Thiadiazine thione derivatives as anti-leishmanial agents: synthesis, biological evaluation, structure activity relationship, ADMET, molecular docking and molecular dynamics simulation studies.
During last decades, 3,5-disubstituted-tetrahydro-2H-thiadiazine-2-thione scaffold remains the center of interest due to their ease of preparation, diverse range substituents at N-3 and N-5 positions, and profound biological activities. In the current study, a series of 3,5-disubstituted-tetrahydro-2H-thiadiazine-2-thiones were synthesized in good to excellent yield, and the structure of the compounds were confirmed by various spectroscopic techniques such as FTIR, 1H-NMR, 13C-NMR and Mass spectrometry, and finally evaluated against Leishmania major. Whereas, all the evaluated compounds (1-33), demonstrate potential leishmanicidal activities with IC50 values in the range of (1.30- 149.98 uM). Among the evaluated compounds such as 3, 4, 6, and 10 exhibited excellent leishmanicidal activities with IC50 values of (2.17 μM), (2.39 μM), (2.00 μM), and (1.39 μM), respectively even better than the standard amphotericin B (IC50 = 0.50) and pentamidine (IC50 = 7.52). In order to investigate binding interaction of the most active compounds, molecular docking study was conducted with Leishmania major. Further molecular dynamic simulation study was also carried out to assess the stability and correct binding of the most active compound 10, within active site of the Leishamania major. Likewise, the physiochemical properties, drug likeness, and ADMET of the most active compounds were investigated, it was found that none of the compounds violate Lipiniski's rule of five, which show that this class of compounds had enough potential to be used as drug candidate in near future.Communicated by Ramaswamy H. Sarma.


Determination of magnetic anisotropy constants and domain wall pinning energy of Fe/MgO(001) ultrathin film by anisotropic magnetoresistance.
It is challenging to determine domain wall pinning energy and magnetic anisotropy since both coherent rotation and domain wall displacement coexist during magnetization switching process. Here, angular dependence anisotropic magnetoresistance (AMR) measurements at different magnetic fields were employed to determine magnetic anisotropy constants and domain wall pinning energy of Fe/MgO(001) ultrathin film. The AMR curves at magnetic fields which are high enough to ensure the coherent rotation of magnetization indicate a smooth behavior without hysteresis between clockwise (CW) and counter-clockwise (CCW) rotations. By analyzing magnetic torque, the magnetic anisotropy constants can be obtained. On the other hand, the AMR curves at low fields show abrupt transitions with hysteresis between CW and CCW rotations, suggesting the presence of multi-domain structures. The domain wall pinning energy can be obtained by analyzing different behaviors of AMR. Our work suggests that AMR measurements can be employed to figure out precisely the contributions of magnetic anisotropy and domain wall pinning energy, which is still a critical issue for spintronics.


The influence of the spring activator on the mobility of the lower jaw in traumatically injured patients.
For functional rehabilitation and improvement of mandibular mobility, 14 patients with dislocated collum or collum fracture dislocations were treated with a spring activator after surgical-conservative treatment. With an interincisal distance of < 12 mm, therapy was started with a loop spring. The average age of the patients was 26.6 years. Eight patients showed additional traumatic injuries, 2 patients were seriously polytraumatically injured. The clinical investigations referring to the maximum mouth opening and maximal interincisal distance resulted in a good to very good functional rehabilitation in all cases. The average maximal interincisal distance of 31.7 mm at the beginning of the spring activator therapy could be increased to 47.3 mm. The largest increase of the maximal interincisal distance was observed after 4 weeks of therapy. The type of reaction, however, differed interindividually. Three patients showed a spontaneous improvement of the interincisal distance within the first 2 to 3 weeks of removal of intermaxillary fixation, whereas 7 patients showed no improvement or only slightly improved values until insertion of the spring activator. An enlargement of the interincisal distance could be achieved in almost every patient within a relatively short period of time despite a drastically reduced mouth opening. Consequently, because of its mode of action in the form of a neuromuscular influence, the spring activator is especially suitable for the functional rehabilitation of patients with fractures of the condylar process.


Intracranial microinfusion of pancreastatin elevates blood glucose, free fatty acids, and corticosterone in rats.
Pancreastatin, a novel peptide recently isolated from porcine pancreas, significantly inhibits insulin and somatostatin release and augments glucagon release from the isolated perfused rat pancreas. This implies a role for endogenous pancreatic pancreastatin in the regulation of blood glucose and free fatty acids, the two major metabolic fuels. Since many peptides have similar biological effects when administered centrally and peripherally, the effects of centrally administered pancreastatin on blood glucose and free fatty acids were examined in 3 studies. Corticosterone was also measured in two of these studies. Intraventricular microinfusion of pancreastatin significantly elevated blood glucose, free fatty acid, and corticosterone concentrations in a dose-related manner. None of these effects was seen after subcutaneous injection of the same doses. Centrally administered pancreastatin appears to produce its effects on glucose and free fatty acids through actions in the brain, and either the brain, the median eminence, and/or pituitary for corticosterone.


Structural and combinatorial constraints on base pairing in large nucleotide sequences.
In this paper we discuss the constraints and combinatorial problems of folding long RNA and single stranded DNA molecules into base paired structures. A computer code FOLD-A was designed to perform base pairing foldings of very long sequence chains and search for low energy configurations. The logic of the FOLD-A algorithm is described in some detail. The applications of FOLD-A to the A-protein gene of MS2 and the whole genome of the phi X 174 phage with over 5300 bases are discussed in the accompanying paper.


Cryptosporidium parvum: an emerging occupational zoonosis in Finland.
Cryptosporidiosis has increased in recent years in Finland. We aimed to identify risk factors for human cryptosporidiosis and to determine the significance of Cryptosporidium parvum as a causative agent. Based on notifications to the Finnish Infectious Disease Register (FIDR), we conducted a case-control study and genotyped Cryptosporidium species from patient samples from July to December 2019. We also retrieved the occupational cryptosporidiosis cases from 2011 to 2019 from the Finnish Register of Occupational Diseases (FROD). Of 272 patient samples analyzed, 76% were C. parvum and 3% C. hominis. In the multivariable logistic regression analysis of 82 C. parvum cases and 218 controls, cryptosporidiosis was associated with cattle contact (OR 81, 95% confidence interval (CI) 26-251), having a family member with gastroenteritis (OR 34, 95% CI 6.2-186), and spending time at one's own vacation home (OR 15, 95% CI 4.2-54). Of the cases, 65% had regular cattle contact. The most common gp60 subtypes identified were IIaA15G2R1 and IIaA13G2R1. In FROD, 68 recognized occupational cryptosporidiosis cases were registered in 2011-2019. C. parvum is the most common Cryptosporidium species found in humans in Finland and poses a moderate to high risk of occupational infection for people working with cattle. The number of occupational notifications of cryptosporidiosis increased between 2011 and 2019. Cryptosporidiosis should be recognized as an important occupational disease among persons working with livestock in Finland, criteria to identify occupational cryptosporidiosis need to be created, and occupational safety in cattle-related work should be improved.


[Metabolic structure of the restitution process following physical loads of a different character].
The result of biochemical and mathematical analysis of restitution processes after various exercises determined the phases of these processes and the interrelationship between metabolic structure of restitution and the character of exercise. Metabolic structure of restitution has some common traits in recovery period after non-fatiguing exercises and exercises causing a rapidly developing fatigue. In contrast, sharp changes of this structure occur after exercises causing a slowly developing exhaustion.


Efficient upconversion luminescence from Ba5Gd8Zn4O21:Yb(3+), Er(3+) based on a demonstrated cross-relaxation process.
Under 971 nm excitation, bright green and red emissions from Yb(3+)/Er(3+) co-doped Ba5Gd8Zn4O21 phosphor can be observed, especially the intense red emission in highly doped samples. The experimental results indicate that Ba5Gd8Zn4O21:Yb(3+), Er(3+) emits stronger upconversion luminescence than NaYF4:Yb(3+), Er(3+) under a low excitation power, and a maximum upconversion power efficiency of 2.7% for Ba5Gd8Zn4O21:Yb(3+), Er(3+) was achieved. More significantly, to explain the red emission enhanced with the dopant concentration, this paper presents a possible cross-relaxation process and demonstrates it based on the rate equation description and temporal evolution. In view of the strong upconversion luminescence, colour tunable ability and stable chemical nature, Yb(3+)/Er(3+) co-doped Ba5Gd8Zn4O21 phosphor could be an excellent candidate for efficient upconversion luminescence generation.


Early gallbladder visualization during Tc-99m RBC scintigraphy.
Gallbladder visualization has been described during delayed Tc-99m RBC blood pool imaging in patients with some combination of anemia, renal disease, and multiple recent blood transfusions. The authors present two cases of gallbladder activity that appeared 1 hour after the injection of Tc-99m RBCs in patients without renal or hematologic abnormalities.


A comparative evaluation of the small leucine-rich proteoglycans of pathological human intervertebral discs.
Proteoglycans are important to the functioning of the intervertebral disc. In addition to aggrecan there are the small leucine-rich proteoglycans (SLRPs). These are less common but in other locations their functions include collagen organisation, sequestering growth factors and stimulating inflammation. We have performed a comparative analysis of the SLRP core protein species present in intervertebral discs with various pathologies. Eighteen intervertebral discs from patients with scoliosis (n = 7, 19-53 years), degenerative disc disease (n = 6, 35-51 years) and herniations (n = 5, 33-58 years) were used in this study. Proteoglycans were dissociatively extracted from disc tissues and the SLRPs (biglycan, decorin, fibromodulin, keratocan and lumican) assessed by Western blotting following deglycosylation with chondroitinase ABC and keratanase. Intact SLRP core proteins and a number of core protein fragments were identified in most of the discs examined. Biglycan and fibromodulin were the most extensively fragmented. Keratocan generally occurred as two bands, one representing the intact core protein, the other a smaller fragment. The intact core protein of lumican was detected in all samples with fragmentation evident in only one of the older scoliotic discs. Decorin was less obvious in the disc samples and showed little fragmentation. In this cohort of pathological intervertebral discs, fragmentation of certain SLRP core proteins was common, indicating that some SLRPs are extensively processed during the pathological process. Identification of specific SLRP fragments which correlate with disc pathology may not only help understand their aetiopathogeneses, but also provide biomarkers which can be used to monitor disease progression or to identify particular disc disorders.


Evaluation of solvent/detergent-treated plasma safety and efficacy in orthotopic liver transplant and thrombotic thrombocytopenic purpura patients: A single center experience.
Solvent/detergent-treated, pooled plasma (SDP) is approved for use in orthotopic liver transplantation (OLT) and thrombotic thrombocytopenic purpura (TTP) patients; however, studies evaluating safety and effectiveness of SDP in these populations are limited. This prospective study included two cohorts: OLT patients (n = 40) who received either SDP (n = 20) or FFP (control group) (n = 20), and TTP patients (n = 20) who received either SDP (n = 10) or FFP (control group) (n = 10) throughout hospitalization. Medical, laboratory, and blood bank records were retroactively assessed for both cohorts for differences in clinical outcomes, laboratory values, and transfusion data from admission to discharge. In the OLT cohort, significant changes in AST and ALP were observed in the control group as compared to SDP (p < .05 each), and creatinine levels improved significantly in the SDP group as compared to the control group (p < .05) from admission to discharge. In the TTP cohort, platelet counts were significantly improved within the control and SDP groups from admission to discharge, but there were no significant differences between groups (p = .31). LDH levels improved between admission and discharge for both groups (70% decrease in the control group, p < .001, and 80% decrease in the SDP group, p = .001). There were no significant differences detected in clinical outcomes in either cohort. As evidenced by the lack of adverse events in either cohort and similar clinical outcomes, we conclude that SDP is comparable in safety and effectiveness to FFP in OLT and TTP patients. Further studies are needed to evaluate the potential for improved safety with SDP.


Enhancement of age-related increases in DNA I-compound levels by calorie restriction: comparison of male B-N and F-344 rats.
Caloric restriction (CR), known to extend median and maximum life spans, improve resistance to carcinogenesis, and significantly retard age-associated degenerative diseases in rodents, was previously reported to modulate levels of indigenous, age-dependent DNA modifications, called I-compounds, in male Brown-Norway (B-N) rats. Since profiles of these adduct-like derivatives are species-, strain-, sex-, and tissue-specific, we explored this apparent CR/I-compound relationship in a comparative study between male B-N and male Fischer 344 (F-344) rats, the latter having a shorter life expectancy and high incidence of renal disease. Control animals were fed NIH-31 diet ad libitum (AL), while the caloric intake of CR animals was limited to 60% of AL, starting at 3.5 months. Liver and kidney DNA from 1, 8, 12, 16, 24 (AL, CR), and 30 (CR only) month old rats was analyzed by 32P-postlabeling. Corresponding tissues from the two strains yielded similar DNA profiles. Total liver I-compound levels displayed 2.3-4.6-fold age-dependent increases from 1 to 24 months, and kidney values at 24 months were 5.2-8 times higher than those at 1 month. In both strains, I-compound levels of CR animals were higher, up to 2-fold, than in age-matched AL rats. Regression analyses indicated linear relationships between most CR relative adduct labeling values (both total and individual fractions) and age, whereas many AL values exhibited this type of link with log age. These findings confirm that a correlation exists between CR and I-compound levels, and, given the above physiological benefits of CR, indicate that I-compounds represent biomarkers of aging with potential utility in intervention studies.


[Functional disorders in the chronological progression of glaucoma].
Glaucomatous optic neuropathy is a complex process, which not only leads to destruction of the retinal ganglion cells but also negatively influences the third and fourth neurons. Therefore, in histological studies of glaucoma a significant cell loss in both the lateral geniculate nucleus and in the visual cortex could be detected. The involvement of the entire visual pathway in glaucoma leads to a variety of functional disturbances, which are presented in this overview. Besides the well-known visual field defects in glaucomatous optic neuropathy, additional disturbances occur in contrast sensitivity, color vision, stereo vision and increased sensitivity to glare. As a result, faces are less easily recognized , the reading speed is reduced, the location of objects is more complicated and the reaction rate decreases. All these alterations are increased with the progression of glaucomatous damage. The consequences of these visual impairments lead to an increasing social isolation and to an increased risk of falls and driving accidents, thereby significantly reducing the quality of life of glaucoma patients. Therefore, increasing awareness of these visual difficulties is necessary in the special care of patients with glaucoma and the domestic environment should be transformed accordingly.


Infantile seizures: infants are not just little children.
Seizure semiology in infants defies the typical characteristics and classification schemata that have been developed for older children and adults. A clear classification system is a necessary first step to facilitate proper diagnosis, choice of treatment, and determination of prognosis. This is an especially challenging task with seizures in infants. A semiologic system based upon simple descriptive terms has been proposed, which the neurologist and pediatrician will recognize as closer to clinical experience.


Joint analysis of longitudinal measurements and survival times with a cure fraction based on partly linear mixed and semiparametric cure models.
In a joint analysis of longitudinal quality of life (QoL) scores and relapse-free survival (RFS) times from a clinical trial on early breast cancer conducted by the Canadian Cancer Trials Group, we observed a complicated trajectory of QoL scores and existence of long-term survivors. Motivated by this observation, we proposed in this paper a flexible joint model for the longitudinal measurements and survival times. A partly linear mixed effect model is used to capture the complicated but smooth trajectory of longitudinal measurements and approximated by B-splines and a semiparametric mixture cure model with the B-spline baseline hazard to model survival times with a cure fraction. These two models are linked by shared random effects to explore the dependence between longitudinal measurements and survival times. A semiparametric inference procedure with an EM algorithm is proposed to estimate the parameters in the joint model. The performance of proposed procedures are evaluated by simulation studies and through the application to the analysis of data from the clinical trial which motivated this research.


Jarzynski equality for the transitions between nonequilibrium steady states.
Jarzynski equality [Phys. Rev. E 56, 5018 (1997)], which has been considered to be valid for the transitions between equilibrium states, is found to be applicable to the transitions between nonequilibrium stationary states satisfying certain conditions. Also numerical results confirm its validity. Its relevance for nonequilibrium thermodynamics of the operational formalism is discussed.


Non-Viral, Lipid-Mediated DNA and mRNA Gene Therapy of the Central Nervous System (CNS): Chemical-Based Transfection.
Appropriate gene delivery systems are essential for successful gene therapy in clinical medicine. Cationic lipid-mediated delivery is an alternative to viral vector-mediated gene delivery. Lipid-mediated delivery of DNA or mRNA is usually more rapid than viral-mediated delivery, offers a larger payload, and has a nearly zero risk of incorporation. Lipid-mediated delivery of DNA or RNA is therefore preferable to viral DNA delivery in those clinical applications that do not require long-term expression for chronic conditions. Delivery of RNA may be preferable to non-viral DNA delivery in some clinical applications, because transit across the nuclear membrane is not necessary and onset of expression with RNA is therefore even faster than with DNA, although both are faster than most viral vectors. Here, we describe techniques for cationic lipid-mediated delivery of nucleic acids encoding reporter genes in a variety of cell lines. We describe optimized formulations and transfection procedures that we previously assessed by bioluminescence and flow cytometry. RNA transfection demonstrates increased efficiency relative to DNA transfection in non-dividing cells. Delivery of mRNA results in onset of expression within 1 h after transfection and a peak in expression 5-7 h after transfection. Duration of expression in eukaryotic cells after mRNA transcript delivery depends on multiple factors, including transcript stability, protein turnover, and cell type. Delivery of DNA results in onset of expression within 5 h after transfection, a peak in expression 24-48 h after transfection, and a return to baseline that can be as long as several weeks after transfection. In vitro results are consistent with our in vivo delivery results, techniques for which are described as well. RNA delivery is suitable for short-term transient gene expression due to its rapid onset, short duration of expression and greater efficiency, particularly in non-dividing cells, while the longer duration and the higher mean levels of expression per cell that are ultimately obtained following DNA delivery confirm a continuing role for DNA gene delivery in clinical applications that require longer term transient gene expression.


Small surfactant-like peptides can drive soluble proteins into active aggregates.
Inactive protein inclusion bodies occur commonly in Escherichia coli (E. coli) cells expressing heterologous proteins. Previously several independent groups have found that active protein aggregates or pseudo inclusion bodies can be induced by a fusion partner such as a cellulose binding domain from Clostridium cellulovorans (CBDclos) when expressed in E. coli. More recently we further showed that a short amphipathic helical octadecapeptide 18A (EWLKAFYEKVLEKLKELF) and a short beta structure peptide ELK16 (LELELKLKLELELKLK) have a similar property. In this work, we explored a third type of peptides, surfactant-like peptides, for performing such a "pulling-down" function. One or more of three such peptides (L6KD, L6K2, DKL6) were fused to the carboxyl termini of model proteins including Aspergillus fumigatus amadoriase II (AMA, all three peptides were used), Bacillus subtilis lipase A (LipA, only L6KD was used, hereinafter the same), Bacillus pumilus xylosidase (XynB), and green fluorescent protein (GFP), and expressed in E. coli. All fusions were found to predominantly accumulate in the insoluble fractions, with specific activities ranging from 25% to 92% of the native counterparts. Transmission electron microscopic (TEM) and confocal fluorescence microscopic analyses confirmed the formation of protein aggregates in the cell. Furthermore, binding assays with amyloid-specific dyes (thioflavin T and Cong red) to the AMA-L6KD aggregate and the TEM analysis of the aggregate following digestion with protease K suggested that the AMA-L6KD aggregate may contain structures reminiscent of amyloids, including a fibril-like structure core. This study shows that the surfactant-like peptides L6KD and it derivatives can act as a pull-down handler for converting soluble proteins into active aggregates, much like 18A and ELK16. These peptide-mediated protein aggregations might have important implications for protein aggregation in vivo, and can be explored for production of functional biopolymers with detergent or other interfacial activities.


Hyperalgesia: an emerging iatrogenic syndrome.
Clinical reports suggest that opioids, intended to abolish pain, can unexpectedly produce hyperalgesia. This paradoxical effect may be mechanistically related to tolerance induced by increasing doses of opioids. Two case reports illustrate a syndrome characterized by increasing pain pursued by escalating opioid doses, which results in a worsening of the clinical picture. Several experimental data may help explain the course of this challenging clinical condition. In escalating opioid doses rapidly, a risk of opioid-induced hyperalgesia should be recognized, as higher doses of opioids may stimulate rather than inhibit the central nervous system by different mechanisms. Alternative procedures should be taken into consideration to break this cycle, should it occur. More data are needed to detect this condition, as currently no diagnostic information on specific markers, clinical or biochemical, exists.


Co-existence of ethanol-related respiratory and motivational learning processes based on a tactile discrimination procedure in neonatal rats.
In rats, high ethanol doses during early postnatal life exert deleterious effects upon brain development that impact diverse social and cognitive abilities. This stage in development partially overlaps with the third human gestational trimester, commonly referred to as the brain growth spurt period. At this stage in development, human fetuses and rat neonates (postnatal days [PD] 3-9) exhibit relatively high respiratory rates that are affected by subteratogenic ethanol doses. Recent studies suggest conditioned breathing responses in the developing organism, given that there are explicit associations between exteroceptive stimuli and the state of ethanol intoxication. Furthermore, studies performed with near-term rat fetuses suggest heightened sensitivity to ethanol's motivational effects. The present study was meant to analyze the unconditioned effects of ethanol intoxication and the possible co-occurrence of learning mechanisms that can impact respiratory plasticity, and to analyze the preference for cues that signal the state of intoxication as well as the effects of the drug, related with motor stimulation. Neonatal rats were subjected to differential experiences with salient tactile cues explicitly paired or not paired with the effects of vehicle or ethanol (2.0 g/kg). A tactile discrimination procedure applied during PDs 3, 5, 7, and 9 allowed the identification of the emergence of ethanol-derived non-associative and associative learning processes that affect breathing plasticity, particularly when considering apneic disruptions. Ethanol was found to partially inhibit the disruptions that appeared to be intimately related with stressful circumstances defined by the experimental procedure. Tactile cues paired with the drug's effects were also observed to exert an inhibitory effect upon these breathing disruptions. The level of contingency between a given tactile cue and ethanol intoxication also resulted in significant changes in the probability of seeking this cue in a tactile preference test. In addition, the state of intoxication exerted motor-stimulating effects. When contrasting the data obtained via the analysis of the different dependent variables, it appears that most ethanol-derived changes are modulated by positive and/or negative (anti-anxiety) reinforcing effects of the drug. As a whole, the study indicates co-existence of ethanol-related functional changes in the developing organism that simultaneously affect respiratory plasticity and preference patterns elicited by stimuli that signal ethanol's motivational effects. These results emphasize the need to consider significant alterations due to minimal ethanol experiences that argue against "safe" levels of exposure in a critical stage in brain development.


Soil-transmitted helminth infections after mass drug administration for lymphatic filariasis in rural southern India.
Targeted deworming is the current strategy for control of morbidity associated with soil-transmitted helminths (STH) among at-risk populations: preschool-aged children, school-aged children and women of childbearing age. We report the prevalence and intensity of STH in a district after lymphatic filariasis (LF) mass drug administration (MDA) in southern India where albendazole was co-administered from 2001. Children aged 2 to 15 years and adults (defined as ≥15 years) in a rural administrative block of Tamil Nadu were recruited using a probability proportional to size method. Stool samples were screened and eggs per gram (EPG) determined by Kato-Katz method. Multilevel logistic regression (MLR) and multilevel negative binomial regression (MNBR) analyses were used to identify factors associated with infection and intensity, respectively. Of 862 participants who provided samples, 60 (7.0%; 95% confidence interval (CI): 5.3-8.7) were positive for STH with a predominance of hookworm infections (n = 57, 6.6%; 95% CI: 5.0-8.3). Increasing age (odds ratio (OR): 1.09; 95% CI: 1.04-1.15) and regular usage of the toilet (OR: 0.32; 95% CI: 0.12-0.88) were independently associated with hookworm infection and age was significantly associated with increasing intensity of hookworm infection (infection intensity ratio (IIR): 1.28; 95% CI: 1.19-1.37). A brief review of STH prevalence in endemic settings before and after the stoppage of LF MDA indicated that, in most settings, a substantial reduction in STH prevalence is seen. Community-wide MDA in all age groups in these post-LF MDA districts with low prevalence and light intensity infections could result in transmission interruption of STH.


High-flux dialysis lowers plasma leptin concentration in chronic dialysis patients.
Leptin is a protein produced by fat cells and involved in body weight regulation. Plasma leptin is significantly higher in some hemodialysis (HD) patients than in normal controls. We examined the influence of dialyzer membrane biocompatibility and flux on elevated plasma leptin concentrations in hemodialysis patients. Employing a crossover design, leptin and tumor necrosis factor-alpha (TNF-alpha) levels were serially determined in eight chronic dialysis patients. Patients were dialyzed sequentially on low-flux cellulosic (TAF) dialyzers, low-flux (F8) polysulfone, high-flux (F80B) polysulfone, then low-flux polysulfone and cellulosic dialyzers again. Mean leptin concentrations were similar when low-flux polysulfone or cellulosic dialyzers were employed (141.9+/-24.2 microg/L versus 137.8+/-18.4 microg/L, respectively (P=NS). In contrast, leptin fell significantly on the high-flux polysulfone dialyzer (99.4+/-16.2 microg/L) compared with cellulosic (P < 0.005), and low-flux polysulfone dialyzers (P < 0.02). Leptin clearance by the high-flux polysulfone dialyzer was significantly higher than the low-flux dialyzers (50.4+/-21.5 v -9.6+/-10.3 mL/min; P=0.043), but did not account fully for the 30% decline in plasma leptin during the high-flux arm of the study. Concentrations of TNF-alpha were lower when high-flux polysulfone dialyzers were employed, but there was no correlation of individual TNF-alpha levels with leptin concentrations. High-flux dialysis lowers plasma leptin concentrations an average of 30%, but biocompatibility does not influence leptin levels. The decrease in plasma leptin on high-flux dialysis cannot be explained solely by enhanced clearance.


International AIDS Society conference update. Male circumcision as a prevention method? Study was controversial from day one.
Investigators presented evidence at the July International AIDS Society conference in Rio de Janeiro, Brazil, in that male circumcision helps reduce the risk of HIV infection among men who have sex with women. The study showed that circumcised men were more than 60% less likely than uncircumcised men to be infected with HIV when having sex with infected female partners. The news was not welcomed by all quarters. Anti-circumcision activists quickly called on the United Nations to classify circumcision of children younger than age 18 as a human rights crime.


Functional subdivisions in the auditory cortex of the guinea pig.
The auditory fields in the cortex of the guinea pig were investigated with microelectrode mapping techniques. Pure tones of varying frequencies and amplitudes were used as acoustic stimuli. Mainly, multiunit activity was recorded. A large tonotopic area is found in the anterior half of the auditory cortex. This area is named the anterior field (field A). Frequency tuning curves of multiunits in field A are generally narrow. Responses to tone stimuli are strong, and latencies are short. Low best frequencies are represented rostrally, high best frequencies caudally. The tonotopy is continuous and quite regular. Field A is narrow dorsally and becomes gradually broader ventrally. Correspondingly, the isofrequency lines slightly diverge from dorsal to ventral. Caudal to the first field, there is a second, smaller tonotopic area. It lies in the dorsal half of the posterior auditory cortex and is therefore named the dorsocaudal field (field DC). The frequency specificity of the cell clusters in this area is as strong as in field A, but the tonotopy is discontinuous: In the dorsal half of field DC, high best frequencies (16-32 kHz) are represented rostrally; the low frequencies (0.5-2.8 kHz) are represented immediately caudal to the high frequencies, while the intermediate frequencies are missing. Ventrally in field DC, the frequency representation is more complete. Except for this discontinuous map, we did not notice any differences between fields A and DC. A third tonotopic field was found rostral to field A. This field extends over a surface of less than 1 mm2 and was named the small field (field S). It contains a complete representation of the frequency range; high best frequencies are located rostrally, low frequencies caudally. The response latencies are slightly longer in field S than in fields A or DC, and the tuning curves are broader. A broad strip of nontonotopic cortex (auditory belt) surrounds fields A and DC caudally. We subdivided this area into the dorsocaudal and the ventrocaudal belt region. In both areas, tuning curves are often broad, and response latencies are longer than in the tonotopic cortex. In the dorsocaudal belt, most multiunits react with a phasic on-response to pure tones; in the ventrocaudal belt, tonic responses occur more frequently. Another nontonotopic region is located in the anterior auditory cortex, rostral to the tonotopic fields, and was therefore named the rostral belt. Tuning curves in this area are broad, latencies are short, and response thresholds are often high. In the discussion, the guinea pig is compared with other mammalian species.(ABSTRACT TRUNCATED AT 400 WORDS)


Effects of chronic exposure to the fungicide vinclozolin on gut microbiota community in an aquatic turtle.
Environmental issues associated with the widespread use of agricultural chemicals are being seriously concerned. Of them, toxicological impacts of fungicides in aquatic organisms are often overlooked. Here, soft-shelled turtle (Pelodiscus sinensis) hatchlings were exposed to different concentrations of vinclozolin (0, 5, 50, 500 and 5000 μg/L) for 60 days to investigate the impact of fungicide exposure on their gut microbial composition and diversity. Vinclozolin exposure significantly affected the composition of the gut microbiota in hatchling turtles. Unexpectedly, gut bacterial diversity and richness of vinclozolin-exposed turtles (but not for the 5000 μg/L-exposed group) were relatively higher than control ones. At the phylum level, the abundance of Firmicutes was decreased, while that of Proteobacteria was increased in high-concentration groups. At the genus level, some bacterial genera including Cellulosilyticum, Romboutsia and Clostridium_sensu_stricto, were significantly changed after vinclozolin exposure; and some uniquely observed in high-concentration groups. Gene function predictions showed that genes related to amino acid metabolism were less abundant, while those related to energy metabolism more abundant in high-concentration groups. The prevalence of some pathogens inevitably affected gut health status of vinclozolin-exposed turtles. Such gut microbiota dysbiosis might be potentially linked with hepatic metabolite changes induced by vinclozolin exposure.


The acceptability of an online intervention using positive psychology for depression: A qualitative study.
Positive psychology interventions may usefully treat depression and can be delivered online to reduce the treatment gap. However, little is known about how acceptable patients find this approach. To address this, the present study interviewed recent users of a positive psychology self-help website. In-depth semi-structured interviews explored the experiences of twenty-three participants from a larger feasibility study. A stratified purposive sampling strategy selected participants with varying intervention experience according to their intervention logins, as well as varying age, gender and depressive symptoms. Framework analysis was used to explore patterns and linkages within and between participants' accounts. Acceptability varied between participants. Those who found it more acceptable felt it was relevant to their depression and reported feeling empowered by a self-help approach. Conversely, participants for whom it was less acceptable perceived the positive focus irrelevant to their depression and found the emphasis on self-action unsupportive. The acceptability of an online positive psychology intervention may be facilitated by a patients' preference for a psychological focus on the positive. However, patients may also have distinct preferences for online self-help. Future research should investigate the importance of the therapeutic orientation of online self-help interventions and whether patients' preferences for these can be reliably identified. This could help to target online self-help in clinical practice.


The COVID-19 pandemic in Ireland: An overview of the health service and economic policy response.
To outline the situation in Ireland with regard to the COVID-19 pandemic. Analyse the evolution of the COVID-19 pandemic in Ireland. Review the key public health and health system responses. Over 1700 people have died with COVID-19 by July 19th while almost 3000 people had been admitted to hospital with COVID-19. A high proportion of the deaths occurred in nursing homes and other residential centres who did not receive sufficient attention during the early phase of the pandemic. Ireland's response to the COVID-19 crisis has been comprehensive and timely. Transparency, a commitment to a relatively open data policy, the use of traditional and social media to inform the population, and the frequency of updates from the Department of Health and the Health Services Executive are all commendable and have led to a high level of compliance among the general public with the various non-medical measures introduced by the government.


Entering a community dialogue.
Entering a new, unstructured community is facilitated when existing members embrace the thoughts, ideas, and experiences of new members. Watson's Caring Healing Model, including the caritas conscious and transpersonal caring components, provides a framework for understanding the experience of being a new community member (e.g., a "newbie") in the Global Nursing Exchange.


Outbreak of Norovirus Gastroenteritis Associated With Ice Cream Contaminated by Frozen Raspberries From China-Minnesota, United States, 2016.
Norovirus is the etiology for about 60% of foodborne outbreaks identified in Minnesota. Contamination of food during preparation by food handlers is by far the most common cause of these outbreaks. Norovirus outbreaks due to commercially distributed foods are rarely reported in the United States, and only 2 have been previously identified in Minnesota, both due to oysters. In August 2016, we investigated an outbreak of norovirus gastroenteritis in Minnesota that was linked to consumption of commercially distributed ice cream at multiple venues. Sanitarians from local public health agencies visited the facilities involved for follow-up, and case-control studies were conducted. The outbreak was identified by linking multiple independent illness reports to a centralized foodborne illness complaint system and subsequently confirmed though genotyping of stool specimens. A total of 15 cases from 4 venues were reported. Raspberry chocolate chip ice cream was statistically associated with illness in 2 analytic studies (6 of 7 cases vs 0 of 7 controls; odds ratio, undefined; P = .005). Norovirus GII.17[P17] (GII.17 Kawasaki) strains from case stool specimens matched norovirus found in frozen raspberries imported from China that were used to make the implicated ice cream. To our knowledge, this is the first norovirus outbreak due to commercially distributed frozen berries identified in the United States. To detect norovirus outbreaks associated with commercially distributed food vehicles, investigators should thoroughly investigate all norovirus outbreaks (including stool testing and genotyping), coordinate complaint and response activities across agencies and jurisdictions, and consider testing food for norovirus when appropriate.


Generation of a zebrafish knock-in line expressing MYC-tagged Sox11a using CRISPR/Cas9 genome editing.
Advances in CRISPR-Cas9 genome editing technology have strengthened the role of zebrafish as a model organism for genetics and developmental biology. These tools have led to a significant increase in the production of loss-of-function mutant zebrafish lines. However, the generation of precisely edited knock-in lines has remained a significant challenge in the field due to the decreased efficiency of homology directed repair (HDR). In this study, we overcame some of these challenges by combining available design tools and synthetic, commercially available CRISPR reagents to generate a knock-in line carrying an in-frame MYC epitope tag at the sox11a locus. Zebrafish Sox11a is a transcription factor with critical roles in organogenesis, neurogenesis, craniofacial, and skeletal development; however, only a few direct molecular targets of Sox11a have been identified. Here, we evaluate the knock-in efficiency of various HDR donor configurations and demonstrate the successful expression and localization of the resulting knock-in allele. Our results provide an efficient, streamlined approach to knock-in experiments in zebrafish, which will enable expansion of downstream experimental applications that have previously been difficult to perform. Moreover, the MYC-Sox11a line we have generated will allow further investigation into the function and direct targets of Sox11a.


A simplified synthetic rhizosphere bacterial community steers plant oxylipin pathways for preventing foliar phytopathogens.
Rhizosphere-enriched microbes induced by foliar phytopathogen infection can be assembled into a functional community to enhance plant defense mechanisms. However, the functions of stably-colonizing rhizosphere microbiota are rarely investigated. In this study, Botrytis cinerea infection changed rhizosphere bacterial communities in tomato plants. The phytopathogen-infected plants recruited specific rhizosphere bacterial taxa, while several bacterial taxa stably colonized the rhizosphere, regardless of phytopathogen infection. Through the analysis of the rhizosphere bacterial community, we established a synthetic community harboring 8 phytopathogen-inducible and 30 stably-colonizing bacteria species. Furthermore, the 38-species community was simplified into a three-species community, consisting of one phytopathogen-inducible (Asticcacaulis sp.) and two stably-colonizing species (Arachidicoccus sp. And Phenylobacterium sp.). The simplified community provided a durable protection for the host plants by synergistic effects, with the phytopathogen-inducible species triggering plant defense responses and the stably-colonizing species promoting biofilm formation. The simplified community exhibited similar protective effects as the 38-species community. Moreover, the activation of oxylipin pathways in the phytopathogen-infected leaves was significantly intensified by the simplified community. However, the inhibited biosynthesis of antimicrobial divinyl ethers, including colneleic and colnelenic acid, fully abolished the community-induced plant disease resistance. In contrast, transgenic plants overexpressing SlLOX5 and SlDES1, with higher levels of divinyl ethers, displayed stronger resistance against B. cinerea compared to wild-type plants. Collectively, these findings provided insights into the utilization of the simplified community for preventing gray mold disease.


Soft Carbon as Cathode with High Rate Performance for Dual-Ion Batteries via Fast PF6 - Intercalation Improved by Surface Effect.
Dual-ion battery is a new type of battery in which both anions and cations participate in the energy storage process. However, this unique battery configuration imposes high requirements on the cathode, which typically presents a poor rate performance due to the sluggish diffusion dynamics and intercalation reaction kinetics of anions. Herein, we report petroleum coke-based soft carbon as the cathode for dual-ion batteries, exhibiting a superior rate performance with a specific capacity of 96 mAh g-1 at a rate of 2 C and 72 mAh g-1 remained even at 50 C. In situ XRD and Raman demonstrate that the anions can directly form lower-stage graphite intercalation compounds during the charge process owing to the surface effect, skipping the long evolutionary process from higher to lower stage, thus significantly improving the rate performance. This study highlights the impact of the surface effect and provides a promising perspective for dual-ion batteries.


[Evaluation of multiple myeloma with bone scintigraphy using Tc 99 diphosphonate. Review of the literature].
Bone Scanning using 99m Tc-Diphosphonate is another diagnostic modality in the evaluation of multiple mieloma which allows the identification of bone lesions not demonstrable by conventional radiography. The use of 99m Tc-Diphosphonate is more convenient and less harmful than other radioactive isotopes utilized before.


Diagnostic modalities for detection of pulmonary embolism in clinical routine: a European survey.
A questionnaire asking for routinely performed modalities to diagnose deep venous thrombosis (DVT) and pulmonary embolism (PE) was sent to 2,500 departments in 23 European countries. Five-hundred-seventy (23%) were received back and evaluated according to hospital size and regional differences. Countries were grouped into: Anglo-Scandinavian (a), German-speaking (g), and Roman (r). Contrast venography is most frequently performed (94%) to diagnose DVT, independent of hospital size and without regional differences. With exception of Doppler ultrasound (71%), noninvasive DVT tests are rarely performed (6-28%). To diagnose PE, pulmonary angiography (PA) and ventilation-perfusion (V-P) scintigraphy are performed in 71%, digital subtraction angiography in only 50%. Frequencies of PE tests strongly depend on hospital size (PA: small hospitals 53-66%, large 83-89%; V-P: small hosp. greater than 80%, large greater than 90%, with 2 exceptions: small German hospitals = 48%, primarily performing only P-scans and large Roman hospitals = 59%, primarily performing PA). Regional differences were also significant (PA: r = 85%, a = 74%, g = 63%, V-P: a = 95%, r = 66%, g = 63%, respectively).


Numerical insights into the phase diagram of p-atic membranes with spherical topology.
The properties of self-avoiding p-atic membranes restricted to spherical topology have been studied by Monte Carlo simulations of a triangulated random surface model. Spherically shaped p-atic membranes undergo a Kosterlitz-Thouless transition as expected with topology induced mutually repelling disclinations of the p-atic ordered phase. For flexible membranes the phase behaviour bears some resemblance to the spherically shaped case with a p-atic disordered crumpled phase and p-atic ordered, conformationally ordered (crinkled) phase separated by a KT-like transition with proliferation of disclinations. We confirm the proposed buckling of disclinations in the p-atic ordered phase, while the expected associated disordering (crumpling) transition at low bending rigidities is absent in the phase diagram.


Building towards common psychosocial measures in U.S. cohort studies: principal investigators' views regarding the role of religiosity and spirituality in human health.
The goal of this study was to understand prospective cohort study Principal Investigators' (PIs') attitudes regarding the importance of religion and spirituality (R/S) on disease etiology in order to identify barriers and opportunities for greater inclusion of these domains in high-quality epidemiological research. One-hour, semi-structured qualitative interviews were conducted with 20 PIs, who represent 24 different National Institutes of Health (NIH)-funded prospective cohort studies in the U.S. Collectively, these PIs collect detailed health data on approximately 1.25 of every 100 adult Americans. Sample size was calculated to achieve thematic saturation. The majority of PIs we interviewed viewed R/S as potentially important factors influencing disease etiology, particularly among minority communities that report higher levels of religiosity. Yet nearly all PIs interviewed felt there was not yet a compelling body of evidence elucidating R/S influences on health, and the potential mechanisms through which R/S may be operating to affect health outcomes. PIs identified 5 key areas that would need to be addressed before they would be persuaded to collect more R/S measures in their cohorts: (1) high-quality, prospective studies that include all appropriate covariates for the outcome under study; (2) studies that posit a plausible biological mechanism of effect; (3) well-validated R/S measures, collected in common across multiple cohorts; (4) the need to address bias against R/S research among investigators; and (5) NIH funding for R/S research. Results of this study provide a roadmap for future R/S research investigating the impact of R/S influences on disease etiology within the context of U.S. prospective cohort studies. Identifying significant R/S influences on health could inform novel interventions to improve population health. Given the higher levels of religiosity/spirituality among minority communities, R/S research may also provide new leverage points for reducing health disparities.


A new approach to shimming: the dynamically controlled adaptive current network.
Magnetic field homogeneity is important in all aspects of magnetic resonance imaging. A new approach to increase field homogeneity is presented that allows dynamic and adaptive control over the flow of current over a single surface using a network of actively controlled solid-state switches. Computer simulations were completed demonstrating the potential of this approach. Wire patterns were produced using the boundary element method to remove magnetic field inhomogeneities over multiple regions of interest. Field maps and regions of interest histograms were compared with and without the shim present. A prototype was constructed confirming the feasibility of this approach within the magnetic resonance environment. Metal-oxide-semiconductor field-effect transistors were used. Two field maps were acquired with the prototype producing gradient and offset field profiles, respectively. The experimental field profiles were compared with simulation. The wire patterns significantly increased field homogeneity over all regions of interest investigated. The field profiles produced by the prototype matched simulation. No imaging artifacts were produced. An approach to control the shape of a current distribution over a single surface has been described. This method has the potential to improve field homogeneity over any desired region of interest and is particularly well suited for dynamic applications. The method is feasible with current technology and construction techniques.


A single layer open anastomosis for all intestinal structures.
Dissatisfaction with time-consuming double layer anastomoses in intestinal surgery and with occasionally questionable stapled anastomoses prompted a review of available techniques for hand sewn suture lines. Single layer anastomoses have been used extensively and their integrity and safety have often been questioned. In 1951, Gambee described a method of single layer anastomosis which, in practice, is a double layer technique. His results at 10 years were comparable to those obtained with other techniques. We have sought a modification to decrease anastomotic complications and improve ease of suture insertion. Along with a description of technique, a review of 170 anastomoses performed from July 1982 to June 1984 is presented without a single clinically apparent leak.


Recent developments in interpositional bone-grafting of the atrophic mandible.
A clinical study on 54 patients, who underwent augmentation of the atrophic mandible by interposed bone-grafts, but in whom routine follow-up vestibuloplasty was deliberately avoided, is presented. The results show a reduced rate of bone resorption in the anterior region and less interference with lip and chin sensibility. An additional study is included concerning the fate of the elevated ridge and associated bone-graft in the body region posterior to the mental foramen. Results suggest that the resorption pattern in this area is very similar to that of a subperiosteal bone-graft. Modification of surgical technique in this regard has produced encouraging results.


Developmental aspect of phenylalanine hydroxylase in the rat -- hormonal influences.
Interpretations of the development of phenylalanine hydroxylase (PAH) in rat liver have been controversial, and the mechanism of ontogenic changes have not yet been elucidated. Fetal PAH activity at a gestational age of 21 days appeared to reach 32% that of adult male level at birth. The in vivo effectiveness of fetal PAH activity was correlated with enhancement of blood tyrosine, while amino-transferase activity appeared only after birth. No sex difference was noted in weaning rats, whereas, in adult females, PAH activity was only 42% that of males. Investigating hormonal influences on liver PAH activity we noted no change of enzyme activity following hydrocortisone, ACTH and estradiol treatment. However, 4 days of testosterone treatment in weaning female rats increased PAH activity (X1.7). Therefore, testosterone could explain increased PAH activity in adult males.


Postoperative Opioid Consumption in Thoracic Surgery Patients: How Much Is Actually Used?
The objective of this initiative was to perform a prospective, multicenter survey of patients after lung resection to assess the amount of opioid medication consumed and the disposition of unused opioids to inform the development of evidence-based prescribing guidelines. Adults undergoing lung resection with either minimally invasive surgery (MIS; n = 108) or thoracotomy (n = 45) were identified prospectively from 3 academic centers (from March 2017 to January 2018) to complete a 28-question telephone survey 21 to 35 days after discharge. Discharge opioids were converted into morphine milligram equivalents (MME) and were compared across patient and surgical details. Of the 153 patients who completed the survey, 89.5% (137) received opioids at discharge with a median prescription of 320 MME (interquartile range [IQR], 225, 450 MME) after MIS and 450 MME (IQR, 300, 600 MME) after thoracotomy (P = .001). Median opioid consumption varied by surgical approach: 90 MME (IQR, 0, 262.5) after MIS and 300 MME (IQR, 50, 382.5 MME) after thoracotomy (P < .001). The majority of patients (73.7%; 101) had residual opioid medication at the time of the survey, and patients after MIS had a relative increase in amount of remaining opioid medication: 58.3% vs 33.3% (P = .05) of the original prescription. Only 5.9% of patients with opioids remaining had properly disposed of them. Although patients undergoing MIS lung resection used significantly less opioid medication over a shorter duration of time than did patients after thoracotomy, they had relatively more excess opioid prescription. Evidence-based, procedure-specific guidelines with tailored pain regimens should be developed and implemented to reduce the amount of postoperative opioid medication remaining in the community.


Prenatal intracranial hypotension syndrome in congenital cephalocele: Insights into pathophysiologic mechanisms and importance of defect coverage.
To compare specific fetal cranial and cerebral findings indicative of prenatal intracranial hypotension (PICH) syndrome between open and closed cephaloceles. Two groups of fetuses with cephalocele who underwent magnetic resonance imaging scan were selected based on the defect coverage: covered ("closed cephalocele" group, n = 4) and uncovered by skin ("open cephalocele" group, n = 8). The presence of signs associated with PICH syndrome was evaluated and findings compared between groups. Cases from the open cephalocele group showed statistically significant differences in comparison with the closed cephalocele group regarding reduction of the interpeduncular angle (p = 0.006), reduced amount of cerebrospinal fluid in the subarachnoid space (p = 0.01), collapsed/severely reduced fourth ventricle (p = 0.03), cephalocele content (p = 0.03), and identification of a vector traction (p = 0.03). There were no differences in the presence of cerebellar tonsillar descent, obstructive ventriculomegaly, and presence of the lemon sign. In comparison with gestational age-matched controls, only the biparietal diameter but not the head circumference was significantly smaller in both the open and closed cephalocele groups (p < 0.05). Congenital cephaloceles present distinct imaging behavior depending on the defect coverage. Therefore, the classification of cephalocele should include, in addition to location and content, the presence or absence of skin fully covering the defect.


The TREX1 C-terminal region controls cellular localization through ubiquitination.
TREX1 is an autonomous 3'-exonuclease that degrades DNA to prevent inappropriate immune activation. The TREX1 protein is composed of 314 amino acids; the N-terminal 242 amino acids contain the catalytic domain, and the C-terminal region (CTR) localizes TREX1 to the cytosolic compartment. In this study, we show that TREX1 modification by ubiquitination is controlled by a highly conserved sequence in the CTR to affect cellular localization. Transfection of TREX1 deletion constructs into human cells demonstrated that this sequence is required for ubiquitination at multiple lysine residues through a "non-canonical" ubiquitin linkage. A proteomic approach identified ubiquilin 1 as a TREX1 CTR-interacting protein, and this interaction was verified in vitro and in vivo. Cotransfection studies indicated that ubiquilin 1 localizes TREX1 to cytosolic punctate structures dependent upon the TREX1 CTR and lysines within the TREX1 catalytic core. Several TREX1 mutants linked to the autoimmune diseases Aicardi-Goutières syndrome and systemic lupus erythematosus that exhibit full catalytic function were tested for altered ubiquitin modification and cellular localization. Our data show that these catalytically competent disease-causing TREX1 mutants exhibit differential levels of ubiquitination relative to WT TREX1, suggesting a novel mechanism of dysfunction. Furthermore, these differentially ubiquitinated disease-causing mutants also exhibit altered ubiquilin 1 co-localization. Thus, TREX1 post-translational modification indicates an additional mechanism by which mutations disrupt TREX1 biology, leading to human autoimmune disease.


Molecular cloning and characterization of a novel glutathione S-transferase gene induced by light stimulation in the protozoan Blepharisma japonicum.
A cDNA clone that is inducible by light stimulation was cloned by a differential screening method from a cDNA library of the protozoan Blepharisma japonicum, and the light-dependent expression was checked by semi-quantitative reverse transcription polymerase chain reaction analysis. Sequence analysis showed that the cDNA encodes a glutathione S-transferase (GST) that has not been characterized in the protozoa. Multiple alignment of B. japonicum GST (BjGST1), known protozoan, and mammalian alpha-, micro-, pi-, sigma-, theta-, zeta-, kappa-, and omega-class GSTs suggested that the BjGST1 may be a novel class GST. Furthermore, highly conserved amino acid residues among the GSTs and the substrate specificity of recombinant BjGST1 showed that BjGST1 is related to alpha-, micro-, pi-, and sigma-class GSTs rather than the other class of GSTs.


Representation of Expression and Identity by Ventral Prefrontal Neurons.
Evidence has suggested that the ventrolateral prefrontal cortex (VLPFC) processes social stimuli, including faces and vocalizations, which are essential for communication. Features embedded within audiovisual stimuli, including emotional expression and caller identity, provide abundant information about an individual's intention, emotional state, motivation, and social status, which are important to encode in a social exchange. However, it is unknown to what extent the VLPFC encodes such features. To investigate the role of VLPFC during social communication, we recorded single-unit activity while rhesus macaques (Macaca mulatta) performed a nonmatch-to-sample task using species-specific face-vocalization stimuli that differed in emotional expression or caller identity. 75% of recorded cells were task-related and of these >70% were responsive during the nonmatch period. A larger proportion of nonmatch cells encoded the stimulus rather than the context of the trial type. A subset of responsive neurons were most commonly modulated by the identity of the nonmatch stimulus and less by the emotional expression, or both features within the face-vocalization stimuli presented during the nonmatch period. Neurons encoding identity were found in VLPFC across a broader region than expression related cells which were confined to only the anterolateral portion of the recording chamber in VLPFC. These findings suggest that, within a working memory paradigm, VLPFC processes features of face and vocal stimuli, such as emotional expression and identity, in addition to task and contextual information. Thus, stimulus and contextual information may be integrated by VLPFC during social communication.


Enhanced UV Emission From Silver/ZnO And Gold/ZnO Core-Shell Nanoparticles: Photoluminescence, Radioluminescence, And Optically Stimulated Luminescence.
The optical properties of core-shell nanoparticles consisting of a ZnO shell grown on Ag and Au nanoparticle cores by a solution method have been investigated. Both the ZnO/Ag and ZnO/Au particles exhibit strongly enhanced near-band-edge UV emission from the ZnO when excited at 325 nm. Furthermore, the UV intensity increases with the metal nanoparticle concentration, with 60-fold and 17-fold enhancements for the ZnO/Ag and ZnO/Au, core-shell nanoparticles respectively. Accompanying the increase in UV emission, there is a corresponding decrease in the broad band defect emission with nanoparticle concentration. Nonetheless, the broad band luminescence increases with laser power. The results are consistent with enhanced exciton emission in the ZnO shells due to coupling with surface plasmon resonance of the metal nanoparticles. Luminescence measurements during and after exposure to X-rays also exhibit enhanced UV luminescence. These observations suggest that metal nanoparticles may be suitable for enhancing optical detection of ionizing radiation.


Vanadate stimulates rat pancreatic enzyme secretion through the release of calcium from an intracellular store.
Orthovanadate accelerates 45Ca efflux and enzyme secretion from the rat pancreas incubated in either control (2.5 mM Ca) or nominally Ca-free buffers. Secretion induced by vanadate does not appear to be mediated by changes in either adenylate cyclase or sodium pump activity. Instead, vanadate appears to act at an intracellular site to cause the release of calcium from the same pool mobilised by acetylcholine. Vanadate action is not inhibited by DIDS. The effect of pH on vanadate action may be accounted for by changes in the distribution of the vanadates. Vanadyl sulphate inhibits secretion evoked by acetylcholine. This suggests that intracellular reduction of vanadate (+5 oxidation state) to the +4 oxidation state may account for an inhibitory component observed during stimulation with vanadate.


Identification of microplastics using a convolutional neural network based on micro-Raman spectroscopy.
Microplastics (MPs) pose a threat to human and environmental health, and have emerged as a global environmental issue. Because MPs are small and complex, methods of quickly and reliably classifying and identifying them are either lacking or in the early stages of development. In this study, micro-Raman spectroscopy and a convolutional neural network (CNN) were combined to establish identification models for 10 MP references and three environmental samples. In addition, an interaction network was established based on pair-wise correlations of Raman bands to determine the influence of environmental stress on MPs. The CNN model achieved average classification accuracies of 96.43% and 95.6% for the 10 MP references and the three environmental samples, respectively. For MPs exposed to environmental stressors, an interaction network can provide highly sensitive, information-dense, and universally applicable signatures for characterizing the environmental processes affecting MP spectra. The results of this study can help establish efficient and automatic analysis for accurate identification of MPs as well as an intuitive exhibition of spectral changes on environmental exposure.


The Influence of Surface Roughening and Polishing on Microbial Biofilm Development on Different Ceramic Materials.
To test the hypothesis that surface roughening and polishing of ceramics have no effect on their surface roughness and biofilm adhesion. Feldspathic ceramic Vitablocks™ TriLuxe forte (VTF), lithium disilicate glass IPS e.max Press™ (IPS) and zirconia reinforced lithium silicate Vita Suprinity™ (VS) ceramic blocks (n = 27 per group) were prepared from sintered CAD blocks using a water-cooled saw. They were further subdivided into 3 subgroups according to the surface treatment protocols (n = 9): as prepared, roughened and polished. The surface roughness of the ceramic blocks was measured using an electro-mechanical profilometer. The ceramic sections were inoculated with Streptococcus mutans and incubated for 48 hours to form a biofilm. The ceramic surfaces with the biofilms were analyzed using Confocal Laser Scanning Microscopy to calculate the percentage of live bacteria and substratum coverage by the biofilm, and further visualized using scanning electron microscopy. Statistical analysis was done with SPSS software using two-way ANOVA, followed by post hoc Bonferroni test to identify significant differences between the groups. The level of significance was set at p = 0.05. As prepared VTF showed significantly higher mean surface roughness values than as prepared IPS and VS. The mean percentage of live bacteria and biofilm coverage of the substrate were significantly higher in the roughened ceramic blocks than the as prepared and polished blocks for all three ceramic types (p < 0.05). Polished specimens of VS significantly lower percentage of biofilm coverage than the other groups (p < 0.05). This study sheds new light that adjustments of ceramic restorations prior to cementation increases the likelihood for formation and adhesion of microbial biofilms on the surface. Polished zirconia reinforced lithium disilicate ceramics demonstrated the lowest bacterial adhesion among the evaluated ceramics.


DNA topoisomerase I phosphorylation in murine fibroblasts treated with 12-O-tetradecanoylphorbol-13-acetate and in vitro by protein kinase.
The phosphorylation of DNA topoisomerase I in quiescent murine 3T3-L1 fibroblasts treated with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) was characterized by in vivo labeling with [32P] orthophosphate and immunoprecipitation with a scleroderma anti-DNA topoisomerase I autoantibody. DNA topoisomerase I phosphorylation was stimulated 4-fold by 2 h of TPA treatment (TPA at 100 ng/ml maximally enhanced phosphorylation). Purified DNA topoisomerase I was phosphorylated in vitro in a Ca2+ and phospholipid-dependent fashion by types I, II, and III protein kinase C. The phosphorylation reaction was stimulated by TPA and had an apparent K(m) of 0.4 microM. DNA topoisomerase I was phosphorylated in vivo and in vitro predominantly at serine. The major tryptic phosphopeptides from DNA topoisomerase I in TPA-treated fibroblasts and phosphorylated by protein kinase C comigrated in thin-layer electrophoresis. The half-life of incorporated phosphate on DNA topoisomerase I was 40 min in both TPA-treated and control cells. These results suggest that phosphorylation is a mechanism for activating DNA topoisomerase I in fibroblasts treated with TPA and that protein kinase C functions in the phosphorylation.


β-caryophyllene enhances the transcriptional upregulation of cholesterol biosynthesis in breast cancer cells.
β-caryophyllene (BCP) exhibits anti-proliferative properties in cancer cells. Here, we examine the hypothesis that BCP induces membrane remodeling. Our data show that high concentrations of BCP increase membrane permeability of human breast cells (hBrC) causing detachment and cell death. At a sub-lethal concentration of BCP, we show that BCP induces a striking upregulation of genes involved in cholesterol biosynthesis, including the gene that encodes for HMGCoA reductase (HMGCR), the rate-determining step in cholesterol biosynthesis. In addition, stearoyl-CoA desaturase (SCD) is also upregulated which would lead to the enhanced formation of monounsaturated fatty acids, specifically oleate and palmitoleate from stearoyl CoA and palmitoyl CoA, respectively. These fatty acids are major components of membrane phospholipids and cholesterol esters. Together, these data suggest that cells respond to BCP by increasing the synthesis of components found in membranes. These responses could be viewed as a repair mechanism and/or as a mechanism to mount resistance to the cytotoxic effect of BCP. Blocking HMGCR activity enhances the cytotoxicity of BCP, suggesting that BCP may provide an additional therapeutic tool in controlling breast cancer cell growth.


Developing multi-cellular tumor spheroid model (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening.
In this work, a 3D MCTS-CCA system was constructed by culturing multi-cellular tumor spheroid (MCTS) in the chitosan/collagen/alginate (CCA) fibrous scaffold for anticancer drug screening. The CCA scaffolds were fabricated by spray-spinning. The interactions between the components of the spray-spun fibers were evidenced by methods of Coomassie Blue stain, X-ray diffraction (XRD) and Fourier transform-infrared spectroscopy (FTIR). Co-culture indicated that MCF-7 cells showed a spatial growth pattern of multi-cellular tumor spheroid (MCTS) in the CCA fibrous scaffold with increased proliferation rate and drug-resistance to MMC, ADM and 5-Aza comparing with the 2D culture cells. Significant increases of total viable cells were found in 3D MCTS groups after drug administration by method of apoptotic analysis. Glucose-lactate analysis indicated that the metabolism of MCTS in CCA scaffold was closer to the tumor issue in vivo than the monolayer cells. In addition, MCTS showed the characteristic of epithelial mesenchymal transition (EMT) which is subverted by carcinoma cells to facilitate metastatic spread. These results demonstrated that MCTS in CCA scaffold possessed a more conservative phenotype of tumor than monolayer cells, and anticancer drug screening in 3D MCTS-CCA system might be superior to the 2D culture system.


Independent association of the M2/ANXA5 haplotype with recurrent pregnancy loss (RPL) in PCOS patients.
The aim of this study was to analyze the contribution of the M2 haplotype of ANXA5 gene, previously identified as a risk factor for RPL and thrombophilia related pregnancy complications, to repeated miscarriage observed in PCOS patients. 100 PCOS patients, 500 fertile women and 533 random population controls were genotyped for M2/ANXA5. M2 haplotype carriers faced a 3.4 fold elevated RPL risk (odds ratio 5.3, 95% confidence interval 3-9.2) compared to female fertile controls and 2.1 (odds ratio 2.6, 95% confidence interval 1.6-4.3) compared to population controls. The relative population risks in subgroups of PCOS patients with primary and secondary RPL were 2.3 (odds ratio 2.5, 95% confidence interval 1.2-5) and 3.3 (odds ratio 3.6, 95% confidence interval 1.5-8.4) respectively. As compared to the fertile women group, the relative risks equaled 4 (odds ratio 5, 95% confidence interval 2.3-10.8) and 6 (odds ratio 7.2, 95% confidence interval 3-17.7). Estimated relative risks for M2 carriers among PCOS RPL patients matched the values previously obtained for repeated miscarriage populations. The essential phenotypes, clinically defining PCOS, associated neither with RPL in their diagnostically relevant combinations, nor with M2 carriage as RPL risk factor in the PCOS RPL subgroups. M2/ANXA5 seems an independent RPL risk factor in PCOS patients that progressively correlates with the number of first trimester pregnancies. From our pilot study in PCOS women it appears relevant to offer M2/ANXA5 diagnostic analysis to such patients with RPL complications, to possibly guide proper therapeutic decisions.


New CeO2 nanoparticles-based topical formulations for the skin protection against organophosphates.
To reinforce skin protection against organophosphates (OPs), the development of new topical skin protectants (TSP) has received a great interest. Nanoparticles like cerium dioxide (CeO2) known to adsorb and neutralize OPs are interesting candidates for TSP. However, NPs are difficult to disperse into formulations and they are suspected of toxicological issues. Thus, we want to study: (1) the effect of the addition of CeO2 NPs in formulations for the skin protection (2) the impact of the doping of CeO2 NPs by calcium; (3) the effect of two methods of dispersion of CeO2 NPs: an O/W emulsion or a suspension of a fluorinated thickening polymer (HASE-F) grafted with these NPs. As a screening approach we used silicone membranes as a skin equivalent and Franz diffusion cells for permeation tests. The addition of pure CeO2 NPs in both formulations permits the penetration to decrease by a 3-4-fold factor. The O/W emulsion allows is the best approach to obtain a film-forming coating with a good reproducibility of the penetration results; whereas the grafting of NPs to a thickener is the best way to obtain an efficient homogenous suspension of CeO2 NPs with a decreased of toxicological impact but the coating is less film-forming which slightly impacts the reproducibility of the penetration results.


Production of fumonisins B1, B 2 and B 3 byFusarium proliferatum Isolated from rye grains.
Using the seed- plate technique, we have isolated a strain ofF. proliferatum from rye grains that produces 3 fumonisins, fumonisin B1 (FB1), FB2 and FB3 on inoculated rice and corn. Inoculated corn and rice were extracted with an aqueous methanol solution and fumonisin concentrations estimated using high performance liquid chromatography. Production of all 3 fumonisins (FB1, FB2 and FB3) was much higher on rice than corn; ranging from 3816, 1068 and 985 ppm to 1643, 350 and 162 ppm respectively. We conclude that all natural substrates whereF. proliferatum is present as a component of the mycoflora should be monitored for the presence of fumonisins.


[Aortic root reconstruction with homograft in bacterial endocarditis].
We describe successful use of respectively an aortic and a pulmonary homograft as total root replacement in two patients with extensive aortic valve endocarditis. At follow-up 18 months after operation both patients were doing well and echocardiography demonstrated excellent graft function with only trivial aortic regurgitation.


The effects of biological fouling control at coastal and estuarine power stations.
The use of low levels of oxidants as antifouling agents in coastal and estuarine power station cooling water circuits can give rise to concerns over the likely production of chlorination byproducts (CBPs) including organohalogens, of largely cryptic identity, loading and impact. In order to review the current understanding of the degree of impact involved this paper describes a recent collaborative programme of work on CBPs within the wider context of a number of allied studies on power station cooling water entrainment and discharge effects. Bromoform was the single most important CBP found in coastal power station effluents. Although bromoform was found to accumulate in the liver of the sea bass Dicentrarchus labrax (L.) continuously exposed to a chlorinated effluent stream, no otherwise untoward impact on continuously exposed individuals was discerned. Populations of the common blue mussel Mytilus edulis L., likewise exposed, exhibited two responses: a high degree of genoplasticity and the evolution of stress proteins--although both may have been due to thermal rather than toxic stress. Experiments on plankton that simulated the conditions of entrainment within cooling water systems isolated the influence of oxidant usage, with mortality varying between taxa and life stage. The results suggest a very limited impact of oxidant use and the associated CBPs on receiving waters both in terms of plume toxicity or any more widespread ecotoxicological influence. Instead, it is in combination with applied temperature (DeltaT), pressure and the other stressors involved in entrainment within the power station cooling water circuits themselves that an impact is most marked.


Serial two-photon tomography for automated ex vivo mouse brain imaging.
Here we describe an automated method, named serial two-photon (STP) tomography, that achieves high-throughput fluorescence imaging of mouse brains by integrating two-photon microscopy and tissue sectioning. STP tomography generates high-resolution datasets that are free of distortions and can be readily warped in three dimensions, for example, for comparing multiple anatomical tracings. This method opens the door to routine systematic studies of neuroanatomy in mouse models of human brain disorders.


METTL16 promotes glycolytic metabolism reprogramming and colorectal cancer progression.
Glycolysis is the key hallmark of cancer and maintains malignant tumor initiation and progression. The role of N6-methyladenosine (m6A) modification in glycolysis is largely unknown. This study explored the biological function of m6A methyltransferase METTL16 in glycolytic metabolism and revealed a new mechanism for the progression of Colorectal cancer (CRC). The expression and prognostic value of METTL16 was evaluated using bioinformatics and immunohistochemistry (IHC) assays. The biological functions of METTL16 in CRC progression was analyzed in vivo and in vitro. Glycolytic metabolism assays were used to verify the biological function of METTL16 and Suppressor of glucose by autophagy (SOGA1). The protein/RNA stability, RNA immunoprecipitation (RIP), Co-immunoprecipitation (Co-IP) and RNA pull-down assays were used to explore the potential molecular mechanisms. SOGA1 is a direct downstream target of METTL16 and involved in METTL16 mediated glycolysis and CRC progression. METTL16 significantly enhances SOGA1 expression and mRNA stability via binding the "reader" protein insulin-like growth factor 2 mRNA binding protein 1 (IGF2BP1). Subsequently, SOGA1 promotes AMP-activated protein kinase (AMPK) complex ubiquitination, inhibits its expression and phosphorylation, thus upregulates pyruvate dehydrogenase kinase 4 (PDK4), a crucial protein controlling glucose metabolism. Moreover, Yin Yang 1 (YY1) can transcriptionally inhibit the expression of METTL16 in CRC cells by directly binding to its promoter. Clinical data showed that METTL16 expression is positively correlated to SOGA1 and PDK4, and is associated with poor prognosis of CRC patients. Our findings suggest that METTL16/SOGA1/PDK4 axis might be promising therapeutic targets for CRC.


Characterization and identification of a chymotryptic hydrolysate of alpha-lactalbumin stimulating cholecystokinin release in STC-1 cells.
Alpha-lactalbumin hydrolysate is of significant interest, due to its potential application as a source of bioactive peptides in nutraceutical and pharmaceutical domains. This study was focused on the cholecystokinin (CCK) family compounds which are small peptides involved in the satiety control. The action of chymotryptic hydrolysate of alpha-lactalbumin on cholecystokinin release from intestinal endocrine STC-1 cells was investigated. We demonstrated for the first time that a chymotryptic hydrolysate of alpha-lactalbumin was able to highly stimulate CCK-releasing activity from STC-1 cells. The peptidic hydrolysate was characterized by LC/MS and MS/MS, thus highlighting the presence of 11 fractions containing 21 peptides, each potentially having the desired activity.


Laparoscopic or open liver resection? Let systematic review decide it.
Laparoscopic liver resection is increasingly being used for the excision of benign and malignant hepatic lesions. The aim of this study was to perform meta-analysis on the compiled data from available observational studies. All the studies comparing laparoscopic versus open liver resections were searched on the available databases. Data were analyzed using Review Manager software version 5.0 (The Cochrane Collaboration, Software Update, Oxford, UK). There was a total of 2,466 patients: 1,161 (47.1%) in the laparoscopic group and 1,305 (52.9%) in the open group. The laparoscopic group was associated with a reduced overall complication rate (odds ratio = .35; 95% confidence interval [CI], .28-.45; P < .001; heterogeneity (HG): P = .51), fewer positive resection margins for malignant tumor resections (odds ratio = .38; CI, .20-.76; P = .006; HG: P = .52) and a decrease in the number of patients requiring blood transfusion (odds ratio = .36; CI, .23-.74; P < .001; HG: P = .30). Laparoscopic liver resection showed a reduced overall morbidity rate and favorable and comparable outcomes when compared with the open group. However, there is still a need for randomized controlled trials to compare laparoscopic versus open hepatic resection in benign and malignant lesions.


Whether weekend warrior activity and other leisure-time physical activity pattern reduce the risk of depression symptom in the representative adults? A population-based analysis of NHANES 2007-2020.
The rapid pace of life nowadays has seen a gradual increase in public involvement in weekend warrior (WW), a physical activity (PA) pattern that allows people to exercise once or twice a week, the recommended moderate-to-vigorous PA per week, since regular PA takes much time. We aim at exploring the effect of WW activity and other PA patterns on depression symptoms in U.S adults. The level of PA was measured by self-reporting activity patterns, (inactive, insufficiently active, WW and regularly active). Participants with Patient Health Questionnaire-9 (PHQ-9) scores above 10 are considered to have depression symptoms. A weighted sample of 23,258 participants representing 1049.8 million non-institutionalized U.S adults aged from 20 to 80. Compared with the inactive group, general adults who met the PA guidelines with PA once or twice per week [WW, adjusted odds ratio (AOR) = 0.790, 95%CI: 0.638, 0.987] or more frequent PA [Regularly active, (AOR = 0.761, 95%CI: 0.671, 0.864)], were inversely associated with depression symptoms, while the association has not been observed in adults with insufficiently active PA (AOR = 0.892, 95%CI: 0.783, 1.017). Increase in minutes, sessions and intensity of PA in regularly active and WW groups brought additional benefits for depression symptoms. WW and other equivalent PA intensities patterns may be sufficient to reduce the risk of depression symptom. With the same recommended levels of PA, whether spread over the week or done in fewer days, adults may achieve the same benefits.


Graph Theoretic Analysis of Resting State Functional MR Imaging.
Graph theoretic analyses applied to examine the brain at rest have played a critical role in clarifying the foundations of the brain's intrinsic and task-related activity. There are many opportunities for clinical scientists to describe and predict dysfunction using a network perspective. This primer describes the theoretic basis and practical application of graph theoretic analysis to resting state functional MR imaging data. Major practices, concepts, and findings are concisely reviewed. The theoretic and practical frontiers of resting state functional MR imaging are highlighted with observations about major avenues for conceptual advances and clinical translation.


Surface structure on abandoned upland blanket peatland tracks.
Temporary permissions are often granted for track use on peatlands. However, even when peatland track designs attempt to minimise environmental impacts via use of mesh systems, such linear disturbances may have persistent impacts. We evaluated the surface peatland structure of five abandoned tracks (four with a mesh surface, one unsurfaced) with varying past usage frequencies, at an upland site in northern England. Simplification of the surface nanotopography was found on all tracks compared to surrounding control areas, with increased micro-erosion patterns in rutted areas, and invasive species on some treatments. The frequency of previous usage was not found to be a significant factor controlling nano-topographic loss. Edge effects and hillslope position were influential in places, but these effects were not consistent across treatments. Nano-topographic recovery was found to be inhibited when track usage commenced within a short time frame after track construction. Mesh tracks appear to create a spatial constraint leading to poor development of plants and a reduced ability to form characteristic structures which are integral to mire function.


A new genus and species of Dictyopharidae (Homoptera) from Rovno and Baltic amber based on nymphs.
Alicodoxa rasnitsynigen. et sp. n. (Dictyopharinae: Orthopagini) is described based on a nymph from Rovno amber; it also occurs in Baltic amber. A small additional wax plate dorsal to the large wax plate of abdominal tergites VI-VIII is first reported in this and other genera of Dictyopharidae. A lectotype is designated for Pseudophana reticulata Germar & Berendt, 1856 transferred to Protepiptera (Achilidae): Protepiptera reticulata (Germar & Berendt, 1856), comb. n.


Salmonella isolated in sewage sludge traced back to human cases of salmonellosis.
The main aim of this study was to investigate a possible connection between the Salmonella content in sewage sludge and human cases of salmonellosis. An additional aim was to survey the antimicrobial resistance situation in Salmonella isolated from Swedish sewage sludge. The Salmonella strains were compared by restriction enzyme analysis combined with pulsed field gel electrophoresis and antimicrobial susceptibility testing. This study suggests a link between Salmonella isolated from sewage sludge and human Salmonella isolates. This study demonstrates that Salmonella spp. isolated in sewage treatment plants (STP) originate from infected humans and survive treatment at STP. It also highlights the risk of spreading resistant Salmonella strains from sewage sludge to the environment. As Salmonella spp. originating from infected humans can survive the treatment at STP, the risk of Salmonella spp. being spread with sewage sludge to the environment and then to people and animals is enhanced. The threat to society is even worse if the bacteria are resistant to antimicrobial agents.


Mixing of Dead Sea and Red Sea waters and changes in their physical properties.
The present work emphasizes on the changes in the Red Sea and Dead Sea mixed waters physical properties including: temperature, pH, dissolved oxygen, density, salinity and viscosity. It focuses on the impacts of changes in mixed water quality on the Dead Sea ecosystem and the current industrial activities. The pilot project site consisted of six water ponds (tanks) located next to Arab Potash Company point of intake about 100 m south of the Dead Sea shores. The Red Sea - Dead Sea water mixing was controlled and done based on the expected mixing ratios between Red Sea and Dead Sea waters to mimic the potential actual situation associated with Red Sea - Dead Sea project conduit. All measured properties of mixed water bodies in tanks 1 to 5 tend to behave differently from similar Dead Sea water (tank 6) properties. The properties variations depend on the rate of diluting the Dead Sea water by Red Sea water and rejected brine. The least altered physical properties were observed when the Red Sea concentrated brine was added to the Dead Sea water (tank 5). The obtained results show that transferring Red Sea water to Dead Sea would lead to dilution of Dead Sea brine and affects significantly the investigated mixed water physical properties. Water mixing project is expected to cease the halite precipitation phenomenon due to the development of stratification in the Dead Sea and halite dissolution. Based on the industrial needs for the Dead Sea brine with its current physical properties, it is recommended to add rejected brine only to the Dead Sea due to its minimal effect on physical properties variations.


ED crowding and the use of nontraditional beds.
In an effort to compensate for crowding, many emergency departments (EDs) evaluate and treat patients in nontraditional settings such as gurneys in hallways and conference rooms. The impact of this practice on ED evaluation time is unknown. A historical cohort of adult ED visits to an academic hospital between August 1, 2009 and August 1, 2010, was used to evaluate the relationship between ED bed assignment (traditional, hallway, or conference room bed) and mean ED evaluation time, defined as the time spent in an ED bed before admission or discharge. Chief complaints were categorized into the 5 most frequent categories: abdominal/genitourinary, joint/muscle, general (fever, malaise), head/neck, and other. Multiple linear regression and marginal prediction were used to calculate the mean ED evaluation times for each bed type, overall, and by chief complaint category. During the study period, 15 073 patient visits met the inclusion criteria. After adjustment for patient and ED factors, assignments to hallway and conference room beds were associated with increases in a mean ED evaluation time of 13.3 minutes (95% confidence interval, 13.2-13.3) and 10.9 minutes (95% confidence interval, 10.8-10.9), respectively, compared with the traditional bed ED evaluation time. This varied by chief complaint category. Use of nontraditional beds is associated with increases in mean ED evaluation time; however, these increases are small and may be further minimized by restricting the use of nontraditional beds to patients with specific chief complaints. Nontraditional beds may have a role in improving ED throughput during times of crowding.


Highly accurate sigmoidal fitting of real-time PCR data by introducing a parameter for asymmetry.
Fitting four-parameter sigmoidal models is one of the methods established in the analysis of quantitative real-time PCR (qPCR) data. We had observed that these models are not optimal in the fitting outcome due to the inherent constraint of symmetry around the point of inflection. Thus, we found it necessary to employ a mathematical algorithm that circumvents this problem and which utilizes an additional parameter for accommodating asymmetrical structures in sigmoidal qPCR data. The four-parameter models were compared to their five-parameter counterparts by means of nested F-tests based on the residual variance, thus acquiring a statistical measure for higher performance. For nearly all qPCR data we examined, five-parameter models resulted in a significantly better fit. Furthermore, accuracy and precision for the estimation of efficiencies and calculation of quantitative ratios were assessed with four independent dilution datasets and compared to the most commonly used quantification methods. It could be shown that the five-parameter model exhibits an accuracy and precision more similar to the non-sigmoidal quantification methods. The five-parameter sigmoidal models outperform the established four-parameter model with high statistical significance. The estimation of essential PCR parameters such as PCR efficiency, threshold cycles and initial template fluorescence is more robust and has smaller variance. The model is implemented in the qpcR package for the freely available statistical R environment. The package can be downloaded from the author's homepage.


Isolation and partial characterization of cyclic lipopeptide antibiotics produced by Paenibacillus ehimensis B7.
The prevalence of drug-resistant bacteria has encouraged the search for novel antimicrobial compounds. Food-associated microorganisms, as a source of new antibiotics, have recently received considerable attention. The objective of this study was to find novel antimicrobial agents produced by food microorganisms. A bacterial strain B7, which has potent antimicrobial activity, was isolated from a sample of dairy waste. This strain was identified as Paenibacillus ehimensis based on the 16S rRNA gene sequence analysis, physiological and biochemical characterization. Two active compounds (PE1 and PE2) were obtained from P. ehimensis B7. Mass spectrometry (MS) analysis showed that the molecular masses of PE1 and PE2 were 1,114 and 1,100 Da, respectively. The tandem MS and amino acid analysis indicated that PE1 and PE2 were analogs of polypeptin, and PE2 was characterized as a new member of this family. Both compounds were active against all tested bacterial pathogens, including methicillin resistant Staphylococcus aureus, Escherichia coli, and pan-drug resistant Pseudomonas aeruginosa clinical isolate. Time-kill assays demonstrated that at 4 × MIC (minimum inhibitory concentration), PE1 and PE2 rapidly reduced the number of viable cells by at least 3-orders of magnitude, indicating that they were bactericidal antibiotics. In the present work, two cationic lipopeptide antibiotics (PE1 and PE2) were isolated from P. ehimensis B7 and characterized. These two peptides showed broad antimicrobial activity against all tested human pathogens and are worthy of further study.


Inclusion body myositis-like phenotype induced by transgenic overexpression of beta APP in skeletal muscle.
Inclusion body myositis (IBM), the most common age-related muscle disease in the elderly population, is an incurable disorder leading to severe disability. Sporadic IBM has an unknown etiology, although affected muscle fibers are characterized by many of the pathobiochemical alterations traditionally associated with neurodegenerative brain disorders such as Alzheimer's disease. Accumulation of the amyloid-beta peptide, which is derived from proteolysis of the larger amyloid-beta precursor protein (betaAPP), seems to be an early pathological event in Alzheimer's disease and also in IBM, where in the latter, it predominantly occurs intracellularly within affected myofibers. To elucidate the possible role of betaAPP mismetabolism in the pathogenesis of IBM, transgenic mice were derived in which we selectively targeted betaAPP overexpression to skeletal muscle by using the muscle creatine kinase promoter. Here we report that older (>10 months) transgenic mice exhibit intracellular immunoreactivity to betaAPP and its proteolytic derivatives in skeletal muscle. In this transgenic model, selective overexpression of betaAPP leads to the development of a subset of other histopathological and clinical features characteristic of IBM, including centric nuclei, inflammation, and deficiencies in motor performance. These results are consistent with a pathogenic role for betaAPP mismetabolism in human IBM.


Subconjunctival epithelial inclusion cyst complicating strabismus surgery: Early excision is better.
Epithelial inclusion cysts can occur following otherwise-uncomplicated strabismus surgery. Because of their tendency to grow posteriorly into the orbit, they should be monitored closely or treated when relatively small. We report and discuss an illustrative case.


Incidence of malignant bone and joint tumors in Olmsted County, Minnesota, 1935 through 1981.
During the 47-year period 1935 through 1981, 30 cases of malignant bone and joint tumors (in 20 male and 10 female patients) were identified among Olmsted County, Minnesota, residents. The incidence rates per 100,000 population, age-adjusted to the 1970 US total white population, were 1.0 overall, 1.4 for male subjects, and 0.7 for female subjects. Mortality rates, likewise age-adjusted, were 0.7 overall and 1.1 and 0.3 for male and female subjects, respectively. These rates are similar to those from tumor registries, a finding that suggests that reporting of these tumors is relatively complete. The similarity of the incidence and the mortality rates is consistent with the high case-fatality rate. A comparison of the Olmsted County cases with Mayo Clinic referral cases provides some evidence for referral bias, as the referral patients were significantly younger and had significantly more high-grade tumors.