[Overexpression of human tumor metastasis-related gene TMSG-1 suppresses cell proliferation and invasion of a highly metastatic prostate cancer cell line PC-3M-1E8 in vitro].
To investigate the effects of tumor metastasis-related gene TMSG-1 overexpression on the proliferation and invasion of a highly metastatic prostate cancer cell line in vitro. The eukaryotic expression plasmids containing full-length TMSG-1 cDNAs were stably transfected into the highly metastatic prostate cancer cell line PC-3M-1E8. Clones highly expressing TMSG-1 were identified by RT-PCR and Western Blot analysis after G418 screening. The cell proliferation was detected by cell growth curve, MTT assay and soft agar colony formation assay. The invasive potential of tumor cells in vitro was tested by Matrigel invasion assay. Three TMSG-1 overexpression clones were selected. Cell growth curve and MTT assay showed that TMSG-1 overexpression clones exhibited a strong inhibition of proliferation compared with that of the parental cells or those transfected with vector alone from the third day of culture (P <0.05). In vitro analysis also showed that the TMSG-1 transfected clones exhibited a decreased clonogenicity in soft agar compared with that of the parental cells or those transfected with vector only (P < 0.05). TMSG-1 expression significantly suppressed cell invasion in vitro of TMSG-1-transfected PC-3M-IE8 cells (P < 0.05). The TMSG-1 protein may serve as a tumor metastasis suppressor due to inhibiting cell proliferation and invasion of the highly metastatic prostate cancer cell line PC-3M-1E8.


Sexual experiences associated with participation in drinking games.
The results of previous research suggest that participation in drinking games may be associated with sexual aggression, but the specific sexual behaviors involved have not been identified. In the present study, the authors attempted to identify specific sexual experiences associated with drinking games. Both men and women reported being taken advantage of sexually during or after play, including someone having sex with them when they were too drunk to give consent. Few women admitted to being perpetrators, but many men reported multiple instances of perpetration. Greater alcohol consumption predicted more sexual experiences in women. In men, sexual motives for playing drinking games were the best predictor of sexual behavior. Alcohol and sexual-assault prevention programs may need to consider the role of drinking games in sexual victimization.


Right Ventricular Ejection Fraction and Beta-Blocker Effect in Heart Failure With Reduced Ejection Fraction.
A low right ventricular ejection fraction (RVEF) is a marker of poor outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Beta-blockers improve outcomes in HFrEF, but whether this effect is modified by RVEF is unknown. Of the 2798 patients in Beta-Blocker Evaluation of Survival Trial (BEST), 2008 had data on baseline RVEF (mean 35%, median 34%). Patients were categorized into an RVEF of less than 35% (n = 1012) and an RVEF of 35% or greater (n = 996). We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) within each RVEF subgroup and formally tested for interactions between bucindolol and RVEF. The effect of bucindolol on all-cause mortality in 2008 patients with baseline RVEF (HR 0.88, 95% CI 0.75-1.02) is consistent with that in 2798 patients in the main trial (HR 0.90, 95% CI 0.78-1.02). Bucindolol use was associated with a lower risk of all-cause mortality in patients with an RVEF of 35% or greater (HR 0.70, 95% CI 0.55-0.89), but not in those with an RVEF of less than 35% (HR 1.02, 95% CI 0.83-1.24, P for interaction = .022). Similar variations were observed for cardiovascular mortality (P for interaction = .009) and sudden cardiac death (P for interaction = .018), but not for pump failure death (P for interaction = .371) or HF hospitalization (P for interaction = .251). The effect of bucindolol on mortality in patients with HFrEF was modified by the baseline RVEF. If these hypothesis-generating findings can be replicated using approved beta-blockers in contemporary patients with HFrEF, then RVEF may help to risk stratify patients with HFrEF for optimization of beta-blocker therapy.


Successful treatment of multidrug-resistant tuberculosis following drug-induced hepatic necrosis requiring liver transplant.
A 28-year-old female developed multidrug-resistant (MDR) tuberculous lymphadenitis following a trip to India. She was initially treated with a four-drug regimen of first-line anti-tuberculosis medications, but when sensitivities indicated resistance to isoniazid and rifampin, her regimen was altered to ciprofloxacin (CFX), pyrazinamide (PZA) and ethambutol. She subsequently developed a rash, flu-like symptoms and fever, which progressed to acute hepatic necrosis despite discontinuation of medication. The clinical presentation and subsequent investigations suggested a hypersensitivity reaction, possibly related to the quinolone. The patient subsequently had an orthoptic liver transplant; second-line anti-tuberculosis medications were restarted to which she responded clinically and radiologically. Our findings raise the possibility that the CFX and PZA combination was responsible for the hepatic necrosis. The patient also illustrates that active, even MDR tuberculosis is not a contraindication to hepatic transplant.


Soundscape and subjective factors affecting residents' evaluation of aircraft noise in the communities under flight routes.
Aircraft noise is one of the most significant sources of environmental pollution in large cities. During the COVID-19 pandemic, strict lockdown in community might increase residents' discomfort with the noise, which could disrupt public activities and reduce subjective well-being. Most of the existing studies considered aircraft noise as a single sound source, which have ignored the influence of other sounds in the community. This paper applied field survey to identify the soundscape and non-acoustic factors related to aircraft noise evaluation. Paper questionnaires were delivered to select residents of three sample residential areas near Shenzhen Bao'an International Airport to investigate residents' general health, evaluation of aircraft noise, community activities, and attitudinal factors. The relationship between respondent's noise evaluations and subjective factors were investigated through statistical analyses controlling for measured aircraft noise levels and the existence of soundscape facilities. The results indicated that the negative effects of aircraft noise were enhanced during the lock down, especially for frequent space users and those residents in poor health status. Under conditions of similar levels of aircraft noise exposure, communities with more birdsong and fountain sounds had lower proportion of highly annoyed respondents and higher level of soundscape ratings. This paper further indicated that personal factors including fear of air travel, noise sensitivity, and the frequency of outdoor activity had increased the level of annoyance to aircraft noise, while higher degree of annoyance to aircraft noise was associated with poor health status. The findings implied the moderating effects of subjective factors and the restorative effects of natural sounds, which could inform aircraft noise control and community consultation strategies by protecting vulnerable populations and creating community soundscape facilities. Future research might conduct a pre- and post-experiment to estimate the potential causal impact of the soundscape intervention.


In situ polymerization of a microencapsulating medium round living cells.
A new process for microencapsulating living cells is described. Pancreatic islet cells in solution in agarose were extruded from a syringe into a paraffin-oil-containing medium. A rigid interface around each bead was produced when the agarose gelled. A polymerizable mixture of monomers containing 30% of acrylamide and 1.5% of bisacrylamide was then added to these beads. Polymerization was initiated by a photochemical process using riboflavin as a photosensitizer, which enabled use of oxygenated solutions. As other polymerizations initiated by an oxido-reduction reaction, this method did not require heating, and could thus be carried out at ambient temperature. The oil phase near the agarose beads effectively prevented any rise in temperature, and also led to formation of an acrylamide concentration gradient in the aqueous phase, which reduced the potential cytotoxicity of the reaction. Radioimmunoassay of insulin liberated from encapsulated islets of Langerhans demonstrated a good viability of the cells.


Formation of a trypsin-borate-4-aminobutanol ternary complex.
The formation of ternary complexes involving serine proteases, borate, and an alcohol has important implications for understanding the physiological actions of borate and for the development of tight binding inhibitors for this class of enzymes. Recent studies of a related enzyme, gamma-glutamyl transpeptidase, which is subject to inhibition by a labile serine/borate mixture, have demonstrated that construction of a non-labile boronate analogue results in an inhibitor with nearly 10(5)-fold greater potency. To evaluate the generalization of this biochemistry to serine proteases, we have observed the ternary complex formed from 4-aminobutanol, borate, and trypsin. A combination of (11)B and (1)H NMR and spectrophotometric assays using acetylarginine p-nitroanilide (Ac-Arg-pNA) as the chromogenic substrate all indicate a cooperative binding interaction in which the borate is esterified by the oxygen atoms of the 4-aminobutanol and trypsin residue Ser(195). Two downfield-shifted proton resonances at 15.5 and 16.6 ppm are proposed to arise from the labile imidazolium protons on His(57), indicating a salt bridge interaction with the negatively charged borate. A cooperativity parameter alpha of 0.2 is derived from the assays. These results provide the first direct evidence for formation of a ternary complex involving a serine protease, borate, and an alcohol, and suggest that this represents a general approach for the development of tight binding ligands.


A new genus and new species of Potamidea (Crustacea: Decapoda: Brachyura: Potamoidae), the first stygomorphic cave crab known from China and East Asia.
A new genus and species of freshwater crab, Diyutamon cereum n. gen., n. sp., is described from a cave in Guizhou, China. This is the first record of a true stygomorphic crab from China and East Asia, possessing pale body coloration, strongly reduced eyes, and long ambulatory legs. While superficially similar to Chinapotamon Dai & Naiyanetr, 1994, and Tiwaripotamon Bott, 1970, the new genus possesses a diagnostic combination of carapace, ambulatory leg, thoracic sternal, and male abdominal characters that easily distinguishes it from other genera. Molecular data derived from the mitochondrial 16S rDNA supports the establishment of the new genus.


A Novel Antimicrobial Endolysin, LysPA26, against Pseudomonas aeruginosa.
The global increase in multidrug resistant (MDR) bacteria has led to phage therapy being refocused upon. A novel endolysin, LysPA26, containing a lysozyme-like domain, was screened against Pseudomonas aeruginosa in this study. It had activity against MDR P. aeruginosa without pretreatment with an outer-membrane permeabilizer. LysPA26 could kill up to 4 log units P. aeruginosa in 30 min. In addition, temperature and pH effect assays revealed that LysPA26 had good stability over a broad range of pH and temperatures. Moreover, LysPA26 could kill other Gram-negative bacteria, such as Klebsiella pneumonia, Acinetobacter baumannii and Escherichia coli, but not Gram-positive bacteria. Furthermore, LysPA26 could eliminate P. aeruginosa in biofilm formation. Our current results show that LysPA26 is a new and promising antimicrobial agent for the combat of Gram-negative pathogens.


Lower-Extremity Muscle Activity, Kinematics, and Dynamic Postural Control in Individuals With Patellofemoral Pain.
Altered lower-extremity muscle activity has been associated with lower-extremity kinematics in individuals with patellofemoral pain (PFP). However, few studies have examined these relationships, and the results are inconsistent. To compare the lower-extremity muscle activity, kinematics, pain level, and reach distance during the anterior reach of the star excursion balance test (SEBT) between participants with PFP and healthy individuals (control [CON] group). Case control. Research laboratory. Twenty-eight (PFP = 14 and CON = 14) participants volunteered. Each participant performed 3 maximal voluntary isometric contractions of the gluteus maximus, gluteus medius (GMED), adductor longus (AL), and vastus medialis, and 5 anterior reaches of the SEBT. Three-dimensional joint kinematics of the hip and knee at the time of touchdown of the SEBT and integrated electromyography of each muscle were recorded during the descent phase of the SEBT. Coactivation ratios between the GMED and AL were calculated (GMED/AL). Pain level was assessed at the baseline and during performance of the SEBT, using a visual analog scale. Participants with PFP demonstrated decreased GMED/AL coactivation ratio (P = .01) and shorter reach distance (P = .01) during anterior reach of the SEBT compared with the CON group. Participants with PFP demonstrated higher pain levels at baseline (P = .03) and during test performance (P < .001) compared with the CON group and increased pain level during the test performance compared with the baseline (P < .001). No other significant differences were observed. There were alterations in muscle activity during SEBT performance, suggesting that overactivity of AL relative to GMED is a unique neural recruitment pattern in those with PFP. However, hip and knee joint kinematics did not seem to contribute to deficits in the anterior reach distance, suggesting a need for continued assessment of these deficiencies.


Effects of stretching and warm-up routines on stability and balance during weight-lifting: a pilot investigation.
The efficacy of warm-up and stretching in weight-lifting remains unknown, especially for the weight-lifter's stability and balance during lifting. 13 subjects were randomly assigned a 10-minute stretching routine (SR) or a 10-minute warm-up routine (WR) and compared against 5 controls (no stretching or warm-up). Before and after the individually assigned routine, the participants' centre of pressure (CoP) was assessed using plantar-pressure sensors. The subjects were measured during 10 repetitions of air squat (no load, "AS"), front squat (FS; 20 kg/15 kg bar), overhead squat (OHS; m: 20 kg / f: 15 kg bar), and a deadlift lifting exercise ("DL"; 20 kg/15 kg bar). The impact on CoP dynamics of the warm-up and stretching routines were examined with repeated two-factor analysis of variances (ANOVA) of the mean and the coefficient of variance (CV, shown in %), as proxies for stability and balance. After stretching, the SR athletes shifted the mean CoP towards the toes (≈1 cm; p < 0.01) while the WR athletes shifted the CoP towards the heels (≈1 cm; p < 0.01) during AS. For the remaining exercises, the SR athletes shifted the CoP towards the heels (between 0.8 cm and 5.7 cm) compared to WR (≈1.9 cm towards the heels in FS, no significant change in OHS (≈1 mm) and DL (≈3 mm)). The controls did not show any change between pre- and post-datasets. After stretching, the CV decreased for the AS and OHS exercises (AS: 10.2% to 7.0%, OHS 9.8% to 7.8%), but increased after WR (AS: 7.1% to 10.1%) or did not change significantly (OHS). Both WR and SR resulted in increased CV values for FS and DL. No change of CV was observed in the controls. SR had a stronger impact on CoP during the assessed exercises than either WR or controls. A reduction in CV after SR exercises (AS, OHS) suggests a clear improvement in stability and balance during weight-lifting. The lack of a significant effect for complex movements (OHS) suggests only a limited effect of a 10-minute warm-up routine on CoP features. 10 minutes stretching might therefore be more efficient for improving stability than a general 10 minute warm-up.


Nutrient menu planning for clinical research centers. Control by computer.
A computer program has been developed for the dietetic service of the Clinical Research Center at the University of Florida. Presently, it is used in menu planning and nutrient analysis for selective, controlled-nutrient diets and for constant diets. The program is able to compute food weights for a patient-selected daily menu which would satisfy up to twenty-three nutrient constraints and which may be optimized with respect to one or more of these. The principal benefit of the program is a saving in the dietetian's time in calculating the nutrient content of the diet and in planning diets with several constrained nutrients. It is also being used as a teaching resource for dietetic interns and dietetic trainees.


Review of the caroticotympanic nerves: Anatomy, function and pathology.
The caroticotympanic nerves provide postganglionic sympathetic fibres to the tympanic plexus. However, there are scant reports in the literature detailing with these nerves in great depth. As the caroticotympanic plexus lies near the often-operated tympanic nerve, it is important for the surgeon to understand the anatomy, pathology and surgical implications of it. Here, we present a review of the available literature regarding the caroticotympanic nerves.


Occupational burnout among radiation therapists in Australia: Findings from a mixed methods study.
Evidence demonstrates that health care professionals in the palliative care context are more burned out than other health professionals. The aims of this study were to examine: (1) occupational burnout levels among radiation therapists in Australia, (2) association between demographic factors on burnout and (3) radiation therapists' perceptions of burnout. A cross-sectional online survey including the Maslach Burnout Inventory was administered to Radiation Therapists in Australia. Data were analysed using SPSS Ver 20 and open ended comments were analysed thematically using Nvivo 10. A total of 200 radiation therapists participated in the survey. RTs had a high mean (±SD) burnout score for emotional exhaustion (38.5 ± 8.2), depersonalisation (17.5 ± 4.7) and personal achievement (30.5.3 ± 4.3) compared to RTs and health workers in other studies. High levels of emotional exhaustion, depersonalisation and low levels of personal achievement were present in 93% (186/200), 87% (174/200) and 61% (122/200) of participants respectively. RTs identified high workload and staff shortages, interpersonal conflict and technology as key sources of stress in the RT work environment. Australian RTs' level of burnout on all three stages of burnout exceed previously reported burnout levels for similar cohorts both locally and internationally. It is important that future interventions aimed at minimising or preventing stressors are identified and implemented in the radiation therapy work environment.


Effect of wearing different types of face masks during dynamic and isometric resistance training on intraocular pressure.
The use of face masks has demonstrated to be an effective strategy to prevent transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Wearing face masks, mainly Filtering Face Piece 2 (FFP2) masks, during exercise practice has demonstrated to affect several physiological measures. This study was aimed at assessing the intraocular pressure (IOP) behaviour during the execution of the dynamic and isometric biceps-curl exercise with a surgical and FFP2 face mask. Twenty two physically active young adults performed sets of 10 repetitions against the 10-RM (repetition maximum) load and 1-minute isometric effort against a load 15% lower than the 10-RM load with the FFP2 and surgical mask and without any mask. A total of six exercise sets (3 experimental conditions [FFP2, surgical and control] × 2 exercise modalities) were performed. A rebound tonometer was used to measure IOP before, during (10 measurements), and after (30-seconds of passive recovery) each training set. At rest, there were not statistically significant IOP differences (p = 0.222). During dynamic exercise, there was a progressive IOP rise (p < 0.001), and a higher IOP response with the FFP2 than without the mask (corrected p-value = 0.003). For the isometric exercise, there was a greater IOP response as a function of accumulated effort (p < 0.001), which was dependent of the face mask used (FFP2> surgical>control; corrected p-values< 0.01). The FFP2 masks cause a heightened IOP response during the execution of dynamic and isometric biceps-curl exercise, suggesting that, when possible, glaucoma patients should limit the use of FFP2 masks during resistance training.


Bouncing-to-Merging Transition in Drop Impact on Liquid Film: Role of Liquid Viscosity.
When a drop impacts on a liquid surface, it can either bounce back or merge with the surface. The outcome affects many industrial processes, in which merging is preferred in spray coating to generate a uniform layer and bouncing is desired in internal combustion engines to prevent accumulation of the fuel drop on the wall. Thus, a good understanding of how to control the impact outcome is highly demanded to optimize the performance. For a given liquid, a regime diagram of bouncing and merging outcomes can be mapped in the space of Weber number (ratio of impact inertia and surface tension) versus film thickness. In addition, recognizing that the liquid viscosity is a fundamental fluid property that critically affects the impact outcome through viscous dissipation of the impact momentum, here we investigate liquids with a wide range of viscosity from 0.7 to 100 cSt, to assess its effect on the regime diagram. Results show that while the regime diagram maintains its general structure, the merging regime becomes smaller for more viscous liquids and the retraction merging regime disappears when the viscosity is very high. The viscous effects are modeled and subsequently the mathematical relations for the transition boundaries are proposed which agree well with the experiments. The new expressions account for all the liquid properties and impact conditions, thus providing a powerful tool to predict and manipulate the outcome when a drop impacts on a liquid film.


Diamonds are forever: the cortisone legacy.
The year 1946 was not only the year that the Society for Endocrinology was founded, but also the year that Edward Kendall's compound E (cortisone) was first synthesised by Louis Sarett. By 1948, sufficient quantities of compound E were available for the rheumatologist Philip Hench to test it successfully for the first time in a patient with rheumatoid arthritis. It was immediately hailed as a 'wonder drug' and was shown to be effective in a number of inflammation-associated conditions, most notably rheumatoid arthritis. The subsequent development of endocrinology as a discipline is inextricably linked to the chemistry, biology and medicine of antiinflammatory glucocorticoids. Sixty years after the first chemical synthesis of cortisone, corticosteroids remain among the top ten most commonly used prescription and over the counter drugs. Basic and clinical studies of glucocorticoid biosynthesis, metabolism and action have trail-blazed developments in endocrinology ever since. This article surveys the extraordinary cortisone timeline, from first synthesis until now. The concluding scientific message is that intracrine metabolism of cortisone to cortisol via 11beta hydroxysteroid dehydrogenase type 1 likely sustains local amplification of glucocorticoid action at sites of inflammation throughout the body. The broader message is that the discovery of compound E by Kendall (basic scientist), its large-scale synthesis by Sarett (industrial chemist) and its therapeutic application by Hench (rheumatologist) serves as a paradigm for modern translational medicine. It is concluded that endocrinology will remain a force in health and disease if it continues to evolve sans frontières at the basic/applied/clinical science interface. A challenge for the Society for Endocrinology is to ensure this happens.


Malignant acanthosis nigricans: an early diagnostic clue.
Acanthosis nigricans (AN) is characterized by velvety, hyperpigmented, verrucous, symmetric and occasionally pruritic plaques along with papillomatous lesions which have a special predilection for neck, axillae, groin, umbilicu and mucosal regions. Rarely, it presents as a paraneoplastic syndrome and prompts a thorough search for an internal malignancy. We present here a case of malignant acanthosis nigricans seen in an elderly patient who was found to have underlying adenocarcinoma of the lower end of esophagus. After diagnosing associated malignancy, he was referred for further evaluation and subsequent surgical resection of tumour.


[Clinical and anatomo-pathologic findings in a case of Cronkhite-Canada syndrome].
We present a case of Cronkhite-Canada Syndrome with gastrointestinal polyposis, which is the first one to be reported in this country. We make a review of the literature and compare the clinical and anatomopathological finding in this case with others described.


Effect of ethanol on glucose transport, key glycolytic enzymes, and proton extrusion in Saccharomyces cerevisiae.
The effect of ethanol on the activities of the key enzymes of the glycolytic pathway and on two membrane functions related with fermentation, the glucose uptake system, and proton extrusion rate are examined. The results indicate that ethanol, up to 2M, does not cause any change of the glucose uptake velocity nor any substantial change in the key glycolytic enzyme activities while the fermentation rate is reduced by about 50%. In a cell extract 3M ethanol as well as incubation of yeast cells with 4M ethanol caused a considerable decrease of pyruvate kinase and hexokinase activities. Phosphofructokinase remained unchanged even at higher ethanol concentrations. Transmembrane proton flow was found to be the most sensitive of the functions tested toward ethanol, and it could represent the first target of ethanol action on fermentation.


Acute Simian Immunodeficiency Virus Infection Triggers Early and Transient Interleukin-7 Production in the Gut, Leading to Enhanced Local Chemokine Expression and Intestinal Immune Cell Homing.
The intestinal barrier, one of the first targets of HIV/simian immunodeficiency virus (SIV) is subjected to major physiological changes during acute infection. Having previously shown that pharmaceutical injection of interleukin-7 (IL-7) triggers chemokine expression in many organs leading to massive T-cell homing, in particular to the intestine, we here explored mucosal IL-7 expression as part of the cytokine storm occurring during the acute phase of SIV infection in rhesus macaques. Quantifying both mRNA and protein in tissues, we demonstrated a transient increase of IL-7 expression in the small intestine of SIV-infected rhesus macaques, starting with local detection of the virus by day 3 of infection. We also observed increased transcription levels of several chemokines in the small intestine. In infected macaques, ileal IL-7 expression correlated with the transcription of four of these chemokines. Among these chemokines, the macrophage and/or T-cell attractant chemokines CCL4, CCL25, and CCL28 also demonstrated increased transcription in uninfected IL-7-treated monkeys. Through immunohistofluorescence staining and image analysis, we observed increased CD8+ T-cell numbers and stable CD4+ T-cell counts in the infected lamina propria (LP) during hyperacute infection. Concomitantly, circulating CCR9+beta7+ CD4+ and CD8+ T-cells dropped during acute infection, suggesting augmented intestinal homing of gut-imprinted T-cells. Finally, CD4+ macrophages transiently decreased in the submucosa and concentrated in the LP during the first days of infection. Overall, our study identifies IL-7 as a danger signal in the small intestine of Chinese rhesus macaques in response to acute SIV infection. Through stimulation of local chemokine expressions, this overexpression of IL-7 triggers immune cell recruitment to the gut. These findings suggest a role for IL-7 in the initiation of early mucosal immune responses to SIV and HIV infections. However, IL-7 triggered CD4+ T-cells and macrophages localization at viral replication sites could also participate to viral spread and establishment of viral reservoirs.


Volatile compounds of young wines from cabernet sauvignon, cabernet gernischet and chardonnay varieties grown in the loess plateau region of china.
In order to elucidate the aroma components of wine produced in the Loess Plateau region of China, volatile compounds of young wines from Cabernet Sauvignon, Cabernet Gernischet and Chardonnay varieties grown in the new ecological region were investigated for the first time in this research. Among the volatile compounds analyzed by HS-SPME with GC-MS, a total of 45, 44 and 42 volatile compounds were identified and quantified in Cabernet Sauvignon, Cabernet Gernischet and Chardonnay wines, respectively. In the volatiles detected, alcohols formed the most abundant group in the aroma compounds of the three wines, followed by esters and fatty acids. According to their odor active values (OAVs), 18 volatile compounds were always present in the three wines at concentrations higher than their threshold values, but ethyl octanoate, ethyl hexanoate, and isoamyl acetate were found to jointly contribute to 92.9%, 93.3%, and 98.7%, of the global aroma of Cabernet Sauvignon, Cabernet Gernischet and Chardonnay wines, respectively. These odorants are associated with "fruity'' and ''ripe fruit'' odor descriptors.


Longitudinal associations between trait neuroticism and negative daily experiences in adolescence.
It is well established that trait neuroticism bears strong links with negative affect and interpersonal problems. The goal of this study was to examine the longitudinal associations between neuroticism and daily experiences of negative affect and interpersonal problems during the developmentally important period of adolescence. Dutch adolescents and their best friends (N = 1,046) completed up to 6 yearly personality trait questionnaires and up to 15 between-year assessment bursts between the ages 13 and 18. During each assessment burst, participants reported on 5 consecutive days about their experiences of negative affect and interpersonal conflict with their mother and their best friend. We estimated a series of multilevel random-intercept cross-lagged panel models to differentiate covariance at the level of constant between-person differences from dynamic processes that occurred within persons. At the level of constant between-person differences, higher neuroticism was associated with more negative daily experiences. At the within-person level, yearly changes in neuroticism were bidirectionally and positively associated with yearly changes in daily negative affect. The most parsimonious, best fitting models did not contain a random intercept for daily conflict with friend and adolescents' contingency between daily experiences of conflict with mother and negative affect. Rank-order differences in these variables were positively associated with subsequent within-person changes in neuroticism. We discuss these results with regard to endogenous versus dynamic theories of personality development and the value of using a differentiated statistical approach. (PsycINFO Database Record (c) 2020 APA, all rights reserved).


Molecular cloning of eucaryotic genes required for excision repair of UV-irradiated DNA: isolation and partial characterization of the RAD3 gene of Saccharomyces cerevisiae.
We describe the molecular cloning of a 6-kilobase (kb) fragment of yeast chromosomal DNA containing the RAD3 gene of Saccharomyces cerevisiae. When present in the autonomously replicating yeast cloning vector YEp24, this fragment transformed two different UV-sensitive, excision repair-defective rad3 mutants of S. cerevisiae to UV resistance. The same result was obtained with a variety of other plasmids containing a 4.5-kb subclone of the 6-kb fragment. The UV sensitivity of mutants defective in the RAD1, RAD2, RAD4, and RAD14 loci was not affected by transformation with these plasmids. The 4.5-kb fragment was subcloned into the integrating yeast vector YIp5, and the resultant plasmid was used to transform the rad3-1 mutant to UV resistance. Both genetic and physical studies showed that this plasmid integrated by homologous recombination into the rad3 site uniquely. We conclude from these studies that the cloned DNA that transforms the rad3-1 mutant to UV resistance contains the yeast chromosomal RAD3 gene. The 4.5-kb fragment was mapped by restriction analysis, and studies on some of the subclones generated from this fragment indicate that the RAD3 gene is at least 1.5 kb in size.


Abnormalities of hippocampal signal intensity in patients with familial mesial temporal lobe epilepsy.
Mesial temporal lobe epilepsy (MTLE) is associated with hippocampal atrophy and hippocampal signal abnormalities. In our series of familial MTLE (FMTLE), we found a high proportion of hippocampal abnormalities. To quantify signal abnormalities in patients with FMTLE we studied 152 individuals (46 of them asymptomatic) with FMTLE. We used NIH-Image for volumetry and signal quantification in coronal T1 inversion recovery and T2 for all cross-sections of the hippocampus. Values diverging by 2 or more SD from the control mean were considered abnormal. T2 hippocampal signal abnormalities were found in 52% of all individuals: 54% of affected subjects and 48% of asymptomatic subjects. T1 hippocampal signal changes were found in 34% of all individuals: 42.5% of affected subjects and 15% of asymptomatic subjects. Analysis of the hippocampal head (first three slices) revealed T2 abnormalities in 73% of all individuals (74% of affected subjects and 72% of asymptomatic subjects) and T1 abnormalities in 59% (67% of affected subjects and 41% of asymptomatic subjects). Affected individuals had smaller volumes than controls (P < 0.0001). There was no difference in hippocampal volumes between asymptomatic subjects and controls, although 39% of asymptomatic patients had hippocampal atrophy. Patients with an abnormal hippocampal signal (133 individuals) had smaller ipsilateral volume, but no linear correlation could be determined. Hippocampal signal abnormalities in FMTLE were more frequently found in the hippocampal head in both affected and asymptomatic family members, including those with normal volumes. These results indicate that subtle abnormalities leading to an abnormal hippocampal signal in FMTLE are not necessarily related to seizures and may be determined by genetic factors.


Relationship between blood radioimmunoreactive beta-endorphin and hand skin temperature during the electro-acupuncture induction of ovulation.
Thirteen cycles of anovulation menstruation in 11 cases were treated with Electro-Acupuncture (EA) ovulation induction. In 6 of these cycles which showed ovulation, the hand skin temperature (HST) of these patients was increased after EA treatment. In the other 7 cycles ovulation was not induced. There were no regular changes in HST of 5 normal subjects. The level of radioimmunoreactive beta-endorphin (r beta-E) fluctuated, and returned to the preacupunctural level in 30 min. after withdrawal of needles in normal subjects. After EA, the level of blood r beta-E in cycles with ovulation declined or maintained the range of normal subjects. But the level of blood r beta-E in cycles in which the induction failed to cause ovulation was kept higher that that of normal. (P less than 0.05). There was a negative correlation in the decrease of blood r beta-E and increase of HST after EA (r = 0.677, P less than 0.01). EA is able to regulate the function of the hypothalamic-pituitary-ovarian axis. Since a good response is usually accompanied with the increase of HST, monitoring HST may provide a rough but simple method for predicting the curative effect of EA. The role of r beta-E in the mechanism of EA ovulation induction was discussed.


Social determinants of health and health inequalities: what role for general practice?
This paper argues that general practice is potentially an important social determinant of health and health inequalities. The way it is influential is consistent with models of causal pathways in the way social and societal factors influence health. General practice clinical care can be thought of as a material resource. Evidence exists at many levels that this resource is inequitably distributed. But encounters in general practice are profoundly social processes, embedded in wider society. Debating and reflecting on the values underpinning relations between GP and patient may help challenge and illuminate wider inequitable processes in society that sustain inequalities in health.


First generation synchrony of isolated Hyphomicrobium swarmer populations.
A method is described for obtaining synchronously growing swarmer cell populations of Hyphomicrobium sp. strain B-522. This was accomplished by isolating young swarmers from random cultures by centrifugation and filtration. Cell multiplication occurred during 38% of the growth cycle in populations synchronized in this manner. Observations were made of the changes in cellular morphology which occurred during the growth cycle. Of the 14.25 h required for the doubling in cell numbers, an average of 5 h passed before the swarmer cells began to develop their hyphae. This time varied over a range of 10 h. The time interval between the beginning of hyphal development and the beginning of bud formation was 3.5 to 4.5 h. The maturation of the first buds and their separation from the mother cells were completed in 5.5 h. The duration of these steps is compared to those measured previously in agar slide cultures.


Age norms for grating acuity and contrast sensitivity measured by Lea tests in the first three years of life.
To determine age norms in the first three years of life for grating visual acuity and contrast sensitivity obtained with Lea grating test and Hiding Heidi low contrast face test. Lea grating test was used to estimate binocular grating acuity and Hiding Heidi low contrast face test was used to estimate contrast sensitivity in 600 healthy infants and children. Age ranged from 3 to 36mo subdivided into 12 groups subjected for full ophthalmologic and pediatric examinations. The grating acuity developed along the first three years of life. It ranged from 1.88±0.32 c/d at 3mo to 30.95±0.77 c/d at 36mo. The most rapid development was during the first 12mo and the slowest development was from 30 to 36mo. The contrast sensitivity showed rapid development in the first two years of life. Its mean value ranged from 4.23±1.17 at 3mo to 78.26±8.21 at 24mo. It was constant at the highest score (80) thereafter. Age norms for grating acuity along with contrast sensitivity offer a more comprehensive measure of spatial vision and should be incorporated in clinical practice for better visual assessment in preverbal and nonverbal children.


TG: HDL-C Ratio as Insulin Resistance Marker for Metabolic Syndrome in Children With Obesity.
Insulin resistance (IR) is an important variable in the diagnosis of metabolic syndrome (MetS). Currently, IR is not part of the existing pediatric definition of MetS, instead elevated fasting blood glucose (FBG) is measured as an indicator of hyperglycemia. Arguably, many obese children with severe IR are still able to regulate their FBG well. Hence, this study aimed to assess the utility of triglyceride-to-high-density lipoprotein cholesterol (TG : HDL-C) ratio as an IR marker in the modeling of pediatric MetS among children with obesity using structural equation modeling (SEM). A total of 524 blood samples from children with obesity (age 10-16 years old) were analyzed for FBG, lipids, insulin, leptin, and adiponectin. Both exploratory (EFA) and confirmatory factor analysis (CFA) were used to examine TG : HDL-C ratio as an IR marker in pediatric MetS. EFA shows that TG: HDL-C ratio (standardized factor loading = 0.904) groups together with homeostasis model assessment-estimated insulin resistance (HOMA-IR) (standardized factor loading = 0.664), indicating a strong correlation to the IR factor. Replacing FBG with TG: HDL-C ratio improved the modeling of MetS structure in children with obesity. Our MetS model of TG: HDL-C ratio as IR component shows comparable model fitness indices (goodness of fit, Akaike's information criterion, and Bayesian information criterion) with leptin:adiponectin ratio (platinum standard for adiposity:IR marker) model. The least model fit was seen when using FBG as an IR surrogate. TG : HDL-C ratio performed better as IR surrogate in MetS structures (standardized factor loading = 0.39) compared to FBG (standardized factor loading = 0.27). TG: HDL-C ratio may be considered as an IR component in pediatric MetS.


Characteristics and Prognosis of Exercise-Related Sudden Cardiac Arrest.
Introduction: The previous studies about exercise-related sudden cardiac arrest (SCA) have mainly focused on sports activity, but information related to SCA in other forms of physical exercise is lacking. Our aim was to identify characteristics and prognosis of SCA victims in the general population who suffered SCA during physical activity. Methods and results: We collected retrospectively all cases of attempted resuscitation in Oulu University Hospital Area between 2007 and 2012. A total of 300 cases were of cardiac origin. We only included witnessed cases with Emergency Medical System arrival time ≤15 min. Cases of low-intensity physical activity were excluded. A total of 47 SCAs occurred during moderate-to-vigorous physical activity (exercise-group) and 43 cases took place at rest (rest-group). The subjects in exercise-group were younger compared to the rest-group (60 ± 14 years vs. 67 ± 14 years, p = 0.016). The initial rhythm recorded was more often ventricular fibrillation (VF) in exercise-group compared to the rest-group (77 vs. 50%, p = 0.010). Pulseless electrical activity (PEA) was rare in exercise-group compared to the rest -group (2.1 vs. 14%, p = 0.033, respectively). Bystander cardiopulmonary resuscitation (CPR) was more often performed when SCA took place during physical exercise (47 vs. 23 %, p = 0.020). Survival rates to hospital discharge were higher in the exercise-group compared to the rest -group (49 vs. 9.3%, p < 0.0001). Conclusions: SCA occurring during physical activity is more frequently a result of VF and bystander CPR is more often performed. There is also a notably better survival rate to hospital discharge.


Reduced intestinal inflammation induced by dextran sodium sulfate in interleukin-6-deficient mice.
Interleukin-6 (IL-6) is a multifunctional cytokine secreted by various cells, and is involved in the acute phase response and the immune response through T and B cell activation. To further define the role of IL-6 in intestinal inflammation, we studied the effects of dextran sulfate sodium (DSS) administration in mice with targeted deletions of the IL-6 gene. Acute colitis was induced in female IL-6-/- and IL-6+/+ mice by giving 4.5% DSS orally in drinking water for 8 days. The colonic mucosal injury and inflammation was evaluated based on survival rate, body-weight changes, total colon length and histological findings. Colonic mRNA expression for tumor necrosis factor (TNF)-alpha, IL-6, IL-10 and inducible nitric oxide synthase (iNOS) was measured by RT-PCR. Colonic IL-6 mRNA levels of wild-type mice continued to increase throughout the study period. At each assessment, colonic injury was significantly attenuated in DSS-treated IL-6-/- mice compared with DSS-treated IL-6+/+ mice. Histological study also showed a reduced infiltration of inflammatory cells, especially neutrophils, and mucosal cell disruption in DSS-treated IL-6-/- mice compared with DSS-treated IL-6+/+ mice. In the colons of DSS-treated IL-6-/- mice, the expression of both TNF-alpha mRNA and iNOS mRNA was reduced on day 5. In contrast, IL-10 mRNA expression was enhanced compared with DSS-treated IL-6+/+ mice. In conclusion, DSS-induced inflammation appears to be significantly inhibited in IL-6-/- mice compared to wild-type mice. These data suggest that persistent and marked blockade of IL-6 bioactivity provides some beneficial effects on intestinal inflammation.


Contribution of the 12-17 hydrophobic region of islet amyloid polypeptide in self-assembly and cytotoxicity.
The islet amyloid polypeptide (IAPP) is a 37-residue aggregation-prone peptide hormone whose deposition as insoluble fibrils in the islets of Langerhans is associated with type II diabetes. Therapeutic interventions targeting IAPP amyloidogenesis, which contributes to pancreatic β-cell degeneration, remain elusive owing to the lack of understanding of the self-assembly mechanisms and of the quaternary proteospecies mediating toxicity. While countless studies have investigated the contributions of the 20-29 amyloidogenic core in self-assembly, IAPP central region, i.e. positions 11 to 19, has been less studied, notwithstanding its potential key role in oligomerization. In this context, the present study aimed at investigating the physicochemical and conformational properties driving IAPP self-assembly and associated cytotoxicity. Computational tools and all-atom molecular dynamics simulation suggested that the hydrophobic 12-17 segment promotes IAPP self-recognition and aggregation. Alanine scanning revealed that the hydrophobic side chains of Leu12, Phe15 and Val17 are critical for amyloid fibril formation. Destabilization of the α-helical folding by Pro substitution enhanced self-assembly when the pyrrolidine ring was successively introduced at positions Ala13, Asn14 and Phe15, in comparison to respective Ala-substituted counterparts. Modulating the peptide backbone flexibility at position Leu16 through successive incorporation of Pro, Gly and α-methylalanine, inhibited amyloid formation and reduced cytotoxicity, while the isobutyl side chain of Leu16 was not critical for self-assembly and IAPP-mediated toxicity. These results highlight the importance of the 12-17 hydrophobic region of IAPP for self-recognition, ultimately supporting the development of therapeutic approaches to prevent oligomerization and/or fibrillization.


Time course of plasma levels and electrophysiologic effects of propranolol in man.
We studied the time course of three electrophysiologic effects of propranolol after intravenous and oral administration and their relationship with plasma levels within the same subjects. Ten patients who had undergone cardiac catheterization for diagnostic purposes received 0.1 mg/kg of propranolol intravenously. Blood was drawn at intervals for 12 hr and heart rate and the effective refractory periods of the atrium (ERPA) and the atrioventricular node (ERPAVN) were determined at the same time. Eight patients continued treatment with propranolol by the oral route for up to 4 days (40 mg every 12 hr). Blood was sampled after each morning dose. Plasma concentrations of propranolol were measured by gas chromatography. Maximal lengthening of ERPA after propranolol (15.1% i.v. and 9.4% oral) was much less marked than that of ERPAVN (23.2% i.v. and 19.4% oral). Heart rate decreased 23.5% (i.v.) and 13.1% (oral). Effects were seen much sooner after intravenous (5-8 min) than after oral administration (86-146 min), but they lasted about twice as long after oral as after intravenous treatment.


Ozone trends across the United States over a period of decreasing NOx and VOC emissions.
In this work, we evaluate ambient ozone trends at urban, suburban, and rural monitoring sites across the United States over a period of decreasing NOx and VOC emissions (1998-2013). We find that decreasing ozone trends generally occur in the summer, in less urbanized areas, and at the upper end of the ozone distribution. Conversely, increasing ozone trends generally occur in the winter, in more urbanized areas, and at the lower end of the ozone distribution. The 95(th) percentile ozone concentrations decreased at urban, suburban, and rural monitors by 1-2 ppb/yr in the summer and 0.5-1 ppb/yr in the winter. In the summer, there are both increasing and decreasing trends in fifth percentile ozone concentrations of less than 0.5 ppb/yr at urban and suburban monitors, while fifth percentile ozone concentrations at rural monitors decreased by up to 1 ppb/yr. In the winter, fifth percentile ozone concentrations generally increased by 0.1-1 ppb/yr. These results demonstrate the large scale success of U.S. control strategies targeted at decreasing peak ozone concentrations. In addition, they indicate that as anthropogenic NOx emissions have decreased, the ozone distribution has been compressed, leading to less spatial and temporal variability.


[A plea for introduction of hepatitis B vaccination at birth in Côte d'Ivoire].
The Côte d'Ivoire National Immunization Technical Advisory Group 2015 work plan included elaboration of an opinion on inclusion of hepatitis B vaccination at birth in the Expanded Program on Immunization (EPI) in Côte d'Ivoire. A task force was set up to conduct this assessment according to a systematized method. The task force analysed scientific articles on the burden of hepatitis B in Côte d'Ivoire, the burden of mother-child transmission, the impact of hepatitis B vaccination at birth in countries which have adopted this strategy, the efficacy and safety of hepatitis B vaccine in newborns, the cost-effectiveness of hepatitis B vaccination at birth, and the best strategy to introduce hepatitis B vaccination at birth in the EPI. The National Immunization Technical Advisory Group of Côte d'Ivoire finally recommended introduction of a dose of hepatitis B vaccine at birth in the context of the Expanded Program on Immunization with maintenance of three doses of pentavalent vaccine (DPT-HepB-Hib) at 6, 10, and 14 weeks of age.


Validation in the cross-cultural adaptation of the Korean version of the Oswestry Disability Index.
Disability questionnaires are used for clinical assessment, outcome measurement, and research methodology. Any disability measurement must be adapted culturally for comparability of data, when the patients, who are measured, use different languages. This study aimed to conduct cross-cultural adaptation in translating the original (English) version of the Oswestry Disability Index (ODI) into Korean, and then to assess the reliability of the Korean versions of the Oswestry Disability Index (KODI). We used methodology to obtain semantic, idiomatic, experimental, and conceptual equivalences for the process of cross-cultural adaptation. The KODI were tested in 116 patients with chronic low back pain. The internal consistency and reliability for the KODI reached 0.9168 (Cronbach's alpha). The test-retest reliability was assessed with 32 patients (who were not included in the assessment of Cronbach's alpha) over a time interval of 4 days. Test-retest correlation reliability was 0.9332. The entire process and the results of this study were reported to the developer (Dr. Fairbank JC), who appraised the KODI. There is little evidence of differential item functioning in KODI. The results suggest that the KODI is internally consistent and reliable. Therefore, the KODI can be recommended as a low back pain assessment tool in Korea.


Rap1 acts via multiple mechanisms to position Canoe and adherens junctions and mediate apical-basal polarity establishment.
Epithelial apical-basal polarity drives assembly and function of most animal tissues. Polarity initiation requires cell-cell adherens junction assembly at the apical-basolateral boundary. Defining the mechanisms underlying polarity establishment remains a key issue. Drosophila embryos provide an ideal model, as 6000 polarized cells assemble simultaneously. Current data place the actin-junctional linker Canoe (fly homolog of Afadin) at the top of the polarity hierarchy, where it directs Bazooka/Par3 and adherens junction positioning. Here we define mechanisms regulating Canoe localization/function. Spatial organization of Canoe is multifaceted, involving membrane localization, recruitment to nascent junctions and macromolecular assembly at tricellular junctions. Our data suggest apical activation of the small GTPase Rap1 regulates all three events, but support multiple modes of regulation. The Rap1GEF Dizzy (PDZ-GEF) is crucial for Canoe tricellular junction enrichment but not apical retention. The Rap1-interacting RA domains of Canoe mediate adherens junction and tricellular junction recruitment but are dispensable for membrane localization. Our data also support a role for Canoe multimerization. These multifactorial inputs shape Canoe localization, correct Bazooka and adherens junction positioning, and thus apical-basal polarity. We integrate the existing data into a new polarity establishment model.


In-depth immune cellular profiling reveals sex-specific associations with frailty.
With advancing age, the composition of leukocyte subpopulations in peripheral blood is known to change, but how this change differs between men and women and how it relates to frailty is poorly understood. Our aim in this exploratory study was to investigate whether frailty is associated with changes in immune cell subpopulations and whether this differs between men and women. Therefore, we performed in-depth immune cellular profiling by enumerating a total of 37 subpopulations of T cells, B cells, NK cells, monocytes, and neutrophils in peripheral blood of 289 elderly people between 60-87 years of age. Associations between frailty and each immune cell subpopulation were tested separately in men and women and were adjusted for age and CMV serostatus. In addition, a random forest algorithm was used to predict a participant's frailty score based on enumeration of immune cell subpopulations. In the association study, frailty was found to be associated with increased numbers of neutrophils in both men and in women. Frailer women, but not men, showed higher numbers of total and CD16- monocytes, and lower numbers of both CD56+ T cells and late differentiated CD4+ TemRA cells. The random forest algorithm confirmed all the findings of the association studies in men and women. In men, the predictive accuracy of the algorithm was too low (5.5%) to warrant additional conclusions on top of the ones derived from the association study. In women however, the predictive accuracy was higher (23.1%), additionally revealing that total T cell numbers and total lymphocyte numbers also contribute in predicting frailty. In-depth immune cellular profiling revealed consistent associations of frailty with elevated numbers of myeloid cell subpopulations in both men and women. Furthermore, additional associations were found between frailty and lower numbers of some T cell subpopulations, in women only. Thus, our study indicates sex-specific associations of immune subpopulations with frailty. We hope that our study will prompt further investigation into the sex-specific immune mechanisms associated with the development of frailty.


Evaluation of the VITEK 2 system for identification and antimicrobial susceptibility testing of medically relevant gram-positive cocci.
A study was conducted to evaluate the new VITEK 2 system (bioMérieux) for identification and antibiotic susceptibility testing of gram-positive cocci. Clinical isolates of Staphylococcus aureus (n = 100), coagulase-negative staphylococci (CNS) (n = 100), Enterococcus spp. (n = 89), Streptococcus agalactiae (n = 29), and Streptococcus pneumoniae (n = 66) were examined with the ID-GPC identification card and with the AST-P515 (for staphylococci), AST-P516 (for enterococci and S. agalactiae) and AST-P506 (for pneumococci) susceptibility cards. The identification comparison methods were the API Staph for staphylococci and the API 20 Strep for streptococci and enterococci; for antimicrobial susceptibility testing, the agar dilution method according to the procedure of the National Committee for Clinical Laboratory Standards (NCCLS) was used. The VITEK 2 system correctly identified to the species level (only one choice or after simple supplementary tests) 99% of S. aureus, 96.5% of S. agalactiae, 96.9% of S. pneumoniae, 92.7% of Enterococcus faecalis, 91.3% of Staphylococcus haemolyticus, and 88% of Staphylococcus epidermidis but was least able to identify Enterococcus faecium (71.4% correct). More than 90% of gram-positive cocci were identified within 3 h. According to the NCCLS breakpoints, antimicrobial susceptibility testing with the VITEK 2 system gave 96% correct category agreement, 0.82% very major errors, 0.17% major errors, and 2.7% minor errors. Antimicrobial susceptibility testing showed category agreement from 94 to 100% for S. aureus, from 90 to 100% for CNS, from 91 to 100% for enterococci, from 96 to 100% for S. agalactiae, and from 91 to 100% for S. pneumoniae. Microorganism-antibiotic combinations that gave very major errors were CNS-erythromycin, CNS-oxacillin, enterococci-teicoplanin, and enterococci-high-concentration gentamicin. Major errors were observed for CNS-oxacillin and S. agalactiae-tetracycline combinations. In conclusion the results of this study indicate that the VITEK 2 system represents an accurate and acceptable means for performing identification and antibiotic susceptibility tests with medically relevant gram-positive cocci.


Lipopolysaccharide Transport System Links Physiological Roles of σE and ArcA in the Cell Envelope Biogenesis in Shewanella oneidensis.
The bacterial cell envelope is not only a protective structure that surrounds the cytoplasm but also the place where a myriad of biological processes take place. This multilayered complex is particularly important for electroactive bacteria such as Shewanella oneidensis, as it generally hosts branched electron transport chains and numerous reductases for extracellular respiration. However, little is known about how the integrity of the cell envelope is established and maintained in these bacteria. By tracing the synthetic lethal effect of Arc two-component system and σE in S. oneidensis, in this study, we identified the lipopolysaccharide transport (Lpt) system as the determining factor. Both Arc and σE, by regulating transcription of lptFG and lptD, respectively, are required for the Lpt system to function properly. The ArcA loss results in an LptFG shortage that triggers activation of σE and leads to LptD overproduction. LptFG and LptD at abnormal levels cause a defect in the lipopolysaccharide (LPS) transport, leading to cell death unless σE-dependent envelope stress response is in place. Overall, our report reveals for the first time that Arc works together with σE to maintain the integrity of the S. oneidensis cell envelope by participating in the regulation of the LPS transport system. IMPORTANCE Arc is a well-characterized global regulatory system that modulates cellular respiration by responding to changes in the redox status in bacterial cells. In addition to regulating expression of respiratory enzymes, Shewanella oneidensis Arc also plays a critical role in cell envelope integrity. The absence of Arc and master envelope stress response (ESR) regulator σE causes a synthetic lethal phenotype. Our research shows that the Arc loss downregulates lptFG expression, leading to cell envelope defects that require σE-mediated ESR for viability. The complex mechanisms revealed here underscore the importance of the interplay between global regulators in bacterial adaption to their natural inhabits.


[Clinical results of repeated intraperitoneal administration of CDDP in patients with ovarian cancer].
CDDP was intraperitoneally administered to 45 ovarian cancer patients (9 cases in Stage Ic, 9 cases in Stage II, 19 cases in Stage III and 8 cases in Stage IV) as the first line chemotherapy to examine response rates and cumulative survival rates by Kaplan-Meier method. Among 18 cases with measurable tumor, there were 5 CR cases, 6 PR cases, 4 NC cases and 3 PD cases. Eleven out of 18 responded, for a response rate of 61.1%. The 3- and 5-year survival rates were 88.9% and 88.9% in Stage I, 46.7% and 0% in Stage II, 48.6% and 41.7% in Stage III, and 0% and 0% in Stage IV, respectively. The 3- and 5-year survival rates in patients with residual tumor smaller than 2 cm in diameter after the first surgery in Stage III or IV were 76.9% and 61.4% respectively, in contrast to 11.5% and 11.5% in patients with residual tumor of 2 cm or larger in diameter. Thus, a significantly better prognosis was demonstrated in patients with residual tumor smaller than 2 cm. These results indicate that intraperitoneal administration of CDDP demonstrated high response rates and proved to be useful as the first line chemotherapy, yet did not manage to improve the long-term prognosis of patients with progressive cancer.


Plant-pollinator interactions under climate change: The use of spatial and temporal transplants.
Climate change is affecting both the timing of life history events and the spatial distributions of many species, including plants and pollinators. Shifts in phenology and range affect not only individual plant and pollinator species but also interactions among them, with possible negative consequences for both parties due to unfavorable abiotic conditions or mismatches caused by differences in shift magnitude or direction. Ultimately, population extinctions and reductions in pollination services could occur as a result of these climate change-induced shifts, or plants and pollinators could be buffered by plastic or genetic responses or novel interactions. Either scenario will likely involve altered selection pressures, making an understanding of plasticity and local adaptation in space and time especially important. In this review, we discuss two methods for studying plant-pollinator interactions under climate change: spatial and temporal transplants, both of which offer insight into whether plants and pollinators will be able to adapt to novel conditions. We discuss the advantages and limitations of each method and the future possibilities for this area of study. We advocate for consideration of how joint shifts in both dimensions might affect plant-pollinator interactions and point to key insights that can be gained with experimental transplants.


Disguised hysteria in a child psychosis?
In this paper the stages are presented in the psychoanalysis of an eight-and-a-half-year-old boy consulting with a worsening symptomatology that has been evolving for more than one year. The trigger element seems to have been the birth of a brother. During the analysis the relation was clear between this brother's birth, the mother's abortions, and the previous death of a brother. The interpretation of the homicidal omnipotent fantasies and the analyst's reception of projective identifications, destructive anxieties, and castrating anxieties of the patient produced, apparently, an unimagined fast improvement of the psychotic symptoms. This took the authors retrospectively to raise the hypothesis that this patient's psychosis could be a disguised child hysteria.


The brain in iodine deficiency.
Global descriptive, epidemiological studies have established the relation of iodine deficiency to endemic cretinism which, in its fully developed form, is characterized by mental deficiency, deaf mutism and spastic diplegia. However, a second less common variant--myxedematous or hypothyroid cretinism--is characterized by severe hypothyroidism with dwarfism. Mixed forms occur. It has been shown that both conditions can be prevented by correction of the iodine deficiency before pregnancy. Cretinism and development--now termed iodine deficiency disorders (IDD). A number of recently developed animal models establish the effect of severe iodine deficiency on brain development. These include the rat, the marmoset monkey and the sheep. These models are all characterized by the production of severe maternal and fetal hypothyroidism which is associated with effects on the maturation of the cerebral cortex and cerebellum. There was a reduced brain weight with a reduced number of cells as indicated by reduced DNA, a greater density of cells in the cerebral cortex and reduced cell acquisition in the cerebellum. Studies of the mechanisms involved have been carried out in the sheep. The findings reveal significant, though less severe, effects of fetal thyroidectomy (late gestation) and a significant effect of maternal thyroidectomy on brain development in mid-gestation. A combination of maternal and fetal thyroidectomy has similar but more severe effects than iodine deficiency. In the light of current knowledge of the embryology of the brain it is suggested that the critical time for the effect of iodine deficiency is the mid-trimester (14-18 weeks) when the neurons of the cerebral cortex and basal ganglia are formed and could be damaged by the effect of iodine deficiency on maternal thyroid function. There is now recent evidence indicating transfer of maternal thyroxine across the placental barrier early in pregnancy. In this way, neurological cretinism might be produced. Impaired fetal thyroid function would follow in the third trimester and augment the effect of reduced maternal thyroid function. Impaired fetal thyroid function alone could produce the hypothyroid form of cretinism. Further experimental studies, particularly into the postnatal period, are required to substantiate these suggestions. Apart from this, further study of the effects of iodine deficiency on brain development at the subcellular and cellular levels are likely to be most productive.


Capping nanoparticles with graphene quantum dots for enhanced thermoelectric performance.
Graphene quantum dots (GQDs) are shown to serve as phase transfer agents to transfer various types of nanoparticles (NPs) from non-polar to polar solvents. Thorough characterization of the NPs proves complete native ligand exchange. Pellets of this GQD-NP composite show that the GQDs limit the crystal size during spark plasma sintering, yielding enhanced thermoelectric performance compared with NPs exchanged with inorganic ions. A photoluminescence study of the GQD-NP composite also suggests energy transfer from GQDs to NPs.


Characterization of scientific studies usually cited as evidence of adverse effects of GM food/feed.
GM crops are the most studied crops in history. Approximately 5% of the safety studies on them show adverse effects that are a cause for concern and tend to be featured in media reports. Although these reports are based on just a handful of GM events, they are used to cast doubt on all GM crops. Furthermore, they tend to come from just a few laboratories and are published in less important journals. Importantly, a close examination of these reports invariably shows methodological flaws that invalidate any conclusions of adverse effects. Twenty years after commercial cultivation of GM crops began, a bona fide report of an adverse health effect due to a commercialized modification in a crop has yet to be reported.


Hepatoprotective effect of Fe-TPEN on carbon tetrachloride induced liver injury in rats.
Fe(II)-tetrakis-N,N,N',N'(2-pyridylmethyl) ethylenediamine (Fe-TPEN) catalyzes the dismutation of superoxide, and blocks the toxic effect of paraquat on Escherichia coli growth and survival. We examined antioxidative effects of Fe-TPEN on lipid peroxidation and t-butyl hydroperoxide induced cell damage. Fe-TPEN inhibited the FeSO4/H2O2 induced lipid peroxidation in the rat liver homogenates with an IC50 value of 30.2 microM, and protected Ac2F cell damage by t-butyl hydroperoxide in a dose-dependent manner (EC50 value is 2.6 microM). Also, hepatoprotective effect of Fe-TPEN (5 mg/kg, i.p.) was investigated using CCl4 induced liver injury in rats. This complex inhibited the elevation of serum alanine aminotransferase (AST) and aspartate aminotransferase (ALT) levels in CCl4 induced liver injuries, and improved submassive necrosis and fatty degeneration of the hepatocytes. Fe-TPEN also prevented the loss of total and nonprotein SH contents, glutathione peroxidase and glutathione-S-transferase activity in cytosol of rat liver. Although the exact mechanism of action is not clear, antioxidative properties as well as attenuation of hepatocellular defense systems by Fe-TPEN seem to be important on its potent hepatoprotective effect in CCl4-intoxicated rat.


Angiotensin II AT1 receptor blockade prolongs the lifespan of spontaneously hypertensive rats and reduces stress-induced release of catecholamines, glucocorticoids, and vasopressin.
A 2-week pretreatment with an Angiotensin II AT(1) antagonist prevented the adrenomedullary and hormonal response to isolation stress. We studied the effect of life-long treatment with the AT(1) receptor antagonist candesartan, 10 mg/kg/day, or vehicle administered orally in the drinking water from 8 weeks of age on the response to stress of stress-sensitive spontaneously hypertensive rats (SHRs) and their normotensive controls, the Wistar Kyoto (WKY). Rats were submitted to 24-h isolation stress at different times during the treatment. Treatment with candesartan extended the lifespan of SHRs. AT(1) receptor blockade retained its capacity to blunt the response to isolation stress over a long period of treatment. The AT(1) antagonist inhibited epinephrine release in SHR but not in WKY rats during the first 3 months, corticosterone release in SHR and WKY rats during 10 months, and vasopressin release in SHR rats during 18 months of treatment when rats were submitted to isolation stress. There were no changes in vasopressin release in WKY rats during stress or after AT(1) receptor blockade. We conclude that the blockade of the stress response by the AT(1) receptor antagonist is long lasting and differs between stress-prone SHR and WKY rats and that the specific components of the stress response (sympathoadrenal activity, hypothalamic-pituitary-adrenal axis activation, and vasopressin release) react differently to AT(1) receptor blockade. The long-term protective effects of AT(1) receptor blockade can be important in animals vulnerable to stress and, in conjunction with the normalization of blood pressure, can prolong lifespan through end-organ protection.


DNA Balance for Native Characterization of Chemically Modified DNA.
Chemical modification is a powerful approach to expand the chemical diversity and functionality of natural DNA. However, when chemically modified oligonucleotides are employed in DNA-based reactions or structures, it becomes quite difficult to predict, understand, and control their kinetics and thermodynamics. To address this challenge, we introduce a rationally designed DNA balance capable of measuring critical thermodynamic and kinetic properties of chemically modified DNA in their native environment. Our DNA balance is operated using the principle of toehold-exchange, where a panel of weight probes were designed by tuning the lengths of forward and reverse toeholds. Once placed on the DNA balance, the chemical modification will be interrogated using the weight probes to determine changes in both Gibbs free energy and hybridization rate constant. Using cyclic-azobenzene (cAB)-modified DNA as a model system, we demonstrated that our DNA balance could not only measure stable chemical modifications, but also solve more challenging issues where unstable chemical modifications and transient isomerization reactions were involved. We anticipate that our DNA balance will find wide uses for measuring important thermodynamic and kinetic parameters for DNA carrying various chemical modifications, as well as for probing transient chemical changes in DNA.


Application of Enhanced Recovery After Surgery in Patients with Osteoporotic Vertebral Compression Fractures Undergoing Percutaneous Kyphoplasty.
The enhanced recovery after surgery (ERAS) program helps patients recover faster and better, postoperatively. The aim of this retrospective study was to assess the clinical effectiveness of the ERAS program after percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures. We enrolled patients with osteoporotic vertebral compression fracture who had undergone PKP between January 2019 and June 2021 and divided them into the control group (CG; n = 296), without the ERAS program, and the intervention group (IG; n = 306), with the ERAS program. The visual analog scale (VAS), Oswestry Disability Index (ODI), and Barthel Index scores of the 2 groups were compared on admission and 2 days and 1, 6, and 12 months postoperatively. Perioperative evaluation parameters included the mean surgery time, length of stay (LOS), and hospitalization expenses. In addition, postoperative complications were compared. Regarding perioperative parameters, LOS and hospitalization expenses were significantly better in IG than in CG (P < 0.001), but the mean surgery time did not differ significantly (P > 0.05). The VAS, Barthel Index, and ODI scores were significantly better in IG than in CG at 2 days and 1 month postoperatively (P < 0.001). None of the clinical effectiveness parameters (VAS, Barthel Index, and ODI scores) differed between IG and CG at 6 or 12 months postoperatively. In addition, 141 patients in CG and 56 patients in IG experienced postoperative complications, including pressure ulcers, deep vein thrombosis, nausea and vomiting, and refracture (P = 0.970, P = 0.036, P < 0.001, P = 0.002 respectively). For patients undergoing PKP, the ERAS program is a reliable and effective perioperative management method that can effectively reduce LOS, postoperative pain, and economic burden and promote recovery of patients.


Control of nanoparticle penetration into biofilms through surface design.
Quantum dots were used as fluorescent probes to investigate nanoparticle penetration into biofilms. The particle penetration behavior was found to be controlled by surface chemical properties.


[Meteorotropy of vasomotor cephalea].
During a period of 823 days (from 1st October 1971 to 31st December 1973), attacks of migraine, non-migraine vascular cephalea and cephalea due to other neighbouring disturbances strong enough to affect working capacity were studied in 4 subjects. 2152 pieces of data were collected. 2) Frequency was at a minimum in summer and peaked in spring and autumn. 3) Comparison with meteorological conditions points to a highly significant recrudescence of disturbances in cold, damp weather, and meteorological periodicity independent of biological (circadian) rhythms.


Anthrax in New Jersey: a health education experience in bioterrorism response and preparedness.
The anthrax attack in 2001 created new challenges to health educators working on the response effort in New Jersey. Never before had there been a need for educating a group of people who had been exposed to a biological weapon. Coming on the heels of the catastrophic World Trade Center collapse on September 11, 2001, the New Jersey Department of Health and Senior Services was entrenched in the response to, and management of, the anthrax attack that placed a heavy emphasis on educating the postal workers of the United States Postal Service Trenton Processing and Distribution Center. This article provides an account of the preparation and delivery of educational materials and activities in the midst of a biological emergency, emphasizes the role health educators play in responding to bioterrorism events, and encourages health educators to become involved in bioterrorism preparedness efforts.


Sexual habits before multiple sclerosis: a national case-control study.
The trigging off agent for multiple sclerosis (MS) is despite intensive epidemiological and biomedical research still unknown. The disease is typically diagnosed in reproductive age and recent findings have suggested that MS could be a sexually transmitted disease. To assess the influence of different sexual practices in young age on the risk of developing MS, and specifically to explore the possible impact of oral sex and oral sperm exposure on this risk. National case-control study. Inclusion: Danish women with a first time MS discharge diagnosis from a neurological department at most 40 years old during the period 1998-2005, and an age and geographically matched control group. The response rate to our postal questionnaires was 75% for cases and 61% for controls. A total of 604/619 completed case/control questionnaires were included in the analysis. Data underwent logistic regression analysis. We found no difference between women with and without MS for years of schooling, oral herpes infections, genital herpes, blood transfusions, age at sexual debut, age at coital debut, number of sexual partners before and after age 20 years, anal sex, condyloma attack or chlamydia infections. Family disposition with an affected father, mother or sibling, increased the risk of MS 9.1, 6.9 and 4.1 times, respectively. A total of 68% of cases and of 72% of controls had oral sex sometimes or often before their 20th year. Among women entertaining oral sex, 53%, respectively, 54% had experienced oral sperm exposure. Also oral sex after 20 years was similar in women with and without MS. Neither oral sex in early reproductive age, oral sperm exposure, oral sex after 20 years, sexual debut, nor number of sexual partners had any association to the risk of later developing MS. This study does not support the hypothesis that MS is a sexually transmitted or acquired disease.


Low level CO2 effects on pulmonary function in humans.
The purpose of the study was to determine whether chamber exposure to low levels of CO2 results in functional alterations in gas mixing and closing volume in humans. Four healthy volunteer subjects were exposed to 0.7% CO2 and to 1.2% CO2. Spirometry, lung volumes, single breath nitrogen washout, diffusing capacity for carbon monoxide (DLCO) by two methods, and cardiac output were measured in triplicate. Values were obtained over two non-consecutive days during the training period (control) and on days 2 or 3, 4, 6, 10, 13, and 23 of exposure to each CO2 level. Measurements were made during the same time of day. There was one day of testing after exposure, while still in the chamber but off carbon dioxide. The order of testing, up until measurements of DLCO and cardiac output, were randomized to avoid presentation effects. The consistent findings were a reduction in diffusing capacity for carbon monoxide and a fall in cardiac output, occurring to a similar degree with both exposures. For the group as a whole, there was no indication of major effects on spirometry, lung volumes, gas mixing or dead space. We conclude that small changes may occur in the function of distal gas exchanging units; however, these effects were not associated with any adverse health effects. The likelihood of pathophysiologic changes in lung function or structure with 0.7 or 1.2% CO2 exposure for this period of time, is therefore, low.


A new method for the screening of unidentified complaints syndrome in pre-, mid- and post-menopausal women.
A new simple test for the screening of pre-, mid- and post-menopausal women with unidentified complaints overlaid by psychiatric disorders has been devised. This test is performed by intravenous injection of conjugated estrogen and by comparing Kupperman's menopausal indices before and after the injection. That is, the discriminant function between groups with and without psychiatric abnormalities was obtained from Kupperman's menopausal indices before and after intravenous injection of conjugated estrogen, and from this function was made a calculative differential diagnosis between the two groups. The calculative diagnosis agreed fairly well with the clinical diagnosis by the psychiatrist.


Danaparoid sodium reduces ischemia/reperfusion-induced liver injury in rats by attenuating inflammatory responses.
This study was undertaken to examine the mechanism by which danaparoid sodium (DS), a heparinoid that contains mainly heparan sulfate, prevents reperfusion-induced hepatic damage in a rat model of ischemia/reperfusion (I/R)-induced liver injury. Administration of DS significantly reduced liver injury and inhibited the decrease in hepatic tissue blood flow in rats. DS attenuated hepatic I/R-induced increases in hepatic tissue levels of tumor necrosis factor (TNF) and myeloperoxidase (MPO) in vivo. In contrast, neither monocytic TNF production nor neutrophil activation was inhibited by DS in vitro. DS enhanced I/R-induced increases in levels of calcitonin-gene related peptide (CGRP), a neuropeptide released from sensory neurons, and of 6-ketoprostaglandin (PG) F (1a) , a stable metabolite of PGI (2) , in liver tissues. The therapeutic effects of DS were not seen in animals pretreated with capsazepine, an inhibitor of sensory neuron activation. The distribution of heparan sulfate in the perivascular area was significantly increased by DS administration in this rat model. DS significantly increased CGRP release from isolated rat dorsal root ganglion neurons (DRG) in vitro, while DX-9065a, a selective inhibitor of activated factor X, did not. DS enhanced anandamide-induced CGRP release from DRG in vitro. These observations strongly suggested that DS might reduce I/R-induced liver injury in rats by attenuating inflammatory responses. These therapeutic effects of DS might be at least partly explained by its enhancement of sensory neuron activation, leading to the increase the endothelial production of PGI (2) .


Serum Levels of NTx and TRACP5b in Giant Cell Tumor of Bone and its Clinical Implications.
To investigate the serum levels of N-terminal telopeptide of type I collagen (NTx) and tartrate-resistant acid phosphatase 5b (TRACP5b) in giant cell tumor of bone (GCT) patients and the clinical implications. 56 GCT patients (29 males and 27 females, 15 to 60 years old with a median age of 28.0 years old) with clinicopathological characteristics of GCT were enrolled in the Department of Bone Cancer, the Affiliated Cancer Hospital of Xinjiang Medical University from October 2008 to October 2014. The enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of NTx and TRACP5b in the patients. Compared with 21 patients who had a GCT of < 5 cm, the serum levels of NTx and TRACP5b in the 35 patients with a GCT of ≥ 5 cm were significantly increased (p < 0.05). Compared with those GCT patients who had a grade I tumor, the levels of NTx and TRACP5b in grade II patients were not increased (p > 0.05), but the levels of NTx and TRACP5b were significantly increased in grade III patients (p < 0.05). Moreover, compared with the patients in histologic stage I, the levels of NTx and TRACP5b in stage II GCT patients were not increased (p > 0.05), whereas the levels in grade III patients were significantly increased (p < 0.05). In addition, the location of the tumor had a significant effect on the serum levels of NTx and TRACP5b (p < 0.05). Our study suggests that serum NTx and TRACP5b are sensitive and simple biomarkers to indicate aberrant bone metabolism in GCT patients, and they may have a clinical significance in GCT diagnosis. Combined examination for both markers helps in the classification of clinicopathological stages of GCT patients and in the prognosis of the disease.


Associations between Maternal and Fetal Inherited Thrombophilias, Placental Characteristics Associated with Vascular Malperfusion, and Fetal Growth.
Pregnancy results in alterations in coagulation processes, which may increase the risk of thrombosis. Inherited thrombophilia mutations may further increase this risk, possibly through alterations in the placenta, which may result in pregnancy complications such as poor fetal growth. The purpose of our study is to evaluate the association of fetal growth, approximated by birth weight for gestational age percentile, with genetic markers of thrombophilia and placental characteristics related to vascular malperfusion. We analyzed data from the Stillbirth Collaborative Research Network's population-based case-control study conducted in 2006-2008. Study recruitment occurred in five states: Rhode Island and counties in Massachusetts, Georgia, Texas, and Utah. The analysis was restricted to singleton, nonanomalous live births ≤42 weeks' gestation with a complete placental examination and successful testing for ≥1 thrombophilia marker (858 mothers, 902 infants). Data were weighted to account for oversampling, differential consent, and availability of placental examination. We evaluated five thrombophilia markers: factor V Leiden, factor II prothrombin, methylenetetrahydrofolate reductase A1298C and C677T, and plasminogen activator inhibitor type 1 in both maternal blood and placenta/cord blood. We modeled maternal and fetal thrombophilia markers separately using linear regression. Maternal factor V Leiden mutation was associated with a 13.16-point decrease in adjusted birth weight percentile (95% confidence interval: -25.50, -0.82). Adjustment for placental abnormalities related to vascular malperfusion did not affect the observed association. No other maternal or fetal thrombophilia markers were significantly associated with birth weight percentile. Maternal factor V Leiden may be associated with fetal growth independent of placental characteristics.


Growth hormone specifically regulates serine protease inhibitor gene transcription via gamma-activated sequence-like DNA elements.
Growth hormone activates gene transcription of the serine protease inhibitors (SPI) 2.1 and 2.2 by an unknown mechanism. In order to define the promoter regions responsible for this effect and to characterize the transcription factors involved, we have performed gel electrophoresis mobility shift assays on nuclear extracts from cell lines transfected with growth hormone receptor cDNA. We have identified a 9-base pair DNA element, the SPI-GLE 1, which forms a complex with nuclear proteins following activation by growth hormone and which, when placed upstream of a minimal thymidine kinase promoter, drives chloramphenicol acetyltransferase expression in a growth hormone-dependent fashion. This element is similar to those from several genes regulated by other cytokines including interferon. The growth hormone-induced complexes formed were dependent on tyrosine phosphorylation but did not contain the interferon-gamma-activated transcription factor Stat 91. Competition studies with oligonucleotides similar to the SPI-GLE 1 reveal the sequence of a consensus element that specifically binds growth hormone-regulated nuclear proteins.


Crystal structure of the leucine aminopeptidase from Pseudomonas putida reveals the molecular basis for its enantioselectivity and broad substrate specificity.
The zinc-dependent leucine aminopeptidase from Pseudomonas putida (ppLAP) is an important enzyme for the industrial production of enantiomerically pure amino acids. To provide a better understanding of its structure-function relationships, the enzyme was studied by X-ray crystallography. Crystal structures of native ppLAP at pH 9.5 and pH 5.2, and in complex with the inhibitor bestatin, show that the overall folding and hexameric organization of ppLAP are very similar to those of the closely related di-zinc leucine aminopeptidases (LAPs) from bovine lens and Escherichia coli. At pH 9.5, the active site contains two metal ions, one identified as Mn(2+) or Zn(2+) (site 1), and the other as Zn(2+) (site 2). By using a metal-dependent activity assay it was shown that site 1 in heterologously expressed ppLAP is occupied mainly by Mn(2+). Moreover, it was shown that Mn(2+) has a significant activation effect when bound to site 1 of ppLAP. At pH 5.2, the active site of ppLAP is highly disordered and the two metal ions are absent, most probably due to full protonation of one of the metal-interacting residues, Lys267, explaining why ppLAP is inactive at low pH. A structural comparison of the ppLAP-bestatin complex with inhibitor-bound complexes of bovine lens LAP, along with substrate modelling, gave clear and new insights into its substrate specificity and high level of enantioselectivity.


Learning from history: The Glasgow Airport terrorist attack.
Glasgow Airport was the target of a terrorist attack on 30th June, 2007. Many people within Scotland had come to believe that Scotland was immune from terrorism. This perception was in large part informed by Scotland's experience during the protracted Troubles in Northern Ireland, during which the Provisional Irish Republican Army's mainland bombing campaign focused on targets in England, sparing both Scotland and Wales. While Glasgow Airport did not expect such an attack to take place, meticulous planning, organising and testing of plans had taken place to mitigate the unlikely event of such an attack. The attack stands up as a shining example of robust business continuity management, where the airport reopened for business as usual in less than 24 hours from the time of the attack. Little is known about how the airport handled the situation in conjunction with other responding agencies as people tend to want to focus on high-profile disasters only. Yet countless such incidents are happening worldwide on a daily basis, in which there are excellent learning opportunities, and, taken in the spirit of converting hindsight into foresight, the likelihood of similar incidents could potentially be reduced in the future.


Acute pancreatitis in the older patient: Is a new risk score required?
The average age of the surgical patient in the UK is increasing. Frailty and cognitive impairment have been shown to be important risk factors in elderly patients with surgical pathology. Limited work has previously assessed the outcomes of acute pancreatitis in the elderly population and the usefulness of current severity scoring methods. We aimed to assess the mortality rates in this cohort and identify any factors that may influence patient outcome. All patients ≥ 80 years admitted with acute pancreatitis between 1 January 2014 and 31 May 2018 were retrospectively identified. Disease severity scores were measured by a modified Ranson score, and patients' co-morbidities were quantified with the Charlson Comorbidity Index. Primary endpoint was whether the patient was alive at discharge; multilevel logistic regression was used to identify any independent risk factors for patient outcomes. Eighty-seven patients were included, with an average age of 86 years. The most common aetiology was gallstones. Nine patients died during admission, and ITU admission was the only predictor of mortality (p = 0.027). Twenty-three patients had died by one year. Endoscopic retrograde cholangiopancreatography was more common in patients with gallstone disease who were alive at one year (p = 0.029). Risk severity and co-morbidity scores are not predictive of outcomes in elderly patients with acute pancreatitis. The use of endoscopic retrograde cholangiopancreatography should be considered in elderly patients with acute gallstone pancreatitis where suitable. Further work is needed to identify improved mortality prediction tools in the elderly with acute pancreatitis and optimal management strategies.


Rtt106p is a histone chaperone involved in heterochromatin-mediated silencing.
Epigenetic inheritance of heterochromatin structure is an important cellular process whose mechanism remains elusive. In this article, we describe the identification of nine enhancers of the silencing defect of a Saccharomyces cerevisiae-PCNA mutant by screening a library of approximately 4,700 viable yeast deletion mutants. Of the nine mutants identified, six (hir1, hir3, sas2, sas4, sas5, and sir1) were previously known to reduce silencing synergistically with a mutation in Cac1p, the large subunit of chromatin assembly factor 1 (CAF-1). The predicted gene products that are affected in three other mutants (nam7, msh2, and rtt106) have not been implicated previously in silencing. Characterization of the rtt106Delta allele revealed that it synergistically reduced heterochromatin silencing when combined with a mutation in Cac1p but not with a mutation in Asf1p (a histone H3 and H4 chaperone). Moreover, Rtt106p interacted with histones H3 and H4 both in vitro and in vivo, and it displayed a nucleosome assembly activity in vitro. Furthermore, Rtt106p interacts with CAF-1 physically through Cac1p. These biochemical and genetic data indicate that Rtt106p is a previously uncharacterized histone chaperone connecting S phase to epigenetic inheritance.


Thematic orders and the comprehension of subject-extracted relative clauses in Mandarin Chinese.
This study investigates the comprehension of three kinds of subject-extracted relative clauses (SRs) in Mandarin Chinese: standard SRs, relative clauses involving the disposal ba construction ("disposal SRs"), and relative clauses involving the long passive bei constructions ("passive SRs"). In a self-paced reading experiment, the regions before the relativizer (where the sentential fragments are temporarily ambiguous) showed reading patterns consistent with expectation-based incremental processing: standard SRs, with the highest constructional frequency and the least complex syntactic structure, were processed faster than the other two variants. However, in the regions after the relativizer and the head noun where the existence of a relative clause is unambiguously indicated, a top-down global effect of thematic ordering was observed: passive SRs, whose thematic role order conforms to the canonical thematic order of Chinese, were read faster than both the standard SRs and the disposal SRs. Taken together, these results suggest that two expectation-based processing factors are involved in the comprehension of Chinese relative clauses, including both the structural probabilities of pre-relativizer constituents and the overall surface thematic orders in the relative clauses.


Working from home during the COVID-19 outbreak in Sweden: effects on 24-h time-use in office workers.
The COVID-19 pandemic has triggered national recommendations encouraging people to work from home (WFH), but the possible impact of WFH on physical behaviors is unknown. This study aimed to determine the extent to which the 24-h allocation of time to different physical behaviors changes between days working at the office (WAO) and days WFH in office workers during the pandemic. Data were collected on 27 office workers with full-time employment at a Swedish municipal division during the COVID-19 outbreak in May-July 2020. A thigh-worn accelerometer (Axivity) was used to assess physical behavior (sedentary, stand, move) during seven consecutive days. A diary was used to identify periods of work, leisure and sleep. 24-h compositions of sedentary, standing and moving behaviors during work and non-work time were examined using Compositional data analysis (CoDA), and differences between days WAO and days WFH were determined using repeated measures ANOVA. Days WFH were associated with more time spent sleeping relative to awake, and the effect size was large (F = 7.4; p = 0.01; ηp2 = 0.22). The increase (34 min) in sleep time during WFH occurred at the expense of a reduction in work and leisure time by 26 min and 7 min, respectively. Sedentary, standing and moving behaviors did not change markedly during days WFH compared to days WAO. Days working from home during the COVID-19 pandemic in Sweden were associated with longer duration of sleep than days working at the office. This behavioral change may be beneficial to health.


Transmission, inheritance and replication of mitochondrial DNA in mammals: implications for reproductive processes and infertility.
The mitochondrial genome contributes key proteins to the electron-transfer chain, which through oxidative phosphorylation, generates the vast majority of cellular ATP. This maternally inherited genome is transmitted to subsequent generations through the oocyte. Its transmission, inheritance and replication are strictly regulated so that fully mature cells can be appropriately populated with mitochondrial DNA once they mature into adult cells. However, gametes do not always acquire the appropriate numbers of mitochondrial DNA copy; this often renders them inappropriate for successful fertilisation outcome. Furthermore, the number of assisted reproductive technologies that can overcome problems associated with infertility and that can provide enhanced genetic outcomes for the offspring is increasing. However, such techniques could also have a detrimental effect on offspring survival. If we are to introduce these technologies into in vitro fertilisation clinics and animal production, then we first need to validate their use carefully.


Topical Cannabadiol in Pain Management: A Call for Formal Clinical Evaluation.
As a medical specialty, pain management is characterized by numerous safety and efficacy issues and many unmet needs. A report by Allied Market Research estimated the 2019 global market for pain relief at $71 billion, with a projected growth rate of nearly 4% per year1 through 2027. The segment of this market most relevant to this discussion, topical pain relief, comprised almost 13% of this market, with a value of $8.9 billion. Higher life expectancy, an aging population and a more comprehensive understanding of pain management are the principal drivers of market growth.