3, while MnCl(2) increases the activity of TLSOD1. KCN inhibits the activity of TLSOD2 and TLSOD3, while a remarkable resistance of TLSOD1 isoenzyme was detected. TLSOD1 is suggested to be a manganese containing isoenzyme while TLSOD2 and TLSOD3 are suggested to be copper/zinc-containing isoenzymes. These results indicate the presence of three different forms of SODs in the larval stage of camel tick. This finding will contribute to our understanding of the physiology of these ectoparasites and the development of non-traditional methods to control them.


CRISPR/Cas13a-Based MicroRNA Detection in Tumor-Derived Extracellular Vesicles.
MicroRNAs (miRNAs) in extracellular vesicles (EVs) play essential roles in cancer initiation and progression. Quantitative measurements of EV miRNAs are critical for cancer diagnosis and longitudinal monitoring. Traditional PCR-based methods, however, require multi-step procedures and remain as bulk analysis. Here, the authors introduce an amplification-free and extraction-free EV miRNA detection method using a CRISPR/Cas13a sensing system. CRISPR/Cas13a sensing components are encapsulated in liposomes and delivered them into EVs through liposome-EV fusion. This allows for accurately quantify specific miRNA-positive EV counts using 1 × 108 EVs. The authors show that miR-21-5p-positive EV counts are in the range of 2%-10% in ovarian cancer EVs, which is significantly higher than the positive EV counts from the benign cells (<0.65%). The result show an excellent correlation between bulk analysis with the gold-standard method, RT-qPCR. The authors also demonstrate multiplexed protein-miRNA analysis in tumor-derived EVs by capturing EpCAM-positive EVs and quantifying miR-21-5p-positive ones in the subpopulation, which show significantly higher counts in the plasma of cancer patients than healthy controls. The developed EV miRNA sensing system provides the specific miRNA detection method in intact EVs without RNA extraction and opens up the possibility of multiplexed single EV analysis for protein and RNA markers.


Effects of caffeinated versus decaffeinated energy shots on blood pressure and heart rate in healthy young volunteers.
To evaluate the effects of a caffeinated 5-hour Energy shot compared with a decaffeinated 5-hour Energy shot as assessed by changes in blood pressure and heart rate in healthy, nonhypertensive volunteers. Randomized, double-blind, controlled, crossover study. University campus. Twenty healthy volunteers. Subjects were randomized to receive either the caffeinated 5-hour Energy shot or the decaffeinated 5-hour Energy shot; after a washout period of at least 6 days, subjects were given the alternate energy shot. Systolic (SBP) and diastolic (DBP) blood pressures were recorded for each subject at baseline and at 1, 3, and 5 hours after consumption of the energy shot. Heart rate, adverse effects, and energy levels were also assessed. Mean ± standard deviation (SD) baseline SBP for all study subjects was 114.06 ± 11.30 mm Hg and DBP was 69.53 ± 7.63 mm Hg. Mean changes in SBP between the caffeinated arm and the decaffeinated arm at the 1- and 3-hour time points were significantly increased compared with baseline (mean ± SD 6.08 ± 7.71 mm Hg at 1 hour [p=0.001] vs 3.33 ± 6.99 mm Hg at 3 hours [p=0.042]). Similarly, mean DBP changes between the caffeinated arm and the decaffeinated arm were significantly increased at the 1- and 3-hour time points compared with baseline (mean ± SD 5.18 ± 8.38 mm Hg at 1 hour [p=0.007] and 5.43 ± 7.21 mm Hg at 3 hours [p=0.005]). Heart rate, adverse effects, and energy levels were similar between the two groups. Caffeinated energy shots significantly increased SBP and DBP over a 3-hour period compared with decaffeinated energy shots in healthy, nonhypertensive individuals.


The outward transport of axoplasmic noradrenaline induced by a rise of the sodium concentration in the adrenergic nerve endings of the rat vas deferens.
The adrenergic nerve endings of the rat vas deferens were loaded with 3H-(-)-noradrenaline; COMT was inhibited by the presence of 10 mumol/l U-0521, and all experiments were carried out with calcium-free solution. After 100 min of wash-out a neuronal efflux of tritium was obtained which remained constant with time (when expressed as fractional rate of loss; FRL); it contained more DOPEG than noradrenaline. The in vitro administration of reserpine-like drugs (reserpine and Ro 4-1284) increased the FRL of tritium, presumably because of an increase in the leakage of noradrenaline from storage vesicles; the efflux of DOPEG increased more than that of noradrenaline, and the ratio NA/DOPEG declined. Inhibition of the membrane ATPase (by omission of potassium from the medium or by the presence of 3 mmol/l ouabain) increased the FRL of tritium, presumably because of an increase in the net leakage of noradrenaline from the storage vesicles (as a consequence of the fall in the concentration of free axoplasmic noradrenaline; see below). Veratridine also increased the FRL of tritium, partly because of its known reserpine-like effect (Bönisch et al. 1983); in the presence of 1 mumol/l veratridine, the efflux of DOPEG increased. Irrespective of the presence or absence of reserpine or Ro 4-1284, inhibition of the membrane ATPase or the presence of veratridine (agents or procedures which increase the axoplasmic sodium concentration) always resulted in a brisk increase of the efflux of noradrenaline that was accompanied by a simultaneous decrease in the efflux of DOPEG (see above for one exception).(ABSTRACT TRUNCATED AT 250 WORDS)


Extent and impacts of winter breeding in the North American monarch butterfly.
Since the 1960s, scientists have observed the North American monarch butterfly (Danaus plexippus) continuing reproductive activities past the fall migration and into the winter months when the climate is mild. Recent work suggests that small populations of winter breeding monarchs are present in western and southeastern USA, as well as northwestern Mexico, with new winter breeding populations forming in areas where non-native milkweeds are planted. The year-round presence of milkweed plants and temperatures suitable for immature monarch development are vital factors allowing for winter breeding. Non-native milkweeds, in conjunction with novel barriers to migration, are likely contributing to the rise in winter breeding behavior. Warmer climates are already impacting milkweed phenology and range, possibly favoring winter breeding behavior. Similar pressures but different implications are expected for eastern and western winter breeding monarchs given the differences in the migration ecology, milkweed species, and climate changes in the two regions.


Germline variants in tumor suppressor FBXW7 lead to impaired ubiquitination and a neurodevelopmental syndrome.
Neurodevelopmental disorders are highly heterogenous conditions resulting from abnormalities of brain architecture and/or function. FBXW7 (F-box and WD-repeat-domain-containing 7), a recognized developmental regulator and tumor suppressor, has been shown to regulate cell-cycle progression and cell growth and survival by targeting substrates including CYCLIN E1/2 and NOTCH for degradation via the ubiquitin proteasome system. We used a genotype-first approach and global data-sharing platforms to identify 35 individuals harboring de novo and inherited FBXW7 germline monoallelic chromosomal deletions and nonsense, frameshift, splice-site, and missense variants associated with a neurodevelopmental syndrome. The FBXW7 neurodevelopmental syndrome is distinguished by global developmental delay, borderline to severe intellectual disability, hypotonia, and gastrointestinal issues. Brain imaging detailed variable underlying structural abnormalities affecting the cerebellum, corpus collosum, and white matter. A crystal-structure model of FBXW7 predicted that missense variants were clustered at the substrate-binding surface of the WD40 domain and that these might reduce FBXW7 substrate binding affinity. Expression of recombinant FBXW7 missense variants in cultured cells demonstrated impaired CYCLIN E1 and CYCLIN E2 turnover. Pan-neuronal knockdown of the Drosophila ortholog, archipelago, impaired learning and neuronal function. Collectively, the data presented herein provide compelling evidence of an F-Box protein-related, phenotypically variable neurodevelopmental disorder associated with monoallelic variants in FBXW7.


Solid volume fraction estimation of bone:marrow replica models using ultrasound transit time spectroscopy.
The acceptance of broadband ultrasound attenuation (BUA) for the assessment of osteoporosis suffers from a limited understanding of both ultrasound wave propagation through cancellous bone and its exact dependence upon the material and structural properties. It has recently been proposed that ultrasound wave propagation in cancellous bone may be described by a concept of parallel sonic rays; the transit time of each ray defined by the proportion of bone and marrow propagated. A Transit Time Spectrum (TTS) describes the proportion of sonic rays having a particular transit time, effectively describing the lateral inhomogeneity of transit times over the surface aperture of the receive ultrasound transducer. The aim of this study was to test the hypothesis that the solid volume fraction (SVF) of simplified bone:marrow replica models may be reliably estimated from the corresponding ultrasound transit time spectrum. Transit time spectra were derived via digital deconvolution of the experimentally measured input and output ultrasonic signals, and compared to predicted TTS based on the parallel sonic ray concept, demonstrating agreement in both position and amplitude of spectral peaks. Solid volume fraction was calculated from the TTS; agreement between true (geometric calculation) with predicted (computer simulation) and experimentally-derived values were R(2)=99.9% and R(2)=97.3% respectively. It is therefore envisaged that ultrasound transit time spectroscopy (UTTS) offers the potential to reliably estimate bone mineral density and hence the established T-score parameter for clinical osteoporosis assessment.


3,3',5'-Triiodothyronine (Reverse T3) in amniotic fluid and cord serum.
3,3',5'-triiodothyronine (reverse T3, rT3) was measured in 122 samples of amniotic fluid obtained between the 29th--40th weeks of gestation, and in the blood of 37 newborn and their mothers. The mean rT3 concentration in amniotic fluid was 0.769 +/- 0.47 ng/ml, with a slight decrease from the 29th--40th weeks of gestation which was not statistically significant. Because of the great scatter of rT3 concentrations in amniotic fluid, its estimation does not seem to be useful in prenatal diagnosis of hypothyroidism. The mean rT3 concentration in cord blood (2.62 ng/ml; range 1.4--4.9 ng/ml) was greatly elevated in comparison to the mean maternal level at delivery (0.34 ng/ml; range 0.08--0.69 ng/ml). The possible use of rT3 measurements in cord blood as a screening test for congenital hypothyroidism is discussed.


Effects of intracerebroventricular administration of 7-nitroindazole on tolerance to ethanol.
Previous studies have shown that nitric oxide (NO) is involved in the development of rapid tolerance to the motor incoordination produced by ethanol. In order to further investigate this involvement, three experiments were undertaken using the tilt-plane and the hypothermia tests. The first demonstrated that 7-nitroindazole (7-NI), a preferential neuronal NO synthase (nNOS) inhibitor, injected by intracerebroventricular (i.c.v.) route, blocked the development of rapid tolerance to ethanol-induced motor incoordination. This effect was prevented by i.c.v. injection of L-arginine. The second experiment showed that D-arginine did not influence the blockade of tolerance produced by 7-NI. The third experiment revealed that i.c.v. injection of 7-NI also blocked the development of tolerance to the hypothermic effect of ethanol. These results support the hypothesis that nNOS-derived NO participates in the development of rapid tolerance to ethanol.


Quantification of tetanus antitoxin in human sera. II. Comparison of counter-immunoelectrophoresis and passive haemagglutination with toxin neutralization in mice.
We described recently an improved counter-immunoelectrophoretic method for quantification of tetanus antitoxin. The toxin neutralization test in mice is considered to correlate well with protection in humans. In the present study, the correlation coefficient between the two methods was 0.89. Sera containing more than 7.0 I.U./ml could be quantified directly by counter-immunoelectrophoresis, while sera containing less tetanus antitoxin had to be concentrated prior to quantification. The passive haemagglutination test was also compared with the toxin neutralization test in mice. The correlation coefficient between the two methods was 0.76.


Spontaneous Eye-Blink Rate as an Index of Reward Responsivity: Validation and Links to Bipolar Disorder.
Extensive research supports the role of striatal dopamine in pursuing and responding to reward, and that eye-blink rate is a valid indicator of striatal dopamine. This study tested whether phasic changes in blink rate could provide an index of reward pursuit. This hypothesis was tested in people with bipolar I disorder (BD; a population with aberrations in reward responsivity), and in those without BD. Thirty-one adults with BD and 28 control participants completed a laboratory task involving effort towards monetary reward. Blink rate was recorded using eye-tracking at baseline, reward anticipation, and post-reward. Those in the BD group completed self-report measures relating to reward and ambition. Results showed that across all participants, blink rates increased from reward anticipation to post-reward. In the BD group, reward-relevant measures were strongly correlated with variation in blink rate. These findings provide validation for phasic changes in blink rate as an index of reward response.


Characteristics of Epstein-Barr virus transformed B cell lines from patients with Alzheimer's disease and age-matched controls.
The characteristics of B cell lines isolated from patients with Alzheimer's disease (AD) and age-matched controls were investigated after having been transformed by Epstein-Barr virus (EBV). After isolation of mononuclear blood cells and in vivo or in vitro EBV infection, 35 and 21 lymphoblastoid cell lines (LCLs) were generated from 19 patients with AD (mean age 79.4 years) and 21 age-matched controls (mean age 80.0 years), respectively. B lymphocytes from AD patients were immortalised more easily than those from controls; the percentage of in vitro EBV infected LCLs (B95-LCLs) obtained in the AD group was significantly higher (76.2% versus 33.3% in the control group) and the mean time required for establishment was significantly lower (20.2 and 21.9 days versus 26.7 and 60.9 days in the control group). The EBV receptor and surface immunoglobulin (Ig) analyses showed no difference between the two groups. The expression of Epstein-Barr early antigens (EA) and viral capsid antigens (VCAs) revealed a tendency to higher viral replication in LCLs from AD patients; however, VCA expression remained limited to a small number of cells and did not affect overall cell growth. Finally, qualitative and quantitative differences were observed in the pattern of Ig production. Whereas spontaneously established LCLs from AD patients were generally monoclonal (80% of LCLs versus 33% in the control group), B95-LCLs were all polyclonal and secreted more IgM and IgA than those from controls; the mean IgM level was significantly higher in B95-LCLs from the AD group. These results suggest that B cells derived from AD patients seemed to be less differentiated than cells from age-matched controls.


Artemisinin based combination therapy in travel medicine.
A steadily increasing number of Western travellers are exposed to malaria. Also, numbers of migrants from malarious areas are increasing. Fast and effective treatment options are needed to ensure effective malaria treatment in these groups in the future. Artemisinin combinations are well tolerated and have shown high efficacy in malaria endemic areas. Since 2001, 42 malaria endemic countries, 23 of them in Africa, have adopted artemisinin based combination therapies recommended by WHO. An additional 14 countries are in the process of changing their malaria treatment policy. Studies in non-immune travellers confirm a rapid parasite clearance time and very low rate of side effects. Outpatient clinics and hospitals in non-endemic countries should have standard operating procedures for diagnosing and managing patients with malaria. In this setting, artemisinin combinations should be available for treatment of uncomplicated malaria as they are clearly superior to any other oral antimalarial in their fast reduction of parasite biomass and in decreasing clinical symptoms. Also, they are the drugs of choice for travellers who are advised to carry stand-by emergency treatment during their journey.


Vegetative Dictyostelium cells containing 17 actin genes express a single major actin.
Although actin is highly conserved between different eukaryotic species, six tissue-specific actins have been characterised in higher vertebrates by complete amino acid sequence analysis (two cytoplasmic actins, two smooth muscle actins and two sarcomeric actins). Their tissue specificity suggests they may differ in some important although unknown physiological property. Actin expression in lower eukaryotes seems to be a simpler process than in higher eukaryotes since biochemical experiments have indicated only one major type in purified preparations from various species. However, Firtel et al. have isolated several recombinant plasmids containing sequences of Dictyostelium discoldeum DNA complementary to actin messenger RNA and have suggested that this unicellular slime mould may have 17 actin genes potentially giving rise to several different actins. We have, therefore, determined the complete amino acid sequence of actin from vegetative Dictyostelium cells. This sequence is unique and agrees with the DNA sequences of four actin genes for that region of the DNA, which is currently known. The protein sequence does not agree with the three other 'genes' and we discuss the possible expression of minor actin species.


A light and electron microscopic immunohistochemical study of vasoactive intestinal polypeptide- and substance P-containing nerve fibers along the cerebral blood vessels: comparison with aminergic and cholinergic nerve fibers.
Vasoactive intestinal polypeptide (VIP)- and substance P-containing nerve fibers were observed in the cerebral blood vessels using an immunohistochemical technique. VIP-containing nerve fibers distributed in a spiral pattern, similar to that of muscle cells. Under electron microscopic observation, VIP-immunoreactive terminals lay close to a muscle cell in the inner layer of the adventitia. In contrast, substance P-containing nerve fibers showed a meshwork pattern in the outer layer of the adventitia. Using both acetylcholinesterase (AChE) staining and VIP immunohistochemistry, AChE-positive and VIP-immunoreactive nerve fibers revealed almost the same distribution in the same specimen. The present data suggest that VIP-containing nerve fibers may play a role in the smooth muscle control of the blood vessels, whereas substance P-containing nerve fibers may not take part in muscle control.


Nanoparticles as labels of specific-recognition reactions for the determination of biomolecules by inductively coupled plasma-mass spectrometry.
Inductively coupled plasma - mass spectrometry (ICP-MS) is an essential tool for quantitative ultratrace elemental and isotopic determinations in the biological and biomedical fields. In addition, sensitive and multiplexed quantification of target biomolecules in biological fluids and single-cells by ICP-MS can be carried out using metal elements or their isotopes as labels of immunoreaction and hybridization specific-recognition reactions. Following similar strategies, the bioimaging of biomolecules in tissues and single-cells by laser ablation (LA)-ICP-MS can be also achieved. Sensitivity can be further increased by resorting to amplification strategies based on the use of labels containing several atoms of a given elemental (or isotopic) reporter, such as inorganic nanoparticles (NPs). In this review, we intend to highlight the progress achieved in this active research area. Following the introduction, a short report of the characteristics of the most relevant NPs used as labels of specific-recognition reactions for ICP-MS detection, as well as the most common labelling routes are given. Then, the applications of NPs-labelled detection probes used in combination with ICP-MS (either with liquid nebulization or LA sampling) for identification and determination of proteins and oligonucleotides in biological samples are thoroughly reviewed. In the conclusions section, the challenges faced and the expected advances in this topic are underlined.


Catheter ablation of atrial fibrillation in patients at low thrombo-embolic risk: efficacy and safety of a simplified periprocedural anticoagulation strategy.
To prevent thrombo-embolic (TE) events during ablation of atrial fibrillation (AF), warfarin is recommended in all patients irrespective of baseline TE risk. We evaluated the efficacy and safety of a simplified periprocedural anticoagulation strategy of aspirin (ASA) and low molecular weight heparin (LMWH) in patients at low TE risk. We collected data from 214 low TE risk patients (CHADS2 score ≤1 and no warfarin at baseline) undergoing pulmonary vein isolation. After discontinuation of ASA, periprocedural antithrombotic therapy consisted of therapeutic subcutaneous LMWH injections (nadroparin 1 mL/kg once daily) from 10 days before until 10 days after the procedure, followed by ASA in all patients. At the time of procedure, transesophageal echocardiography (TEE) was not performed on a routine basis. During the procedure, unfractionated heparin was administered to achieve an ACT between 350 and 400 seconds. Data on TE events (stroke or transient ischemic attack), cardiac tamponade/perforation, and major vascular access complications within 3 months after the procedure were collected. Mean CHADS2 was 0.3 ± 0.5. TEE was performed in 3% of patients. No periprocedural TE events occurred. No cardiac tamponade/perforation was observed. Major vascular access complications occurred in 3 patients (1.4%). No permanent injury was observed (0%). In selected low TE risk patients undergoing ablation for AF, a short period of periprocedural therapeutic anticoagulation with LMWH together with aspirin is an effective and safe strategy to prevent TE events. If confirmed in a randomized trial, this approach might simplify periprocedural antithrombotic management in ablation of selected AF patients.


A morphometric analysis of ischemic canine myocardium with and without reperfusion.
Progressive morphological changes have been quantitated in ischemic and control regions of canine hearts previously assessed biochemically and physiologically. Muscle strips removed after a 5 or 10-min occlusion of the left circumflex artery were compared to those removed after reperfusion for 20 or 60 min following 10 min occlusion and to those removed immediately from normal and sham-operated dogs. Decreased glycogen content and decreased mitochondrial matrix were observed in fibers from ischemic regions as early as 5 min after ligation. Changes in the mitochondrial volume fraction were calculated by the point counting method and changes in the number of lipid droplets per unit area were determined. Mitochondrial volume fractions in ischemic regions were not significantly higher when compared to control regions of the same hearts, and were similar to the values measured for 10 and 70-min sham-operated dogs. We conclude that in early acute ischemia considerable variability in the different control groups emerges with extensive sampling and must be considered in interpreting ultrastructural changes.


ABCA7-Associated Clinical Features and Molecular Mechanisms in Alzheimer's Disease.
Alzheimer's disease (AD) is the most common type of neurodegenerative disease and its pathogenesis is still unclear. Genetic factors are thought to account for a large proportion of the overall AD phenotypes. ATP-binding cassette transporter A7 (ABCA7) is one of the most important risk gene for AD. Multiple forms of ABCA7 variants significantly increase the risk of AD, such as single-nucleotide polymorphisms, premature termination codon variants, missense variants, variable number tandem repeat, mutations, and alternative splicing. AD patients with ABCA7 variants usually exhibit typical clinical and pathological features of traditional AD with a wide age of onset range. ABCA7 variants can alter ABCA7 protein expression levels and protein structure to affect protein functions such as abnormal lipid metabolism, amyloid precursor protein (APP) processing, and immune cell function. Specifically, ABCA7 deficiency can cause neuronal apoptosis by inducing endoplasmic reticulum stress through the PERK/eIF2α pathway. Second, ABCA7 deficiency can increase Aβ production by upregulating the SREBP2/BACE1 pathway and promoting APP endocytosis. In addition, the ability of microglia to phagocytose and degrade Aβ is destroyed by ABCA7 deficiency, leading to reduced clearance of Aβ. Finally, disturbance of lipid metabolism may also be an important method by which ABCA7 variants influence the incidence rate of AD. In the future, more attention should be given to different ABCA7 variants and ABCA7 targeted therapies for AD.


Prolidase deficiency: report of a second case with quantitation of the excessively excreted amino acids.
The second documented case of prolidase deficiency is presented. Clinical manifestations include chronic otitis media and sinusitis, dermatitis, and splenomegaly. Prolidase is undetectable in the white blood cells of the patient and near or less than the lower range of normal in each parent. The peptide chromatographic pattern of the urine is similar to that of the previously reported patient with prolidase deficiency. The quantity of amino acids excreted in urine per 24 hours is at least three times that of the upper range of normal (of these same amino acids) for the patients age group. More than 80% of the total amino acids excreted are in peptide form. The proline-to-hydroxyproline ratio suggests that the dipeptides are the catabolic products of other proteins in addition to collagen.


Survival of microvascular free flaps in mandibular reconstruction: A systematic review and meta-analysis.
Free tissue transfer is commonly used in the reconstruction of post-ablative defects of the mandible. Due to lack of statistical power, comparing the survival of various free flaps, even in large studies, is challenging. The purpose of this study was to perform a meta-analysis comparing the survival of the most commonly used free flaps for mandibular reconstruction. We searched PubMed, EMBASE, and SCOPUS for relevant studies. A meta-analysis using the Peto one-step odds ratio (OR) with 95% confidence intervals (CI) was used to compare the pooled survival of the most commonly used free flaps for mandibular reconstruction. Of the 25,303 studies reviewed, 17 were selected for data extraction. A total of 1,221 subjects received 1,262 free flaps. Sixty-five free flaps failed. The pooled survival of all free flaps used for mandibular reconstruction was 94.8%. The deep circumflex iliac artery (DCIA) flap was associated with a seven-fold increase in failure when compared to the radial forearm free flap (Peto OR 7.40; 95% CI 1.38, 39.75, P = 0.02). There was no difference in survival when comparing other commonly used free flaps. The results of this study suggest that free flap reconstruction of the mandible is highly successful. With the exception of the increased survival of the radial forearm when compared to the DCIA, there is no difference in recipient site survival when comparing various free flaps for mandibular reconstruction.


Vibrational spectroscopy of N-phenylmaleimide.
A combination of infrared, Raman and inelastic neutron scattering (INS) spectroscopies with density functional theory (DFT) calculations is used to provide a complete assignment of the vibrational spectra of N-phenylmaleimide and N-(perdeuterophenyl)maleimide. DFT is shown to give very good results for the frequencies and atomic displacements in the modes. These are used to generate INS spectra which are excellent agreement with the observed. The calculated infrared and Raman spectra are much less reliable, although this may be more of a presentation problem than a real failing.


Hypercholesterolemia induces regression in neointimal thickening due to apoptosis of vascular smooth muscle cells in the hamster endothelial injury model.
Hypercholesterolemia is a major risk factor in the development of atherosclerosis. Although matrix metalloproteinase may play a key role in plaque rupture, apoptosis of vascular smooth muscle cells (VSMCs), which is induced by cholesterol and its oxides may also contribute to instability and rupture of plaque. Thus, we investigated the roles of hypercholesterolemia in vascular remodeling following endothelial injury in the hamster femoral artery. The endothelium was injured by photochemical reaction between green light and the photosensitizer dye, Rose Bengal. Photochemical reaction is routinely used in our laboratory to produce endothelial injury without mechanical stretching in experimental animals. In normocholesterolemic hamsters (NCH), neointimal thickening gradually progressed within a 3-week observation period after endothelial injury. In hypercholesterolemic hamsters (HCH), neointimal thickening gradually progressed until the second week after endothelial injury. In contrast, at the third week neointimal thickening regressed and was thinner than that at the second week. There was no significant difference in in vivo proliferation of VSMCs detected by in vivo BrdU uptake between HCH and NCH. Apoptotic cells in the neointima and the media were observed in HCH from 2 to 4 weeks after endothelial injury, but not in NCH. At 2 weeks after endothelial injury, the numbers of TUNEL-positive VSMCs in HCH were significantly higher than those in NCH (neointima; 1.2 +/- 0.3 vs. 0.3 +/- 0.1%, P<0.05, media; 2.9 +/- 0.6 vs. 0.6 +/- 0.2%, P<0.01). Cholesterol deposit, which is detected by oil red O staining was observed in a neointimal or medial area in HCH, but not in NCH. These findings suggest that hypercholesterolemia with endothelial injury may induce VSMC apoptosis, followed by the regression of neointimal thickening, further hypercholesteremia might play a role in inducing plaque rupture through apoptosis of VSMC.


Expression of the ASV src gene in hybrids between normal and virally transformed cells: specific suppression occurs in some hybrids but not others.
Somatic cell hybrids have been made between clones of rat cells transformed by avian sarcoma virus and rat or mouse cells that are untransformed. Intraspecies hybrids were either predominantly morphologically normal or predominantly transformed, some clones that formed transformed intraspecies hybrids yielding normal interspecies hybrids. Untransformed hybrids usually showed no detectable alteration in the structure or location of the integrated provirus, but viral RNA and pp60src kinase activities were much reduced. No decrease in viral gene expression was seen in transformed hybrids. Thus hybrid suppression of viral transformation, mediated in trans by the untransformed parent, is a specific event that depends on both untransformed and transformed parental parameters.


How directed evolution reshapes the energy landscape in an enzyme to boost catalysis.
The advent of biocatalysts designed computationally and optimized by laboratory evolution provides an opportunity to explore molecular strategies for augmenting catalytic function. Applying a suite of nuclear magnetic resonance, crystallography, and stopped-flow techniques to an enzyme designed for an elementary proton transfer reaction, we show how directed evolution gradually altered the conformational ensemble of the protein scaffold to populate a narrow, highly active conformational ensemble and accelerate this transformation by nearly nine orders of magnitude. Mutations acquired during optimization enabled global conformational changes, including high-energy backbone rearrangements, that cooperatively organized the catalytic base and oxyanion stabilizer, thus perfecting transition-state stabilization. The development of protein catalysts for many chemical transformations could be facilitated by explicitly sampling conformational substates during design and specifically stabilizing productive substates over all unproductive conformations.


Beta gamma dimers of G proteins inhibit atrial muscarinic K+ channels.
It has been proposed that beta gamma dimers of signal-transducing G proteins mediate muscarinic activation of atrial K+ channels. We examined this hypothesis by testing the effects of beta gamma dimers from four sources (human erythrocytes, human placenta, bovine brain, and bovine retina) on single channel muscarinic K+ (K+[acetylcholine (ACh)]) currents in inside-out membrane patches of adult guinea pig atria. None of the four beta gamma dimer preparations stimulated K+[ACh] currents; on the contrary, each inhibited the currents whether the currents were activated with GTP alone (agonist-independent activity) or with GTP plus a muscarinic agonist (agonist-dependent activity). Detergents at concentrations used to suspend erythrocyte, brain, and placental beta gamma dimers had no effect by themselves, and detergents were not used with the retinal beta gamma dimers. We conclude that beta gamma dimers do not mediate stimulatory effects of the endogenous G protein that regulates the K+ channels. In fact beta gamma dimers appear to inhibit activation by the endogenous G alpha subunits. Further insight into the role of beta gamma dimers came from the observation that agonist-independent GTP-activated K+[ACh] currents were inhibited by beta gamma dimers at about one-tenth the concentration required to inhibit agonist-dependent activation. One possibility is that dimeric beta gamma may have a higher affinity for free alpha subunits than for alpha subunits associated with agonist-occupied receptors. Thus, in addition to the known requirement of beta gamma dimers for the interaction of alpha subunits with receptors, beta gamma dimers may also improve the signal-to-noise ratio for agonists by reducing agonist-independent background activities.


Efficacy of a standardized technique of trans-vaginal entry into the peritoneal cavity for post-hysterectomy vaginal vault suspension.
The aim of this paper is to describe the efficacy and safety of a standardized technique of trans-vaginal entry into the peritoneal cavity for post-hysterectomy vault prolapse and determine how well the pre-operative pelvic examination predicted successful peritoneal entry. A retrospective review of patients undergoing post-hysterectomy trans-vaginal apical suspensions using a standardized technique of peritoneal entry was employed in this study. A subset of patients underwent a standardized pre-operative evaluation to predict what organ was behind the vaginal cuff and posterior cul-de-sac. Peritoneal entry was attempted in 280 patients, and successfully achieved in 223(80%). One cystotomy and one proctotomy (0.3%) occurred during attempted entry. Of those who underwent the standardized pre-operative evaluation, peritoneal entry was successful 86% of the time when small bowel was predicted to lie behind the vaginal cuff or posterior cul-de-sac. Peritoneal entry can be safely achieved in the majority of post-hysterectomy prolapse patients. Pre-operative examination assists in predicting successful peritoneal entry.


Posterior urethral valves.
During the past decade some urologists and radiologists have doubted the existence of posterior urethral valves. It has been suggested that the primary lesion in patients thought to have urethral valves is bladder neck obstruction. During the past seven years we have seen an average of three new cases of posterior urethral valves per annum. In all cases the valves themselves, not the bladder neck, obstructed the urethra. The urologist may miss valves at urethroscopy, but use of the new fibreoptic endoscope has improved his chances of seeing them. Posterior urethral valves may not be demonstrated radiologically if the radiologist does not use a rapid recording device or if the patient does not micturate forcefully during micturating cystourethrography. Failure to detect the valves may lead to an erroneous diagnosis of bladder neck obstruction.


A clonogenic progenitor with prominent plasmacytoid dendritic cell developmental potential.
Macrophage and dendritic cell (DC) progenitors (MDPs) and common DC progenitors (CDPs) are bone marrow (BM) progenitors with DC differentiation potential. However, both MDPs and CDPs give rise to large numbers of conventional DCs (cDCs) and few plasmacytoid DCs (pDCs), implying that more dedicated pDC progenitors remain to be identified. Here we have described DC progenitors with a prominent pDC differentiation potential. Although both MDPs and CDPs express the macrophage colony stimulating factor (M-CSF) receptor (M-CSFR), the progenitors were confined to a M-CSFR(-) fraction, identified as Lin(-)c-Kit(int/lo)Flt3(+)M-CSFR(-), and expressed high amounts of E2-2 (also known as Tcf4) an essential transcription factor for pDC development. Importantly, they appeared to be directly derived from either CDPs or lymphoid-primed multipotent progenitors (LMPPs). Collectively, our findings provide insight into DC differentiation pathways and may lead to progenitor-based therapeutic applications for infection and autoimmune disease.


Pulmonary mycetoma caused by an atypical isolate of Paecilomyces species in an immunocompetent individual: case report and literature review of Paecilomyces lung infections.
The first case of pulmonary fungus ball caused by Paecilomyces species is reported. The diagnosis was established by isolation of the fungus in culture from specimens obtained by percutaneous transthoracic needle aspiration in an immunocompetent individual. The isolate was atypical, as it failed to produce fruiting structures on routine mycological media. Identification was achieved by sequencing polymorphisms of the internal transcriber spacer regions of the ribosomal DNA. The antifungal susceptibility profile was also determined. This report underscores the increasing importance of Paecilomyces species in human infections. Paecilomyces should be included among the etiological agents of pulmonary mycetoma.


Prevalence and genetic basis of tetracycline resistance in Vibrioparahaemolyticus isolates recovered from food products in Shenzhen, China during 2013 to 2021.
Understanding tetracycline resistance in Vibrio parahaemolyticus from food products is crucial for effective control measures against this foodborne pathogen. This study aimed to investigate the prevalence, evolution routes, and mechanism of transmission of tetracycline resistance in Vibrio parahaemolyticus isolates collected from food products in Shenzhen, China. A total of 2342 non-duplicate Vibrio parahaemolyticus were isolated from 3509 food samples during the period 2013-2021. Among these 2342 Vibrio parahaemolyticus strains, 530 (21.37 %) were resistant to tetracycline. These tetracycline-resistant Vibrio parahaemolyticus strains were mainly isolated from shrimp samples, with the highest resistance rate (46.9 %) observed in 2019. Phylogenetic and genomic analyses of 387 isolates carrying the tet genes revealed that five different types of tet genes (tet(34), tet(A), tet(B), tet(M), and tet(E)) were present. The tet(A) gene was the most common (65 % of isolates), while tet(E) and tet(M) genes were only detected in specific years. Although tet(A) is the most commonly detected gene, it only encodes resistance in a low percentage of strains (47/129). On the other hand, the resistance rate is highest in isolates carrying tet(B) (41/55). Interestingly, V. parahaemolyticus carrying the tet genes were not necessarily tetracycline-resistant, and vice versa. A total of six different types of plasmids and two transposable units were found to carry the tet genes. V. parahaemolyticus strains that harbored these plasmids were often resistant to multiple antibiotics, indicating that horizontal transfer of antibiotic resistance genes is common among V. parahaemolyticus strains. Our findings suggest a high prevalence of tetracycline resistance in Vibrio parahaemolyticus strains recovered from food products in Shenzhen, China. These results provide valuable insight into the evolution and transmission of tetracycline resistance in foodborne Vibrio parahaemolyticus isolates and highlight the need for effective control measures to prevent the spread of antibiotic resistance.


Effectiveness of an intraoral thermoformed splint with magnet device in patients with xerostomia and hyposalivation: A pilot study.
The aim of the study was to examine the effectiveness of intraoral thermoformed splint with a magnet device over a period of 3 months, that is, to assess acceptability of this method of treatment using both objective and self-reported measures. This study was designed as a prospective clinical pilot trial. 22 patients with xerostomia and hyposalivation were included. Xerostomia was assessed using a 4-question xerostomia questionnaire score and a test for unstimulated salivary flow rates. Evaluations were performed before the treatment and 3 months after the treatment using a thermoformed splint with a magnet device. There was a significant reduction in subjective symptoms after using a thermoformed splint with a magnet device for 3 months. For all 4 scored items, there was a statistically significant difference (P < .001) in median VAS scores before and 3 months after treatment. There was also a statistically significant difference in USFR before (0,15 ± 0,04 ml/min) and after treatment (0,24 ± 0,03 mL/min). Our findings indicate that the use of this device alleviated oral dryness and stimulated the function of the submandibular salivary gland. An intraoral thermoformed splint with a magnet device is safe, physiologically indifferent, useful, and effective in treating xerostomia and hyposalivation.


Hand Foot Syndrome Secondary to Low Dose Docetaxel.
Hand-foot syndrome (palmoplantar erythrodysesthesia or Burgdorf reaction), is a distinctive skin toxicity affecting the palms and soles after certain chemotherapeutic drugs. Docetaxel induced hand-foot syndrome is rare, dose-dependent adverse event. Here in we report a case of Docetaxel induced grade III hand-foot syndrome at low doses (75/m(2)).


Protein binding of ketamine and its active metabolites to human serum.
Ketamine is an anaesthetic agent extensively used in intensive care patients, and it has proved its efficacy in the management of burned patients. In these patients, alterations in serum protein binding occur that may have significant clinical implications. Scarce data were observed in the literature about the binding of ketamine to human plasma proteins, and no data about the binding of its active metabolites, norketamine (NK) and dehydronorketamine (DHNK) were found. In this study, protein binding of ketamine, NK and DHNK in human serum were determined using the ultrafiltration technique. The percentage of drug bound to serum proteins at 30 degrees C was found to be 69%, 60% and 50% for DHNK, ketamine and NK, respectively, while these percentages were 75%, 64% and 54% for DHNK, ketamine and NK respectively at 20 degrees C. The binding of ketamine and its metabolites was independent of drug concentration.


The relationship between spinal trabecular bone mineral content and iliac crest trabecular bone volume.
The relationship between spinal trabecular bone mineral density and iliac crest trabecular bone volume has been studied in 84 patients, 23 with primary osteoporosis, 19 with osteoporosis secondary to inflammatory bowel disease, and 42 with nonsteroid-treated rheumatoid arthritis. Spinal trabecular bone mineral density was measured in the first three lumbar vertebrae by quantitative computed tomography, and iliac crest trabecular bone volume was assessed histomorphometrically in sections from trans-iliac biopsies using computerized techniques. In all 84 patients, there was a significant positive correlation between the two measurements (r = 0.60, P less than 0.001). However, when the three patient groups were analyzed separately, a significant correlation was found in the group with secondary osteoporosis (r = 0.65, P less than 0.01) but not in the patients with primary osteoporosis (r = 0.07) or rheumatoid arthritis (r = 0.19). These results indicate that the relationship between spinal trabecular bone mineral density and iliac crest trabecular bone volume differs according to the underlying disease process, these differences possibly reflecting variations in skeletal patterns of bone loss in different types of osteoporosis.


Lomitapide for use in patients with homozygous familial hypercholesterolemia: a narrative review.
Lomitapide is a drug recently approved for the treatment of patients with homozygous familial hypercholesterolemia. In this article we discuss briefly the pharmacology of this drug followed by a comprehensive narrative review of the available preclinical and clinical data on its safety and efficacy. Only data published as full papers are presented, with the exception of one long-term open-label extension study, which is available only in abstract form.


Tachycardia and apparent sino-atrial block due to concealed sinus node re-entry.
The role of the middle intercaval area ("internodal pathway") in the genesis of atrial re-entry was studied using microelectrode techniques and the extrastimulus method in the rabbit heart. Following surgical interruption of the anterior and posterior internodal tracts, two patterns of re-entry were observed using the middle internodal pathway manifesting alternatively as tachy- and brady-arrhythmias. Re-entry which was produced by critically timed extrastimulation at the septal branch of the crista terminalis (CT) caused tachycardia reciprocating between the sinus node (SN) and intercaval area. Spontaneous re-entrant impulses were also observed, particularly following the addition of cedilanid (0.04 mg/L). In addition, in association with critical prolongation of conduction in the sino-septal area, premature discharge of the dominant pacemaker fibers was observed and resulted in the appearance of bradyarrhythmias. These were commonly manifest as bigeminy and trigeminy on the surface septal electrogram. Hence concealed sinus node re-entry could manifest itself as apparent sino-atrial block or sino-atrial re-entry tachycardia.


Adrenoceptor involvement in the cardiovascular responses to B-HT 920 in sinoaortic denervated rats.
1. A study was made relating the involvement of alpha-adrenoceptors in the cardiovascular responses to intracerebroventricular (i.c.v.) injection of B-HT 920, a clonidine-type drug, in conscious sham-operated and sinoaortic-denervated rats. 2. Wistar rats were used, 7 days after the sham operation or sinoaortic denervation. For i.c.v. injection of drugs, a guide cannula had been previously implanted in the left lateral ventricle. 3. In sham-operated rats, cardiovascular responses to B-HT 920 (10-60 microg) were increased blood pressure and bradycardia; but, in sinoaortic-denervated rats, after the pressor response, a decrease in blood pressure also was seen. The responses to this agent were greater in sinoaortic-denervated rats than in sham-operated animals. Treatment with the alpha2-adrenoceptor antagonist yohimbine (30 microg), the imidazoline receptor antagonist idazoxan (15 microg) and the alpha1A-adrenoceptor antagonist 5-methylurapidil (15 microg) blocked the responses to B-HT 920 (30 microg). The alpha1-adrenoceptor antagonist prazosin (15 microg) and the alpha1B-adrenoceptor antagonist chloroethylclonidine (100 microg) did not modify the responses to agonist. 4. Sinoaortic denervation enhances the cardiovascular responses to B-HT 920. Moreover, the effects of i.c.v. administration of B-HT 920 could be mediated by several types of brain receptors: imidazoline receptors and alpha1A- and alpha2-adrenoceptors.


Effects of prenatal phthalate exposure on thyroid hormone levels, mental and psychomotor development of infants: The Hokkaido Study on Environment and Children's Health.
Di (2-ethylhexyl) phthalate (DEHP) is commonly used phthalates and concerns of adverse effects of prenatal DEHP exposure on neonatal thyroid hormone (TH) and neurodevelopment are increasing. However, there is no report regarding association between prenatal DEHP exposure and infant neurodevelopment including TH levels in Japanese population. Thus the aim of present study was to evaluate the associations between prenatal DEHP exposure and mental and psychomotor development of infants 6 and 18months along with investigating influence on neonatal free thyroxine (FT4) and thyroid stimulating hormone (TSH) levels in the prospective birth cohort study. Maternal blood samples collected between 23 and 41weeks of gestation was analyzed for mono (2-ethylhexyl) phthalate (MEHP), metabolite of DEHP levels. Neonatal FT4 and TSH were obtained from mass screening data. Infant neurodevelopment was assessed by Bayley Scale of Infant Development second edition at 6 and 18month of age. For the final analysis, 328 participants were included. The median levels of maternal MEHP was 10.6ng/ml, neonatal TSH and FT4 was 2.20 μU/ml and 2.03ng/ml, respectively. We did not find any associations between prenatal DEHP exposure and neonatal TH levels or infant mental and psychomotor development at 6 and 18month. In this study, prenatal DEHP exposure did not show adverse effects on infant TH levels or mental and psychomotor development in early life stage. However, our previous study revealed negative effects of prenatal DEHP exposure on sex hormone levels, continuous investigation on neurodevelopment in later life in association with prenatal DEHP exposure is necessary.


Laparoscopic adrenalectomy --- is it any different in phaeochromocytoma and non-phaeochromocytoma?
Laparoscopic adrenalectomy (LA) for phaeochromocytoma is a feasible, safe and effective treatment. The effects of associated catecholamine release render LA more challenging, although with comparable morbidity to LA for other diseases of the adrenal gland. Data from case records of 44 patients who underwent LAs between May 2002 and May 2006 were analysed retrospectively. The patients were divided into a phaeochromocytoma group (Group I) and a non-phaeochromocytoma group (Group II). The aim of this study was to assess the operative course and outcome of LA in the two groups. The mean operating time and blood loss were slightly higher in LA for phaeochromocytomas compared to LA for other pathologies, but these differences were not statistically significant. The mean hospital stay was 3.84 days in both groups. The phaeochromocytoma group had a slightly higher complication rate of 21% compared to 12%. None of the procedures needed open conversion. A terminal hand assist was employed in two patients in Group I and one patient in Group II. Two patients with bilateral phaeochromocytoma had single stage bilateral LA. LA is feasible and effective in phaeochromocytoma. It is associated with a slightly longer operating time, more blood loss and complications when compared with non-phaeochromocytoma masses. LA can be done in a single operation for bilateral masses. Terminal hand assist is a viable and effective option for very large masses.


Molecular mechanisms for large conductance Ca2+-activated K+ channel activation by a novel opener, 12,14-dichlorodehydroabietic acid.
Our recent study has revealed that 12,14-dichlorodehydroabietic acid (diCl-DHAA), which is synthetically derived from a natural product, abietic acid, is a potent opener of large conductance Ca(2+)-activated K(+) (BK) channel. Here, we examined, by using a channel expression system in human embryonic kidney 293 cells, the mechanisms underlying the BK channel opening action of diCl-DHAA and which subunit of the BK channel (alpha or beta1) is the site of action for diCl-DHAA. BK channel activity was significantly enhanced by diCl-DHAA at concentrations of 0.1 microM and higher in a concentration-dependent manner. diCl-DHAA enhanced the activity of BKalpha by increasing sensitivity to both Ca(2+) and membrane potential without changing the single channel conductance. It is notable that the increase in BK channel open probability by diCl-DHAA showed significant inverse voltage dependence, i.e., larger potentiation at lower potentials. Since coexpression of beta1 subunit with BKalpha did not affect the potency of diCl-DHAA, the site of action for diCl-DHAA is suggested to be BKalpha subunit. Moreover, kinetic analysis of single channel currents indicates that diCl-DHAA opens BKalpha mainly by decreasing the time staying in a long closed state. Although reconstituted voltage-dependent Ca(2+) channel current was significantly reduced by 1 microM diCl-DHAA, BK channels were selectively activated at lower concentrations. These results indicate that diCl-DHAA is one of the most potent BK channel openers acting on BKalpha and a useful prototype compound to develop a novel BK channel opener.


[Therapy for angiomas of the oromaxillofacial region].
The AA, describe the treatment of the hemangiomas of the oral and maxillofacial district, on the light of the last acquisitions.


Hypertension in elderly people in a preventive health program.
Control of hypertension is increasingly being recognized as a significant component of any preventive health care program for the elderly because of the high prevalence of hypertension in this group and its impact on health, particularly cardiovascular diseases. This study evaluates the hypertension screening component in one of the oldest and largest health promotion programs for the elderly in the United States, the Preventive Health Care for the Aging Program (PHCAP) in California. Our findings show that 26.7% of PHCAP participants had hypertensive readings on examination. Of these, 20% had mild hypertension, 5.6% moderate hypertension, and 1.1% severe hypertension. Urban participants were more likely than rural participants to have hypertension. Of those with severe hypertension, living alone was a significant factor when controlling for other variables. Overall, 40.2% of the hypertensive patients were not aware of their hypertension, and whites and Hispanics were less aware than blacks of their hypertensive status. Men were also less aware than women. These findings suggest ways to improve hypertension control programs for healthy elderly people who are self-referred to community-based preventive health care programs.


Sex-based differences in effector cells of the adaptive immune system during Alzheimer's disease and related dementias.
Neurological conditions such as Alzheimer's disease (AD) and related dementias (ADRD) present with many challenges due to the heterogeneity of the related disease(s), making it difficult to develop effective treatments. Additionally, the progression of ADRD-related pathologies presents differently between men and women. With two-thirds of the population affected with ADRD being women, ADRD has presented itself with a bias toward the female population. However, studies of ADRD generally do not incorporate sex-based differences in investigating the development and progression of the disease, which is detrimental to understanding and treating dementia. Additionally, recent implications for the adaptive immune system in the development of ADRD bring in new factors to be considered as part of the disease, including sex-based differences in immune response(s) during ADRD development. Here, we review the sex-based differences of pathological hallmarks of ADRD presentation and progression, sex-based differences in the adaptive immune system and how it changes with ADRD, and the importance of precision medicine in the development of a more targeted and personalized treatment for this devastating and prevalent neurodegenerative condition.


Noradrenergic reinnervation of the rat vas deferens after vasovasostomy following vasectomy.
1. Anastomosis (vasovasostomy) of epididymal and prostatic halves of vasa deferentia was carried out in rats in which unilateral or bilateral medial transection (vasectomy) had been performed 4 weeks previously. 2. Noradrenaline levels in epididymal halves of vasa deferentia, 8 weeks after anastomosis with prostatic halves, were approximately 40% of those in epididymal halves of contralateral, unoperated vasa deferentia. Catecholamine fluorescence was partially restored after anastomosis. 3. Responses of epididymal halves of transected vasa deferentia to electrical field stimulation (1 ms, 60 V, 10 pulses at 0.01-50 Hz) were partially restored 8 and 15 weeks after anastomosis. 4. Noradrenaline was equipotent in causing contraction of epididymal halves of unoperated and anastomosed vasa deferentia at 8 and 15 weeks after vasovasostomy. The ability of nisoxetine (0.1 mumol/l) to potentiate the effects of noradrenaline was partially restored by vas deferens repair. 5. Noradrenaline levels and neurotransmission in prostatic halves of vasa deferentia were relatively unaffected by vasectomy and subsequent vasovasostomy. 6. Fertility was restored 4-8 weeks after bilateral anastomosis performed in a group of eight rats 4 weeks after bilateral vasectomy. 7. These observations show that in the rat the noradrenergic denervation of the epididymal segment of the vas deferens after medial transection is partially reversible by anastomosis 4 weeks later, and that full noradrenergic reinnervation of the organ is not essential for the return of fertility after vasectomy and vasovasostomy in this species.


Primary Intestinal Lymphangiectasia (Waldmann's Disease) Presenting with Chylous Effusions in a 15-Year-Old.
Primary Intestinal Lymphangiectasia (PIL) is a rare disease of unknown aetiology which presents in the paediatric age group with anasarca, diarrhoea, hypoproteinaemia, lymphoedema and chylous effusions. Tuberculosis, filariasis, chest trauma, malignancies and haematological disorders usually contribute to most cases of secondary lymphangiectasia and chylous effusions. We hereby describe a case of PIL presenting with chylous effusions which remained undiagnosed for eight years.


Effect of clozapine on psychological outcomes of caregivers of patients with treatment resistant schizophrenia.
There is limited information on caregiver outcomes of patients with treatment-resistant schizophrenia (TRS). This study aimed to evaluate the impact of short-term treatment with clozapine (i.e. 3 months) on caregiver burden, expressed emotions, caregiver abuse, and psychological morbidity among the caregivers in patients with TRS. 52 caregivers of patients with TRS were evaluated on the Family Burden Interview Schedule, Perceived Criticism Measure, Caregiver Abuse Screening Questionnaire, and General Health Questionnaire-12. Maximum caregiver burden was seen in the domain of disruption of routine family activities, and this was followed by the domains of disruption of family leisure, disruption of family interaction, and the effect on mental health on others. At the baseline assessment, three-fourth of the caregivers scored ≥12 on the objective burden. With 3 months of clozapine therapy, there was a significant reduction in the caregiver burden in all the domains of objective burden, subjective burden, and the global objective burden as per the clinician rating, in the expressed emotions as per both patients and the caregivers, caregiver abuse, and psychological morbidity among the caregivers. To conclude, this study suggests that caregivers of patients with TRS, experience significantly higher caregiver burden, and a large proportion of them suffer from psychological morbidity and indulge in expressed emotions and abuse of the patient. Treatment with clozapine for 3 months leads to a reduction in the caregiver burden, expressed emotions, caregiver abuse, and psychological morbidity among the caregivers.


Distribution of glyoxalase I (GLO) variants in Western Europe and the Indian subcontinent.
English, Italian (including Sardinian), and Spanish populations from Europe and Muslim, Hindu, Sikh, Punjabi, and other populations from the Indian subcontinent currently living either in Birmingham or in India were screened for electrophoretically detectable genetic variants of red cell glyoxalase I (GLO), and their frequencies were reported. All the western European populations investigated, including those reported, exhibited an incidence of close to 44% for the GLO1 gene. The frequency distribution of the GLO1 gene in various populations from the Indian subcontinent, in contrast, was found to range between 0.15 and 0.33. These observations suggest that the European populations in general are genetically more homogeneous than are the populations of the Indian subcontinent.


[Salicylic and jasmonic acids in regulation of the proantioxidant state in wheat leaves infected by Septoria nodorum Berk].
Influence of mediators of the signal systems of salicylic (SA) and jasmonic (JA) acids and their mixture on reactive oxygen species' (ROS) (superoxide radical O2*- and H2O2) generation and activity of oxidoreductases (oxalate oxidase, peroxidase and catalase) in leaves of wheat Triticum aestivum L. infected by Septoria leaf blotch pathogen Septoria nodorum Berk. has been studied. Presowing treatment of seeds by SA and JA decreased the development rate of fungus on wheat leaves. SA provided earlier inductive effect on production of O2*- and H2O2 compared with JA. The protective effect of the salicylic and jasmonic acids against Septoria leaf blotch pathogen was caused by activation of oxalate oxidase, induction of anion and cation peroxidases, and decrease of catalase activity. Ability of compounds to stimulate ROS in the plant tissues can be used as criteria for evaluation of immune-modulating activity of new substances for protection of the plants.


A large-area single-filament infrared emitter and its application in a spectroscopic ethanol gas sensing system.
Nondispersive infrared (NDIR) spectroscopy is an important technology for highly accurate and maintenance-free sensing of gases, such as ethanol and carbon dioxide. However, NDIR spectroscopy systems are currently too expensive, e.g., for consumer and automotive applications, as the infrared (IR) emitter is a critical but costly component of these systems. Here, we report on a low-cost large-area IR emitter featuring a broadband emission spectrum suitable for small NDIR gas spectroscopy systems. The infrared emitter utilizes Joule heating of a Kanthal (FeCrAl) filament that is integrated in the base substrate using an automated high-speed wire bonding process, enabling simple and rapid formation of a long meander-shaped filament. We describe the critical infrared emitter characteristics, including the effective infrared emission spectrum, thermal frequency response, and power consumption. Finally, we integrate the emitter into a handheld breath alcohol analyzer and show its operation in both laboratory and real-world settings, thereby demonstrating the potential of the emitter for future low-cost optical gas sensor applications.


Pelvic floor ultrasound evaluation in the diagnosis of exposure of synthetic implanted materials in the lower urinary tract.
To evaluate the diagnostic performance of pelvic floor ultrasound (PFUS) to recognize prosthetics exposure in the bladder and/or urethra in women with lower urinary tract symptoms (LUTS). A cross-sectional study evaluating patients with LUTS after mesh/sling surgery. PFUS was performed with both transvaginal (TVUS) and translabial (TLUS) approaches. A distance of 1 mm or less from the bladder and/or urethra was considered highly suspect for mesh exposure. After PFUS, patients underwent diagnostic urethrocystoscopy. A total of 100 consecutive women were analyzed. According to urethrocystoscopy, the rate of tape exposure in the lower urinary tract was 3%. PFUS showed 100% sensitivity and 98%-100% specificity in detecting lower urinary tract mesh exposure. The negative predictive value was 100% and the positive predictive value ranged from 33% to 50% for urethral and 100% for bladder exposure. PFUS represents an effective and reliable non-invasive screening test to exclude prosthetics exposure in the bladder and/or urethra in women with LUTS.


The identification and quantification of three new 6alpha-hydroxylated corticosteroids in human neonatal urine.
The 24 hours urines of six two days old fullterm newborn infants were investigated for polar corticosteroids. 6alpha-hydroxy-tetrahydrocortisone, 6alpha-hydroxy-20alpha-cortolone and 6alpha-hydroxy-20beta-cortolone were identified by gas chromatographic-mass spectrometric comparison of the urinary steroids to compounds synthesized previously. These 6alpha-hydroxylated corticosteroids as well as seven other polar corticosteroids were quantified by gas chromatography or mass fragmentography. It was shown that the newly identified steroids constituted a quantitatively important part of the neonatal urinary corticosteroids. The unconjugated- and glucuronic acid conjugated steroids were quantified separately. It was found that the extent of glucuronoconjugation decreased with increasing polarity of the steroid moiety.


Flor yeast immobilization in microbial biocapsules for Sherry wine production: microvinification approach.
Sherry wine is a pale-yellowish dry wine produced in Southern-Spain which features are mainly due to biological aging when the metabolism of biofilm-forming yeasts (flor yeasts) consumes ethanol (and other non-fermentable carbon sources) from a previous alcoholic fermentation, and produces volatile compounds such as acetaldehyde. To start aging and maintain the wine stability, a high alcohol content is required, which is achieved by the previous fermentation or by adding ethanol (fortification). Here, an alternative method is proposed which aims to produce a more economic, distinctive Sherry wine without fortification. For this, a flor yeast has been pre-acclimatized to glycerol consumption against ethanol, and later confined in a fungal-based immobilization system known as "microbial biocapsules", to facilitate its inoculum. Once aged, the wines produced using biocapsules and free yeasts (the conventional method) exhibited chemical differences in terms of acidity and volatile concentrations. These differences were evaluated positively by a sensory panel. Pre-acclimatization of flor yeasts to glycerol consumption was not successful but when cells were immobilized in fungal pellets, ethanol consumption was lower. We believe that immobilization of flor yeasts in microbial biocapsules is an economic technique that can be used to produce high quality differentiated Sherry wines.


Sarcopenia, osteoporosis and frailty.
Muscles and bones are intricately connected tissues displaying marked co-variation during development, growth, aging, and in many diseases. While the diagnosis and treatment of osteoporosis are well established in clinical practice, sarcopenia has only been classified internationally as a disease in 2016. Both conditions are associated with an increased risk of adverse health outcomes such as fractures, dysmobility and mortality. Rather than focusing on one dimension of bone or muscle mass or weakness, the concept of musculoskeletal frailty captures the overall loss of physiological reserves in the locomotor system with age. The term osteosarcopenia in particular refers to the double jeopardy of osteoporosis and sarcopenia. Muscle-bone interactions at the biomechanical, cellular, paracrine, endocrine, neuronal or nutritional level may contribute to the pathophysiology of osteosarcopenia. The paradigm wherein muscle force controls bone strength is increasingly facing competition from a model centering on the exchange of myokines, osteokines and adipokines. The most promising results have been obtained in preclinical models where common drug targets have been identified to treat these conditions simultaneously. In this narrative review, we critically summarize the current understanding of the definitions, epidemiology, pathophysiology, and treatment of osteosarcopenia as part of an integrative approach to musculoskeletal frailty.


Purine metabolism in microplasmodia of Physarum polycephalum.
The uptake and utilization of purine nucleosides and purines in microplasmodia of Physarum polycephalum were investigated. The results revealed a unique pattern, namely that exogenous purine nucleosides are readily taken up and metabolised, while free purine bases are hardly taken up. The pathways of incorporation have been elucidated in studies with whole cells and with cell-free extracts. The ribonucleosides (adenosine, inosine and guanosine) can be converted into ribonucleotides in two ways; either directly catalysed by a kinase or by a phosphorolytic cleavage to the free base (adenine, hypoxanthine and guanine respectively) which can then be activated by a purine phosphoribosyltransferase. Apparently the purine phosphoribosyltransferases do not react with exogenous purine bases. The deoxyribonucleosides (deoxyadenosine, deoxyinosine and deoxyguanosine) are also phosphorolysed by purine nucleoside phosphorylase to adenine, hypoxanthine and guanine respectively. A portion of deoxyadenosine is directly phosphorylated to dAMP. It appears that only a minor part of the soluble nucleotide pool can be synthesised from exogenous supplied nucleosides and that none of the deoxyribonucleosides specifically label DNA. There is no catabolism of the purine moiety. In agreement with the above findings, we have found that analoguees of purine nucleosides are more toxic than their corresponding purine base analogues.


Distribution in cesium chloride gradients of proteoglycans of chick embryo brain and characterization of a large aggregating proteoglycan.
Proteoglycans were extracted from 14-day chick embryo brains, which had been labelled in vitro with [35S]sulfate or 3H-labelled amino acids. 4.0 M guanidinium chloride (containing proteinase inhibitors) extracted 94% of the 35S-labelled glycoconjugates. Following cesium chloride equilibrium centrifugation, the proteoglycans in each fraction were characterized by chromatography on Sepharose CL-2B. The most dense fraction (D1), which contained no detectable non-proteoglycan proteins, contained a large, aggregating chondroitin sulfate proteoglycan in addition to small chondroitin sulfate and heparan sulfate proteoglycans. The less dense fractions (D2-D6) contained both small chondroitin sulfate and heparan sulfate proteoglycans. Removal of hyaluronate from the D1 sample by digestion with Streptomyces hyaluronidase in the presence of proteinase inhibitors showed that aggregation of the large chondroitin sulfate proteoglycan is hyaluronate-dependent. Aggregation was restored by re-addition of hyaluronate. Reduction and alkylation, which blocked aggregation of a cartilage A1 proteoglycan, did not interfere with aggregation of the large brain proteoglycan.


Predictors of clinical response of acid suppression in Chinese patients with gastroesophageal reflux disease.
Up to 40% of patients with gastroesophageal reflux disease fail to respond to proton pump inhibitor therapy. To determine predictors of clinical response of proton pump inhibitor therapy. Consecutive patients with gastroesophageal reflux disease were enrolled prospectively. All patients underwent upper endoscopy and 24-h multichannel intraluminal impedance and pH monitoring before receiving esomeprazole 20 mg b.i.d. for 2 months. Multivariate logistic regression analysis was used to determine the independent predictors of clinical response to proton pump inhibitor therapy. A total of 204 patients with typical reflux symptoms were recruited and screened. Among them 153 patients (mean age 46.3 ± 10.6 years, 51.0% female) completed all the examinations and were assigned to proton pump inhibitor therapy. Ninety-five patients (62.1%) responded to acid suppression after 2 months. Multivariate logistic analysis showed that the predictor for response was pathological distal esophageal acid reflux (P = 0.001). The factors associated with proton pump inhibitor therapy failure were the presence of irritable bowel syndrome alone (P = 0.006), depression (P = 0.005), and overlap of irritable bowel syndrome and functional dyspepsia (P = 0.002). The clinical response of acid suppression on gastroesophageal reflux disease could be predicted by clinical and pH parameters rather than impedance data.


Neurochemical changes in rat brain amines after short- and long-term inhibition of monoamine oxidase by a low dose of tranylcypromine.
The effects of short- and long-term administration of a low dose of tranylcypromine on brain and urine levels of several biogenic amines and on brain activity of monoamine oxidases (MAO) A and B were investigated. MAO-A and MAO-B were inhibited by greater than 85% on day 1, and this inhibition continued to increase over the course of the study (42 days). Levels of 5-hydroxytryptamine in brain continued to increase up to day 21 and did not decline from day 21 to day 42, and levels of tranylcypromine itself continued to increase up to day 42. Dopamine concentrations peaked at day 10 and were not significantly different from that value by day 42. Brain levels of tryptamine and beta-phenylethylamine showed dramatic elevations after the first dose of the drug and remained essentially unchanged from those high values throughout the course of the drug treatment. Brain and urine increases in tryptamine and beta-phenylethylamine showed similar patterns, whereas urinary 5-hydroxytryptamine excretion reached maximal levels earlier than did brain levels.