First experience with BAK-free travoprost 0.004% in topical glaucoma medication.
Benzalkonium chloride (BAK)-free travoprost 0.004% (Travatan Z(®), Alcon Laboratories, Inc, Fort Worth, TX) is a new formulation that was developed with the aim of creating a formulation of travoprost that would maintain the intraocular pressure (IOP)-lowering efficacy and have an improved overall safety profile, particularly improved ocular surface tolerability. Thirty newly diagnosed primary open-angle glaucoma (POAG) patients were treated with BAK-free travoprost 0.004%. IOP readings were recorded at baseline before initiating treatment, at 4-6 weeks, and after 12 weeks of starting treatment. In addition, patient demographics, subjective symptoms (ie, burning, foreign-body sensation, itching, and stinging), and objective clinical signs such as conjunctival hyperemia were collected. Subjective symptoms were evaluated using a four-point scale ranging from "no symptoms," "mild symptoms," "moderate symptoms" to "severe symptoms." As for clinical signs, severity of conjunctival hyperemia was evaluated. All other adverse events were collected. BAK-free travoprost 0.004% provided an IOP decrease in all patients, with an overall mean of 28.3 ± 2.1 mmHg at baseline to a mean of 18.7 ± 1.6 mmHg at 4-6 weeks, and a mean of 18.4 ± 1.4 mmHg after 12 weeks. Both subjective symptoms and objective clinical signs were very few after treatment. The results demonstrate that BAK-free travoprost 0.004% is an effective, well tolerated, and safe medication in POAG patients.


[Influence of hospital location on short-term fate of premature infants born at 34 weeks of gestation].
In France, new care units have emerged in maternity wards for the treatment of moderate prematurity, called mother-child units (MCU). We compared the length of hospitalization between the MCUs and the neonatal units (NNUs) for premature infants born at 34 weeks of amenorrhea at Grenoble university hospital. This was a retrospective, single-center study, including 99 premature infants born from 34 of amenorrhea to 34 weeks+6 days between 2004 and 2009. Were included all premature 34-week infants hospitalized in the NNU or the MCU excluding those with respiratory distress, birth defects, and including infants whose birth weight was less than 1500g admitted to the neonatal intensive care unit or transferred secondarily to the MCU. The characteristics of both groups were similar apart from a lower birth weight in the NNU group (1892 vs. 2182g) and gestational age less than in the NNU group (34.1 vs. 34.3 SA). Our primary outcome, length of hospital stay, was significantly shorter in the MCU (15.4 vs. 20.7 days in the NNU, P<0.01) as well as the duration of nasogastric tube feeding (2.8 vs. 9.1 days, P<0.01). This difference remained after adjustment for birth weight and gestational age. Our retrospective study shows that the length of hospitalization of premature infants born at 34 weeks gestation and hospitalized in our center is significantly shorter when they are admitted to the MCU rather than neonatology. For this reason, this mode of hospitalization in maternity MCUs can be recommended.


Editorial: Large Datasets, Small Effect Sizes: Considerations Regarding Optimized Approaches to Identify Targets for Early Interventions Fostering Brain Health.
The origins of youth psychopathology are best studied by integrating clinical and developmental science, an approach known as developmental psychopathology.1 This relatively young scientific discipline views youth psychopathology as the result of the dynamic interplay of neurobiological, psychological, and environmental risk and protective factors that transcend traditional diagnostic categories. Etiological questions within this framework include whether clinically relevant phenotypes, such as perturbed emotion regulation cross-sectionally linked to atypical brain morphometry, drive deviations from normative neurodevelopmental trajectories or should be viewed as the consequence of atypical brain maturation. The answer to such questions will have important treatment implications but necessitates the skillful integration of different levels of analysis across time. So, studies employing such an approach are rare.


A novel adaptive time delay identification technique.
In this work, a novel online adaptive time delay identification method is proposed for a class of signal processing and communication applications, where the received signal is a combination of the transmitted signal and its delayed forms with the delay values being uncertain and required to be estimated. The design relies on a filtered form of a prediction error-like term which is then used in the design of the novel nonlinear adaptive update law. The stability of the identification algorithm is then investigated via novel Lyapunov based tools and the time delay identification is proven to be globally uniformly ultimately bounded. Several numerical simulations are conducted to evaluate the performance of the proposed identifier where constant, slowly varying and suddenly changing delays are successfully identified even in the presence of additive noise.


Maxillofacial reconstruction using polyetheretherketone patient-specific implants by "mirroring" computational planning.
In the vast majority of cases, precise symmetric reconstruction of maxillofacial defects remains an unsolved problem for craniofacial surgeons. Computer-designed alloplastic implants have contributed considerably to improvement in the accuracy and reliability of facial rehabilitation, rapidly becoming an irreplaceable part of the surgical armamentarium. In recent years, the subsequently developed new generation of computational technologies has allowed planning to be done by preoperative "mirroring" using the healthy side as a template to fabricate an ideal prosthesis for reestablishment of facial symmetry. Two cases of facial defects are reported, one of the midface and another of the lower face reconstructed using a computer-designed polyetheretherketone (PEEK) patient-specific implant (PSI) technique based on "mirroring" computational planning. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors at www.springer.com/00266.


[Idiopathic non-cirrhotic portal hypertension: An update].
Idiopathic non-cirrhotic portal hypertension is an under-estimated cause of portal hypertension. The diagnosis requires the exclusion of cirrhosis, common causes of chronic liver disease and venous obstruction of the portal and hepatic veins. It has been associated with various extra-hepatic conditions that are most frequently immunologic, prothrombotic, hematologic and toxic. The most frequent clinical complications are variceal hemorrhage and portal vein thrombosis. Complications of portal hypertension should be managed as in patients with cirrhosis.


Ocular pigmented spots and eyelid myxomas.
Ophthalmic abnormalities are part of a recently recognized syndrome that includes myxomas, spotty pigmentation, and endocrine overactivity. The complex is familial with mendelian dominant mode of inheritance. The 63 patients (27 males and 36 females) we have identified with this complex had the following ophthalmic abnormalities: facial and eyelid lentigines in 44 patients (70%); pigmented lesions on the caruncle or conjunctival semilunar fold in 17 patients (27%); and eyelid myxomas in ten patients (16%). Because these findings usually preceded the most serious component of the syndrome, cardiac myxoma, early recognition of their significance is important.


Airway obstruction following bronchoscopic photodynamic therapy in early centrally located lung cancer requiring extracorporeal membrane oxygenation.
Photodynamic therapy (PDT) is a treatment modality of early central located non-small-cell lung cancer, and in patients who are unsuitable for surgical intervention. Most complications of PDT reported in the literature are minor and can be easily handled. We report a case presenting with nearly fatal complication: airway obstruction following bronchoscopic photodynamic therapy for early endobronchial lung cancer, requiring extracorporeal membrane oxygenation. An 81-year-old man was admitted to thoracic surgery division due to an early centrally located lung cancer. Due to multiple comorbidity and high surgical risk we performed bronchoscopic PDT instead of aggressive lung resection for the patient. After the procedure, he developed severe airway obstruction by tumor debris and required temporary cardiopulmonary support with extracorporeal membrane oxygenation. The patient recovered smoothly after the episode and was free from tumor recurrence for >2 years without any neurological sequelae.


The alkaloidal responses of wild tobacco to real and simulated herbivory.
I compared the induced alkaloidal response in undamaged leaves of plants subjected to herbivory by the larvae of Manduca sexta and to different simulations of this herbivory; all herbivory treatments removed similar amounts of leaf mass. Although larval feeding induced a significant increase (2.2x) in alkaloid concentrations compared to undamaged plants, the alkaloid responses to larval feeding were significantly lower than the responses to an herbivory simulation (4x controls) which involved removing the same amount of leaf area from the same positions on the leaf, over a similar time period. Moreover, another herbivory simulation, identical in amount of leaf mass removed and duration of damage to the larval feeding, but without regard to spatial array of leaf damage, resulted in an alkaloidal response (5.5x controls) higher still than the previous herbivory simulation. In a second experiment the importance of leaf vein damage on the induced alkaloidal response was examined. Here, leaf removal that involved cutting leaf tissues from between secondary veins before removing the midrib, resulted in alkaloidal responses that were significantly lower (1.7x controls) than responses from leaf removal that involved cutting both veins and midribs along with the intervein tissues (2.6x controls). Vein damage alone did not produce a significant response. These results indicate that herbivory is difficult to simulate: that how a leaf is damaged can be as important as the magnitude of leaf damage in determining a plant's response to damage.


Putrescine regulates nitric oxide accumulation in Ganoderma lucidum partly by influencing cellular glutamine levels under heat stress.
When fungi are subjected to abiotic stresses, the polyamines (PAs) level alter significantly. Here, we reveal that the polyamine putrescine (Put) could play an important role in alleviating heat stress(HS)-induced accumulation of nitric oxide (NO). Ornithine decarboxylase (ODC)-silenced mutants that were defective in Put biosynthesis exhibited significantly lower NO levels than the wild type (WT) when subjected to HS. With addition of 5 mM exogenous Put, the ODC-silenced mutant endogenous Put obviously increased under HS. At the same time, the contents of NO in the ODC-silenced mutants recovered to approximately WT levels after the administration of exogenous Put. However, the elevated NO content in the ODC-silenced mutants disappeared when exogenous Put and carboxy-PTIO (PTIO is a specific scavenger of NO) were added. Intriguingly, the content of glutamine (Gln) was significantly increased in the ODC-silenced strains. When exogenous Put was added to the WT, the Gln content was significantly decreased. The appearance of a high level of Gln was accompanied by nitrate reductase (NR) activity reduction. Further studies showed that Put influenced ganoderic acids (GAs) biosynthesis by regulating NO content, possibly through NR, under HS. Our work reported that Put regulates HS-induced NO accumulation by changing the cellular Gln level in filamentous fungi. IMPORTANCE: In our present work, it was HS as an ubiquitous environmental stress that affects the important pharmacological secondary metabolite (GAs) content in G. lucidum. Afterwards, we began to explore the network formed between multiple substances to jointly reduce the massive accumulation of GAs content caused by HS. We firstly focused on Put, a substance that enhances resistance to multiple stresses. Further, we discovered an influence on Put could changing the NO content, which has been shown to decrease the accumulation of GAs via HS. Then, we also found the change of NO content may be due to Put level that would affect intracellular Gln content. It has never been reported. And ultimately, it is Put related network that could reduce HS-inducing secondary metabolite mess in fungi.


Studies on nicotinic acid interaction with bilirubin metabolism.
The mechanism by which intravenous administration of nicotinic acid (NA) increases serum unconjugated bilirubin in patients with the Gilbert's syndrome has been investigated. Studies using the technique of percutaneous transhepatic catheterization of the splenic vein and coil planet centrifuge suggested that following intravenous injection of NA some of the circulating erythrocytes were rendered osmotically fragile and trapped by the spleen and that unconjugated bilirubin increased in the splenic vein blood. In patients with liver cirrhosis, the increments of unconjugated bilirubin were closely correlated with the weights of the spleens removed for the management of varices. In rats, intravenous NA injection enhanced heme oxygenase activities in the spleen, but not uridine-5'-diphosphate (UDP)-glucuronyltransferase activity in the liver. These results are consistent with the hypothesis that NA-induced unconjugated hyperbilirubinemia is a result of complex reactions which include increased erythrocyte fragility, increased splenic heme oxygenase activity, and increased formation of bilirubin in the spleen.


Predicting outcome in acute interstitial nephritis: a case-series examining the importance of histological parameters.
The clinical significance of common histological parameters in acute interstitial nephritis (AIN) is uncertain. We aimed to evaluate the utility of histology in predicting clinical outcomes in patients with AIN. Adult renal biopsies yielding a diagnosis of AIN between 2000 and 2015 were re-examined. Patients were divided into groups based on: (i) the percentage of non-fibrotic cortex containing inflammation (NFI score) (NFI-1 = 0-24%; NFI-2 = 25-74%; NFI-3 = 75-100%) and (ii) the percentage of cortex containing tubular atrophy (TA score) (TA1 = 0-9%; TA2 = 10-24%; TA3 = 25-100%). The primary outcome was a composite of ≥50% reduction in serum creatinine (sCr) or an estimated glomerular filtration rate (eGFR) > 60 ml/min/1.73 m2 1 year post-biopsy. From a total of 2817 native renal biopsies, there were 120 patients with AIN and adequate data for analysis. Of these, 66 (56%) achieved the primary outcome. On univariable logistic regression, NFI-3 was associated with a 16 times increased likelihood of achieving the primary outcome compared to NFI-1 [odds ratio (OR) = 16, 95% confidence interval (CI) = 5.2-50)]. In contrast, TA3 was associated with a 90% reduced likelihood of achieving the primary outcome compared to TA1 (OR = 0.10, 95% CI = 0.0-0.3). Maximal clinical utility was achieved by combining TA and NFI into a single prognostic 'TANFI' score, which had an independent predictive effect on the primary outcome in a multivariable regression model consisting of age, sex, baseline sCr and identified drug cause. In patients with biopsy-proven AIN, a lower percentage of cortical tubular atrophy and, paradoxically, a higher percentage of inflammation in non-fibrosed cortex were associated with an increased likelihood of a positive clinical outcome.


Physiology of ice hockey.
Ice hockey is characterized by high intensity intermittent skating, rapid changes in velocity and duration, and frequent body contact. The typical player performs for 15 to 20 minutes of a 60-minute game. Each shift lasts from 30 to 80 seconds with 4 to 5 minutes of recovery between shifts. The intensity and duration of a particular shift determines the extent of the contribution from aerobic and anaerobic energy systems. The high intensity bursts require the hockey player to develop muscle strength, power, and anaerobic endurance. The length of the game and the need to recover quickly from each shift demands a good aerobic system. Physical characteristics of elite players show that defensemen are taller and heavier than forwards probably due to positional demands. Hockey players are mesomorphic in structure. They are relatively lean since excess mass is detrimental to their skating performance. There is a large interindividual variability in VO2 during skating. Both the aerobic and anaerobic energy systems are important during a hockey game. Peak heart rates during a shift on the ice exceed 90% of HRmax with average on-ice values of about 85% of HRmax. Blood lactate is elevated above resting values confirming the anaerobic nature of the game. Glycogen depletion studies show a preferential utilisation of glycogen from the slow twitch fibres but also significant depletion from the fast twitch fibres. Elite hockey players display a muscle fibre composition similar to untrained individuals. Physiological profiles of elite hockey teams reveal the importance of aerobic endurance, anaerobic power and endurance, muscular strength and skating speed. Training studies have attempted to improve specific components of hockey fitness. Using traditional laboratory tests, a season of hockey play shows gains in anaerobic endurance but no change in aerobic endurance. On-ice tests of hockey fitness have been recommended as an essential part of the hockey player's physiological profile. Existing training procedures may develop chronic muscular fatigue in hockey players. Lactic acidosis is associated with the onset and persistence of muscle fatigue. Muscle force output remains impaired throughout the hockey player's typical cycle of practices and games. A supplementary programme of low-intensity cycling during the competitive phase of training was unsuccessful in altering VO2max. Strength decrements during the hockey season are attributed to a lack of a specifically designed strength maintenance programmes. On-ice and off-ice training programmes should focus on the elevation of aerobic endurance, anaerobic power and endurance, muscular strength and skating speed.


Development of an acetylcholinesterase-choline oxidase based biosensor for acetylcholine determination.
In this article, a novel amperometric acetylcholine (ACh) biosensor with immobilization of acetylcholinesterase-choline oxidase (AChE-ChO) on electrochemically polymerized polyaniline-polyvinylsulphonate (PANI-PVS) film has been successfully developed for the first time. AChE and ChO enzymes were immobilized on PANI-PVS film by cross-linking with using glutaraldehyde (GA) and bovine serum albumin (BSA). Determination of ACh was carried out by oxidation of enzymatically produced H2O2 at +0.4 V versus Ag/AgCl. Optimum pH and temperature were found to be 8.0 and 60 °C, respectively. The linear part was in the region 1.0 × 10(-7)-6.0 × 10(-7) M (R(2) = 0.990). Storage stability and operation stability of the enzyme electrode were also studied.


Seasonal flooding, soil salinity and primary production in northern prairie marshes.
Hydrologic regime is an important control of primary production in wetland ecosystems. I investigated the coupling of flooding, soil salinity and plant production in northern prairie marshes that experience shallow spring flooding. Field experiments compared whitetop (Scolochloa festucacea) marsh that was: (1) nonflooded, (2) flooded during spring with 25 cm water and (3) nonflooded but irrigated with 1 cm water · day-1. Pot culture experiments examined whitetop growth response to salinity treatments. The electrical conductivity of soil interstitial water (ECe) at 15 cm depth was 4 to 8 dS· m-1 lower in flooded marsh compared with nonflooded marsh during 2 years. Whitetop aboveground biomass in flooded marsh (937 g · m-2, year 1; 969 g · m-2, year 2) exceeded that of nonflooded marsh (117 g · m-2 year 1; 475 g · m-2, year 2). Irrigated plots had lower ECe and higher aboveground biomass than nonflooded marsh. In pot culture, ECe of 4.3 dS · m-1 (3 g · L-1 NaCl) reduced total whitetop biomass by 29 to 44% and ECe of 21.6 dS · m-1 (15 g · L-1 NaCl) reduced biomass by more than 75%. Large reductions of ECe and increases of whitetop growth with irrigation indicated that plants responded to changes in soil salinity and not other potential environmental changes caused by inundation. The results suggest that spring flooding controls whitetop production by decreasing soil salinity during spring and by buffering surface soils against large increases of soil salinity after mid-summer water level declines. This mechanism can explain higher marsh plant production under more reducing flooded soil conditions and may be an important link between intermittent flooding and primary production in other wetland ecosystems.


Toward a theoretical approach to medical error reporting system research and design.
The release of the Institute of Medicine (Kohn et al., 2000) report "To Err is Human", brought attention to the problem of medical errors, which led to a concerted effort to study and design medical error reporting systems for the purpose of capturing and analyzing error data so that safety interventions could be designed. However, to make real gains in the efficacy of medical error or event reporting systems, it is necessary to begin developing a theory of reporting systems adoption and use and to understand how existing theories may play a role in explaining adoption and use. This paper presents the results of a 9-month study exploring the barriers and facilitators for the design of a statewide medical error reporting system and discusses how several existing theories of technology acceptance, adoption and implementation fit with many of the results. In addition we present an integrated theoretical model of medical error reporting system design and implementation.


Cerebral infarction after fractionated stereotactic radiation therapy of benign anterior skull base tumors.
The purpose of this study was to examine the occurrence of cerebral infarction (ischemic stroke), in a large combined cohort of patients with anterior skull base meningiomas, pituitary adenomas and craniopharyngiomas, after fractionated stereotactic radiation therapy (FSRT). All patients, 18 years and older, with anterior skull base meningiomas, pituitary adenomas and craniopharyngiomas, treated with fractionated stereotactic radiation, in our center, from January 1999 to December 2015 were identified. In total 169 patients were included. The prescription dose to the tumor was 54 Gy for 164 patients (97%) and 46.0-52.2 Gy for 5 patients (3%). Cases of cerebral infarctions subsequent to FSRT were identified from the Danish National Patient Registry and verified with review of case notes. The rate of cerebral infarction after FSRT was compared to the rate in the general population with a one sample t-test after standardization for age and year. We explored if age, sex, disease type, radiation dose and dose per fraction was associated with increased risk of cerebral infarction using univariate Cox models. At a median follow-up of 9.3 years (range 0.1-16.5), 7 of the 169 patients (4.1%) developed a cerebral infarction, at a median 5.7 years (range 1.2-11.5) after FSRT. The mean cerebral infarction rate for the general population was 0.0035 and 0.0048 for the FSRT cohort (p = 0.423). Univariate cox models analysis showed that increasing age correlated significantly with the cerebral infarction risk, with a hazard ratio of 1.090 (p = 0.013). Increased risk of cerebral infarction after FSRT of anterior skull base tumors was associated with age, similar to the general population. Our study revealed that FSRT did not introduce an excess risk of cerebral infarction.


Obstetric care. Is there risk of pressure damage after epidural anaesthesia?
Anecdotal evidence suggests that there is an increase in the incidence of pressure damage to women in labour. This appears to be associated with epidural anaesthesia. Epidural anaesthesia used to control pain in childbirth causes loss of sensation and a degree of motor block, which removes the women's reflexes and ability to reposition to prevent pressure damage. The large amount of fluids present during childbirth may also increase the risk of pressure damage, especially in association with shear and friction. A combination of unfamiliarity of pressure ulcer prevention techniques among midwives, and the type of delivery room equipment, that is currently available, may leave young healthy women at risk of developing pressure ulcers.


Determination of human rotavirus VP4 using serotype-specific cDNA probes.
The VP4 genetic groups of 151 field strains of human rotaviruses obtained from infants and young children with diarrhea from four locations in Malaysia were analyzed. The strains were adapted to growth in tissue culture and studied further by molecular hybridization of northern blotted RNA to PCR-generated cDNA probes representing amino acids 84-180 of the KU strain VP4, 83-181 of the DS-1 strain VP4, and 83-180 of either the 1076 or K8 strain VP4, representing VP4 genetic groups 1-4 (P1A, P1B, P2, and P3), respectively. The majority (79% of the field strains hybridized with the KU VP4 genetic group 1 probe and were associated with G1, G3, G4, untypable, or mixed G serotypes. VP4 genetic group 1 (P1A) strains were the most common in all locations in Malaysia between 1978-1988. Three strains which exhibited G3 and subgroup I specificity hybridized with the K8 VP4 genetic group 4 probe. These three VP4 genetic group 4 (P3) strains were detected in two different years and locations, extending the initial detection of this VP4 genetic group (the K8 strain) in Japan to a larger geographical area of Asia.


Oxycodone vs. tramadol in postoperative parent-controlled intravenous analgesia in children: a prospective, randomized, double-blinded, multiple-center clinical trial.
Management of acute postoperative pain is one of the major challenges in pediatric patients. Oral oxycodone has shown good pain relief in postoperative pain relief in children, but no studies have investigated intravenous oxycodone in this context. whether oxycodone PCIA can provide adequate and safe postoperative pain relief, in comparison to tramadol as reference opioid drug. a randomized, double-blind, parallel, multi-center clinical trial. five university medical centers and three teaching hospitals in China. patients aged 3-month-old to 6-year-old undergoing elective surgery under general anesthesia. patients were randomly allocated to either tramadol (n = 109) or oxycodone (n = 89) as main postoperative opioid analgesic. Tramadol or oxycodone were administered with a loading dose at the end of surgery (1 or 0.1 mg.kg-1, respectively), then with a parent-controlled intravenous device with fixed bolus doses only (0.5 or 0.05 mg.kg-1, respectively), and a 10-min lockout time. the primary outcome was adequate postoperative pain relief, defined as a face, legs, activity, cry, and consolability (FLACC) score < 4/10 in the post-anesthesia care unit (PACU), with no need for an alternative rescue analgesia. FLACC was measured 10 min after extubation then every 10 min until discharge from PACU. Analgesia was currently conducted with the boluses of either tramadol or oxycodone if FLACC was ≥ 3, up to three bolus doses, after what rescue alternative analgesia was administered. tramadol and oxycodone provided a similar level of adequate postoperative pain relief in PACU and in the wards. No significant differences were either noted for the raw FLACC scores, the bolus dose demand in PACU, the time between the first bolus dose and discharge from PACU, analgesic drug consumption, bolus times required in the wards, function activity score, or the parents' satisfaction. The main observed side effects in both groups were nausea and vomiting, with no difference between groups. However, patients in the oxycodone group showed less sedation levels and had a shorter stay in the PACU, compared with the tramadol group. an adequate postoperative analgesia can be achieved with intravenous oxycodone, this with less side effects than tramadol. It can therefore be a choice for postoperative pain relief in pediatric patients. The study was registered at www.chictr.org.cn (Registration number: ChiCTR1800016372; date of first registration: 28/05/2018; updated date:06/01/2023).


A single amino acid substitution deregulates a bacterial lactate dehydrogenase and stabilizes its tetrameric structure.
We have engineered a variant of the lactate dehydrogenase enzyme from Bacillus stearothermophilus in which arginine-173 at the proposed regulatory site has been replaced by glutamine. Like the wild-type enzyme, this mutant undergoes a reversible, protein-concentration-dependent subunit assembly, from dimer to tetramer. However, the mutant tetramer is much more stable (by a factor of 400) than the wild type and is destabilized rather than stabilized by binding the allosteric regulator, fructose 1,6-biphosphate (Fru-1,6-P2). The mutation has not significantly changed the catalytic properties of the dimer (Kd NADH, Km pyruvate, Ki oxamate and kcat), but has weakened the binding of Fru-1,6-P2 to both the dimeric and tetrameric forms of the enzyme and has almost abolished any stimulatory effect. We conclude that the Arg-173 residue in the wild-type enzyme is directly involved in the binding of Fru-1,6-P2, is important for allosteric communication with the active site, and, in part, regulates the state of quaternary structure through a charge-repulsion mechanism.


When continuous surgical site infection surveillance is interrupted: the Royal Hobart Hospital experience.
The prevalence of surgical site infections (SSI) is second only to urinary tract infections in hospitalized patients. They continue to threaten the health of hospitalized patients and impact negatively on the financial solvency of hospitals through prolonged hospitalization, increased rates of rehospitalization, and significantly increased health care costs. We describe the effect of a 12-year surveillance program that included postdischarge follow-up and feedback to clinicians on the rate of SSI and the effect when surveillance is interrupted. Surgical procedures performed at the Royal Hobart Hospital (RHH), a university teaching hospital in Australia, between 1988 and 2001 were monitored for evidence of SSI in hospitals and for up to 30 days postoperatively. The surveillance program was inadvertently disrupted for 15 months from October 1990 to January 1992 and then recommenced. It has been ongoing since that time, apart from a 3-month interruption in 1998. Infection rates were determined on a regular basis, and these results were provided to surgeons, theatre staff, and surgical ward staff every 6 months. Patients included all adult surgical patients with an incisional wound, excluding burn patients and day-only surgical patients. Over the 12-year active surveillance period, 47,581 surgical procedures were followed for SSI. In-hospital SSI rates declined significantly over the study period from 4.7% (95% CI: 3.9%-5.6%) in 1988-1989 to 1.2% (95% CI: 0.8%-1.7%) in 2001 (P < .0001). Infection rates fell rapidly following the commencement of the program. This decline was halted during the period from October 1990 to January 1992 when the program was suspended. In-hospital SSI rates declined once again following the recommencement of the surveillance program, and these lower rates have been maintained. In contrast, postdischarge infection rates rose significantly from 1.2% (95% CI: 0.8%-1.7%) in 1988-1989 to 2.1% (95% CI: 1.6%-2.7%) in 2001 (P < .0001). The introduction of a program of continuous SSI surveillance at the RHH was associated with a reduction in the in-hospital and total SSI rate. This phenomenon was repeated following the recommencement of the program after a temporary interruption. Increasing numbers of SSIs are arising after hospital discharge. Many of these patients are readmitted to the hospital for further management of the SSI. Surveillance programs that do not perform postdischarge surveillance will have difficulty in capturing this data. Our experience supports the Study on the Efficacy of Nosocomial Infection Control (SENIC) findings, showing that health care facilities can achieve improved levels of infection management with active surveillance programs.


Intraocular lens optic capture in eyes with zonular weakness in cataract patients.
We desribe a technique for managing cataracts in eyes with zonular weakness. The technique is a combination of microhook iris retractors to fixate the capsulorhexis, a capsular tension ring, and intraocular lens optic capture. Results of this technique in 70 eyes after a 13-month mean follow-up are reported.


Association between three genetic polymorphisms of glutathione S-transferase Z1 (GSTZ1) and susceptibility to bipolar disorder.
The association between polymorphisms of glutathione S-transferase Z1 (GSTZ1) and susceptibility to bipolar disorder (BPD) is investigated. This study was performed on 228 BPD patients and 234 control subjects. Among early-onset patients, the variant alleles of Glu32Lys and G-1002A increased BPD susceptibility. The haplotype "-1002G, 32Glu, 42Gly" versus the other haplotypes was significantly decreased among early-onset patients compared to controls (P=0.016).


Lactobacillemia--report of nine cases. Important clinical and therapeutic considerations.
Serious infections due to lactobacilli have been rarely cited. We report our findings in nine recent patients with lactobacillemia. In the combined literature and current experience, endocarditis and sepsis from localized suppuration were the most common clinical syndromes, most frequently arising from prior oropharyngeal infections. Lactobacillus endocarditis showed a predilection for left-sided cardiac involvement (100 per cent) and systemic arterial embolization (55 per cent). The nine clinical isolates were tested for minimal inhibitory and bactericidal concentrations (MICs and MBCs) against five drugs with broad gram-positive spectrums; of note, these organisms demonstrated a high incidence of both unachievable MBCs (64 per cent) and widely disparate (greater than 100 fold) MIC:MBC ratios (38 per cent). This is in accord with observations in Lactobacillus endocarditis of poor in vivo clinical response despite "appropriate" regimens and achievable MICs of the organisms. Bactericidal synergistic studies on two endocarditis isolates indicated that the penicillins plus aminoglycosides may be potentially useful in the treatment of deep-seated Lactobacillus infections when single antimicrobials fail to achieve a cure.


Single-crystal to single-crystal phase transition of cucurbit[5]uril hydrochloride hydrates: large water-filled channels transforming to layers of unusual stability.
Cucurbit[5]uril hydrochloride hydrate crystals with large water-filled channels transform to a highly stable layer structure via a single-crystal to single-crystal mechanism; (129)Xe NMR showed that porosity in CB[5] samples depends critically on the method of preparation.


[The significance of beta 2-microglobulin in diagnosis and therapy].
This article describes the significance of beta 2-microglobulin (beta 2m) determination both in urine and serum for the estimation of proximal renal tubular function and glomerular filtration rate. The usefulness of beta 2m in therapy, cancer diagnosing, epidemiologic investigations of industrial exposure to cadmium, lead, mercury and in evaluating etiologic factors of environmental nephropathies was also discussed.


Selenium Deficiency Mainly Influences Antioxidant Selenoproteins Expression in Broiler Immune Organs.
Selenoprotein has many functions in chicken, and the expression of selenoproteins is closely associated with the selenium (Se) level. However, little is known about the expression patterns of selenoproteins in chicken immune organs. Here, we investigated the effect of dietary Se deficiency on the expressions of 23 selenoproteins in broiler immune organs. In this study, 150 broilers were randomly divided into two groups (75 chickens per group). The chickens were maintained either on a diet supplemented with Se through the addition of 0.2 mg/kg of Se (C group) via sodium selenite or on a Se-deficient granulated diet (L group) until the broilers exhibited an onset of exudative diathesis (ED). Following euthanasia, the samples from the immune tissues (including the spleen, thymus, and bursa of Fabricius) were quickly collected, and the messenger RNA (mRNA) expression levels of 23 selenoproteins were examined by real-time quantitative PCR and analyzed using principal component analysis. The results showed that Se deficiency decreased the mRNA levels of 23 selenoproteins in the thymus, spleen, and bursa of the Fabricius tissues of broiler chickens. Furthermore, we found that among 23 selenoproteins, the mRNA levels of Dio1 in the thymus, Txnrd2 in the spleen, and Txnrd3 in the bursa of Fabricius decreased significantly (90.9 %, 83.3 %, and 96.8 %, respectively). In addition, the principal component analysis (PCA) results suggested that Se deficiency mainly influenced the expression of antioxidative selenoproteins, especially glutathione peroxidases (Gpxs), thioredoxin reductases (Txnrds), and iodothyronine deiodinases (Dios) in chicken immune organs. The results of this study are valuable for understanding the relevance of selenoprotein activity in vivo.


Cholinergic suppression of glutamatergic synaptic transmission in hippocampal region CA3 exhibits laminar selectivity: Implication for hippocampal network dynamics.
Acetylcholine may help set the dynamics within neural systems to facilitate the learning of new information. Neural models have shown that if new information is encoded at the same time as retrieval of existing information that is already stored, the memories will interfere with each other. Structures such as the hippocampus have a distinct laminar organization of inputs that allows this hypothesis to be tested. In region CA1 of the rat (Sprague Dawley) hippocampus, the cholinergic agonist carbachol (CCh) suppresses transmission in stratum radiatum (SR), at synapses of the Schaffer collateral projection from CA3, while having lesser effects in stratum lacunosum-moleculare (SLM), the perforant path projection from entorhinal cortex (Hasselmo and Schnell, 1994). The current research extends support of this selectivity by demonstrating laminar effects in region CA3. CCh caused significantly greater suppression in SR than in SLM at low concentrations, while the difference in suppression was not significant at higher concentrations. Differences in paired-pulse facilitation suggest presynaptic inhibition substantially contributes to the suppression and is highly concentration and stratum dependent. This selective suppression of the recurrent excitation would be appropriate to set CA3 dynamics to prevent runaway modification of the synapses of excitatory recurrent collaterals by reducing the influence of previously stored associations and allowing incoming information from the perforant path to have a predominant influence on neural activity.


Superoxide dismutase and glutathione peroxidase in erythrocytes of patients with iron deficiency anemia: effects of different treatment modalities.
To test whether the activities of erythrocyte superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) can be affected by oral iron (OI) treatment, parenteral iron (PI) treatment, and parenteral iron treatment with vitamin E supplementation (PIE) in iron deficiency anemia. Twenty-eight patients with iron deficiency anemia and 18 healthy controls were included in the study. Anemic patients were systematically allocated into 3 treatment groups. The first group (n=8) received OI, the second group (n=10) PI, and the third group (n=10) PIE. SOD and GSH-Px activities were determined using commercial kits. Before the treatment, SOD activity was significantly lower in anemic patients than in the control group (Kruskal-Wallis test, p<0.05). After the treatment, SOD activity significantly increased in all three patient groups and reached the values found in the control group (Wicoxon signed-rank test, p=0.017 for OI, p=0.047 for PI, and p=0.037 for PIE group). Before the treatment, GSH-Px activities in anemic patients were similar to that of control group (Kruskal-Wallis test, p>0.05). Although there was no significant decrease in GSH-Px activity after OI treatment, both PI and PIE treatments significantly decreased GSH-Px activity (Wilcoxon signed-ranks test, p=0.007 for PI and p=0.005 for PIE). PIE was more effective than PI treatment in maintaining GSH-PX activity. Oral iron treatment improved the iron deficiency anemia and recovered antioxidant defense system by increasing SOD activity and maintaining GSH-Px activity at normal level. When parenteral iron treatment is inevitable, vitamin E supplementation together with PI treatment may be effective in partially restoring the antioxidant status in this type of anemia.


Case Management Reduces Drinking During Pregnancy among High Risk Women.
Estimate the efficacy of Case Management (CM) for women at high risk for bearing a child with Fetal Alcohol Spectrum Disorders (FASD). Women were recruited from antenatal clinics and engaged in 18 months of CM. A South African community with a subculture of heavy, regular, weekend, recreational drinking and high documented rates of FASD. Forty-one women who were high risk for bearing a child with FASD. Statistical analysis of trends in drinking and other risk factors. At intake 87.8% were pregnant, most had previous alcohol-exposed pregnancies, most/all of their friends drink alcohol (67.5%), and 50.0% had stressful lives. CM was particularly valuable for pregnant women, as statistically significant reductions in alcohol risk were obtained for them in multiple variables: total drinks on weekends after six months of CM (p = .026) and estimated peak blood alcohol concentration (BAC) at six (p < .001) and 18 months (p < .001). For participants completing 18 months of CM, AUDIT scores improved significantly by 6-month follow-up (from 19.8 to 9.7, p = .000), and even though rising at 12 and 18 months, AUDIT scores indicate that problematic drinking remained statistically significantly lower than baseline throughout CM. Happiness scale scores correlated significantly with reduced drinking in most time periods. An enduring change in drinking behavior is difficult in this social setting. Yet, CM provided by skilled and empathic case managers reduced maternal drinking at critical times, and therefore, alcohol exposure levels to the fetus.


Current challenges for 3D printing complete dentures: experiences from a multi-centre clinical trial.
Aims To develop an optimal clinical and laboratory protocol for the fabrication of 3D printing dentures.Design A prospective feasibility study across three UK dental schools.Material and methods Each patient received one conventional and one 3D-printed denture. Both dentures were constructed using the same impression, jaw registration and wax trial denture. Variables investigated included methods of digitisation of the impression and optional use of a 3D-printed baseplate for jaw registration.Results Clinicians strongly preferred 3D-printed baseplates. Patients felt that conventional and printed dentures were similar in retention and stability. More patients favoured conventional dentures over 3D-printed dentures in terms of comfort.Discussion It is feasible to combine conventional clinical work with digital techniques to produce 3D-printed dentures. 3D-printed baseplates offer a cost-effective alternative to conventional bases at the jaw registration stage. Challenges were faced in tooth positioning and managing occlusion, particularly where roots required adjustment.Conclusion 3D printing is suitable for producing baseplates for jaw registration blocks and wax trial insertions. It is feasible to produce 3D-printed dentures using conventional clinical techniques for impressions, jaw registration and wax trial insertion. The workflow used in this study for 3D-printed dentures is not superior to conventional dentures. Further work is required.


Modular design of SPIRO-OMeTAD analogues as hole transport materials in solar cells.
We predict the ionisation potentials of the hole-conducting material SPIRO-OMeTAD and twelve methoxy isomers and polymethoxy derivatives. Based on electronic and economic factors, we identify the optimal compounds for application as p-type hole-selective contacts in hybrid halide perovskite solar cells.


Overview of the SACLA facility.
In March 2012, SACLA started user operations of the first compact X-ray free-electron laser (XFEL) facility. SACLA has been routinely providing users with stable XFEL light over a wide photon energy range from 4 to 15 keV and an ultrafast pulse duration below 10 fs. The facility supports experimental activities in broad fields by offering high-quality X-ray optics and diagnostics, as well as reliable multiport charge-coupled-device detectors, with flexible experimental configurations. A two-stage X-ray focusing system was developed that enables the highest intensity of 10(20) W cm(-2). Key scientific results published in 2013 and 2014 in diverse fields are reviewed. The main experimental systems developed for these applications are summarized. A perspective on the facility upgrade is presented.


Assessment of community pharmacy management towards self-medication requests of tetracyclines for pregnant women: a simulated client study in Upper Egypt.
Background Self-medication is a worldwide phenomenon of using medications without medical supervision. It is even more prevalent in low-income countries, where individuals seek community pharmacies because of accessibility and affordability. Although self-medication is associated with an increased risk of medication errors, few studies have been conducted to examine the quality of community pharmacy management towards self-medicating individuals of at-risk populations such as pregnant women. Objective We sought to investigate the quality of community pharmacies management of self-medication requests of tetracyclines for pregnant women. Setting The study was conducted in community pharmacies in Minya, Egypt. Methods A random sample of 150 community pharmacies was chosen from the urban areas of five districts of Minya, Egypt. To evaluate the actual practice, a simulated client was trained to visit pharmacies and purchase doxycycline for a pregnant woman. In a random subset of the sampled pharmacies (n = 100), interviews were conducted to evaluate pharmacy staff knowledge and attitudes regarding information gathering and dispensing practice. Main outcome measure Dispensing rate of doxycycline for pregnant women. Results From simulated client visits, almost all pharmacy staff (99.1%) dispensed doxycycline without requesting a prescription or collecting any information. About 25% of staff members did not abstain from dispensing even after knowing about pregnancy. On the other hand, most interviewed pharmacy staff (91.5%) reported that they ask about pregnancy before dispensing. Conclusion Our findings show that the current community pharmacy practice puts pregnant women at high risk of experiencing harmful self-medication outcomes. Therefore, strict legislative measures and pharmacy education programs should be considered in Egypt to lessen inappropriate dispensing rates in community pharmacies.


Retraction: The Use of CT Coronary Angiography and CT Fractional Flow Reserve in the Investigation of Patients With Suspected Coronary Artery Disease.
[This retracts the article DOI: 10.7759/cureus.7908.].


Cognitive and hedonic responses to meal ingestion correlate with changes in circulating metabolites.
We have previously shown that meal ingestion induces cognitive perception (sensations) with a hedonic dimension (well-being) that depends on the characteristics of the meal and the appropriateness of the digestive response. The aim of the present study is to identify metabolomic biomarkers of the cognitive response to meal ingestion. In 18 healthy subjects, the response to a test meal (Edanec, 1 kcal/mL) ingested until maximum satiation (50 mL/min) was assessed. Perception measurements and blood samples were taken before, at the end of the meal, and 20 min after ingestion. The cognitive response and the hedonic dimension were measured on 10 cm scales. Metabolomic analysis was performed using nuclear magnetic resonance (NMR) spectroscopy and values of triglycerides, insulin, peptide YY (PYY), and glucagon-like peptide-1 (GLP-1) were determined using conventional laboratory techniques. Ingestion up to maximum satiation induced sensation of fullness and decreased digestive well-being. The total amount ingested by each subject correlated with the basal sensation of hunger, but not with other sensations or blood metabolite levels. Immediately after ingestion, satiation correlated with an increase in glucose (R = 0.49; p = 0.038) and valine levels (R = 0.48; p = 0.043). Twenty-minutes after finalizing ingestion, triglyceride levels had significantly increased which correlated with the recovery in well-being (R = 0.48; p = 0.046) and the decrease in desire to eat a food of choice (R = -0.56; p = 0.016). The increase in lipids inversely correlated with abdominal discomfort (R = -0.51; p = 0.032). Cognitive and hedonic responses to meal ingestion correlate with changes in circulating metabolites, which may serve as objective biomarkers of perception.


Fictitious pancreatitis in choledochal cyst.
The classical presentation of choledocal cyst has been regarded as a triad of abdominal pain, jaundice and a palpable abdominal mass; unusual presentations include rupture of the choledocal cyst with bile peritonitis, pancreatitis and bleeding esophageal varices. We are reporting 3 children presenting clinically as recurrent acute pancreatitis with elevated serum amylase and found to have type I choledocal cyst. Despite elevated serum amylase there was no evidence of pancreatic inflammation at laparotomy. High amylase concentration was found in fluid contained within the cyst. This was probably responsible for the elevated serum amylase and also the inflammatory reaction seen in the wall of the choledocal cyst. These cases support the hypothesis that pancreatic reflux into the bile ducts is the etiological factor in the development of choledocal cyst. Our 3 cases were treated by cyst excision and have remained asymptomatic. The presence of hyperamylasemia should not delay appropriate surgical management. The treatment of choice is cyst excision, since it will eliminate factors contributing to the development of cholangitis and hyperamylasemia.


Attenuation of radionuclide activity by metal-cup arthroplasties.
The half-value layers of stainless steel, bone cement, and polyethylene were measured for 99mTc, 67Ga, 111In, and 201TI to render some insight into the attenuating effects of the metallic cup and other components used in surface-replacement revision arthroplasty. On theoretic consideration, a twofold increase in 99mTc-methylene diphosphonate in bone inside the cup should not be attenuated to the point of escaping detection on the radionuclide images of the hip. 67Ga, using the 184 and 300 keV peaks, and 111In have greater half-value layers than 99mTc and are subject to less attenuation by the metallic cup.


Grip function of the healthy hand in a standardized hand function test. A study of the Rancho Los Amigos test.
In an experimental study 30 healthy subjects performed the tests of prehensile function in the Rancho Los Amigos test. The subjects were allowed a free choice of grip instead of those prescribed when the test is used for clinical purposes. The hand-grips were filmed and registered by means of a descriptive code system and the results were subjected to automatic data processing. The results showed that healthy subjects performing the RLA test used a stereo-typed grip pattern as a consequence of the uniform purpose of the hand-grips. Comparison with the results from a standardized meal study in the same subjects showed that functional assessment of a patient with a test of this type is not directly applicable to integrated daily activities, as several of the hand-grips most frequent in daily activities were rarely used. Comparison with types of grip prescribed for clinical use of the test showed that normal subjects often did not spontaneously handle the objects in the manner intended by the test.


Anxiety, Depression, and Symptom Severity in Patients with Pulsatile and Non-Pulsatile Tinnitus.
To compare the rates of anxiety and depression between patients with pulsatile (PT) and non-pulsatile tinnitus (NPT), and their correlation with tinnitus severity. A prospective cross-sectional study of consecutive patients presenting either to the otolaryngology clinic for pulsatile (PT) and NPT or to a tertiary care tinnitus habituation program (THP) were administered the tinnitus handicap inventory (THI), 7-item general anxiety disorder scale (GAD-7), and 9-item patient health questionnaire (PHQ-9). Median scores between groups and correlation of scores within groups were calculated and compared. Median THI scores were significantly higher for THP and PT patients as compared with unselected NPT patients (58 and 44 vs. 20, p ≤ 0.001). Median GAD-7 (10 vs. 2.5 and 2, p ≤ 0.001) and PHQ-9 (7 vs. 4 and 4, p = 0.04) scores were highest in THP patients compared with PT and NPT. The strongest correlation between tinnitus handicap and psychiatric measures was seen in THP patients. THP patients report higher levels of anxiety and depression compared with PT and other NPT patients. Tinnitus severity correlates more strongly with GAD-7 and PHQ-9 scores in THP patients compared with other patient groups. PT patients have a greater self-perceived tinnitus handicap than the general cohort of NPT patients, statistically comparable to THP patients. Despite this, anxiety and depression are not more severe in patients with PT as they are in THP patients. 2B Laryngoscope, 133:683-688, 2023.


Hydroindenic-guanylhydrazones. Synthesis and evaluation as inotropic agents.
The synthesis and inotropic activity of two families of hydroindenic compounds are described. Among them, a bis-guanylhydrazone derivative has demonstrated to produce an interesting positive inotropic effect on guinea pig atria, displaying at higher dosis a similar effect to that elicited by digoxin.


Role of dopamine transporter genotype and maternal prenatal smoking in childhood hyperactive-impulsive, inattentive, and oppositional behaviors.
To examine the joint effects of a dopamine transporter (DAT) polymorphism and maternal prenatal smoking on childhood hyperactivity-impulsivity and inattentiveness. A cohort of 161 children was followed prospectively from age 6 months to 60 months. Primary outcomes were the DSM-IV hyperactive-impulsive and inattentive scales of the Conners' Parent Rating Scale Revised-Long Version (CPRS R:L). A secondary outcome was the oppositional scale. Predictors included DAT genotype and maternal report of prenatal smoking. Children homozygous for the 480-bp DAT allele (DAT +/+) were compared with all other children (DAT +/- or -/-). In multivariate analyses, children with both prenatal smoke exposure and the DAT +/+ genotype had significantly elevated hyperactive-impulsive scores (beta, 7.5; SE, 2.9; P<.01) compared with children with no smoke exposure and DAT +/- or -/-. Inattentive scores were not significantly elevated in this group, but oppositional scores were a full standard deviation higher. Neither prenatal smoke exposure alone nor DAT +/+ genotype alone was significantly associated with increased scores. Child hyperactivity-impulsivity and oppositional behaviors were associated with a DAT polymorphism but only when the child also had exposure to maternal prenatal smoking. This study emphasizes the importance of incorporating environmental cofactors in genetic studies of attention deficit hyperactivity disorder.


Review article: pharmacological aspects of anti-TNF biosimilars in inflammatory bowel diseases.
Anti-tumour necrosis factor (anti-TNF) monoclonal antibodies have shown efficacy in inflammatory bowel diseases (IBD). As these therapies lose patent protection, biosimilar versions of the originator products are being developed, such as the infliximab biosimilar CT-P13; however, some uncertainty exists regarding their pharmacology in IBD. To review the literature on anti-TNF biosimilars focusing on pharmacokinetics, pharmacodynamic properties and comparative effectiveness, related to their use in IBD. A PubMed literature search was performed using the following terms individually or in combination: 'biosimilars,' 'CT-P13,' 'Crohn's disease,' 'inflammatory bowel disease,' 'ulcerative colitis,' 'anti-TNFα therapy,' 'infliximab,' 'adalimumab,' 'pharmacokinetics,' 'immunogenicity.' Bioequivalence of CT-P13 and infliximab was shown in ankylosing spondylitis (AS) and therapeutic equivalence in rheumatoid arthritis (RA). Preliminary results of CT-P13 in IBD come from small post-marketing registries and case series with a relatively short-term follow-up period and suggest comparable efficacy and safety to infliximab. Inter- and intra-individual differences in exposure and response are well known for the original molecules but dosing regimens and concomitant medications are different for RA compared to IBD, limiting the ability to translate some of the pharmacology data in RA to IBD. Uncertainty exists about cross-reactivity of anti-drug antibodies and whether similar exposure-response relationships will be observed for biosimilars and efficacy thresholds for therapeutic drug monitoring can be used interchangeably. It is likely that biosimilars will be widely used for the treatment of IBD due to their cost savings and comparable efficacy. Nevertheless, robust post-marketing studies and pharmacovigilance are warranted in the coming years.


Collagen gel contraction serves to rapidly distinguish epithelial- and mesenchymal-derived cells irrespective of alpha-smooth muscle actin expression.
Mesenchymal-like cells in the stroma of breast cancer may arise as a consequence of plasticity within the epithelial compartment, also referred to as epithelial-mesenchymal transition, or by recruitment of genuine mesenchymal cells from the peritumoral stroma. Cells of both the epithelial compartment and the stromal compartment express alpha smooth muscle actin (alpha-sm actin) as part of a myoepithelial or a myofibroblastic differentiation program, respectively. Moreover, because both epithelial- and mesenchymal-derived cells are nontumorigenic, other means of discrimination are warranted. Here, we describe the contraction of hydrated collagen gels as a rapid functional assay for the distinction between epithelial- and mesenchymal-derived stromal-like cells irrespective of the status of alpha-sm actin expression. Three epithelial-derived cell lines and three genuine mesenchymal-derived breast cell lines were plated on top of hydrated collagen lattices. Reduction in gel height was measured every hour for 6 h and after 22 h using an x-y-z automated position table. Significantly, the epithelial-derived cells, irrespective of a high alpha-sm actin expression, had a fivefold lower contractility (10.0% reduction in gel height) than their true mesenchymal counterparts (53.1% reduction in gel height). To test whether at all force generation could be induced in the nonmesenchymal cells by alpha-sm actin, transductions were performed to obtain a tetracycline-dependent expression. Expression under these conditions did not augment contractility. It is concluded that epithelial-derived mesenchymal-like cells are functionally defective within a connective tissue environment irrespective of an apparent contractile phenotype.


Sensitive ferrocene reagents for derivatization of amines for high-performance liquid chromatography with electrochemical detection.
Six reagents possessing ferrocene as an electrophore were prepared and evaluated for pre-column derivatization of amino compounds for their determination by high-performance liquid chromatography with electrochemical detection. The utility of these reagents was investigated employing phenethylamine as a model compound. Among these six, N-succinimidyl 3-ferrocenylpropionate was the best with respect to reactivity, stability and electrochemical properties. The developed method was applied to the determination of putrescine formed from ornithine by ornithine decarboxylase.


What do Turkish, Spanish, and Pakistani medical students value in specialty training positions? A discrete choice experiment.
The aim of this study was to find out specialty training preferences of senior medical students from three medical schools in Turkey, Spain, and Pakistan. A Discrete Choice Experiment was carried out using an electronic form for students in three countries in 2021-2022 term. Each choice set in the form consisted of two hypothetical specialty training positions. The attributes were location, earnings, working conditions, personal perspective, quality of education, probability of malpractice, and prestige. Conditional logit model was used to estimate participants' preferences and "willingness to accept" values. The most valued attribute was "personal perspective on specialty area" for Turkish and Spanish students, while this attribute was not meaningful for Pakistani students. Turkish students needed a 204% of change in their income for a swap between the specialty that they like and not like. This tradeoff necessitated a 300% change for Spanish students. The most valued attribute for Pakistani students, which was "working conditions", necessitated a 97% increase in income to switch from working in good conditions to working in poor conditions. In this first multinational DCE study in the medical education literature, we found the preferences of medical students in Turkey, Spain, and Pakistan are affected to various extents by several factors.


Synchronous presentation of cardiac and abdominal paragangliomas.
A 28-year-old male presenting with a hypertensive crisis was found to have synchronous right atrial and retrocaval masses. Serum normetadrenaline was elevated in keeping with functional paragangliomas. After preoperative optimization both masses were successfully excised, including a saphenous vein graft to the right coronary artery. Serum catecholamines returned to the normal range postoperatively and all antihypertensive therapy was ceased.


Advanced sensing technologies of phenolic compounds for pharmaceutical and biomedical analysis.
Phenolic compounds are bioactive natural products of considerable interest in pharmaceuticals and biomedicines. Due to their bioactive functions, phenolic compounds have received increasing attention in recent years. Therefore, it is necessary to develop new and advanced analytical methods for determination of phenolic compounds in relation to pharmaceutical and biomedical applications. However, in majority, their detection has been largely conducted by sensitive yet bulky and expensive laboratory instruments, such as gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. Compared with those laboratory scale instruments, the advanced sensing technologies are extremely attractive due to the advantages of their low cost, time saving, user-friendly, simplified sample pre-treatment, high sensitivity, and excellent selectivity. The aim of this review is to provide critical information on the advanced sensing technologies for detecting phenolic compounds, with emphasis on optical sensors, electrochemical sensors and biosensors. Besides, the present status, critical issues and future trends of the related sensing technologies are outlined.


Management of penetrating neck injury in the emergency department: a structured literature review.
The management of patients with penetrating neck injuries in the prehospital setting and in the emergency department has evolved with regard to the necessity for spinal immobilisation and the use of multidetector computed tomographic (MDCT) imaging. Questions also arise as to choices of securing a threatened or compromised airway. A structured review of the medical literature was conducted to provide current recommendations for the management of patients with penetrating neck injury. Databases for PubMed, MEDLINE, CINAHL and Cochrane EBM Reviews were electronically searched using the subject headings "penetrating neck injury", "penetrating neck trauma", "cervical immobilization", "multi-detector CTA" and "airway management". The results generated by the search were limited to English language articles and reviewed for relevance to the topic. 122 citations were identified that met the criteria for emphasis on emergency department care, cervical spine immobilisation, use of multidetector CT angiography or airway management. After excluding case series, non-peer reviewed articles and editorials, 20 articles were identified and reviewed. The current literature suggests that prehospital cervical immobilisation may not be necessary unless the patient has focal neurological deficits. Studies show that patients with penetrating neck trauma who are haemodynamically stable and exhibit no "hard signs" of vascular injury may be evaluated initially by MDCT imaging even when platysma violation is present. Airway management is evolving, but traditional laryngoscopy continues to be the mainstay of airway stabilisation.


Vagal afferent C fibers projecting to the lateral descending trigeminal complex of crotaline snakes.
The primary vagal axons and terminals in the lateral descending trigeminal complex (dlv-DLV complex) in crotaline snakes were studied following HRP injections into the vagal nerve. Labeled fibers and terminals were found in the marginal neuropil, which was made up entirely of unmyelinated fibers, i.e., C fibers. The general features of vagal input to the dlv-DLV complex in snakes with infrared sensitivity (Boidae and Crotalinae) are discussed.


Nuclear expression of MDM2 in hibernoma: a potential diagnostic pitfall.
Hibernoma is a rare benign adipocytic tumor composed of a proliferation of brown and white fat cells varying in their proportions. The tumor may also contain fat cells resembling lipoblasts, which makes it difficult to distinguish it from atypical lipomatous tumor/well differentiated liposarcoma (ALT/WDLS). Although nuclear expressions of murine double minute 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) are widely used as immunohistochemical surrogate markers for ALT/WDLS, the utility of these proteins in distinguishing between hibernoma and ALT/WDLS still remains to be elucidated. We evaluated immunohistochemical expressions of MDM2 and CDK4 in 10 hibernomas expressing uncoupling protein-1 (UCP-1), a mitochondrial protein transporter consistently expressed in brown fat cells, and lacking MDM2 gene amplification, which was analyzed by fluorescence in situ hybridization (FISH). In contrast to the data previously obtained, nuclear expression of MDM2 was observed in 100% (10/10 cases) of the hibernomas irrespective of the proportion of brown fat cells, whereas no cases were positive for CDK4. The tumors also showed almost concurrent expression of p53 (in 9/10 cases) and ubiquitin-specific-processing protease 7 (USP7) (in 10/10 cases), which deubiquitinates and stabilizes MDM2, potentially resulting in its nuclear expression without MDM2 gene amplification. MDM2 expression may thus be a diagnostic pitfall for hibernoma particularly in differentiating it from ALT/WDLS.


Hypertension awareness, treatment and control among ethnic minority populations in Europe: a systematic review and meta-analysis.
Ethnic minority populations (EMPs) are disproportionally affected by hypertension-mediated complications compared with European host populations (EHPs), which might be due to disparities in hypertension awareness, treatment and control. We conducted a systematic review and meta-analysis to compare awareness, treatment and control rates among EMPs with EHPs. MEDLINE, EMBASE and Web of Science were searched from inception to 29 January 2020. Critical appraisal was performed according to methods of Hoy et al. Pooled odds ratios with corresponding 95% confidence intervals were calculated for these rates, stratified by ethnic group, using either random or fixed effect meta-analysis based on I2-statistics. Study was registered in PROSPRO (CRD42020107897). A total of 3532 records were screened of which 16 were included in the analysis with data on 26 800 EMP and 57 000 EHP individuals. Compared with EHPs, African origin populations were more likely to be aware (odds ratio 1.26, 95% confidence interval 1.02-1.56) and treated (1.49, 1.18-1.88) for hypertension, but were less likely to have their blood pressure controlled (0.56, 0.40-0.78), whereas South Asian populations were more likely to be aware (1.15, 1.02-1.30), but had similar treatment and control rates. In Moroccan populations, hypertension awareness (0.79, 0.62-1.00) and treatment levels (0.77, 0.60-0.97) were lower compared with EHPs, while in Turkish populations awareness was lower (0.81, 0.65-1.00). Levels of hypertension awareness, treatment and control differ between EMPs and EHPs. Effort should be made to improve these suboptimal rates in EMPs, aiming to reduce ethnic inequalities in hypertension-mediated complications.


Novel dihydropyridines with positive inotropic action through activation of Ca2+ channels.
Transmembrane influx of extracellular calcium through specific calcium channels is now accepted to have an important role in the excitation-contraction coupling of cardiac and smooth muscle. The importance of such slow calcium channels has been underlined by the development of specific calcium channel blocking agents, the 'calcium antagonists', typified by verapamil, nifedipine and diltiazem. These drugs have been used to investigate the properties of slow calcium channels in a variety of tissues. We have found that small modifications to the nifedipine molecule produce other dihydropyridine derivatives (see Fig. 1) with effects diametrically opposite to those of the calcium antagonists: cardiac contractility is stimulated and smooth muscle is contracted. These effects are competitively antagonized by nifedipine. Apparently, nifedipine and the novel compounds bind to the same specific dihydropyridine binding sites in or near the calcium channel. In contrast to nifedipine, however, the new compounds promote--instead of inhibiting--the influx of Ca2+ ions. We report here the properties of BAY K 8644 (methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)- pyridine-5-carboxylate), one of the most potent of these novel compounds.


Biochemical profile of halophilous microalgae strains from high-andean extreme ecosystems (NE-Chile) using methodological validation approaches.
The main goal of this work is to characterize the biochemical profile of three halophilous microalgal strains isolated from extreme ecosystems in northern Chile to assess their potential as possible sources of technological and commercial advantages. A procedure for the validation of a routine method for determining the total protein, carbohydrate, lipid and chlorophyll a (Chl-a) contents in Chlorella fusca, Dunaliella salina and Spirulina sp. has been developed. Detection limits of 10.8 μg/mg, 2.7 μg/mg and 5.6 μg/mg for total protein content and 3.5 μg/mg, 1.8 μg/mg and 8.8 μg/mg for total carbohydrate content were determined in C. fusca, D. salina and Spirulina sp., respectively. Most of the biological macromolecule levels measured in the microalgae were in accordance with the magnitude of previously reported data for other strains of the same taxa. However, lower levels than expected of lipids and Chl-a were measured in C. fusca and Spirulina sp., which may be associated with an imbalance between specific growth rates and the rate of macromolecule synthesis. The protein values measured in Spirulina sp. (52.3 ± 2.2 μg/mg DW) were close to the lower limit of the range reported in the literature for non-halophilous strains of the same genus. Except for the Chl-a quantification procedure, the analytical methods for macromolecules had a high degree of repeatability and reproducibility. The variability among repeated measurements of Chl-a was associated with auto-degradation processes during pigment extraction.


Nontoxic concentration of ceftazidime and flomoxef sodium for intravitreal use--evaluated by in-vitro ERG.
The effects of ceftazidime (CAZ) and flomoxef sodium (FMOX) on the in-vitro electroretinogram (ERG) of albino rabbits were studied. The a-wave, the b-wave and the oscillatory potential (OP) were unchanged by 0.3mM (0.19mg/ml) CAZ-containing solution. The OP was suppressed by 0.5mM (0.32mg/ml) CAZ. The a-wave, the b-wave and the OP were unchanged by 0.5mM (0.26mg/ml) FMOX. The OP was suppressed and its peak latency was delayed by 2mM (0.52mg/ml) FMOX. The concentration of 0.3mM (0.19mg/ml) CAZ was higher than its minimum inhibitory concentration (MIC) against Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, Serratia marcescens and Propionibacterium acnes. The concentration of 0.5mM (0.26mg/ml) FMOX was higher than its MIC against Staphylococcus aureus, Staphylococcus epidermidis, Serratia marcescens and Propionibacterium acnes.


Synthesis of a cosalane analog with an extended polyanionic pharmacophore conferring enhanced potency as an anti-HIV agent.
A novel cosalane analog having an extended polyanionic pharmacophore was synthesized in order to target specific cationic residues on the surface of CD4. The design rationale is based on a hypothetical binding model of cosalane to the surface of the protein. The new analog displayed an EC50 of 0.55 microM as an inhibitor of the cytopathic effect of HIV-1RF in CEM-SS cells, which represents a significant increase in potency over cosalane itself (EC50 5.1 microM). Both cosalane and the new analog are inhibitors of viral entry into target cells.


Progress and challenges of metal-organic frameworks-based materials for SR-AOPs applications in water treatment.
As environmental problems become more and more severe, sulfate radical (SO4-) based advanced oxidation processes (SR-AOPs) are widely recognized for their high removal efficiency of recalcitrant organic pollutants in water. Metal-organic frameworks (MOFs) have attracted wide attention in SR-AOPs due to their outstanding properties (e.g. large surface area, ultra-high porosity, and diversity of material design, etc). Herein, we present an overview of the development and challenges in the synthesis of different types of MOFs, combination of MOFs with other materials (metal centers, conductors, cellulose, etc.) and the construction of catalysts with special structures (core-shell structures and hollow structures) as well as their applications in SR-AOPs for the degradation of organic pollutants. Several review papers have already mentioned the application of a branch of MOFs or simple composites of MOFs in SR-AOP, whereas the latest progresses on the application of MOFs-based materials to SR-AOPs was described rarely. Besides, the degradation mechanism of MOFs as catalysts has not been systematically discussed. To this end, the mechanisms of MOFs and MOF-based materials as catalysts to activate PMS/PS in different systems are analyzed, including radicals and non-radicals pathways. Meanwhile, considering that the research in this field is still in its infancy, a lot of improvements are still needed to effectively promote and implement this technology.


Radiation cross-linked ultra-absorbent hydrogel to rationalize irrigation water and fertilizer for maize planting in drought conditions.
The study addresses the potential negative impacts of climate change on water resources, specifically irrigation water for crops. The radiation technique produces the biomaterial hydrogel as a soil conditioner by polymerizing hydroxy ethyl cellulose/acrylamide (HEC/AAm) at various irradiation doses and copolymer concentrations. A maximum swelling of 23.4 g/g is attained by (HEC/PAAm) hydrogel at 1/7.5 ratio, prepared by 10 kGy gamma irradiation. The study introduces a new class of ultra-absorbent hydrogel (UAH) to address the low swelling limitation for soil conditioner applications. The alkaline hydrolysis treatments with NaOH, LiOH, and KOH enhance the water absorbency of (HEC/PAAm) hydrogel, with the highest capacity of 1220 g/g achieved by the KOH treatment, surpassing NaOH (622 g/g) and LiOH (540 g/g). The cumulative release of fertilizers from the UAH sample shows a slow and controlled release behavior. Urea takes 22 days to reach 100 % release. The UAH demonstrates water retention for 28 days, improving the growth of Zea mays L. at drought stress levels of 0 %, 25 %, 50 %, and 100 %, revealing an increase in shoot length by 16 %, 19 %, 24 %, and 20 %, respectively. Also, UAH increased the contents of chlorophyll a, b, a + b, and carotenoid on maize plant leaves compared to the control sample.


Experiences of parents of children with psychiatric disorder from Covid-19 pandemic and its related quarantine: A qualitative study.
Owing to the considerable mortality caused by Covid-19, different countries have made some decisions for dealing with this virus, one of which was quarantine. It was shown that a range of behavioral and emotional changes may exacerbate in children while staying more at home, and parents may then experience these positive or negative behavioral changes. The present study was conducted to examine the experiences of families with children with psychiatric disorders in a psychiatric outpatient clinic in Iran. The phenomenological method, which is a qualitative approach, was used in this study. The population was the parents of children with psychiatric disorders referred to the pediatric psychiatric clinic of Imam Hossein Hospital. Sampling was purposeful, which continued until data saturation. Finally, the number of included participants reached 14. As well, the Colaizzi method was used for data analysis. The results of this study included 12 secondary codes and 10 tertiary codes, which were divided into three main thematic groups as follows: effective factors for improving behavior, effective factors for worsening behavior, and affective factors on creating a new behavior during quarantine. In conclusion, quarantine, social restrictions, closure of schools, and online classes can affect the mental health status of children and adolescents in different ways, especially in children with a history of psychiatric disorders.


New autoantigens in rheumatoid arthritis (RA): screening 8268 protein arrays with sera from patients with RA.
To identify new IgG autoantibodies in sera from patients with rheumatoid arthritis (RA). We tested serum samples from 19 patients with RA with given human leukocyte antigen (HLA)-DR genotypes, from 7 patients with spondylarthropathy, 2 patients with lupus, 4 patients with systemic sclerosis and 10 healthy individuals on 8268 human protein arrays. We identified four antigens (peptidyl arginine deiminase 4 (PAD4), protein kinase Cbeta1 (PKCbeta1), phosphatylinositol 4 phosphate 5 kinase type II gamma (PIP4K2C) and v raf murine sarcoma viral oncogene homologue B1 catalytic domain (BRAF)) that were recognised almost uniquely by sera from patients with RA on protein arrays. Using purified proteins, we confirmed that PAD4 and BRAF are recognised almost uniquely by patients with RA. We identified PAD4 and BRAF as RA specific autoantigens.


Ratio of high-, medium-, and low-molecular weight serum adiponectin to the total adiponectin value in children.
In 760 children age 9 to 10 years, the serum adiponectin composition (high molecular weight [HMW], hexameric medium molecular weight [MMW], and trimeric low molecular weight [LMW]) was found to vary markedly depending on whether the total adiponectin value was high or low. A lower total adiponectin value was associated with a lower ratio of HMW adiponectin.


Spatial and temporal trend of Chinese manure nutrient pollution and assimilation capacity of cropland and grassland.
Dynamics of livestock and poultry manure nutrient was analyzed at a provincial scale from 2002 to 2008. The nutrient capacity of 18 kinds of croplands and grasslands to assimilate nutrients was assessed in the same temporal-spatial scale. Manure nitrogen (N) had increased from 5.111 to 6.228 million tons (MT), while manure phosphorus (P) increased from 1.382 to 1.607 MT. Manure N and P share similar spatial patterns of yields, but proportion of specialized livestock husbandry and contribution of leading livestock categories (swine, cattle, cow, sheep, layer chicken, broiler chicken) were different. The nutrients generated from dominant seven provinces took more than about half of total manure N in China. After subtracting the chemical fertilizers, there were some manure nutrient capacities in western part of China. Risk analysis of manure nutrient pollution overload in eastern and southern parts of China was serious, which should restrict livestock's developments. Amount of chemical fertilizers applied should be reduced to make room for manure nutrients. For the sake of greenhouse effects, the emission of methane (CH4) and nitrous oxide (NO x ) emissions in China is serious for the global change, thus merits further statistics and studies. The spatial and temporal pattern of Chinese manure nutrient pollution from livestock and the assimilation capacity of cropland and grassland can provide useful information for policy development on Chinese soil environment and livestock.


The performance of three visual coding procedures and three computer programs in classification of electrocardiograms according to the Minnesota Code.
A test library composed of the ECG's of 228 patients with clinically proven myocardial infarction and 294 subjects without clinical evidence of infarction was used to assess the performance of three visual coding procedures and three computer programs designed to classify ECGs according to the Minnesota Code. The results showed that visual coding performed by one experienced senior coder tended to be more consistent than visual coding relying on two less experienced coders and arbitration of disagreements by a supervisor. There was no significant difference in coding results when only one preprocessed complex was coded in comparison with the more elaborate coding of the whole source ECG using majority rule. The coding performance of the three computer programs was similar to that of the visual coding procedures. It is concluded that computer coding of ECGs according to the Minnesota Code is feasible. Combined optimal use of automated coding and visual verification of selected items may still further improve coding precision. However, when judged against an ECG independent standard, the accuracy of all coding procedures in discriminating infarcts from non-infarcts according to the Minnesota code criteria is rather limited. 'Soft' criteria give a reasonable sensitivity with low specificity whereas the use of 'hard' criteria with adequate specificity results in a substantial drop in sensitivity.


Homoagglomeration and heteroagglomeration of TiO2, in nanoparticle and bulk form, onto freshwater and marine microalgae.
TiO2 nanoparticles (TiO2 NPs) are employed in many products (paints, personal care products, especially sunscreens, plastics, paper, water potabilization and food products) and are then released into the environment from these products. These nanoparticles present potential risk to freshwater and marine microalgae. The primary toxicity mechanism is adsorption between NPs and microalgae (heteroagglomeration); however, studies of interactions of this kind are scarce. We investigated the heteroagglomeration process that occurs between two forms of TiO2 material, nanoparticles and bulk, and three different microalgae species, and under different environmental conditions (freshwater and marine water), in order to assess the influence of pH and ionic strength (IS). The heteroagglomeration process was examined by means of co-settling experiments and the Derjaguin-Landau-Verwey-Overbeek (DLVO) approach. The homoagglomeration process (only NPs to NPs) did not show differences between culture media (freshwater and marine water). However, in the heteroagglomeration process between NPs and cells, IS played an important role. Ions can compress the electro-double layer between NPs and microalgae, allowing a heteroagglomeration process to take place, as shown by settling experiments. TiO2 NPs presented a settling rate higher than bulk TiO2. The DLVO theory could only partially explain heteroagglomeration because, in this model, it is not considered that NP-NP and Cell-Cell homoagglomeration co-occur. In this study neither the role of exopolymeric substances in the interaction between NPs and cells nor detoxification are considered. The authors suggest that the interaction between NPs and microalgae could be considered as the first stage in the process by which nanoparticles affect microalgae.


Isotopic Dependence of Vapor Pressure in Xenon.
The vapor pressure isotopic effect (VPIE) of xenon has been measured using cryogenic distillation. The still is calibrated with argon and krypton and yields a measurement of ln(p 130/p 136) ≃ (0.26 ± 0.04) × 10-3, where p 130 and p 136 are the vapor pressures of 130Xe and 136Xe at the nominal boiling point, respectively. The dependence of the VPIE across the isotopes for the three elements is found to be approximately linear with atomic mass, and all values are consistent with theoretical expectations.


Simultaneous quantification of ten constituents of Xanthoceras sorbifolia Bunge using UHPLC-MS methods and evaluation of their radical scavenging, DNA scission protective, and α-glucosidase inhibitory activities.
The present study was designed to investigate the bioactive constituents of Xanthoceras sorbifolia in terms of amounts and their antioxidant, DNA scission protection, and α-glucosidase inhibitory activities. Simultaneous quantification of 10 X. sorbifolia constituents was carried out by a newly established ultra-high performance liquid chromatography-quadrupole mass spectrometry method (UHPLC-MS). The antioxidant activities were evaluated by measuring DPPH radical scavenging and DNA scission protective activities. The α-glucosidase inhibitory activities were investigated by using an assay with α-glucosidase from Bacillus Stearothermophilus and disaccharidases from mouse intestine. We found that the wood of X. sorbifolia was rich in phenolic compounds with the contents of catechin, epicatechin, myricetin, and dihydromyricetin being 0.12-0.19, 1.94-2.16, 0.77-0.91, and 6.76-7.89 mg·g(-1), respectively. The four constituents strongly scavenged DPPH radicals (with EC50 being 4.2, 3.8 and 5.7 μg·mL(-1), respectively) and remarkably protected peroxyl radical-induced DNA strand scission (92.10%, 94.66%, 75.44% and 89.95% of protection, respectively, at a concentration of 10 μmol·L(-1)). A dimeric flavan 3-ol, epigallocatechin-(4β→8, 2β→O-7)-epicatechin potently inhibited α-glucosidase with an IC50 value being as low as 1.2 μg·mL(-1). The established UHPLC-MS method could serve as a quality control tool for X. sorbifolia. In conclusion, the high contents of antioxidant and α-glucosidase inhibitory constituents in X. sorbifolia support its use as complementation of other therapeutic agents for metabolic disorders, such as diabetes and hypertension.


Semiconductors in anaesthetic vapour analysis.
The use of chemically sensitive semiconductors and their performance during the measurement of the vapour concentration of five volatile anaesthetic agents is described.


The reaction of N-ethylmaleimide at the active site of succinate dehydrogenase.
Since 1938 mammalian succinate dehydrogenase has been thought to contain thiol groups at the active site. This hypothesis was questioned recently, because irreversible inhibition by bromopyruvate and N-ethylmaleimide appeared not to satisfy the requisite criteria for reaction at the active site. These recent observations of incomplete inactivation of succinate dehydrogenase by N-ethylmaleimide and incomplete protection by substrates can, however, be explained adequately by the presence of oxalacetate and other strong competitors of the inactivation process in the enzyme used in these studies. Substrates, competitive inhibitors, and anions which activate succinate dehydrogenase protect the enzyme from inhibition by N-ethylmaleimide. Inhibition of succinate dehydrogenase by N-ethylmaleimide involves at least two second order reactions which are pH dependent, with pKa values of 8.0 to 8.2. This pH dependence, the known reactivity of N-ethylmaleimide toward thiols, and the protection by substrate and competitive inhibitors indicate that sulfhydryl residues are required for catalytic activity and perform an essential, not secondary, role in the catalysis. Just as the presence of tightly bound oxalacetate prevents inhibition by N-ethylmaleimide, alkylation of the sulfhydryl residue(s) at the active site prevents the binding of [14C]oxalacetate. Thus, these thiol groups at the active site also may be the site of tight binding of oxalacetate during the activation-deactivation cycle.


Colorimetric and chemiluminescence based enzyme linked apta-sorbent assay (ELASA) for ochratoxin A detection.
Ochratoxin A (OTA) is one of the most widespread mycotoxin found to contaminate various food products such as cereals, spices, groundnuts, coffee, wine, beer etc. It is also carried over from contaminated feed and fodder to milk, blood, meat, kidney and liver of animals consuming it. Enzyme-linked to biorecognition molecules like antibodies or aptamers are very popular due to their ability to be used as labels or tags in biosensing formats. In this work, OTA aptamer based colorimetric and chemiluminescence biosensing formats were evaluated for the detection of OTA. The colorimetric enzyme linked apta-sorbent assay (Co-ELASA) and chemiluminescence enzyme linked apta-sorbent assay (Cl-ELASA) showed a linear detection range from 1 pg/mL to 1 μg/mL with a limit of detection (LOD) of 0.84 pg/mL for Co-ELASA (limit of quantification (LOQ) = 2.54 pg/mL) and 1.29 pg/mL for Cl-ELASA (LOQ = 3.94 pg/mL) under optimized buffer conditions. Comparison of ELASA methods with sandwich ELISA indicated that the developed techniques had sensitivity similar to the conventional technique which indicated a LOD of 1.13 pg/mL and LOQ of 3.41 pg/mL. Studies in simulated contaminated food samples by spiking OTA in groundnut and coffee bean at concentrations of 0.1, 1 and 10 ppb, indicated recoveries in the range of 50.21 to 113.27% for Co-ELASA, 90.47 to 107.72% for Cl-ELASA and 76.23 to 141.49% for ELISA. Results of the study indicate that Co-ELASA and Cl-ELASA assays could be an alternate approach for ultrasensitive detection of OTA in food samples, which can also be adapted for biosensor development.


Increased auditory stimulus intensity results in an earlier and faster rise in corticospinal excitability.
Increasing the intensity of auditory stimuli has been shown to produce faster simple reaction times (RTs). Typical explanations for this effect involve earlier detection of the more intense stimulus; however, these explanations fail to consider how stimulus intensity may impact response initiation processing. To investigate the mechanism responsible for the auditory stimulus intensity effect, transcranial magnetic stimulation (TMS) was applied at various times during the simple RT interval (equivalent to 0, 30, 45, 60, and 75% of baseline RT) to examine changes in corticospinal excitability after a go-signal of varying intensity (60, 70, 80, or 90 dB). Premotor RT data confirmed a stimulus intensity effect whereby the 90 dB stimulus resulted in faster RTs than all other intensities. Analysis of motor evoked potential (MEP) amplitude elicited by TMS across stimulus intensity conditions revealed that in the 80 dB and 90 dB conditions, corticospinal excitability began to increase earlier from baseline (pre-stimulus) levels, supporting the detection hypothesis. In addition, MEP amplitude increased at a greater rate during the RT interval for the 90 dB condition, indicative of impacts on response initiation. These results indicate that stimulus intensity effects result from a combination of earlier detection and faster initiation.


Growth and cell structure of Proteus vulgaris when cultivated in weightlessness in the Cytos apparatus.
Growth data and electron-microscopic analyses are presented for Proteus vulgaris cultures which were grown during space flight in polyethylene packets in a semisolid medium with Tryptose for 96 h. In the suboptimal culture conditions the growth and morphological characteristics of the flight and ground control variants were nearly identical, but we were able to detect a number of differences between the cellular ultrastructure of these variants. These differences testify to changes in the bacterial cell metabolism during space flight.


Conditions of occurrence for primeval processes of transphosphorylations.
Model reactions of the phosphate group transfer through hydrolysis-condensation processes without enzymic catalysts are studied in dilute aqueous solutions. Tripolyphosphate and acetylphosphate are used as energy and phosphate donors to perform syntheses of pyrophosphate. Results are discussed in terms of the variation versus pH of the overall standard free enthalpy change.


Image-guided abscess drainage in children with perforated appendicitis - can it wait?
Image-guided drainage is the management of choice for perforated appendicitis with intra-abdominal abscess/es. However, there is paucity of data regarding the optimal time for intervention in children. The purpose of this study is to assess the relationship between the time from diagnosis of a drainable abscess to abscess drainage (delta time) and the clinical outcome in patients with complicated acute appendicitis. This is an institutional review board (IRB)-approved retrospective study comprising 80 pediatric patients who had image-guided abscess drainage due to perforated acute appendicitis. Delta time was associated with clinical outcome including length of stay, catheter dwell time, need for additional interventions, and need for tissue plasminogen activator (t-PA). Gamma regression models were used to assess the adjusted effect of delta time on the "length of stay" and "catheter dwell time" using "volume of the largest abscess" and "number of collections" as severity indices. Logistic regression was used to assess the effect of delta time on the "need for the t-PA" and "need for additional interventions." Mean age (SD) was 10.2 (3.8) years. Mean time between diagnosis and intervention (delta time) was 1.5 (1.2) days. There was no evidence that delta time effects the length of stay, catheter dwell time, need for t-PA, and need for additional interventions (P > 0.05). However, there was an association between the number of collections and volume of the largest abscess with length of stay (P = 0.006; P = 0.058), catheter dwell time (P = 0.029; P < 0.001), and need for additional interventions (P = 0.029; P = 0.016). Our results suggest that time between diagnosis of an appendicitis associated abscess and intervention is not significantly associated with need for tPA, need for additional intervention, drain dwell time, or length of stay.


Differentiated digestion resistance and physicochemical properties of linear and α-1,2/α-1,3 branched isomaltodextrins prepared by 4,6-α-glucanotransferase and branching sucrases.
Isomaltodextrins (IMDs) are starch-based dietary fibers (DF) prepared enzymatically, which show great potential as a functional food ingredient. In this study, a series of novel IMDs with diverse structures were generated by 4,6-α-glucanotransferase GtfBΔN from Limosilactobacillus fermentum NCC 3057, combined with two α-1,2 and α-1,3 branching sucrases. Results indicated that α-1,2 and α-1,3 branching significantly improved the DF contents of α-1,6 linear products up to 60.9-62.8%. When altering the ratios of [sucrose]/[maltodextrin], IMDs containing 25.8-89.0% α-1,6 bonds, 0-59.6% α-1,2 bonds and 0-35.1% α-1,3 bonds and Mw ranged from 1967 to 4876 Da were obtained. Physicochemical property analysis showed that grafting with α-1,2 or α-1,3 single glycosyl branches can improve the solubility of the α-1,6 linear product, in which α-1,3 branched products were better. Moreover, α-1,2 or α-1,3 branching did no effect on the viscosity of the products but Mw did, the larger Mw the greater viscosity. In addition, α-1,6 linear and α-1,2 or α-1,3 branched IMDs all exhibited strong acid-heating stabilities, freeze-thaw stabilities, and good resistance to browning caused by the Maillard reaction. Branched IMDs showed excellent storage stabilities at room temperature for one year at a concentration of 60%, whereas 45% α-1,6 linear IMD precipitated quickly within 12 h. Most importantly, α-1,2 or α-1,3 branching remarkably increased the contents of resistant starch in the α-1,6 linear IMDs to 74.5-76.8%. These clear qualitative assessments demonstrated the outstanding processing and application properties of the branched IMDs and were expected to provide valuable perspectives toward the technological innovation of functional carbohydrates.


Bile duct measurements after ceruletide as an aid to the ultrasound diagnosis of choledocholithiasis.
Despite good results in gallbladder imaging, ultrasound (US) diagnosis of choledocholithiasis remains a challenge. The value of US before and after a provocative injection of the decapeptide ceruletide was examined in 25 patients with suspected common duct stones immediately prior to diagnostic retrograde cholangiography. An abnormal response (increase in US duct diameter) was seen in 4 of 6 patients with an obstructed duct, giving a sensitivity of 67% and predictive value of 80% for the procedure. There was a normal response (decrease in US diameter of a dilated duct or decrease/no change in a normal duct) in 14 of 19 with an unobstructed duct (specificity 79%, predictive value 93%) and an equivocal response (no change in diameter of a dilated duct) in 5 patients. In 1 patient a calculus not seen on the initial US became visible as the duct distended by ceruletide administration. Symptoms after ceruletide were few and not discriminatory. Although it added to the time and difficulty of performing biliary US, ceruletide administration proved a useful adjunct to the diagnosis of choledocholithiasis.