Evaluation of the Current Techniques and Introduction of a Novel Approach for Estimating Maxillary Anterior Teeth Dimensions.
Several techniques and methods have been proposed to estimate the anterior teeth dimensions in edentulous patients. However, this procedure remains challenging especially when preextraction records are not available. Therefore, the purpose of this study is to evaluate some of the existing extraoral and intraoral methods for estimation of anterior tooth dimensions and to propose a novel method for estimation of central incisor width (CIW) and length (CIL) for Saudi population. Extraoral and intraoral measurements were recorded for a total of 236 subjects. Descriptive statistical analysis and Pearson's correlation tests were performed. Association was evaluated between combined anterior teeth width (CATW) and interalar width (IAW), intercommisural width (ICoW) and interhamular notch distance (IHND) plus 10 mm. Evaluation of the linear relationship between central incisor length (CIL) with facial height (FH) and CIW with bizygomatic width (BZW) was also performed. Significant correlation was found between the CATW and ICoW and IAW (p-values <0.0001); however, no correlation was found relative to IHND plus 10 mm (p-value = 0.456). Further, no correlation was found between the FH and right CIL and BZW and right CIW (p-values = 0.255 and 0.822). The means of CIL, CIW, incisive papillae-fovea palatinae (IP-FP), and IHND were used to estimate the central incisor dimensions: CIL = FP-IP distance/4.45, CIW = IHND/4.49. It was concluded that the ICoW and IAW measurements are the only predictable methods to estimate the initial reference value for CATW. A proposed intraoral approach was hypothesized for estimation of CIW and CIL for the given population. Based on the results of the study, ICoW and IAW measurements can be useful in estimating the initial reference value for CATW, while the proposed novel approach using specific palatal dimensions can be used for estimating the width and length of central incisors. These methods are crucial to obtain esthetic treatment results within the parameters of the given population.


Hyperleukocytosis in childhood acute lymphoblastic leukemia: complications and treatment outcome.
Hyperleukocytosis, defined as a peripheral leukocyte count ≥ 100x109/L, is seen in 5-20% of newly diagnosed cases of childhood leukemia and is a poor prognostic factor. In this study, we aimed to examine the presenting clinical and laboratory features, complications, and treatment outcome of 47 children with acute lymphoblastic leukemia (ALL) and hyperleukocytosis who were diagnosed and treated in four medical centers of İzmir between January 1990 and January 2001. The median age was 5.0 years (range: 0.1-16.3 years). Median white blood cell count was 495x109/L (range: 107x109/L- 794x109/L). Forty-two of 47 patients (90%) had hepatosplenomegaly, 5 (11%) had respiratory distress, 3 (6%) had neurologic symptoms, 3 (6%) had diffuse cervical lymphadenopathy, and 3 (6%) had acute renal failure at admission. Ten of 47 patients (21%) had central nervous system involvement, and 17 (36%) had mediastinal mass. Ten patients (21%) had coagulopathy and 15 patients (32%) had metabolic complications (8 patients had hyperuricemia, 4 had hyperphosphatemia, 2 had hyperuricemia, hyperphosphatemia and hypercalcemia, and 1 had hypocalcemia) before the initiation of therapy. Forty of 47 patients (85%) with hyperleukocytosis were effectively managed with intravenous hydration, alkalinization, and allopurinol therapy. Early death during remission induction therapy occurred in 5 patients (11%) with respiratory distress and sepsis. Kaplan-Meier estimates of event free survival and overall survival were 37.0% and 40.5%, respectively.


Mathematical modeling of blood coagulation cascade: kinetics of intrinsic and extrinsic pathways in normal and deficient conditions.
A mathematical model has been developed to simulate the generation of thrombin through intrinsic and extrinsic pathways. The time course of clotting factor activation during coagulation was calculated, and the sensitivity of the kinetics due to a decrease or deficiency in the concentrations of coagulation proteins or their activities was studied. The model gives reasonable predictions without the adjustment of any parameter values. The calculated clotting time was approximately 44 s for the intrinsic pathway and approximately 8.6 s for the extrinsic pathway using normal protein concentrations in plasma. Various prolonged clotting times were observed in different factor-deficient disorders using this model.


Control of relative direction and amplitude in extension/contraction motions of molecular strands induced by ion binding.
The shape of ligand strands composed of six-membered aza-heterocycles (het) connected at the alpha and alpha' positions by hydrazone (hyz) units is determined in a predictable fashion by the nature of the heterocyclic groups (pyridine, pyrimidine, pyrazine etc.), and covers the range from extended linear to compact helical structures. The binding of metal ions to the coordination subunits, defined by the het-hyz sequences, leads to marked shape changes by inter-converting bent and linear conformations of the subunits, thus inducing relative motions of strand domains either in the same (con-sense, "twirling") or in opposite (dis-sense, "flapping") directions. The amplitude of the motion induced by metal-ion binding and release and the relative directions of the formal motions can be controlled by the nature of the heterocyclic units. Thus, motions around a central 4,6-disubstituted pyrimidine are dis-sense motions, whereas there are con-sense motions around a central 2,5-disubstituted pyrazine unit, as illustrated by model ligands 1 and 2, respectively. The more extended helical 3 and undulating (zigzag shape) 4 ligands undergo larger-amplitude motions combining the relative displacements displayed by 1 and 2. Ligands 3 and 4 form linear tetranuclear Pb(II) and Zn(II) complexes, thus producing an extension motion. The same holds for [Ru(4)(terpy)(4)](PF(6))(8) (terpy=terpyridine). Reversible acid-base-triggered molecular motions have been generated with [Zn(4)(4)(OTf)(8)] (TfOH=triflic acid).


Scatter reduction for high resolution image detectors with a region of interest attenuator.
Compton scatter is the main interaction of x-rays with objects undergoing radiographic and fluoroscopic imaging procedures. Such scatter is responsible for reducing image signal to noise ratio which can negatively impact object detection especially for low contrast objects. To reduce scatter, possible methods are smaller fields-of-view, larger air gaps and the use of an anti-scatter grid. Smaller fields of view may not be acceptable and scanned-beam radiography is not practical for real-time imaging. Air gaps can increase geometric unsharpness and thus degrade image resolution. Deployment of an anti-scatter grid is not well suited for high resolution imagers due to the unavailability of high line density grids needed to prevent grid-line artifacts. However, region of interest (ROI) imaging can be used not only for dose reduction but also for scatter reduction in the ROI. The ROI region receives unattenuated x-rays while the peripheral region receives x-rays reduced in intensity by an ROI attenuator. The scatter within the ROI part of the image originates from both the unattenuated ROI and the attenuated peripheral region. The scatter contribution from the periphery is reduced in intensity because of the reduced primary x-rays in that region and the scatter fraction in the ROI is thus reduced. In this study, the scatter fraction for various kVp's, air-gaps and field sizes was measured for a uniform head equivalent phantom. The scatter fraction in the ROI was calculated using a derived scatter fraction formula, which was validated with experimental measurements. It is shown that use of a ROI attenuator can be an effective way to reduce both scatter and patient dose while maintaining the superior image quality of high resolution detectors.


Protective effect of Pulsatilla saponin A on acute myocardial infarction via miR-24-3p/p16.
The effect of Pulsatilla saponin A (PsA) on acute myocardial infarction (AMI) was unknown. This study targeted to examine the roles of PsA on hypoxia-triggered toxicity to H9c2 cells and reveal the potential mechanism. H9c2 cells were maintained under a hypoxic environment for 12 h to construct the AMI cell model and the cells were pretreated by PsA. Hypoxia triggered toxicity to H9c2 cells and the anti-toxicity effect of PsA was evaluated by CCK8, TUNEL, and Western blot. The levels of miR-24-3p and p16 in H9c2 cells, AMI group tissues, and their respective controls were assessed using qRT-PCR. The dual-luciferase assay was applied to verify the targeting mechanism of miR-24-3p on p16. Then the effects of miR-24-3p inhibitor or/and si-p16 on H9c2 cells treated with PsA under hypoxia were detected by CCK8, TUNEL, and Western blot. Flow cytometry was executed to determine the cell cycle. Hypoxia decreased viability and proliferation and increased apoptosis of H9c2 cells, which were ameliorated by PsA pretreatment. The level of miR-24-3p was diminished, but p16 expression was elevated in hypoxia-treated cells and AMI group tissues. MiR-24-3p could sponge p16 in hypoxia-treated cells. Furthermore, the impact of applying miR-24-3p inhibitor on PsA and hypoxia-treated cells could be reversed by si-p16. PsA relieved hypoxia-triggered cell toxicity via miR-24-3p/p16 axis. These findings provided some fresh insights into the potential therapeutic effects of the application of PsA in AMI.


Serum level of placental growth hormone is raised in pregnancy rhinitis.
To describe any relationship between pregnancy rhinitis and weight gain or serum levels of estradiol, progesterone, placental growth hormone, or insulinlike growth factor I. Twenty-seven nonsmoking healthy pregnant women aged 22 to 38 years (mean age, 28 years) who had no history of respiratory allergy or chronic nasal or sinus problems volunteered to enter the study. They had no nasal complaints at entry. Nasal patency was registered daily from early pregnancy until 1 month after delivery. Nasal and oral peak expiratory flow rates were established, and the subjective blockage was scored from 0 to 4, with 0 indicating no blockage. Serum samples were collected and weight was measured on 4 occasions during pregnancy and again at the end of the study. Pregnancy rhinitis was diagnosed if the subjective nasal obstruction score was 1 or higher every morning for at least 6 weeks immediately preceding delivery, then returned to 0 within 2 weeks and remained at 0 until the end of the study. If on any day other signs of respiratory tract infection occurred, that day was excluded. Pregnancy rhinitis was diagnosed in 5 women. These 5 women showed significantly higher levels of placental growth hormone than the women without the diagnosis. No significant difference was found between the 2 groups regarding body weight or any of the other serum levels studied. Serum level of placental growth hormone is raised in pregnancy rhinitis and may be involved in its pathogeny. Pregnancy rhinitis does not significantly raise weight gain or serum levels of estradiol, progesterone, or insulinlike growth factor I.


Photoacoustic detection of H-D exchange in the system H(2)S-D(2)S.
A method is described which allows a single-pulse analysis of photoacoustic signals. Isotope specific excitation of D(2)S and HDS is performed with a TEA CO(2) laser, and the concentration change of the two species caused by H-D exchange after fast mixing of H(2)S and D(2)S is monitored. No influence of the laser radiation on the exchange reaction could be detected. Thus the progress of an independent chemical reaction was analyzed by a concentration measurement. The time resolutions is determined by the repetition rate of the laser.


Balancing Activity and Stability in Halogen-Bonding Catalysis: Iodopyridinium-Catalyzed One-Pot Synthesis of 2,3-Dihydropyridinones.
A one-pot cascade reaction for 2,3-dihydropyridinone synthesis was accomplished with 3-fluoro-2-iodo-1-methylpyridinium triflate as the halogen bond catalyst. The desired [4+2] cycloaddition products, bearing aryl, heteroaryl, alkyl, and alicyclic substituents, were successfully furnished in 28-99% yields. Mechanistic investigations proved that a strong halogen-bonding interaction forged between the iodopyridinium catalyst and imine intermediate was essential to dynamically masking the vulnerable C-I bond on the catalyst and accelerating the following aza-Diels-Alder reaction.


Synthesis of a C-Nucleoside Phosphonate by Base-Promoted Epimerization.
The efficient synthesis of a [2'S] C-nucleoside phosphonate and its corresponding prodrug has been realized. A phosphonomethoxy group was stereoselectively introduced at the anomeric 5'-carbon atom through glycosylation of a benzoyl protected [5'R]-acetoxy-[2'R]-9-deazaadenine. An unexpected epimerization at the 2'-position of the sugar moiety occurred upon removal of the protecting groups, but this was further exploited as a key reaction for improved synthesis of the target compound.


[Neuroprotective effect of epigallocatechin gallate on oxidative-stress-injured retinal cells].
To investigate the neuroprotective effect of epigallocatechin gallate(EGCG), the main extract from green tea, on the oxidative-stress-injured retinal ganglion cells. Rat retinal ganglion cells (RGC-5) were cultured into 3 groups (normal control; H2O2; H2O2 + EGCG or Trolox or NU1025). In-situ TUNEL was used to detect the apoptosis of the RGC-5 cells. Dihydroethidium (DHE) assay was used to observe the intracellular ROS generation. The activation of nuclear enzyme, PARP-1 was quantitatively detected by Western blot and the cell viability was measured by MT method. Hydrogen peroxide reduced RGC-5 cell viability in a time-concentration-dependent manner. The treatment of 500 micromol/L H2O2 for 24 hours reduced RGC-5 cell viability by about 50% of control. Hydrogen peraoxide caused apoptosis of the RGC-5 cell, obviously increased intracellular ROS generation and up-regulated the PARP-1 expression. The pretreatment with EGCG was able to markedly reduce the number of apoptotic cells, attenuate intracellular ROS generation. Furthermore, MTT assay showed that the pretreatment with EGCG (50 micromol/L) increased the most cell viability to 87% of control, but pretreatment with Trolox (100 micromol/L) and NU1025 (100 micromol/L, a PARP-1 inhibitor) recovered the most cell viability to 62% and 71% of control respectively. EGCG is able to effectively protect retinal ganglion cell against oxidative-stressed injury and can be used as a very potential neuroprotective drug.


The relationship between self-esteem and psychological distress in critical care nurses.
Self-esteem can be described as negative or positive beliefs people have about themselves. It is an important personal source to combat stress and protect health, and related to job satisfaction. The aim of this study was to examine the relationship between self-esteem and psychological distress in critical care nurses. A cross-sectional study. The research population of study consisted of 121 critical care nurses working at a university hospital in Edirne, Turkey between January and April 2017. A questionnaire consisting of 26 questions was used to obtain the personal and demographic information. The Symptom Check List-90-R test was used to determine the emotional status and the self-esteem scale was used to determine the self-esteem status of the participants. Participants were divided into two groups according to the self-esteem scale median score (Group 1: below 60, and Group 2: 60 and above). The general severity index of the nurses was 1.11 (95% confidence interval [CI] 1.00-1.21). The general severity index of those with a self-esteem scale score below 60 was 1.47 (95% CI 1.37-1.57), while for those who with a self-esteem score of 60 and above, it was 0.73 (95% CI 0.59-0.87). The general severity index of the nurses in Group 1 was statistically significantly higher than that for those in Group 2. The number of nurses with a high symptom level in Group 1 was statistically significantly higher than those in Group 2. The study showed that the general severity index and poor symptom level ratios associated with mental well-being are high in critical care nurses. However, critical care nurses with high self-esteem had fewer psychological problems than those with lower self-esteem. Critical care nurses with low self-esteem should be given assertiveness, resilience, and interpersonal communication skills training, even outside of health care.


Connective tissue growth factor expression in precancerous lesions of human esophageal epithelium and prognostic significance in esophageal squamous cell carcinoma.
Connective tissue growth factor (CTGF, CCN2), a secreted protein, is involved in the development and progression of esophageal squamous cell carcinoma (ESCC). However, it remains unclear how CTGF expression affects the progression of ESCC. Our study implicated differences of CTGF protein status in precancerous lesions, and retrospectively examined the associations of CTGF mRNA and protein levels with clinical prognosis in ESCC patients. Here immunohistochemistry and the quantitative real-time real-time reverse transcription polymerase were performed for predicting the CTGF protein status and mRNA levels in ESCC patients, respectively. Different degrees of CTGF protein status presented in normal human esophageal epithelium and precancerous lesions, and CTGF protein was highly expressed in ESCCs. Survival analysis showed that CTGF protein status was significantly related to poor survival of ESCC patients (P= 0.024), while no significant difference was observed between CTGF mRNA levels and the survival of ESCC patients (P= 0.196). Multivariate Cox analysis demonstrated that CTGF protein status was the independent factor in prognosis of ESCC patients. In that way, CTGF protein status might elevate the progression of ESCC, and would be significant for the diagnosis of precancerous lesions or early ESCC.


Gender influences headache characteristics with increasing age in migraine patients.
Migraine headache is one of the most common primary headache disorders and is three times more prevalent in women than in men, especially during the reproductive ages. The neurobiological basis of the female dominance has been partly established. The present study aimed to investigate the effect of gender on the headache manifestations in migraine patients. The study group consisted of 2082 adult patients from five different hospitals' tertiary care-based headache clinics. The relationship between headache characteristics and gender was evaluated in migraine with aura (MwA) and migraine without aura (MwoA). The duration, severity, frequency of headache and associated symptoms were evaluated in both genders and age-dependent variations and analyzed in two subgroups. Women with migraine were prone to significantly longer duration and intensity of headache attacks. Nausea, phonophobia and photophobia were more prevalent in women. Median headache duration was also longer in women than in men in MwA (p = 0.013) and MwoA (p < 0.001). Median headache intensity was higher in women than in men in MwA (p = 0.010) and MwoA (p = 0.009). The frequency of nausea was significantly higher in women than in men in MwA (p = 0.049). Throbbing headache quality and associated features (nausea, photophobia, and phonophobia) were significantly more frequent in women than in men in MwoA. The gender impact varied across age groups and significant changes were seen in female migraineurs after age 30. No age-dependent variation was observed in male migraineurs. Gender has an influence on the characteristics of the headache as well as on the associated symptoms in migraine patients, and this impact varies across the age groups, particularly in women.


Observations on cannabinoid content in Cannabis sativa L. grown in Tuscany, Italy.
The paper summarizes the analytical results on 114 Cannabis sativa L. samples seized in Tuscany. The percentage of delta 9-tetrahydrocannabinol content in adult plants and the phenotype ratio of young plants were determined to differentiate fibre-type from drug-type cannabis plants. The analysis revealed that 71.9 per cent of the total sample were cannabis plants of a drug type.


Betaine Supplementation Enhances Lipid Metabolism and Improves Insulin Resistance in Mice Fed a High-Fat Diet.
Obesity is a major driver of metabolic diseases such as nonalcoholic fatty liver disease, certain cancers, and insulin resistance. However, there are no effective drugs to treat obesity. Betaine is a nontoxic, chemically stable and naturally occurring molecule. This study shows that dietary betaine supplementation significantly inhibits the white fat production in a high-fat diet (HFD)-induced obese mice. This might be due to betaine preventing the formation of new white fat (WAT), and guiding the original WAT to burn through stimulated mitochondrial biogenesis and promoting browning of WAT. Furthermore, dietary betaine supplementation decreases intramyocellular lipid accumulation in HFD-induced obese mice. Further analysis shows that betaine supplementation reduced intramyocellular lipid accumulation might be associated with increasing polyunsaturated fatty acids (PUFA), fatty acid oxidation, and the inhibition of fatty acid synthesis in muscle. Notably, by performing insulin-tolerance tests (ITTs) and glucose-tolerance tests (GTTs), dietary betaine supplementation could be observed for improvement of obesity and non-obesity induced insulin resistance. Together, these findings could suggest that inhibiting WAT production, intramyocellular lipid accumulation and inflammation, betaine supplementation limits HFD-induced obesity and improves insulin resistance.


Development of blueberry liquor: influence of distillate, sweetener and fruit quantity.
In this work different formulations of blueberry liquor were tested and characterised based on their physico-chemical and sensory characteristics. Three factors were evaluated: the distillate used to produce the liquor (wine spirit or grape marc spirit); the sweetener (white sugar or honey) and the fruit quantity (two doses). For each liquor, pH, total acidity, dry soluble solids content, dry extract, alcoholic strength, reducing sugars, colour intensity, methanol content, acetaldehyde and fusel alcohols were determined. Sensory tests were carried out with a trained panel. The three factors studied significantly influenced the physico-chemical features of the liquors, being the quantity of fruit the most discriminating factor, except for the volatile compounds which were mainly influenced by the distillate. As regards the sensory analysis, it was found that the most appreciated liquor was that prepared with wine spirit, sugar and a lower dose of blueberry, and the less appreciated formulation was the one made with grape marc spirit, honey and a lower quantity of blueberry. © 2017 Society of Chemical Industry.


iTRAQ-based quantitative proteome analysis reveals metabolic changes between a cleistogamous wheat mutant and its wild-type wheat counterpart.
Wheat is one of the most important staple crops worldwide. Fusarium head blight (FHB) severely affects wheat yield and quality. A novel bread wheat mutant, ZK001, characterized as cleistogamic was isolated from a non-cleistogamous variety Yumai 18 (YM18) through static magnetic field mutagenesis. Cleistogamy is a promising strategy for controlling FHB. However, little is known about the mechanism of cleistogamy in wheat. We performed a FHB resistance test to identify the FHB infection rate of ZK001. We also measured the agronomic traits of ZK001 and the starch and total soluble sugar contents of lodicules in YM18 and ZK001. Finally, we performed comparative studies at the proteome level between YM18 and ZK001 based on the proteomic technique of isobaric tags for relative and absolute quantification. The infection rate of ZK001 was lower than that of its wild-type and Aikang 58. The abnormal lodicules of ZK001 lost the ability to push the lemma and palea apart during the flowering stage. Proteome analysis showed that the main differentially abundant proteins (DAPs) were related to carbohydrate metabolism, protein transport, and calcium ion binding. These DAPs may work together to regulate cellular homeostasis, osmotic pressure and the development of lodicules. This hypothesis is supported by the analysis of starch, soluble sugar content in the lodicules as well as the results of Quantitative reverse transcription polymerase chain reaction. Proteomic analysis has provided comprehensive information that should be useful for further research on the lodicule development mechanism in wheat. The ZK001 mutant is optimal for studying flower development in wheat and could be very important for FHB resistant projects via conventional crossing.


Unusual manifestations of salmonellosis--a surgical problem.
From January 1981 to December 1992, of 6250 cases of salmonellosis treated at the Christian Medical College and Hospital, Vellore, India, 100 patients with focal pyogenic infection caused by salmonellae required surgical intervention in addition to medical therapy. Thirty-one had involvement of the hepatobiliary system, and 10 more had other intra-abdominal infections. Involvement of bone and joint as well as soft tissue constituted 15% each. The site of infection in patients with soft tissue abscesses included skin (7), parotid (2), thyroid (2), breast (1) inguinal node (1), branchial sinus (1) and injection site (1). Three patients had arterial infections. Noteworthy among the cases of genital infections was one case of salmonella infection in a pre-existing hydrocele, and one case of epididymo-orchitis with a loculated salmonella infection. Salmonella infection in a pre-existing ovarian cyst was seen in a patient with endometriosis. The salmonella serotypes most frequently encountered were S. typhi (36) and S. typhimurium (36), followed by S. paratyphi A (15). The importance of recognition of these protean manifestations of salmonellosis in an endemic setting is discussed. The microbiological evaluation of properly obtained specimens is mandatory in such unusual pyogenic infections.


Ultrasonically guided percutaneous nephrostomy.
Ultrasonically guided percutaneous nephrostomy was planned in 98 patients with a total of 128 nephrostomies. The success rate was over 90%. The catheters were maintained from a 1/2 day to 150 days with a median duration of 13 days. 26% of the patients had the catheter replaced, mainly because of displacement. Two major complications were seen, one perforation of the gallbladder and one case of major haemorrhage resulting in a nephrectomy. Two of the 26 patients infected at the puncture died from sepsis. Among cases with low ureteral obstruction untreated prostatic carcinoma and ureteral tumors were the two only categories in which a palliative nephrostomy was beneficial.


Expression of growth hormone, growth hormone releasing hormone, and somatostatin genes is unperturbed in the streptozotocin-induced diabetic rat.
The effects of streptozotocin diabetes on the level of growth hormone, growth hormone releasing hormone, and somatostatin mRNA was measured in control rats, in diabetic rats maintained on insulin, and in diabetic rats in which insulin had been withheld for 3 days. Total cytoplasmic RNA samples were prepared from the pituitary and hypothalamic tissues of each animal and analyzed by dot blot or Northern blot hybridization. No significant difference was observed between control and insulin-treated groups with regard to body weight or plasma glucose concentration. The insulin withdrawal group had significantly higher plasma glucose concentrations and lower body weights, confirming diabetic status. There was no significant difference in the level of growth hormone, growth hormone releasing hormone, and somatostatin mRNA among any of the three groups however. We conclude that alterations in the regulation of circulating growth hormone in the streptozotocin-induced diabetic rat, removed from insulin treatment for 3 days, did not occur at the transcriptional or RNA processing level. This conclusion extends to hypothalamic growth hormone releasing hormone, and somatostatin gene expression as well. Regulatory changes in growth hormone level previously noted during insulin withdrawal in the streptozotocin-induced diabetic rat could be the result of post-transcriptional processes operating at the level of hormone synthesis or release.


Application of guidelines on preoperative antibiotic prophylaxis in León, Nicaragua.
To determine adherence to the guideline for preoperative antibiotic use in Nicaragua. An observational study in the University Hospital of León, Nicaragua. All surgical patients in the departments of general surgery, orthopaedics, gynaecology and obstetrics, and paediatrics during a four-week period were included. Patients with infections prior to surgery were excluded. Main outcome measures were the proportion of patients that received appropriate preoperative antibiotics based on wound classification, suspected pathogens, administered antibiotics (type and dose), therapy duration and timing according to the local protocol. In the study, 297 patients received a total of 395 antibiotics with 2595 doses for a total of 1087 days. Only 68% of patients received antibiotic prophylaxis for indications mentioned in the protocol. Antibiotics were given without indication or as treatment in 23%. In 9% of the cases no preoperative antibiotic therapy was given (no indication for 6%, but indicated for 3%). Of the 201 patients with an indication for prophylaxis, 25% received more antibiotic therapies than indicated. Antibiotic choice was discordant with the protocol in 69%, dose in 20%, and both the moment of administration and duration in 78%. Overall adherence was achieved in 7% of patients. Complete protocol violations were observed in 12%. The 243 patients in the prophylaxis group received 1707 doses, 83% of which were administered unnecessarily. Protocol violations are frequent in preoperative antibiotic prophylaxis in Nicaragua leading to considerable overprescription. Educational strategies to reinforce protocolised antibiotic use are essential for reducing costs and antibiotic resistance rates.


[Drugs under temporary use authorisation: 50 years of French drug development].
Drug under temporary use authorisation (authorisation temporaire d' utilisation - ATU) was created in 1994 in France. Before this date, various procedures controlled patients' use of imported drug and drug in process. The AIDS pandemy development in 80's and the need to control news drugs patients' use contributed to the ATU statement setting up. This regulatory statement allows companies to sell drugs without market drug authorisation (autorisation de mise sur le marché - AMM), the letter being done in adequation with good pharmaceutical quality and a satisfactory level of benefices/ risks ratio. It's a recent French drug evaluation evolution.


Testing antimicrobials against biofilm bacteria.
Standard laboratory methods are needed to assess the efficacy of antimicrobial agents that are applied to biofilm bacteria. Existing standard suspension tests and dried surface tests show much greater efficacy than antimicrobial agents applied to biofilms. The greater resistance of biofilm bacteria to antimicrobial agents can be attributed to a number of interacting factors, including reaction and diffusion processes that limit an agent's accessibility to bacteria, phenotypic changes in biofilm bacteria caused by stress, and adaptation of the bacteria. Because biofilm systems are so diverse, a variety of new biofilm tests with features that differ in important ways from existing tests will ultimately be required. For example, the biofilm test apparatus may include a pump and a continuous-flow stirred tank reactor. This report provides an overview of biofilm testing and suggests a strategy for creating standard test methods.


The effect of silicone gel sheets on perfusion of hypertrophic burn scars.
The mechanism of action of topical silicone gel sheets on hypertrophic scars is not well understood and their effect on the blood flow within hypertrophic scars has not been investigated. The purpose of this study was to examine whether application of silicone gel sheets produced any acute effects on blood flow in hypertrophic burn scars. Perfusion of hypertrophic scars and adjacent normal skin was measured using a laser Doppler with and without application of silicone gel sheets. Continuous measurements were made for 5 minutes before gel application, for 30 minutes during gel application and for 5 minutes following gel removal. Surface temperature of the scar was continuously monitored. An occupational therapist, blinded to the perfusion level, rated each scar using the Vancouver Scar Scale. Eighteen scars and adjacent control sites in sixteen adult burn patients (11 male, 5 female; mean age: 42 +/- 14 years) were evaluated. The mean scar age was 5.4 +/- 3.7 months. The mean Vancouver Scar Scale was 5.5 +/- 2.4. Hypertrophic scars demonstrated higher perfusion measurements at baseline compared to control areas (58.5 +/- 19.3 flux units vs 25.0 +/- 8.4 flux units; P < 0.001). Application of silicone sheeting gel did not significantly alter perfusion in either the hypertrophic scar or normal tissue from the baseline measurements. However, application of silicone gel sheeting did significantly increase the mean baseline surface temperature of the hypertrophic scar from 29 +/- 0.8 degrees C to 30.7 +/- 0.6 degrees C (P < 0.001). The mechanism of action of silicone gel sheeting probably does not involve an acute alteration in blood flow within the scar. However, surface temperature of the scar increased significantly following gel application, raising the possibility that temperature alteration is involved in the mechanism of action.


Testosterone pulses paired with a location induce a place preference to the nest of a monogamous mouse under field conditions.
Changing social environments such as the birth of young or aggressive encounters present a need to adjust behavior. Previous research examined how long-term changes in steroid hormones mediate these adjustments. We tested the novel concept that the rewarding effects of transient testosterone pulses (T-pulses) in males after social encounters alter their spatial distribution on a territory. In free-living monogamous California mice (Peromyscus californicus), males administered three T-injections at the nest spent more time at the nest than males treated with placebo injections. This mimics T-induced place preferences in the laboratory. Female mates of T-treated males spent less time at the nest but the pair produced more vocalizations and call types than controls. Traditionally, transient T-changes were thought to have transient behavioral effects. Our work demonstrates that in the wild, when T-pulses occur in a salient context such as a territory, the behavioral effects last days after T-levels return to baseline.


Dopamine transporter inhibition is required for cocaine-induced stereotypy.
The primary mechanism by which cocaine induces stereotypy has been difficult to discern because cocaine has three high-affinity targets: the reuptake transporters for dopamine (DAT), norepinephrine, and serotonin. To dissect out the role of DAT in cocaine effects, we generated a knock-in mouse line with a cocaine-insensitive DAT (DAT-CI mice). DAT-CI mice provide a powerful tool that can directly test whether DAT inhibition is important for cocaine-induced stereotypy. We found that acute cocaine failed to produce stereotypy in DAT-CI mice. In fact, 40 mg/kg cocaine suppressed stereotypy in DAT-CI mice but produced profound stereotypy in wild-type mice. These findings suggest that DAT inhibition is necessary for cocaine-induced stereotypy. Furthermore, mechanisms independent of DAT inhibition appear to inhibit stereotypy.


Stereotypies in caged parrots, schizophrenia and autism: evidence for a common mechanism.
Spontaneously occurring abnormal behaviors in animals have recently received considerable attention, both in veterinary medicine and as a potential model for abnormal behavior in several human mental disorders. Stereotypies are abnormal repetitive, unvarying, and functionless behaviors that are often performed by captive and domesticated animals housed in barren environments. They closely resemble the stereotypies of autistic and mentally retarded patients, stereotypies of unmedicated chronic schizophrenic patients, certain classes of simple tic in Tourette's syndrome, and several drug-induced behaviors. However, evidence for a common mechanism has been lacking. Stereotypies in human mental disorders are indicative of profound brain dysfunction involving the basal ganglia, and are associated with pervasive voluntary-motor impairments and psychological distress. Here we show that stereotypy in captive Orange-Wing Amazon Parrots (Amazona amazonica) is correlated with poor performance on the same psychiatric task (the 'gambling task') as stereotypy in autistic and schizophrenic patients. The task measures recurrent perseveration-the tendency to inappropriately repeat responses. Thus, the more stereotypy a parrot performed, the more likely it was to inappropriately repeat itself from trial-to-trial on the task; and the more rapidly it made repeated, but not switched, responses. These results parallel the executive motor impairments seen in human patients, and therefore suggest that, like in human patients, stereotypy in caged parrots reflects a general disinhibition of the behavioral control mechanisms of the dorsal basal ganglia. If this result holds true in other laboratory species, stereotypic animals are likely to be of questionable utility in behavior, neuroscience, and neuropharmacological experiments. In humans, stereotypies and obsessive-compulsive behaviors are considered to be mutually exclusive categories of behavior, with different neural substrates, and different treatment strategies. These results, therefore, suggest that the pharmacological treatment of stereotypies in veterinary medicine based on the assumption that they are equivalent to human Obsessive-Compulsive Disorder may be inappropriate. As stereotypies in captive animals develop in response to the captive environment, these results also emphasize the role that the environment may play in eliciting or exacerbating stereotypy in human patients. Finally, by parallel to human patients, there is a potential psychological distress in animals showing these behaviors.


The ANF-RGC gene motif (669)WTAPELL(675) is vital for blood pressure regulation: biochemical mechanism.
ANF-RGC is the prototype membrane guanylate cyclase, both the receptor and the signal transducer of the hormones ANF and BNP. After binding them at the extracellular domain, it, at its intracellular domain, signals activation of the C-terminal catalytic module and accelerates production of the second messenger, cyclic GMP. This, in turn, controls the physiological processes of blood pressure, cardiovascular function, fluid secretion, and others: metabolic syndrome, obesity, and apoptosis. The biochemical mechanism by which this single molecule controls these diverse processes, explicitly blood pressure regulation, is the subject of this study. In line with the concept that the structural modules of ANF-RGC are designed to respond to more than one yet distinctive signals, the study demonstrates the construction of a novel ANF-RGC-In-gene-(669)WTAPELL(675) mouse model. Through this model, the study establishes that (669)WTAPELL(675) is a vital ANF signal transducer motif of the guanylate cyclase. Its striking physiological features linked with their biochemistry are the following. (1) It controls the hormonally dependent cyclic GMP production in the kidney and the adrenal gland. Its deletion causes (2) hypertension and (3) cardiac hypertrophy. (4) These mice show higher levels of the plasma aldosterone. For the first time, a mere seven-amino acid-encoded motif of the mouse gene has been directly linked with the physiological control of blood pressure regulation, a detailed biochemistry of this linkage has been established, and a model for this linkage has been described.


Drugs and other chemicals involved in fatal poisoning in England and Wales during 2000 – 2011.
Fatal poisoning data can reveal trends in the poisons encountered, which can help guide prescribing practices and product safety and other legislation, and more recently has helped to monitor the use of emerging drugs of abuse ( ' legal highs ' ). We searched Mortality Statistics – Injury and poisoning, Series DH4 (2000 – 2005), Mortality Statistics – Deaths registered in England and Wales, Series DR (2006 – 2011), and the Office for National Statistics drug poisoning database for information on fatal poisoning during 2000 – 2011. We also searched the Pubmed database for ' fatal ' and ' poisoning ' and ' England ' and ' Wales ' : this search yielded seven papers that gave relevant information on deaths reported during 2000 – 2011 that were not superseded by later publications. DEATHS FROM POISONING: The annual number of deaths from poisoning fell from 2000 (3092) to 2010 (2749), before increasing to 3341 in 2011. This increase was due in part to a change in the ICD coding relating to alcohol poisoning, suggesting that such deaths had been under-recorded previously. Although fatalities from dextropropoxyphene declined (287 in 2004 and 18 in 2011) following the withdrawal of co-proxamol (paracetamol [acetaminophen] and dextropropoxyphene [propoxyphene] mixture) during 2005 – 2007, deaths involving codeine and most notably tramadol (836 deaths during 2000 – 2011) increased. Deaths from paracetamol poisoning either alone, or with alcohol reached 89 in 2011, the lowest annual figure since 1974. However, in reality there has been no marked downward trend since 1999 despite reductions in pack size, continued publicity as to the dangers of paracetamol overdose, and improved liver failure treatment, including transplantation. The annual number of deaths from antidepressants remained relatively stable (median: 397, range: 335 – 469). Although the number of deaths from dosulepin [dothiepin] decreased (186 in 2000 and 49 in 2011), the number of deaths involving selective serotonin reuptake inhibitors increased (50 in 2000 and 127 in 2011). Although annual numbers of deaths involving diamorphine/morphine (88% unintentional) declined, deaths involving methadone (89% unintentional) increased and the total annual number of deaths from these drugs showed little change (2000: 1061, 2011: 995). Deaths involving amfetamine/metamfetamine remained relatively constant at about 50 annually, and whilst cocaine-related deaths fell by 48% during 2008 – 2011, and deaths involving MDMA and related compounds fell by 69% over this same period, deaths involving ' legal highs ' , notably γ -hydroxybutrate/ γ -butyrolactone and ketamine, increased. Alterations in the availability of paracetamol and of prescription drugs such as dextropropoxyphene and dosulepin have not been accompanied by decreases in the number of deaths from poisoning. Despite intense media and other interest, the annual number of deaths (250 – 300) involving ' recreational ' drugs remains small in relation to the 1000 or so deaths a year from diamorphine and/or methadone.


Ion-specific excluded-volume correlations and solvation forces.
Realistic ion-ion and ion-surface potentials from explicit-water simulations are used in implicit-solvent Monte Carlo simulations to study the ionic structure and double-layer forces in a nanometer slab confinement. The highly salt-specific results can be reproduced and rationalized by a simple nonlocal Poisson-Boltzmann theory of a nonadditive primitive model, in which effective hard-sphere radii are obtained from the short-ranged part of the pair potentials. Steric corrections to solvation forces are mainly repulsive and strongly coupled to the ion-surface interactions.


Determination of inlet transmission and conversion efficiencies for in situ measurements of the nocturnal nitrogen oxides, NO3, N2O5 and NO2, via pulsed cavity ring-down spectroscopy.
Pulsed cavity ring-down spectroscopy is a highly sensitive method for direct absorption spectroscopy that has been applied to in situ detection of NO3, N2O5 and NO2 in the atmosphere from a variety of platforms, including ships, aircraft, and towers. In this paper, we report the development of schemes to significantly improve the accuracy of these measurements. This includes the following: (1) an overall improvement in the inlet transmission efficiencies (92 +/- 2% for NO3 and 97 +/- 1% for N2O5) achieved primarily through a reduction in the inlet residence time; and (2) the development of a calibration procedure that allows regular determination of these efficiencies in the field by addition of NO3 or N2O5 to the inlet from a portable source followed by conversion of NO3 to NO2. In addition, the dependence of the instrument's sensitivity and accuracy to a variety of conditions encountered in the field, including variations in relative humidity, aerosol loading, and VOC levels, was systematically investigated. The rate of degradation of N2O5 transmission efficiency on the inlet and filter system due to the accumulation of inorganic aerosol was determined, such that the frequency of filter changes required for accurate measurements could be defined. In the absence of aerosol, the presence of varying levels of relative humidity and reactive VOC were found to be unimportant factors in the instrument's performance. The 1 sigma accuracy of the NO3, N2O5, and NO2 measured with this instrument are -9/+12, -8/+11, +/- 6%, respectively, where the -/+ signs indicate that the actual value is low/high relative to the measurement. The largest contribution to the overall uncertainty is now due to the NO3 absorption cross section rather than the inlet transmission efficiency.


Hierarchical Fluid Interface Enables Spatiotemporal Regulation of Ligand Distribution to Increase Kinetics and Thermodynamics of Interfacial Binding Reaction.
In nature, regulation of the spatiotemporal distribution of interfacial receptors and ligands leads to optimum binding kinetics and thermodynamics of receptor-ligand binding reactions within interfaces. Inspired by this, we report a hierarchical fluid interface (HieFluidFace) to regulate the spatiotemporal distribution of interfacial ligands to increase the rate and thermodynamic favorability of interfacial binding reactions. Each aptamer-functionalized gold nanoparticle, termed spherical aptamer (SAPT), is anchored on a supported lipid bilayer without fluidity, like an "island", and is surrounded by many fluorescent aptamers (FAPTs) with free fluidity, like "rafts". Such ligand "island-rafts" model provides a large reactive cross-section for rapid binding to cellular receptors. The synergistic multivalency of SAPTs and FAPTs improves interfacial affinity for tight capture. Moreover, FAPTs accumulate at binding sites to bind to cellular receptors with clustered fluorescence to "lighten" cells for direct identification. Thus, HieFluidFace in a microfluidic chip achieves high-performance capture and identification of circulating tumor cells from clinical samples, providing a new paradigm to optimize the kinetics and thermodynamics of interfacial binding reactions.


ELF18-INDUCED LONG NONCODING RNA 1 evicts fibrillarin from mediator subunit to enhance PATHOGENESIS-RELATED GENE 1 (PR1) expression.
Plant immune response is initiated upon the recognition of pathogen-associated molecular patterns such as elf18. Previously, we identified an Arabidopsis ELF18-INDUCED LONG NONCODING RNA 1 (ELENA1), as a positive transcriptional regulator of immune responsive genes. ELENA1 associated with Mediator subunit 19a (MED19a) to enhance enrichment of the complex on PATHOGENESIS-RELATED GENE 1 (PR1) promoter. In vitro and in vivo RNA-protein interaction experiments showed that ELENA1 can also interact with FIBRILLARIN 2 (FIB2). Co-immunoprecipitation and bimolecular fluorescence complementation assay showed that FIB2 directly interacts with MED19a in nucleoplasm and nucleolus. Analysis of fib2 mutant showed that FIB2 functions as a negative transcriptional regulator for immune responsive genes, including PR1. Genetic and biochemical analyses demonstrated that ELENA1 can dissociate the FIB2/MED19a complex and release FIB2 from PR1 promoter to enhance PR1 expression. ELENA1 increases PR1 expression by evicting the repressor (FIB2) from the activator (MED19a). Our findings uncover an additional layer of complexity in the transcriptional regulation of plant immune responsive genes by long noncoding RNA.


Castleman's disease with TAFRO syndrome: a case report from Syria.
Castleman's disease is a rare disorder, yet a rarer newly described syndrome called TAFRO syndrome was discovered to accompany it. TAFRO represents the constellation of symptoms (Thrombocytopenia, Anasarca, MyeloFibrosis, Renal failure, Organomegaly). Most cases were described in Japan. We present the first case of TAFRO syndrome in Syria. A 58-year-old Caucasian male with no relevant history presented with fatigue, oliguria, decreased platelets, increased creatinine level, hepatosplenomegaly, ascites, pitting edema and lymph node enlargement. Possible differential diagnoses were excluded by laboratory, radiologic and cytologic tests including TB, malignancy and autoimmune diseases. A biopsy of a supraclavicular lymph node confirmed Castleman disease. Our patient had Catleman's disease, and presented with only four diagnostic criteria for TAFRO syndrome (Myelofibrosis was absent) in addition to other minor characteristics (microcytic anemia, negative HIV and HHV-8 infections.) which make the presentation consistent with TAFRO syndrome described in the Japanese cases. The criteria for diagnosing TAFRO syndrome are still changing, and the pathophysiology behind it is unclear. We recommend further research to understand this syndrome taking into account that its prevalence might be worldwide.


Targeting autocrine and paracrine VEGF receptor pathways inhibits human lymphoma xenografts in vivo.
The role of angiogenesis in lymphoproliferative diseases is not well established. We demonstrate here that human lymphoma cells secrete vascular endothelial growth factor (VEGF) and express VEGF receptor 1 (VEGFR-1) and VEGFR-2. Proliferation of non-Hodgkin lymphoma (NHL) cells under serum-free conditions was enhanced by the addition of VEGF and was blocked by VEGFR-1- and VEGFR-2-specific antibodies. To differentiate between VEGF-mediated autocrine and paracrine effects on lymphoma growth, NOD/SCID mice engrafted with human diffuse large B-cell lymphoma (DLBCL) were treated with species-specific antibodies against human VEGFR-1 (6.12), human VEGFR-2 (IMC-1C11), murine VEGFR-1 (MF-1), or murine VEGFR-2 (DC101). Treatment with 6.12 or DC101 (targeting tumor VEGFR-1 and host VEGFR-2) reduced established DLBCL xenograft growth, whereas treatment with IMC-1C11 or MF-1 (targeting tumor VEGFR-1 and host VEGFR-1) had no effect. Decreased tumor volumes after 6.12 and DC101 treatment correlated with increased tumor apoptosis and reduced vascularization, respectively, supporting the presence of autocrine VEGFR-1- and paracrine VEGFR-2-mediated pathways in lymphomagenesis. Inhibition of paracrine VEGF interactions (DC101) in these models was equivalent to their inhibition with rituximab. Combining DC101 with therapeutic agents (rituximab, 6.12, methotrexate) consistently improved tumor responses over those of single-agent therapy. These data support the further clinical development of VEGFR-targeted approaches for the therapy of aggressive DLBCL.


Examining the polymorphisms in the hypoxia pathway genes in relation to outcome in colorectal cancer.
Colorectal cancer is a common malignancy. Identification of genetic prognostic markers may help prognostic estimations in colorectal cancer. Genes that regulate response to hypoxia and other genes that are regulated under the hypoxic conditions have been shown to play roles in cancer progression. In this study, we hypothesized that genetic variations in the hypoxia pathway genes were associated with the risk of outcome in colorectal cancer patients. This study was performed in two phases. In the first phase, 49 SNPs from six hypoxia pathway genes (HIF1A, HIF1B, HIF2A, LOX, MIF and CXCL12) in 272 colorectal cancer patients were analyzed. In the second phase, 77 SNPs from seven hypoxia pathway genes (HIF1A, HIF1B, HIF2A, HIF2B, HIF3A, LOX and CXCL12) were analyzed in an additional cohort of 535 patients. Kaplan Meier, Cox univariate and multivariable regression analyses were performed to analyze the relationship between the SNPs and overall survival (OS), disease free survival (DFS) or disease specific survival (DSS). Since this was a hypothesis-generating study, no correction for multiple testing was applied. In phase I, one SNP (HIF2A rs11125070) was found to be associated with DFS in multivariable analysis; yet association of a proxy polymorphism (HIF2A rs4953342) was not detected in the phase II patient cohort. In phase II, associations of two SNPs (HIF2A rs4953352 and HIF2B rs12593988) were significant in both OS and DFS multivariable analyses. However, association of HIF2A rs4953352 was not replicated in the phase I cohort using a proxy SNP (HIF2A rs6706003). Overall, our study did not find a convincing evidence of association of the investigated polymorphisms with the disease outcomes in colorectal cancer.


Neural Networks Applied for Predictive Parameters Analysis of the Refill Friction Stir Spot Welding Process of 6061-T6 Aluminum Alloy Plates.
Refill friction stir spot welding (RFSSW) technology is a solid-state joint that can replace conventional welding or riveting processes in aerospace applications. The quality of the new welding process is directly influenced by the welding parameters selected. A finite element analysis was performed to understand the complexity of the thermomechanical phenomena during this welding process, validated by controlled experiments. An optimization model using neural networks was developed based on 98 parameter sets resulting from changing 3 welding parameters, namely pin penetration depth, pin rotation speed, and retention time. Ten parameter sets were used to verify the learning results of the optimization model. The 10 results were drawn to correspond to a uniform distribution over the training domain, with the aim of avoiding areas that might have contained distortions. The maximum temperature and normal stress reached at the end of the welding process were considered output data.


Myotonic dystrophy: update on progress to define the gene.
Using standard likelihood linkage techniques, the gene for dystrophia myotonica has been localized to the proximal long arm of chromosome 19. Several large families provided the substrate for detecting linkage of restriction fragment length polymorphisms which were developed in the laboratory from flow-sorted chromosome 19 genomic libraries. In over 500 family members from five families only a single cross-over with ApoC2 was detected. Thus a useful probe for antenatal and preclinical diagnosis is now available. Details of the strategy employed within the framework of clinical diagnosis, genetic epidemiology and recombinant DNA techniques is described.


Tissue markers of potentially malignant human oral epithelial lesions.
Tissue markers of potential malignancy have been sought for many years. Cell surface markers, particularly blood group and histocompatibility antigens, have shown great promise and several squamous carcinoma antigens have been identified--but not fully studied in potentially malignant lesions. Growth factors and receptors also need further study. Cytoplasmic markers of potential malignancy have been examined and, of these, keratins, filaggrin, and some carcinoma antigens show most promise. Nuclear analyses have promise but are time-consuming and expensive. Image cytometric analyses appear to be sensitive and predictive: oncogene and tumour suppressor analyses remain to be fully evaluated. New investigative techniques at the cellular and molecular level show increasing promise at defining potentially malignant oral epithelial lesions but more prospective studies are required.


Association of genetic variants in the Sirt1 and Nrf2 genes with the risk of metabolic syndrome in a Chinese Han population.
Metabolic syndrome (MetS) is a complex of interrelated risk factors, including central adiposity, increased blood pressure, hyperglycemia, elevated triglyceride levels and low high-density lipoprotein. Few studies have reported the genetic variants in the Sirt1 and Nrf2 genes (Sirt1 rs7895833 A > G, Sirt1 rs2273773 C > T and Nrf2 rs6721961 C > A) that increase the risk of type 2 diabetes mellitus and are correlated with some glycemic and metabolic traits in the Chinese Han population. Our study recruited 141 individuals with MetS and 549 individuals without MetS to investigate the associations between three single nucleotide polymorphisms (SNPs) of Sirt1 and Nrf2 and the risk of MetS in a Chinese Han population using the PCR-CTPP method. This research showed that the risk of MetS was 2.41 times higher for the AA genotype (P = 0.038) and 1.94 times higher for the AG genotype (P = 0.016) compared with carriers of the GG genotype. The serum levels of low-density lipoprotein cholesterol and HOMA-IR were significantly higher (P < 0.05) in carriers of the AA genotype of Sirt1 rs7895833 than in carriers of the AG and GG genotypes in the general population. The serum level of total cholesterol in the AA genotype was lower (P = 0.033) than that in the other two genotypes. However, the genotype frequencies of Sirt1 rs2273773 and Nrf2 rs6721961 in the MetS group were not significantly different from those in the control subjects, and those two genetic variants were not correlated with metabolic traits. These results underscore the contributions of SNPs of Sirt1 rs7895833 to MetS susceptibility as well as glycemic and metabolic traits in a Chinese population.


Artificial intelligence improves transfer times and ischemic stroke workflow metrics.
Rapid initiation of mechanical thrombectomy (MT) for the treatment of large-vessel occlusion (LVO) critically improves patient outcomes. Artificial intelligence algorithms aid in the identification of LVOs and improve door to puncture times as well as patient transfer times. We aimed to determine whether the implementation of an LVO detection algorithm that provides immediate active notification to the thrombectomy team provider's cell phone would improve ischemic stroke workflow at our institution and aid in patient transfer from outlying hospitals when compared to our prior system of passive computed tomography perfusion software analysis and radiologist interpretation and notification. A retrospective review of our institutional thrombectomy registry was performed for all patients who underwent MT between January 2020 and March 2022. Demographic, radiographic, and stroke workflow metrics and notification times were collected. Transfer times and stroke metrics were compared pre- and post-implementation of the Viz.ai (Viz.ai, San Francisco, California, USA) smartphone application. Two hundred sixty-two patients underwent MT during the study period. Door-to-puncture time decreased 15 min (p = 0.009) after the implementation of Viz.ai at our Comprehensive Stroke Center. Transfer time from outside hospitals that implemented Viz.ai was reduced by 37 min (p = 0.04). There was no significant change in transfer time over the same time period in outlying hospitals that did not implement the Viz.ai software. Active notification of the neurosurgical team significantly reduces patient transfer time and initiation of MT.


Is referral to a spine surgeon a double-edged sword?: patient concerns before consultation.
To assess the concerns of adult patients with spine-related complaints during the period between referral to and consultation with a spine surgeon. Prospective survey. Toronto, Ont. A total of 338 consecutive, nonemergent patients before consultation with a single spine surgeon over a 5-month period. Patient concerns, effect of referral to a spine surgeon, and effect of waiting to see a spine surgeon. The issues patients reported to be most concerning were ongoing pain (45.6% rated this as most concerning), loss of function (23.4%), need for surgery (12.1%), and permanence of the condition (9.6%). Regression analysis demonstrated that older age was an independent predictor of increased level of concern regarding pain (P=.01) and disability (P=.04). Forty-seven percent of all patients listed the need for surgery among their top 3 concerns. Mere referral to a spine surgeon (P=.03) was an independent predictor of increased concern regarding the need for surgery. Sex, diagnosis, surgical candidacy, and actual wait time were not predictive of increased concerns. Patients reported family physicians to be their most influential information source regarding spinal conditions. Timely provision of more specific information regarding the benign and non-surgical nature of most degenerative spinal conditions might substantially reduce patients' exaggerated concerns regarding the probability of surgery for a considerable number of patients referred to spine surgeons.


In-line Raman spectroscopic monitoring and feedback control of a continuous twin-screw pharmaceutical powder blending and tableting process.
The integration of Process Analytical Technology (PAT) initiative into the continuous production of pharmaceuticals is indispensable for reliable production. The present paper reports the implementation of in-line Raman spectroscopy in a continuous blending and tableting process of a three-component model pharmaceutical system, containing caffeine as model active pharmaceutical ingredient (API), glucose as model excipient and magnesium stearate as lubricant. The real-time analysis of API content, blend homogeneity, and tablet content uniformity was performed using a Partial Least Squares (PLS) quantitative method. The in-line Raman spectroscopic monitoring showed that the continuous blender was capable of producing blends with high homogeneity, and technological malfunctions can be detected by the proposed PAT method. The Raman spectroscopy-based feedback control of the API feeder was also established, creating a 'Process Analytically Controlled Technology' (PACT), which guarantees the required API content in the produced blend. This is, to the best of the authors' knowledge, the first ever application of Raman-spectroscopy in continuous blending and the first Raman-based feedback control in the formulation technology of solid pharmaceuticals.


Immunohistochemical localization of inducible and endothelial nitric oxide synthase in porcine ovaries and effects of NO on antrum formation and oocyte meiotic maturation.
The present study is to investigate the immunolocalization of endothelial and inducible nitric oxide synthase (eNOS, iNOS) in porcine ovary and the effect of nitric oxide (NO) on antrum formation and oocyte meiotic resumption. In Experiment 1, preantral follicles (250-300 microm in diameter) were cultured in 0 (Control), 0.1, 0.3, 0.5 or 1 mM sodium nitroprusside (SNP), a NO donor. In Experiment 2, the cumulus-oocyte complexes (COCs) aspirated from medium follicles (3-6 mm in diameter) were incubated in 0.1mM SNP or two inhibitors for NOS, 10 mM aminoguanidine bicarbonate salt (AG) or 1 mM Nomega-nitro-l-arginine methyl ester (L-NAME), alone or concomitantly. In Experiment 3, ovarian tissues, corpus luteum (CL), corpus albican (CA) and COCs from small (1-2 mm in diameter), medium (3-6 mm) and large follicles (7-10 mm) were isolated, rinsed, fixed, paraffin embedded and stained by the conventional avidin-biotin complex method for the detection of eNOS and iNOS production. The results showed that 0.1mM SNP had no effect on antrum formation (P > 0.05) while 0.3, 0.5 or 1 mM significantly inhibited the antrum formation (P < 0.05). AG markedly inhibited porcine oocyte meiotic resumption (P < 0.05) while L-NAME inhibited first polar body (PB1) extrusion (P < 0.05). The immunoreactivity of eNOS in early antral follicles was restricted to oocyte and it increased from small, medium to large follicle-enclosed oocytes. Cumulus cells from large follicles showed weak eNOS immunoreactivity but those from small or medium follicles not. In CL, eNOS-positive staining was shown in granulosa lutein cells. In CA, it was in some parenchymal cells. In contrast, no immunoreactivity for iNOS was found in primordial, early antral follicle or the COCs aspirated from small and medium follicles. The large follicle-enclosed oocyte showed weak immunoreactivity. In CL, some granulosa lutein cells showed iNOS-positive cytoplasm. Such immunostaining was not found in CA. The results demonstrate that porcine ovaries have distinct cell-specific expression of both eNOS and iNOS, and that NO derived from both NOS is actively involved in meiotic resumption. Nitric oxide is not involved in the antrum formation of preantral follicles but exogenous NO inhibits the antrum formation. Endothelial nitric oxide synthase and inducible nitric oxide synthase might be differently functional in CL development and regression.


Comparison of effects of rosuvastatin and atorvastatin on plaque regression in Korean patients with untreated intermediate coronary stenosis.
Serial intravascular ultrasound (IVUS) was used to compare the effects of moderate doses of rosuvastatin and atorvastatin on plaque regression in patients with intermediate coronary stenosis. This was a prospective, randomized, and comparative study for lipid-lowering therapy with rosuvastatin 20mg (n=65) and atorvastatin 40mg (n=63) using serial IVUS (baseline and 11-month follow-up). Efficacy parameters included changes in total atheroma volume (TAV) and percent atheroma volume (PAV) from baseline to follow-up. Changes of TAV (-4.4±7.3 vs. -3.6±6.8mm(3), P=0.5) and PAV (-0.73±2.05 vs. -0.19±2.00%, P=0.14) from baseline to follow-up were not significantly different between the 2 groups. Plaque was increased in 15% in the rosuvastatin group and in 30% in the atorvastatin group at follow-up (P=0.064). The plaque increase group had higher baseline high-sensitivity C-reactive protein (hs-CRP; 1.28±2.70mg/dl vs. 0.54±1.16mg/dl, P=0.034) and higher follow-up low-density lipoprotein cholesterol (LDL-C) (78±24mg/dl vs. 63±21mg/dl, P=0.002) compared with the plaque non-increase group. Follow-up LDL-C (odds ratio [OR]=1.038, 95% confidence interval [CI]=1.003-1.060, P=0.036) and baseline hs-CRP (OR=1.025, 95%CI=1.001-1.059, P=0.046), not the type of statin, were the independent predictors of plaque increase at follow-up. Moderate doses of rosuvastatin and atorvastatin could contribute to effective plaque regression. Follow-up LDL-C and baseline hs-CRP are associated with plaque progression in patients with intermediate coronary stenosis.


Misfolded SOD1 Accumulation and Mitochondrial Association Contribute to the Selective Vulnerability of Motor Neurons in Familial ALS: Correlation to Human Disease.
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder, with a 10% genetic linkage, of which 20% of these cases may be attributed to mutations in superoxide dismutase (SOD1). Specific mutations in SOD1 have been associated with disease duration, which can be highly variable ranging from a life expectancy of 3 to beyond 10 years. SOD1 neurotoxicity has been attributed to aberrant accumulation of misfolded SOD1, which in its soluble form binds to intracellular organelles disrupting their function or forms insoluble toxic aggregates. To understand whether these biophysical properties of the mutant protein may influence disease onset and duration, we generated 19 point mutations in the SOD1 gene, based on available clinical data of disease onset and progression from patients. By overexpressing these mutants in motor-neuron-like NSC-34 cells, we demonstrate a variability in misfolding capacity between the different mutants with a correlation between the degree of protein misfolding and mutation severity. We also show a clear variation of the different SOD1 mutants to associate with mitochondrial-enriched fractions with a correlation between mutation severity and this association. In summary, these findings reveal a correlation between the accumulation of misfolded SOD1 species and their mitochondrial association with disease duration but not with disease onset, and they have implications for the potential therapeutic role of suppressing the accumulation of misfolded SOD1.


Evaluation of performance-enhancing drugs seized by Israeli enforcement agencies 2012-2017: implications for policy and regulatory change.
Illicit performance-enhancing substances are used mostly by athletes to enhance performance in sports, and by bodybuilders to gain muscle and body mass. Among performance-enhancing substances, the most common and known substances are anabolic-androgenic steroids, which are associated with a range of short and long-term adverse medical and psychiatric effects. While the sale and distribution of performance-enhancing substances are considered criminal offenses per the Israeli local pharmacy ordinance, the use and personal possession of these substances are not. Presently, the Division of Enforcement and Inspection of the Israel Ministry of Health cooperates with police and customs agents in performance-enhancing substance-related enforcement activities, which chiefly include seizures carried out at suspicious sites. Moreover, the Division of Enforcement and Inspection provides professional guidance, lab analysis services, and expert opinions on the toxicological and pharmaceutical nature of products seized. This paper presents a contemporary sub-analysis of registered seizures of performance-enhancing substances carried-out by Israel enforcement agencies. The main aim of this analysis is to characterize current patterns of performance-enhancing substances, thus providing the possibility of better assessment of current enforcement and health policy. A sub-analysis of 712 seizures of performance-enhancing substances seized by Israeli enforcement authorities during a six-year period ranging from January 2012 to December 2017. This study demonstrates that Israel faces a challenge regarding the importation and distribution of illicit performance-enhancing substances. The most common substances seized were anabolic androgenic steroids (N = 539). Most seizures were carried out in the central mail processing sites, (38.4%), followed by seizures in private premises such as homes and warehouses (29.6%). Significant differences were found between anabolic-androgenic steroids and other substances, relating to place and year of seizure. Among seizures with known sources (N = 355), the most frequent geographic region given as the source of substances was Eastern Europe (47.6%), followed by East Asia (24.8%), West Asia (19.4%), and Western Europe (5.9%). Bulgaria was the country with the highest frequency of seizures (N = 71) followed by Jordan (N = 45), Thailand (N = 37) and Moldova (N = 36). Significant regional differences were found based on the variables of gender, place of seizure, and type of substance. The most frequent month of seizures was August (N = 129), followed by July (N = 119), and June (N = 118). While data analysis focused on the supply side of the performance-enhancing substances market, the high number of seizures of performance-enhancing substances in Israel represents evidence of the existence of a high demand and a large consumer base for these products. Consequently, there is a need for developing further enforcement, treatment, and prevention policies that do not currently exist in Israel. Policymakers should consider prioritizing law enforcement action and incentivizing intelligence sharing to monitor suspected shipment sources and specific points of entry. Additionally, the results demonstrate that there is a need in reforming the penal law to discourage the use of performance-enhancing substances. Similar measures have already been applied in countries like Spain, Italy, and Belgium. Furthermore, policy-makers should consider enhancing health ministry agencies with a higher enforcement capacity by giving them further investigative and inquiry authority. Due to the troubling magnitude of the phenomenon, policymakers should also prioritize educational and prevention strategies.


Effects of government policies and the Nowruz holidays on confirmed COVID-19 cases in Iran: An intervention time series analysis.
Public health policies with varying degrees of restriction have been imposed around the world to prevent the spread of coronavirus disease 2019 (COVID-19). In this study, we aimed to evaluate the effects of the implementation of government policies and the Nowruz holidays on the containment of the COVID-19 pandemic in Iran, using an intervention time series analysis. Daily data on COVID-19 cases registered between February 19 and May 2, 2020 were collected from the World Health Organization (WHO)'s website. Using an intervention time series modeling, the effect of two government policies on the number of confirmed cases were evaluated, namely the closing of schools and universities, and the implementation of social distancing measures. Furthermore, the effect of the Nowruz holidays as a non-intervention factor for the spread of COVID-19 was also analyzed. The results showed that, after the implementation of the first intervention, i.e., the closing of universities and schools, no statistically significant change was found in the number of new confirmed cases. The Nowruz holidays was followed by a significant increase in new cases (1,872.20; 95% CI, 1,257.60 to 2,476.79; p<0.001)), while the implementation of social distancing measures was followed by a significant decrease in such cases (2,182.80; 95% CI, 1,556.56 to 2,809.04; p<0.001). The Nowruz holidays and the implementation of social distancing measures in Iran were related to a significant increase and decrease in COVID-19 cases, respectively. These results highlight the necessity of measuring the effect of health and social interventions for their future implementations.


Aristolochic acid nephropathy and the peritoneum: Functional, structural, and molecular studies.
Aristolochic acid nephropathy (AAN) is a rapidly progressive interstitial nephropathy linked to the exposure to aristolochic acid (AA) and characterized by extensive fibrosis and urothelial atypia. Although the fibrotic process has been documented in extrarenal tissues, the involvement of the peritoneum, as well as the efficacy of peritoneal dialysis in AAN patients, remain uncertain. The structure of the peritoneal membrane and the expression of basic fibroblast growth factor (bFGF), collagen type III, endothelial nitric oxide synthase (eNOS), and aquaporin-1 (AQP1) were investigated in peritoneal biopsies from an index AAN patient, four other AAN patients, four regular peritoneal dialysis patients, and two controls. Similar methods were used to investigate a rabbit model of AAN after intraperitoneal exposure to high-dose AA. AA-DNA adducts were screened by 32P-postlabeling analysis. The AAN patients had renal failure, renal fibrosis, and urothelial atypia. The peritoneum of AAN patients had a normal structure, lacked cellular atypia, and, in comparison with regular peritoneal dialysis patients and controls, did not show abnormal regulation of fibrotic and endothelial markers. Furthermore, specific AA-DNA adducts were not identified in the peritoneum of AAN patients. In contrast, AA-DNA adducts were detected in peritoneal and kidney tissues of all exposed rabbits, and one of them developed a malignant mesothelioma. These data demonstrate the lack of fibrotic and vascular alterations and the absence of cellular atypia in the peritoneum from AAN patients. Thus, peritoneal dialysis should not be discouraged in these patients. Nevertheless, studies in a rabbit model of high-dose AA exposure may suggest a potential risk of peritoneal malignancy.


A Nomogram to predict parotid gland overdose in head and neck IMRT.
To generate a nomogram to predict parotid gland (PG) overdose and to quantify the dosimetric benefit of weekly replanning based on its findings, in the context of intensity-modulated radiotherapy (IMRT) for locally-advanced head and neck carcinoma (LAHNC). Twenty LAHNC patients treated with radical IMRT underwent weekly computed tomography (CT) scans during IMRT. The cumulated PG dose was estimated by elastic registration. Early predictors of PG overdose (cumulated minus planned doses) were identified, enabling a nomogram to be generated from a linear regression model. Its performance was evaluated using a leave-one-out method. The benefit of weekly replanning was then estimated for the nomogram-identified PG overdose patients. Clinical target volume 70 (CTV70) and the mean PG dose calculated from the planning and first weekly CTs were early predictors of PG overdose, enabling a nomogram to be generated. A mean PG overdose of 2.5Gy was calculated for 16 patients, 14 identified by the nomogram. All patients with PG overdoses >1.5Gy were identified. Compared to the cumulated delivered dose, weekly replanning of these 14 targeted patients enabled a 3.3Gy decrease in the mean PG dose. Based on the planning and first week CTs, our nomogram allowed the identification of all patients with PG overdoses >2.5Gy to be identified, who then benefitted from a final 4Gy decrease in mean PG overdose by means of weekly replanning.


[Fast multi-resolution volume rendering method of large medical data sets].
A Fast Multi-resolution Volume Rendering Method (FMVRM) based on wavelet and Shear-Warp is herein proposed. In this method, the medical volume data is compressed using wavelet transformation first. Then based on the set resolution, the medical volume data is decompressed guided by Opacity transfer function (OTF). Finally, the 3D medical image is reconstructed on the basis of Shear-Warp using Block-based run length encoded (BRLE) data structure, in which, the aliasing artifacts resulting from under-sampling in Shear-Warp is avoided by the pre-integrated volume rendering technology. Experiments demonstrate the good performance of the proposed method.


Structural details of crystalline cellulose from higher plants.
It is commonly assumed that cellulose from higher plants contains the Ialpha and Ibeta crystalline allomorphs together with surface and disordered chains. For cellulose Ialpha, the evidence for its presence in higher plants is restricted to the C-4 signals in the solid-state (13)C NMR spectrum, which match those of crystalline cellulose Ialpha from algal sources. Algal cellulose Ialpha can be converted to the Ibeta form by high-temperature annealing. We used this approach to generate cellulose samples differing in Ibeta content from flax fibers and celery collenchyma, which respectively are representative of textile (secondary-wall) and primary-wall cellulose. It was then possible to isolate the detailed spectral contributions of the surface, Ibeta and Ialpha-like phases from linear combinations of the observed (13)C NMR and FTIR spectra. The (13)C NMR spectra resembled those of highly crystalline tunicate or algal cellulose Ibeta and Ialpha, with slight differences implying increased disorder and minor conformational discrepancies. The FTIR spectrum of the Ibeta form was closely similar to its more crystalline counterparts, but the FTIR spectrum of the Ialpha form was not. In addition to increased bandwith indicative of lower order, it showed substantial differences in the profile of hydroxyl stretching bands. These results confirm that higher plants synthesize cellulose Ibeta but show that the Ialpha-like chains, although conformationally quite similar to crystalline algal cellulose Ialpha, sit in a different hydrogen-bonding environment in higher plants. The differences are presumably occasioned by the small diameter of the crystallites and the influence of the crystallite surface on chain packing.


Exploring surface electromyography (EMG) as a feedback variable for the human-in-the-loop optimization of lower limb wearable robotics.
Human-in-the-loop (HITL) optimization with metabolic cost feedback has been proposed to reduce walking effort with wearable robotics. This study investigates if lower limb surface electromyography (EMG) could be an alternative feedback variable to overcome time-intensive metabolic cost based exploration. For application, it should be possible to distinguish conditions with different walking efforts based on the EMG. To obtain such EMG data, a laboratory experiment was designed to elicit changes in the effort by loading and unloading pairs of weights (in total 2, 4, and 8 kg) in three randomized weight sessions for 13 subjects during treadmill walking. EMG of seven lower limb muscles was recorded for both limbs. Mean absolute values of each stride prior to and following weight loading and unloading were used to determine the detection rate (100% if every loading and unloading is detected accordingly) for changing between loaded and unloaded conditions. We assessed the use of multiple consecutive strides and the combination of muscles to improve the detection rate and estimated the related acquisition times of diminishing returns. To conclude on possible limitations of EMG for HITL optimization, EMG drift was evaluated during the Warmup and the experiment. Detection rates highly increased for the combination of multiple consecutive strides and the combination of multiple muscles. EMG drift was largest during Warmup and at the beginning of each weight session. The results suggest using EMG feedback of multiple involved muscles and from at least 10 consecutive strides (5.5 s) to benefit from the increases in detection rate in HITL optimization. In combination with up to 20 excluded acclimatization strides, after changing the assistance condition, we advise exploring about 16.5 s of walking to obtain reliable EMG-based feedback. To minimize the negative impact of EMG drift on the detection rate, at least 6 min of Warmup should be performed and breaks during the optimization should be avoided. Future studies should investigate additional feedback variables based on EMG, methods to reduce their variability and drift, and should apply the outcomes in HITL optimization with lower limb wearable robots.


Successful aortic valve replacement for Heyde syndrome with confirmed hematologic recovery.
Aortic valve stenosis can be complicated by recurrent gastrointestinal bleeding, particularly that due to angiodysplasia, also called Heyde syndrome. Recently, acquired type 2A von Willebrand disease, which is characterized by the loss of the large multimer of von Willebrand factor by the shear stress of aortic valve stenosis, was reported to be associated with this hemorrhagic syndrome. A 78-year-old woman, with severe aortic stenosis, presented with advanced anemia due to recurrent gastrointestinal bleeding and was diagnosed Heyde syndrome. By perioperative supplementation of von Willebrand factor and factor VIII, aortic valve replacement was safely performed without gastrointestinal bleeding. After the operation, the multimer of von Willebrand factor was normalized and thereafter no gastrointestinal bleeding occurred. This case reports the successful aortic valve replacement for Heyde syndrome, with confirmed hematologic recovery.


Retrieving space-dependent polarization transformations via near-optimal quantum process tomography.
An optical waveplate rotating light polarization can be modeled as a single-qubit unitary operator. This analogy can be exploited to experimentally retrieve a polarization transformation within the paradigm of quantum process tomography. Standard approaches to tomographic problems rely on the maximum-likelihood estimation, providing the most likely transformation to yield the same outcomes as a set of experimental projective measurements. The performances of this method strongly depend on the number of input measurements and the numerical minimization routine that is adopted. Here we investigate the application of genetic and machine learning approaches to this problem, finding that both allow for accurate reconstructions and fast operations when processing a set of projective measurements very close to the minimal one. We apply these techniques to the case of space-dependent polarization transformations, providing an experimental characterization of the optical action of spin-orbit metasurfaces having patterned birefringence. Our efforts thus expand the toolbox of methodologies for optical process tomography. In particular, we find that the neural network-based scheme provides a significant speed-up, that may be critical in applications requiring a characterization in real-time. We expect these results to lay the groundwork for the optimization of tomographic approaches in more general quantum processes, including non-unitary gates and operations in higher-dimensional Hilbert spaces.


Characterization of the minimal DNA-binding domain of the HIV integrase protein.
The human immunodeficiency virus (HIV) integrase (IN) protein mediates an essential step in the retroviral lifecycle, the integration of viral DNA into human DNA. A DNA-binding domain of HIV IN has previously been identified in the C-terminal part of the protein. We tested truncated proteins of the C-terminal region of HIV-1 IN for DNA binding activity in two different assays: UV-crosslinking and southwestern blot analysis. We found that a polypeptide fragment of 50 amino acids (IN220-270) is sufficient for DNA binding. In contrast to full-length IN protein, this domain is soluble under low salt conditions. DNA binding of IN220-270 to both viral DNA and non-specific DNA occurs in an ion-independent fashion. Point mutations were introduced in 10 different amino acid residues of the DNA-binding domain of HIV-2 IN. Mutation of basic amino acid K264 results in strong reduction of DNA binding and of integrase activity.


Identification of a rat liver microsomal esterase as a target protein for bromobenzene metabolites.
The hepatotoxicity of bromobenzene and many other simple organic molecules has been associated with their biotransformation to chemically reactive metabolites and the subsequent covalent binding of those metabolites to cellular macromolecules. To identify proteins targeted by bromobenzene metabolites, we incubated [14C]bromobenzene in vitro with liver microsomes from phenobarbital-induced rats under conditions which typically led to covalent binding of 2-4 nmol equiv of bromobenzene/mg of protein. Microsomal proteins were solubilized with detergent, separated by chromatography and electrophoresis, and analyzed for 14C by phosphorimaging of stained blots. Much of the radioactivity was associated with several bands of proteins of ca. 50-60 kDa, plus another prominent band around 70 kDa, but labeling density appeared to vary considerably overall. A major radiolabeled protein was purified by preparative electrophoresis and submitted to automated Edman microsequencing. Its N-terminal sequence was found to correspond to that of a known rat liver microsomal carboxylesterase (E.C. 184.108.40.206) previously identified as a target for reactive metabolites of halothane. The extent to which covalent modification of this protein by reactive metabolites contributes to the production of hepatotoxic effects remains to be determined.


Chirotopical properties of cisoid enones from circular dichroism (CD) and anisotropic circular dichroism (ACD) spectroscopy.
Substituted cisoid 4-en-6-one steroids with isotropically distributed and partially oriented molecules were analyzed by circular dichroism (CD) and anisotropic circular dichroism (ACD) spectroscopy, respectively. CD and ACD data supplement their respective phenomenological information. For a series of C3-substituted enones 1 to 7, the difference of CD (Delta epsilon) and ACD (Delta epsilon(A)) values, that is, Delta epsilon -Delta epsilon(A), vary in the n-* transition region in the same direction, independently of the nature and position (3 alpha or 3 beta) of the substituent. For 7-bromo-substituted enones 5 and 6 the sign of the n-pi* CD band is opposite to that predicted by the enone helicity rule. The ACD data indicate that this behavior is a consequence of the effect of vibronic coupling caused by the 7-bromo substituent. In contrast to the results obtained for the series of C7-unsubstituted compounds 1 to 4, the intensity of the CD bands for 5 and 6 is determined by the vibrational progressions of a different symmetry. Therefore, the helicity rule must fail in both cases because the rule can only be applied to those vibrational transitions for which the rule was developed. The sign of the coordinates Delta epsilon(*)(II), estimated from the ACD data, yields additional stereochemical information that cannot be obtained from the CD data alone. The CD and ACD spectra in the region of the pi-pi* transition vary for enones 1 to 4 in a different fashion and indicate dependence upon spatial orientation (3 alpha or 3 beta) of substituents. This dependence may lead to the possibility of extracting additional stereochemical information from the ACD spectra. Furthermore, the experimental findings indicate that the second CD band located at about 220 nm belongs to a forbidden transition and not to an allowed pi-pi* transition.


The germline p53 activation syndrome: A new patient further refines the clinical phenotype.
The tumor suppressor p53 has well known roles in cancer development and germline cancer predisposition disorders, but increasing evidence supports the role of activation of this transcription factor in the pathogenesis of inherited bone marrow failure and chromosomal instability disorders. Here we report a patient with red cell aplasia, which was steroid responsive, as well as intellectual disability, seizures, microcephaly, short stature, cellular radiosensitivity, and normal telomere lengths, who had a germline heterozygous C-terminal frameshift variant in TP53 similar to others that activate the transcription factor. This is the third reported individual with a germline p53 activation syndrome, with several unique features that refine the clinical disease associated with these variants.


Prodorylaimus baikalensis sp. n. and Mononchus minutus sp. n. (Nematoda) from Lake Baikal, Russia.
Two new nematode species found in Lake Baikal (Russia) are described and illustrated. Prodorylaimus baikalensis sp. n. is morphologically close to P. irminii Vinciguerra Orselli, 2011 and P. obesus Ahmad Jarajpuri, 1982. From the first species it differs by the shorter and thinner body, longer tail, longer odontostyle and greater number of ventromedian supplements. From the second species it differs by the longer and more slender tail, shorter odontophore, longer female prerectum and greater number of ventromedian supplements in males. Mononchus minutus sp. n. is similar to M. niddensis Skwarra, 1921 and M. agilis Gagarin Mataphonov, 2004. The new species differs from M. niddensis by the shorter body, more slender tail, longer buccal cavity, longer spicules and smaller number of ventromedian supplements in males. From M. agilis it differs by the shorter and thinner body, shorter tail, longer spicules and smaller number of ventromedian supplements in males.


Radiofrequency and microwave ablation in combination with transarterial chemoembolization induce equivalent histopathologic coagulation necrosis in hepatocellular carcinoma patients bridged to liver transplantation.
Bridging therapy plays an increasingly important role in the management of patients with hepatocellular carcinoma (HCC) awaiting liver transplantation (LT). Combination therapy with drug-eluting bead transarterial chemoembolization (DEB-TACE) and percutaneous thermal ablation, such as radiofrequency ablation (RFA) or microwave ablation (MWA), has shown success at prolonging survival and bridging patients to LT. However, few studies have evaluated the two combination therapy regimens head-to-head at a single institution, and fewer have compared histopathology. This retrospective study compares tumor coagulation on explanted livers in patients with HCC treated with DEB-TACE sequentially combined with RFA versus MWA. From 2005 to 2015, 42 sequential patients underwent combination therapy prior to LT by Milan criteria, with 11 patients (11 tumors; mean, 2.9 cm; range, 1.8-4.3 cm) in the DEB-TACE/RFA cohort and 31 patients (40 tumors; mean, 2.4 cm; range, 1.1-5.4 cm) in the DEB-TACE/MWA cohort. The mean TACE procedures in the RFA and MWA cohorts were 1.3 (range, 1-2) and 1.3 (range, 1-3), respectively. The mean thermal ablations in the RFA and MWA cohorts were 1.2 (range, 1-2) and 1.3 (range, 1-3), respectively. Tumor coagulation was evaluated on explanted livers. Mean tumor coagulation in the RFA and MWA cohorts were 88.9% (range, 0-100%) and 90.5% (range, 30-100%), respectively (P=0.82). Rates of complete tumor coagulation in the RFA and MWA cohorts were 45% and 53%, respectively (P=0.74). No difference in tumor coagulation was found between the cohorts when separating tumors <3 cm (P=0.21) and >3 cm (P=0.09). Among all 51 tumors, the 36 in complete response (CR) on imaging at LT demonstrated mean tumor coagulation of 95.8%. No correlation was found between tumor coagulation and initial tumor size or time interval to LT. No tumor seeding was seen along the ablation tracts. RFA and MWA in sequential combination with DEB-TACE, used as a bridge to LT, are equally efficacious at inducing HCC tumor coagulation.


Acute cholecystitis.
Two thousand and twenty-one patients treated surgically for acute cholecystitis over a 42 year period with a mortality of 3.4 per cent are reported. This experience reveals that acute cholecystitis among patients 65 years of age and older is a serious condition and is associated with an appreciable operative mortality. However, nonsurgical management results in an even greater mortality. An aggressive surgical approach, cholecystectomy without prolonged delay after the demonstration of calculous disease of the biliary tract, is urged. In the future, this should diminish the proportion of patients 65 years of age and older with acute cholecystitis.


Improved chelation therapy of intramuscularly deposited thorium by CaDTPA in the rat.
Comparative studies on the translocation and retention of intramuscularly (i.m.) injected thorium nitrate (234Th 46 ng + 232Th 5 microg per rat) in solutions of citrate, CaDTPA or citrate + CaDTPA in rats have been conducted. Results showed that only thorium in mixed-ligand solution was entirely translocated from the muscle, with the greatest part being excreted from the body. In this case, the whole-body retention of thorium decreased to 16% of the injected radioactivity within 2 d, 13% being retained in the skeleton. Studies on the decorporation of 234Th + 232Th nitrates from a rat wound simulated with i.m. injection have also been carried out. The greatest translocation of thorium and its excretion was achieved with a single local injection of the mixed-ligand (citrate + CaDTPA) solution when compared with those of citrate or CaDTPA alone. The efficiency of mixed-ligand treatment decreased with its delay. On day 2 post-therapy, the whole-body content of thorium decreased to 30, 37 and 55% of injected radioactivity when the local treatment started immediately, postponed to 1 h or 24 h, after i.m. injection of thorium, respectively. In control rats without treatment, there was only a slight decrease in the content of thorium in the whole body.


Characteristics of Prehospital Heat Illness Cases During the Annual Heat Wave Period in Telangana, India.
Global warming and more intense heat wave periods impact health. Heat illness during heat waves has not been studied in the prehospital setting of a low- and middle-income country (LMIC). Early intervention in the community and in the prehospital setting can improve outcomes. Hence, this paper aims to describe the characteristics of heat illness patients utilizing the ambulance service in Telangana state, India with the aim of optimizing public prevention and first aid strategies and prehospital response to this growing problem. This retrospective observational study reviewed patients presenting to Telangana's prehospital emergency care system with heat illness symptoms during the heat wave period from March through June in 2018 and 2019. Descriptive analysis was done on the prehospital, dispatch, and environmental data looking at the patients' characteristics and prehospital intervention. There were 295 cases in 2018 and 230 cases in 2019 from March-June. The overall incidence of calls with heat illness symptoms was 1.5 cases per 100,000 people. The Scheduled Tribes (ST) had the highest incidence of 4.5 per 100,000 people. Over 96% were from the white income group (below poverty line) while two percent were from the pink income group (above poverty line). From geospatial mapping of the cases, the highest incidence of calls came from the rural, tribal areas. However, the time to response in rural areas was longer than that in an urban area. Males with an average age of 47 were more likely to be affected. The three most common symptoms recorded by the first responders were vomiting (44.4%), general weakness (28.7%), and diarrhea (15.9%). The three most common medical interventions on scene were oxygen therapy (35.1%), oral rehydration salt (ORS) solution administration (26.9%), and intravenous fluid administration (27.0%), with cold sponging infrequently mentioned. This descriptive study provides a snapshot of the regions and groups of people most affected by heat illness during heat waves and the heterogeneous symptom presentation and challenges with management in the prehospital setting. These data may aid planning of prehospital resources and preparation of community first responders during heat wave periods.