Defensive behaviors evoked from the ventrolateral periaqueductal gray of the rat: comparison of opioid and GABA disinhibition.
Microinjection of morphine into the ventrolateral periaqueductal gray (PAG) disinhibits output neurons resulting in immobility and antinociception. Disinhibition also can be produced by microinjection of the GABA antagonist bicuculline. If morphine and bicuculline disinhibit the same class of neurons, then the behavioral effects evoked should be the same. Microinjection of morphine (5 microg/0.4 microl) into the ventrolateral PAG produced antinociception in 46 of 85 rats (54%). Subsets of rats with and without morphine antinociception were subsequently injected with bicuculline (2.5, 5, 10, and 25 ng/0.4 microl) into the same PAG site. Microinjection of bicuculline produced an increase in hot plate latency that was independent of the effect of the prior morphine microinjection. Bicuculline administration also produced an increase in locomotor activity in most rats, not immobility as with morphine microinjections. These differences between morphine and bicuculline microinjections indicate three things: (a) disinhibition of PAG neurons whether by morphine or bicuculline is an effective means of producing antinociception; (b) the circuitry underlying the behavioral effects of morphine and bicuculline differ; (c) the ventrolateral PAG appears capable of supporting a range of defensive behaviors from immobility to flight.


Flupirtine effectively prevents development of acute neonatal seizures in an animal model of global hypoxia.
Current first-line drugs for the treatment of neonatal seizures have limited efficacy and are associated with side effects. Uncontrolled seizures may exacerbate brain injury and contribute to later-life neurological disability. Therefore, it is critical to develop a treatment for neonatal seizures that is effective and safe. In early-life, when the γ-aminobutyric acid (GABA) inhibitory system is not fully developed, potassium channels play an important role in controlling excitability. An earlier study demonstrated that flupirtine, a KCNQ potassium channel opener, is more efficacious than diazepam and phenobarbital for the treatment of chemoconvulsant-induced neonatal seizures. In newborns, seizures are most commonly associated with hypoxic-ischemic encephalopathy (HIE). Thus, in the present study, we examined the efficacy of flupirtine to treat neonatal seizures in an animal model of global hypoxia. Our results showed that flupirtine dose dependently blocks the occurrence of behavioral seizures in pups during hypoxia. Additionally, flupirtine inhibits the development of hypoxia-induced clinical seizures and associated epileptiform discharges, as well as purely electrographic (subclinical) seizures. These results suggest that flupirtine is an effective anti-seizure drug, and that further studies should be conducted to determine the time window within which it's administration can effectively treat neonatal seizures.


A "pre-satiety sequence" in rats drinking sucrose solutions.
Food-deprived rats were given intermittent access or, in a replication, continuous access to a 20% sucrose solution. Both drinking and nondrinking behaviors were recorded. During the ensuing drinking bout, latency of lapping after snout apposition, and duration of lapping bouts, did not change. Approaches to the sipper tube usually eventuated in lapping, though aborted approaches increased in frequency late in the session. Drinking was interrupted by nondrinking behaviors which appeared in a characteristic rostro-caudal sequence: partial head withdrawal from the drinking aperture, then full head withdrawal, then movements of the front paws, then movement of the hind paws with full-body locomotion. All these behavioral changes occurred before there was any appreciable reduction in rate of lapping.


Platelet monoamine oxidase: low activity in cigarette smokers.
Platelet monoamine oxidase (MAO) activity and plasma thiocyanate concentration (an index of smoking behavior) were measured in 109 normal male and female volunteers. MAO activity was significantly lower and plasma thiocyanate concentration significantly higher in smoking volunteers than in nonsmoking volunteers. A significant negative correlation between MAO activity and thiocyanate concentration was observed in female smokers (rs = 0.43, n = 36) but not for male smokers (rs = 0.02, n = 31). In nine smokers who gave up smoking, mean (+/- SD) platelet MAO activity increased significantly (17.5 +/- 4.1 nmole/mg/hour to 24.6 +/- 4.2 nmole/mg/hour). At the same time, mean (+/- SD) plasma thiocyanate concentrations decreased significantly (144 +/- 41 microM to 50 +/- 12 microM). These data suggest that smoking directly or indirectly reduced platelet MAO activity.


Kienböck's disease in cerebral palsy.
The incidence of Kienböck's disease is known to be higher in cerebral palsy patients, but little has been written on treatment. We report a case of Kienböck's disease in a young man affected by cerebral palsy. A proximal row carpectomy was done, which relieved spasticity at the same time as treating the disease.


Efficacy of atenolol as a single antihypertensive agent in hyperthyroid cats.
beta-Adrenergic blockers, particularly atenolol, are often recommended for the tachycardia and hypertension that accompany hyperthyroidism; however, the effects of monotherapy with atenolol on both systolic blood pressure (SBP) and heart rate (HR) have not been reported. Twenty hyperthyroid cats with SBP > or = 160 mmHg were studied retrospectively to investigate the SBP and HR lowering effects of atenolol. Median pre-treatment SBP and HR for all cats were 186.5 mmHg and 231 beats/min, respectively. All cats were treated with atenolol at a dosage of 1-2 mg/kg PO q 12h for a minimum of 5 days prior to reassessment and treatment with radioactive iodine. SBP and HR both decreased following atenolol therapy in this group of cats to median values of 171.5 mmHg (P=0.0088) and 185/min (P=0.0003). However, when successful clinical control of hypertension was defined as a post-treatment SBP < 160 mmHg, atenolol monotherapy was ineffective in 70% of the cases. There was no statistically significant difference in baseline serum total thyroxine or atenolol dosage between clinical responders and non-responders. While atenolol effectively reduces HR in most cats with hyperthyroidism, elevated SBP is poorly controlled, and the addition of another vasodilator such as amlodipine or an angiotensin converting enzyme inhibitor is needed to treat associated hypertension.


Blastocyst trophectoderm biopsy and preimplantation genetic diagnosis for familial monogenic disorders and chromosomal translocations.
Modern in vitro fertilization practices involve transfer of embryos as blastocysts, when anabolic metabolism is well established and pregnancy rates can be maintained while transferring embryos singly to avoid multiple pregnancies. Embryo biopsy for preimplantation genetic diagnosis (PGD), however, is generally performed on day 3, when the embryo comprises just 6 to 8 cells, one or two of which are removed for testing. Implantation rates and clinical pregnancy rates have remained relatively low and a harmful effect from losing one or more cells from such early embryos has not been excluded. We performed a sequential study involving 399 egg retrievals and 1879 embryo biopsies for patients undergoing PGD to avoid a serious monogenic disease or an unbalanced chromosomal translocation. We compared implantation and viable pregnancy rates after biopsies taken on day 3 (cleavage-stage biopsy) with biopsies delayed until day 5 or 6, when the embryo is a blastocyst and 5 or more cells can be sampled from the trophectoderm while the inner cell mass, from which the fetus develops, remains intact. All embryos were transferred as blastocysts. Despite fewer blastocysts than cleavage embryos biopsied and tested (3.6 compared to 6.6), implantation rates per embryo transferred were 43.4% if biopsied at the blastocyst stage and 25.6% if biopsied at the cleavage stage (P < 0.01), with ongoing or live-birth pregnancy rates per egg retrieval of 34.2% (average transfer number 1.1) for blastocyst biopsies and 25.5% (transfer number 1.6) for cleavage stage biopsies (P < 0.05, 1-tailed). The multiple pregnancy rate for monogenic disease exclusion fell from 16.7% to 2% (P = 0.04, 1-tailed). For exclusion of genetic disease, day 5-6 blastocyst-stage biopsies are more likely to be followed by implantation and singleton births than is the case after PGD performed on day 3.


#Who: Investigation of Who Creates Laryngology Content Posted on Instagram.
The objective of this study was to examine the types of accounts that create posts related to laryngology on Instagram, using hashtags derived from common diagnoses and procedures within the field, in order to assess the source and ownership of laryngology social media discussions. Fellowship-trained laryngologists were surveyed to determine the most common diagnoses treated and procedures performed in laryngology. These terms were then queried as hashtags on Instagram. The top 15 posts found per hashtag were classified by the category of individual who shared the content. The categories included laryngologists/otolaryngologists, speech-language pathologists (SLP), vocalists, other physicians, and "other individuals." After surveying 20 fellowship-trained laryngologists, 25 different hashtags related to common diagnoses and procedures in laryngology were created and queried for the top 15 posts on Instagram. 260 posts on Instagram were identified, out of which 30.8% were posted by laryngologists/otolaryngologists, 19.2% by SLPs, 3.1% by vocalists, 6.1% by other physicians, and 40.8% by "other individuals." A significant portion of top resulted posts on Instagram sharing laryngology-related content is not posted by laryngologists. This raises an issue of the reliability of health information available on social media to patients regarding laryngological conditions.


The effect of photoperiod on development of sexual behavior and fertility in golden hamsters.
Male hamsters were raised on short (SD) or long (LD) photoperiods from birth, and the expression of sexual behavior at 6, 7, 10, and 14 weeks was compared. Neither mounting, intromissions, ejaculations, nor ultrasonic vocalizations differed in the two groups until 14 weeks of age, when these behaviors were performed more often by LD males. Sperm appeared in daily penile smears at an earlier age in SD than LD males, but LD males had larger flank glands and testes beginning at 6 and 7 weeks, respectively. Female siblings of the males in this study were mated around 7 weeks of age to adult males. Almost all females on both photoperiods conceived normally, and greater than 90% of the offspring delivered survived to weaning in both groups. Together, these results show that hamsters reared on SD are behaviorally and physiologically capable of reproducing for a period of time after puberty. The possibility that social influences or environmental factors other than photoperiod act on the juvenile hamster to retard reproductive development is discussed.


Population Trends in Frailty in Older Adults with Benign Urological Conditions in Northern California.
We sought to understand regional variation of frailty across health service areas (HSAs) in Northern and Central California among older adults with benign urological conditions. This retrospective study utilizes the University of California, San Francisco Geriatric Urology Database, which includes adults ≥65 years old with benign urological conditions who underwent a Timed Up and Go Test (TUGT) between December 2015 and June 2020. The TUGT is a validated proxy for frailty, whereby a TUGT ≤10 seconds represents robust individuals and a TUGT >10 seconds represents prefrail and frail individuals. Subjects were assigned to the HSA wherein they live, and HSAs were stratified by mean TUGT scores. Analyses were conducted at the HSA level. Characteristics associated with prefrail/frail HSAs were identified using multivariable logistic regression. Least square means were used to determine variation in adjusted mean TUGT scores. A total of 2,596 subjects were stratified into 69 HSAs in Northern and Central California. Twenty-one HSAs were categorized as robust and 48 HSAs were categorized as prefrail/frail. Prefrail/frail HSAs were significantly associated with older age (adjusted odds ratio [aOR] 4.03, CI 3.29-4.94, p <0.001), female sex (aOR 1.10, CI 1.07-1.11, p <0.001), non-White race (aOR 1.12, CI 1.10-1.14, p <0.001), underweight body mass index (BMI; aOR 1.14, CI 1.07-1.22, p <0.001) and obese BMI (aOR 1.06, CI 1.04-1.08, p <0.001). There was a 1.7-fold difference in mean TUGT values across HSAs. Older age, non-White race, and underweight and obese BMIs are associated with prefrail/frail HSAs. Further investigation into health disparities as they pertain to geography and frailty is needed to expand upon these findings.


Optimal pathways for upgrading China's wastewater treatment plants for achieving water quality standards at least economic and environmental cost.
Wastewater treatment plants (WWTPs) in China must be upgraded to meet new discharge standards, but this incurs both economic and environmental costs and benefits. To select the optimal upgrade pathway, we developed ten upgrade paths based on two common decision-making scenarios for WWTP upgrade in developing countries. Using model simulation, life-cycle assessment, life-cycle cost, and multiple-attribute decision-making, we incorporated the full costs and benefits associated with the construction and operation into the decision-making process. We used a weighting scheme of attributes for the three regions and ranked the upgrade paths using the technique for order preference by similarity to an ideal solution (TOPSIS). The results showed that constructed wetlands and sand filtration were advantageous in terms of lower economic costs and environmental impacts, while the denitrification filter pathways required less land. Optimal pathways differed by region, highlighting the importance of a detailed and integrated assessment of the costs and benefits of WWTP upgrade options over the full life cycle. Our findings can inform decision-making on upgrading China's WWTPs to meet stringent discharge standards and protect inland water and coastal environments.


The Hidden Dangers of Beaches: Cardiorespiratory Arrest Induced by Thermal Shock.
Thermal shock is widely recognized by modern medicine. Its pathophysiological mechanisms are known, as are its possible consequences, but scientific reports in the literature about clinical cases with severe consequences are sparse. The authors present a case of cardiorespiratory arrest after prolonged sun exposure followed by a dive in the ocean. Other aetiological causes were ruled out, by exclusion, leading to the diagnosis of cardiorespiratory arrest caused by thermal shock. It is important to inform the public in general of the risks of negligent behaviour on the beach.


Evaporative light scattering detection based reversed-phase ultra-high-performance liquid chromatography method to quantify intermediates and end products of biodiesel production.
A fast method based on reversed-phase ultra-high-performance liquid chromatography using evaporative light scattering detection (RP-UHPLC-ELSD) was developed for monitoring the intermediates and end products of biodiesel production. Gradient elution of water, acetonitrile, and a mixture of acetonitrile:2-propanol:n-hexane was used. With a minimal and easy sample preparation, fatty acid methyl esters (FAME), fatty acid ethyl esters (FAEE), free fatty acids (FFA), monoacylglycerols (MAG), diacylglycerols (DAG), and triacylglycerols (TAG) were successfully separated. The developed method was used to monitor an ethylic enzymatic transesterification of soybean oil and to characterize the ester content of methyl and ethyl biodiesel. The ester content obtained was compared with the reference method by gas chromatography and flame ionization detector (GC-FID), with similar results for both methyl and ethyl biodiesel. The presented method is a simple and fast alternative, a 17 min run, to monitor the transesterification process, simultaneously quantifying all the analytes produced in the reaction: biodiesel and its intermediates. Limits of detection (LOD, between 29 and 307 ng) and quantification (LOQ, between 48 and 614 ng), linearity (R2>0.99), precision (between 0.30 and 6.58%), and accuracy (between 81.6 and 119.9%) were determined for the twenty-one compounds.


Selective extraction of plant bioactive compounds with deep eutectic solvents: Iris sibirica L. as example.
Deep eutectic solvents (DESs) are promising extractants with tuneable properties. However, there is a lack of reports about the influence of the nature of the original DES on obtaining the metabolomic profile of a plant. The aim of this study is to investigate the possibility of obtaining Iris sibirica L. chromatographical profiles with DESs based on various hydrogen bond donors and acceptors as extraction solvents. DESs were prepared by mixing choline chloride or tetrabutylammonium bromide with various hydrogen bond donors and investigated for the extraction of bioactive substances from biotechnological raw materials of I. sibirica L. The obtained extracts were analysed by HPLC with diode array detector (DAD) and Q-MS. Chromatographic profiles for I. sibirica L. extracts by eight choline chloride DESs and six tetrabutylammonium DESs have been obtained. It has been found that selective recovery of bioactive substances can be achieved by varying the composition of DESs. Eleven phenolic compounds were identified in I. sibirica L. using HPLC-MS. Phase separation was observed with acetonitrile for four DESs. New flavonoid derivatives have been found in DES extracts compared with methanol extracts. The results showed the possibility of DES usage for extraction without water addition. Selectivity of DESs varies depending on the chemical composition of hydrogen bond donors and acceptors. Choline chloride is a more suitable hydrogen bond acceptor for the flavonoid extraction. Choline chloride-lactic acid (1:1) DES has demonstrated a metabolic profile that was the closest to the methanol one and enhanced the extraction up to 2.6-fold.


Prevention of wound contamination using DuraPrep solution plus Ioban 2 drapes.
The use of the preoperative skin preparation DuraPrep is thought to enhance the adhesion qualities of an incise drape. If there is less drape lift it was hypothesized that there may be a reduction in wound contamination. We did a single-center, randomized trial to determine if a preoperative skin preparation containing DuraPrep solution plus Ioban 2 drapes reduced wound contamination in total joint replacement surgery compared with a povidone iodine scrub and paint plus Ioban 2 drapes. Secondary research questions focused on comparisons of differences in drape lift and cost between the two groups. Of the 176 evaluable patients, the proportion of patients with a contaminated wound was similar in the two groups (DuraPrep 28.0% versus povidone iodine 36.4%). The mean drape lift in the DuraPrep group was less than the povidone iodine group (1.5 cm versus 9.9 cm respectively). The mean cost of prepping was lower for the DuraPrep group compared with the povidone iodine group (dollars 93.36 and dollars 248.91, respectively). A preoperative skin preparation regimen containing DuraPrep solution plus Ioban 2 drapes is equivalent to a povidone iodine scrub and paint and Ioban 2 for the prevention of wound contamination during total joint replacement surgery. Improved drape lift and cost may influence the choice between the two methods.


Eye protection in racquet sports.
This article summarizes the clinical and experimental data leading to the Canadian Standards Association (CSA) certification of six eyeguards for racquet sports in Canada in November 1986. A parallel approach involving the American Standard of Testing and Materials (ASTM) is discussed and eyeguards meeting specifications are illustrated.


Improved Butanol Production Using FASII Pathway in E. coli.
n-Butanol is often considered a potential substitute for gasoline due to its physicochemical properties being closely related to those of gasoline. In this study, we extend our earlier work to convert endogenously producing butyrate via the FASII pathway using thioesterase TesBT to its corresponding alcohol, i.e., butanol. We first assembled pathway genes, i.e., car encoding carboxylic acid reductase from Mycobacterium marinum, sfp encoding phosphopantetheinyl transferase from Bacillus subtilis, and adh2 encoding alcohol dehydrogenase from S. cerevisiae, responsible for bioconversion of butyrate to butanol in three different configurations (Operon, Pseudo-Operon, and Monocistronic) to achieve optimum expression of each gene and compared with the clostridial solventogenic pathway for in vivo conversion of butyrate to butanol under aerobic conditions. An E. coli strain harboring car, sfp, and adh2 in pseudo-operon configuration was able to convert butyrate to butanol with 100% bioconversion efficiency when supplemented with 1 g/L of butyrate. Further, co-cultivation of an upstream strain (butyrate-producing) with a downstream strain (butyrate to butanol converting) at different inoculation ratios was investigated, and an optimized ratio of 1:4 (upstream strain: downstream strain) was found to produce ∼2 g/L butanol under fed-batch fermentation. Further, a mono-cultivation approach was applied by transforming a plasmid harboring tesBT gene into the downstream strain. This approach produced 0.42 g/L in a test tube and ∼2.9 g/L butanol under fed-batch fermentation. This is the first report where both mono- and co-cultivation approaches were tested and compared for butanol production, and butanol titers achieved using both strategies are the highest reported values in recombinant E. coli utilizing FASII pathway.


Long-term Outcomes of Computerized Tomography-Guided Sphenopalatine Ganglion-Targeted Pulsed Radiofrequency for Refractory Cluster Headache.
To further evaluate the efficacy and safety of computerized tomography-guided sphenopalatine ganglion-targeted pulsed radiofrequency treatment for patients with refractory episodic and chronic cluster headache (CH). Forty-five patients with refractory episodic CH and 14 patients with chronic CH who underwent computerized tomography-guided sphenopalatine ganglion-targeted pulsed radiofrequency between January 2011 and December 2018 at the Beijing Tiantan Hospital were included and analyzed in this retrospective cohort study. A total of 59 patients underwent 106 computerized tomography-guided pulsed radiofrequency procedures throughout the observational period. Effective remission was observed in 95.6% and 64.3% of patients with refractory episodic and chronic CH, respectively. Repeated computerized tomography-guided sphenopalatine ganglion-targeted pulsed radiofrequency procedures for recurrent CH was also proven to be effective. No severe side effects or complications were observed in this study. The computerized tomography-guided sphenopalatine ganglion-targeted pulsed radiofrequency procedure is an effective, safe, and repeatedly effective strategy for refractory CH. For patients who have not responded to conservative treatment, this minimally invasive intervention is a reliable alternative.


X-ray diffraction with micrometre spatial resolution for highly absorbing samples.
X-ray diffraction with high spatial resolution is commonly used to characterize (poly)crystalline samples with, for example, respect to local strain, residual stress, grain boundaries and texture. However, the investigation of highly absorbing samples or the simultaneous assessment of high-Z materials by X-ray fluorescence have been limited due to the utilization of low photon energies. Here, a goniometer-based setup implemented at the P06 beamline of PETRA III that allows for micrometre spatial resolution with a photon energy of 35 keV and above is reported. A highly focused beam was achieved by using compound refractive lenses, and high-precision sample manipulation was enabled by a goniometer that allows up to 5D scans (three rotations and two translations). As experimental examples, the determination of local strain variations in martensitic steel samples with micrometre spatial resolution, as well as the simultaneous elemental distribution for high-Z materials in a thin-film solar cell, are demonstrated. The proposed approach allows users from the materials-science community to determine micro-structural properties even in highly absorbing samples.


Making love in the time of corona - considering relationships in lockdown.
The COVID-19 pandemic and the resulting social changes that were required to slow the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) have resulted in lockdowns across many countries and led to substantial numbers of people being quarantined. For single people, their opportunities to meet a partner were completely lost. For couples who lived apart, this meant that they were not able to see their partner for many months. However, by contrast, for cohabiting couples, lockdown meant that they were forced to spend 24 h a day with each other, and perhaps their children or housemates, for months at a time. As lockdowns have loosened around the world, the possibility of a second wave arises, and lockdowns are being reinstated in many regions. The prospect of potential long-term lockdowns means that adjusting to this new normal in relationships is an important consideration. In this Viewpoint, three specialists in sexology and psychology discuss the effects of lockdown on intimacy and consider how it can be considered an opportunity as well as an obstacle for making love in the time of corona.


History and epidemiology of Swine influenza in Europe.
In Europe, swine influenza is considered one of the most important primary pathogens of swine respiratory disease and infection is primarily with H1N1, H1N2 and H3N2 influenza A viruses. The antigenetic characteristics of these viruses distinguish them from others circulating at a global level in pigs. These viruses have remained endemic in European pig populations but significant differences in the circulation of these strains occur at a regional level across Europe. The dynamic of co-circulation of viruses, impact of prior immunity, husbandry practices and other local factors all contribute to the complex epidemiology. Surveillance programmes in European pigs did not reveal the presence of pandemic H1N1 virus prior to its detection in humans in 2009 but there is evidence that the virus can be maintained in European pigs even when there are relatively good levels of herd immunity to other H1 viruses. Evidence for the pig as a 'mixing vessel' of influenza viruses of non-swine-origin has been demonstrated in Europe on several occasions. Furthermore significant and highly variable genetic diversity occurs at the whole genome level for all virus subtypes and this has contributed to changing patterns of virus epidemiology over time.


An in situ study of the hypothalamo-neurohypophysial complex of the freshwater teleost Ompok bimaculatus (Bloch) with a note on the tetrapodan features of its vascularization.
In Ompok bimaculatus the neurosecretory axons of both the pars magnocellularis and pars parvocellularis component of the nucleus preopticus contribute to the formation of the left and right main tracts. At rostral levels, one third of the tracts are loosely built forming a king of curtain, while they become more compact at caudal levels. The caudal two thirds of the main tracts give off several pairs of lateral tracts which join at the midline to form the paired median tracts. The median and the main tract jointly enter the pituitary as a common tract which, on entering the proximal pars distalis, separates into two and enters the pars intermedia. The hypothalamic and the hypophysial arteries take their origin from the internal carotid artery. The former contribute to the formation of the primary capillary plexus of the median eminence, whereas the latter enter the pituitary directly and ramify in the neuroadeno-interface. The primary capillary plexus is in close topographical contact with the neurosecretory axonal complex where the median and common tracts are formed. At this site at least some axons might have their endings on the capillary plexus. Thus, this region my be comparable in structure to the median eminence of the tetrapods. The neurons of the nucleus lateralis tuberis of O. bimaculatus are AF-positive. The infundibular cavity extends into the main neurohypophysial trunk and is lined by ependymal cells like the third ventricle.


Effect of (18)F-fluorodeoxyglucose extravasation on time taken for tumoral uptake to reach a plateau: animal and clinical PET analyses.
The present study aimed to investigate the effect of (18)F-fluorodeoxyglucose (FDG) extravasation on the time taken for tumoral uptake to reach a plateau. For the animal experiment, FDG extravasation was conducted in the tails of HCT116 tumor-bearing xenograft mice models in three groups (no extravasation, 40 % extravasation, and 80 % extravasation; n = 5, each). Dynamic positron emission tomography (PET) images were acquired over a period of 2 h following injection. Time-activity curves for FDG in the tails and tumors were calculated. For the clinical experiment, 22 patients (male:female, 14:8; age range, 70.8 ± 9.2 years) were subjected to PET/computed tomography (PET/CT) 1 h after the injection of FDG. The inclusion criteria were as follows: (1) submitted to both whole-body and subsequent regional scanning; (2) entire extravasation activity visualized in the whole-body images; (3) tumor visualized on both whole-body and additional regional images; and (4) status of tumor either confirmed by biopsy or clinically suspected for malignancy. The standardized uptake values (SUVs) of the tumors (on the whole-body and additional PET images) and extravasation sites were recorded. There were no significant differences in the time taken for tumoral uptake to reach a plateau and that to reach minimum activity at the extravasation site among the three groups of mice. However, the mean tumoral activity and activity at the extravasation site were negatively correlated at 1 h post-injection. According to the clinical PET findings, the differences in SUV between the whole-body and regional images were not significantly correlated with the interval between injection of FDG and start of whole-body scanning, interval between the start of whole-body scanning and start of regional scanning, extravasation volume, maximum SUV of the extravasation site, or total activity at the extravasation site. The time taken for tumoral uptake to reach a plateau is not affected by extravasation, even at extensive degrees. Thus, in routine practice, the imaging time of approximately 60 min post-injection need not be modified even if extravasation is identified. However, tumor SUV may be underestimated in cases of extravasation.


The International Committee of the Red Cross and the protection of world war dead.
The first Geneva Conventions were signed in 1864 and this initial effort to put humanity in war has since developed into a network of international conventions and customary rules which include the dead as a group that must be protected during and following armed conflicts. During the First and Second World Wars, parties to the conflict were obliged to recover the dead from battlefields, document identifying marks including the collection of identification discs, and to bury the body in a marked grave. Those parties' signatory to the laws regulating war at the time, could not have predicted the millions of losses of civilians and combatants resulting in the thousands of casualties left unrecovered at the end of both world wars. The prolonged requirement to recover, identify and bury newly-found World War dead is managed differently by each country; albeit with no universal approach that acknowledges the need to integrate the moral imperative of dignified post-war care of the dead with rapidly changing technology and equally rapidly ageing of families of the missing. The International Committee of the Red Cross is a longtime actor in providing humanitarian service to soldiers and civilians in war. This includes expertise in the legal framework regulating armed conflict, in the provision of a central system to aid in tracing those who go missing during war, including those from the world wars, and in the growing field of humanitarian forensics. This paper will discuss the applicable international frameworks for the protection world war dead, while promoting the ICRC's role as resource and advocate.


Accumulation and relationship of metals in different soil aggregate fractions along soil profiles.
Different aggregates vary in their ability to retain or adsorb metals in soil. Five soil profiles were sampled from different soil horizons and grouped, and the concentrations of Al, Mg, Ca, Fe, Mn, Cd, Cu and Pb were determined in six sizes of aggregates (> 2, 2-1, 1-0.6, 0.6-0.25, 0.25-0.053, < 0.053 mm). Significantly high (p < 0.05) structural stability indexes (SSI) and aggregate stability indexes (ASI) were recorded in the topsoil horizon, which may be attributed to the high soil organic matter (SOM) content in aggregates from topsoil. In addition, ASI and SSI were positively correlated (r = 0.569, p < 0.05) with each other, which indicated that the stability of soil aggregates could contribute to the structural stability of bulk soil. Moreover, accumulation factors (AF), principal component analysis (PCA) and Pearson's correlation coefficients were used for metal element assessment. The results indicated that SOM was not a key factor affecting the accumulation of Ca, Mg, Al, Fe, Mn, Pb, Cd and Cu in soil aggregates. In general, AF values for metal elements in microaggregates (< 0.25 mm) were high, which showed that metals preferred to accumulate in fine soil aggregates. The PCA and Pearson's correlation coefficients indicated that soil parent materials primarily controlled the distribution of Al, Ca, Fe, Mg and Mn, while materials derived from technogenic sources have important impacts on the distribution of Cd, Cu and Pb in soil aggregates along the soil profile.


The utility of preoperative endometrial sampling for the detection of uterine sarcomas.
Uterine sarcomas are aggressive cancers, often not recognized prior to surgical exploration. The goal of this study was to determine the utility of endometrial sampling in detecting uterine sarcomas and to examine factors associated with diagnostic inaccuracy. All uterine tumors identified at hysterectomy from 1990 to 2006 were reviewed. Included patients underwent preoperative endometrial sampling reviewed at our center. Pathologic data was documented through review of hospital records. Statistical analysis was performed using Chi square test. 938 patients were identified. Preoperative sampling was available for review in 730 (78%) subjects. Uterine sarcomas occurred in 142 patients; 72 (51%) underwent preoperative sampling. Overall, endometrial sampling identified an invasive tumor in 84% (600/713), and the correct histology in 79% (564/713). Among women with sarcomas, preoperative sampling suggested an invasive tumor in 86% (62/72) and predicted the correct histologic diagnosis in 64% (46/72). The rate of detection of an invasive cancer by preoperative sampling was not statistically different among sarcomas and epithelial tumors (86% vs. 84%, p=0.76). Preoperative sampling was significantly less reliable in predicting the correct histology for uterine sarcomas (64% vs. 81%, p<0.0001). Similar trends were seen when sarcoma patients were compared to low-grade and high-grade epithelial cancers. Both biopsy and curettage had similar accuracy in diagnosing sarcomas (p=0.84). Endometrial sampling has a significantly lower predictive value in diagnosing uterine sarcomas compared to epithelial uterine malignancies. Biopsy and curettage have similar accuracy. Novel diagnostic techniques are needed to accurately identify uterine sarcomas preoperatively.


Clinicopathological value of immunohistochemical detection of occult involvement in pT3N0 gastric cancer.
BACKGROUND: In cases of pT3 gastric cancer, even when standard histological staining reveals no evidence of metastases in the regional lymph nodes, patients still may die of postoperative recurrence of the tumor. An attempt was made in the present study to explain the unfavorable outcome of such patients by investigating the presence of occult cancer cells in lymph nodes by immunostaining of cytokeratin.METHODS: We examined 2310 lymph nodes that had been removed from 83 patients with stage II gastric cancer (pT3, N0, M0). Two consecutive sections of 4 &mgr;m thick were prepared for simultaneous staining with hematoxylin and eosin and immunostaining with the CAM 5.2 monoclonal antibody against cytokeratin, respectively.RESULTS: Evidence of occult involvement was found in 299 of 2310 (13%) lymph nodes and in 54 of 83 (65%) patients with pT3 gastric cancer. An analysis of survival demonstrated the limited 5-year survival of patients with occult involvement in their resected lymph nodes, as compared with that of patients without involvement ( P < 0.01). Moreover, the patients in whom group 2 lymph nodes had occult cancer cells had a significantly poorer prognosis than those in whom occult involvement was limited to group 1 lymph nodes ( P < 0.05).CONCLUSIONS: The accuracy of predictions of prognosis of patients with pT3 gastric cancer should be greatly enhanced if cytokeratin-specific immunostaining is performed in conjunction with routine histopathological examination of lymph nodes.


Malignant hyperthermia-like syndrome in acute chlorfenapyr poisoning - A case report.
Chlorfenapyr is a pesticide that interferes with mitochondrial oxidative phosphorylation, resulting in the disruption of ATP production and cellular death. We present a fatal case of chlorfenapyr poisoning presented with malignant hyperthermia- like syndrome after intubation. A 49-year-old male presented with fatigue and diaphoresis four days after ingesting emamectin chlorfenapyr. IV hydration was given, and two sessions of hemoperfusion were performed. He was intubated for airway protection on Day 3 because of drowsiness. Immediately after intubation, he developed tachycardia and hyperthermia (temperature 41 °C), followed by cardiac arrest. During resuscitation, we noted he had severe diaphoresis and generalized muscle rigidity. Peri-arrest ABG showed abrupt onset of severe type 2 respiratory failure, lactate acidosis, and hyperkalemia. The clinical manifestation and ABG result lead to the possible diagnosis of malignant hyperthermia. The resuscitation was unsuccessful, and the patient eventually passed away. Propofol might be the culprit drug in this case as it is known to affect mitochondrial metabolism via uncoupling oxidative phosphorylation. We suggest monitoring for signs and symptoms of malignant hyperthermia in chlorfenapyr poisoning, especially after intubation. Propofol should be avoided or used with caution during induction for intubation. Further research on the possible antidote and usage of early RRT in ED is needed.


Modulatory Effects of Dopamine D2 Receptors on Spreading Depression in Rat Somatosensory Neocortex.
Spreading depression (SD) is a propagating wave of depolarization followed by depression of the neuroglial activities and can modulate extracellular dopamine concentrations in the neocortex. It has been shown that the dopaminergic system plays a role in migraine. SD has been suggested as a critical phenomenon in the pathophysiology of migraine. The aim of this study was to investigate the effect of dopamine D2 receptors on the characteristic features of SD in rat neocortical tissues. The effect of dopamine D2 receptor agonist quinpirole and D2 receptor antagonist sulpiride was tested on different characteristic features (amplitude, duration and velocity) of KCl-induced SD in somatosensory neocortical slices of adult rats. The effect of above-mentioned substances on production of long-term potentiation (LTP) in the neocortex was also evaluated. The present data revealed a dose-dependent suppression of the amplitude and duration of SD in the presence of the dopamine D2 receptor antagonist sulpiride in the neocortex. D2 dopamine receptor agonist quinpirole dose-dependently enhanced the amplitude and duration of the neocortical SD. Furthermore, application of D2 receptor antagonist significantly suppressed induction of LTP. These results indicate that D2 receptors modulate the initiation of SD in the neocortex. This finding refers to the potential role of D2 receptor antagonist in treatment of migraine pain.


Multiply protonated betaine clusters are stable in the gas phase.
Multiply protonated clusters of betaine are formed via electrospray ionisation and fragment via competitive betaine neutral loss and charge separation; theoretical calculations suggest the [M(n)+2H](2+) ions consist of a [M(2)+2H](2+) core based on the hydrogen bonded carboxylic acid dimer.


Serous lymphocytic exudates in Iraq: the value of various methods of investigation.
Fifty cases of lymphocytic exudate of the pleura and peritoneum were studied to determine the cause. Though tuberculosis was suspected provisionally in the majority, isolation of M. tuberculosis was rare and other investigations proved more helpful. Histological examination of material obtained by laparoscopy was the most reliable method followed by pleural biopsy, especially if it was an open one. This procedure has the invaluable advantage of a rapid diagnosis without the need to await the results of culture. The specific gravity and the cell count were of help to determine the exudative nature of the fluid. The protein content, the lactic dehydrogenase value of the fluid and its ratio to the blood value were more useful in determining a possible aetiology. A definite diagnosis of tuberculosis was made in 21 cases. A further 13 cases (3 with highly suggestive histological appearances) were judged to be tuberculosis in view of their suggestive history and excellent response to specific antituberculosis chemotherapy. Eleven cases proved to be due to malignant disease.


Rhythms for Cognition: Communication through Coherence.
I propose that synchronization affects communication between neuronal groups. Gamma-band (30-90 Hz) synchronization modulates excitation rapidly enough that it escapes the following inhibition and activates postsynaptic neurons effectively. Synchronization also ensures that a presynaptic activation pattern arrives at postsynaptic neurons in a temporally coordinated manner. At a postsynaptic neuron, multiple presynaptic groups converge, e.g., representing different stimuli. If a stimulus is selected by attention, its neuronal representation shows stronger and higher-frequency gamma-band synchronization. Thereby, the attended stimulus representation selectively entrains postsynaptic neurons. The entrainment creates sequences of short excitation and longer inhibition that are coordinated between pre- and postsynaptic groups to transmit the attended representation and shut out competing inputs. The predominantly bottom-up-directed gamma-band influences are controlled by predominantly top-down-directed alpha-beta-band (8-20 Hz) influences. Attention itself samples stimuli at a 7-8 Hz theta rhythm. Thus, several rhythms and their interplay render neuronal communication effective, precise, and selective.


Epidemiology of Facial Injuries in Sport.
Facial injuries can pose a large health burden for athletes, potentially resulting in time loss and surgery. This article reviews the incidence, common mechanisms, and risk factors of facial injuries in several sports globally. Estimates of facial injury rates are complicated by a lack of, or inconsistent, reporting on specific types of injury. Much of the epidemiologic literature is based on hospital-based injury surveillance and there is a paucity of literature examining sport-specific risk factors. Future research should focus on prospective injury surveillance methodologies with consistent injury definitions examining risk factors and the effectiveness of facial injury prevention efforts.


Identification of Bulinus forskalii as a potential intermediate host of Schistosoma hæmatobium in Senegal.
Understanding the transmission of Schistosoma hæmatobium in the Senegal River Delta requires knowledge of the snails serving as intermediate hosts. Accurate identification of both the snails and the infecting Schistosoma species is therefore essential. Cercarial emission tests and multi-locus (COX1 and ITS) genetic analysis were performed on Bulinus forskalii snails to confirm their susceptibility to S. hæmatobium infection. A total of 55 Bulinus forskalii, adequately identified by MALDI-TOF mass spectrometry, were assessed. Cercarial shedding and RT-PCR assays detected 13 (23.6%) and 17 (31.0%), respectively, Bulinus forskalii snails parasitized by S. hæmatobium complex fluke. Nucleotide sequence analysis identified S. hæmatobium in 6 (11.0%) using COX1 and 3 (5.5%) using ITS2, and S. bovis in 3 (5.5%) using COX1 and 3 (5.5%) using ITS2. This result is the first report of infection of Bulinus forskalii by S. hæmatobium complex parasites in Senegal using innovative and more accurate identification methods to discriminate this snail and characterize its infection by S. hæmatobium.


Minimally Invasive Surgery: Standard of Care for Mitral Valve Endocarditis.
Background. Minimally invasive surgery via right mini-thoracotomy has become the standard of care for the treatment of mitral valve disease worldwide, particularly at high-volume centers. In recent years, the spectrum of indications has progressively shifted and extended to fragile and higher-risk patients, also addressing more complex mitral valve disease and ultimately including patients with native or prosthetic infective endocarditis. The rationale for the adoption of the minimally invasive approach is to minimize surgical trauma, promote an earlier postoperative recovery, and reduce the incidence of surgical wound infection and other nosocomial infections. The aim of this retrospective observational study is to evaluate the effectiveness and the early and late outcome in patients undergoing minimally invasive surgery for mitral valve infective endocarditis. Methods. Prospectively collected data regarding minimally invasive surgery in patients with mitral valve infective endocarditis were entered into a dedicated database for the period between January 2007 and December 2022 and retrospectively analyzed. All comers during the study period underwent a preoperative evaluation based on their clinical history and anatomy for the allocation to the most appropriate surgical strategy. The selection of the mini-thoracotomy approach was primarily driven by a thorough transthoracic and especially transesophageal echocardiographic evaluation, coupled with total body and vascular imaging. Results. During the study period, 92 patients underwent right mini-thoracotomy to treat native (80/92, 87%) or prosthetic (12/92, 13%) mitral valve endocarditis at our institution, representing 5% of the patients undergoing minimally invasive mitral surgery. Twenty-six (28%) patients had undergone previous cardiac operations, whereas 18 (20%) presented preoperatively with complications related to endocarditis, most commonly systemic embolization. Sixty-nine and twenty-three patients, respectively, underwent early surgery (75%) or were operated on after the completion of the targeted antibiotic treatment (25%). A conservative procedure was feasible in 16/80 (20%) patients with native valve endocarditis. Conversion to standard sternotomy was necessary in a single case (1.1%). No cases of intraoperative iatrogenic aortic dissection were reported. Four patients died perioperatively, accounting for a thirty-day mortality of 4.4%. The causes of death were refractory heart or multiorgan failure and/or septic shock. A new onset stroke was observed postoperatively in one case (1.1%). Overall actuarial survival rate at 1 and 5 years after operation was 90.8% and 80.4%, whereas freedom from mitral valve reoperation at 1 and 5 years was 96.3% and 93.2%, respectively. Conclusions. This present study shows good early and long-term results in higher-risk patients undergoing minimally invasive surgery for mitral valve infective endocarditis. Total body, vascular, and echocardiographic screening represent the key points to select the optimal approach and allow for the extension of indications for minimally invasive surgery to sicker patients, including active endocarditis and sepsis.


Concurrent sintilimab with sequential chemoradiotherapy for unresectable, stage III non-small cell lung cancer: a retrospective study.
Concurrent programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors with sequential chemoradiotherapy (SCRT) have been reported in only a limited number of studies involving patients with unresectable stage III non-small-cell lung cancer (NSCLC). A retrospective study was conducted to systematically analyze the efficacy and safety of the emerging therapy among Chinese patients. We included patients with unresectable, stage III NSCLC who received concurrent sintilimab with chemotherapy or chemotherapy alone for 3-6 cycles, followed by radical radiotherapy at the First Hospital of Jilin University from Dec 15, 2019, to Jul 15, 2022. The primary end point was the objective response rate (ORR). The secondary end points included progression-free survival (PFS), overall survival (OS), 12-month and 18-month PFS rates, the duration of response (DoR), and safety. The retrospective study involved 77 patients, of which 49 receiving concurrent sintilimab with SCRT were assigned to cohort A, and 28 receiving SCRT alone were assigned to cohort B. The ORR was significantly higher in cohort A (79.6%, 95% CI 65.7-89.8) than in cohort B (35.7%, 95% CI 18.6-55.9) (p<0.001). Median PFS was significantly longer in cohort A than in cohort B (NR [95% CI 21.4-NR] vs. 16.0 months [13.0-22.5]; HR 0.375, 95% CI 0.192-0.735; p=0.003). The PFS rates at 12 and 18 months were 84.8% (95% CI 75.0-95.9) and 71.3% (95% CI 58.7-86.7) in cohort A and 75.0% (95% CI 60.6-92.9) and 38.3% (95% CI 23.7-61.7) in cohort B, respectively. Grade 3 or 4 adverse events (AEs) were reported in 19 patients (38.8%) and seven patients (25.0%) in two cohorts, respectively. Grade 3 or 4 pneumonitis or immune-mediated pneumonitis, radiation pneumonitis, and pneumonia occurred in five (10.2%), four (8.2%), and two (4.1%) cohort A patients, and zero, two (7.1%), and two (7.1%) cohort B patients, respectively. Only cohort A reported AE leading to death in one (2.0%) patient (immune-mediated pneumonitis). Concurrent sintilimab with SCRT resulted in a significantly better ORR and longer PFS than SCRT alone, with manageable safety profiles in Chinese patients with unresectable stage III NSCLC.


Methoxytyrosine formation as an indicator of catechol-O-methyltransferase activity in rat liver in vivo.
The O-methyl derivative methoxytyrosine accumulated rapidly in rat liver after an intraperitoneal injection of L-dopa (50 mg/kg) in combination with 3-hydroxybenzylhydrazine, an inhibitor of the aromatic amino acid decarboxylase. Methoxytyrosine levels reached a plateau 40--60 min after i.p. injection of L-dopa, of which the tissue concentration declined monoexponentially. Injection of various doses of L-dopa revealed that methoxytyrosine formation was saturable and followed enzyme kinetics in rat liver. The catechol-O-methyltransferase inhibitors pyrogallol, tropolone and alpha-propyldopacetamide as well as the inhibitor of the aromatic amino acid decarboxylase benserazide inhibited the formation of methoxytyrosine dose-dependently and concomitantly increased the tissue concentration of dopa. The accumulation of methoxytyrosine from exogeneously applied L-dopa appears to be a reliable indicator of the in vivo activity of catechol-O-methyltransferase.


Transcriptome-wide analysis of the AP2/ERF transcription factor gene family involved in the regulation of gypenoside biosynthesis in Gynostemma pentaphyllum.
Gynostemma pentaphyllum is a traditional Chinese medicinal herb, serving as natural source of gypenosides (triterpene saponins). The APETALA2/ethylene response factor (AP2/ERF) transcription factors, playing essential regulation roles in plant biotic and abiotic stress responses and secondary metabolism biosynthesis. However, the regulation roles of AP2/ERF transcription factors in gypenosides biosynthesis in G. pentaphyllum remains little understood. In the present study, 125 AP2/ERF genes were identified from G. pentaphyllum transcriptome datasets. Phylogenetic, conserved motifs and expression pattern were employed to comprehensively analyze the 125 GpAP2/ERF genes. Based on the sequence similarity and phylogeny tree, the 125 GpAP2/ERF genes can be classified into 10 groups. Moreover, the distribution of conserved motifs among GpAP2/ERF proteins in phylogenetic trees was consistent with previous studies, thus supporting the classification. Expression profiling indicated that the 125 GpAP2/ERF genes exhibited distinct tissue-specific expression patterns. As confirmed by qRT-PCR, the four candidate GpAP2/ERF genes and gypenoside biosynthetic genes were highly expressed in leaves and/or flowers, and show similar expression patterns in response to MeJA. Base on the expression patterns and phylogenetic relationships, two GpAP2/ERF genes were considered as potential regulatory genes for gypenoside biosynthesis. Our study enhances understanding roles of GpAP2/ERF genes in regulation of gypenosides biosynthesis.


Brainstem auditory-evoked responses to different rates of clicks in small-for-gestational age preterm infants at term.
To clarify further the influence of intrauterine growth retardation (IUGR) on early neural development. In 30 small-for-gestational age (SGA) preterm infants at term, brainstem auditory-evoked responses (BAERs) were recorded with clicks of different repetition rates. All infants had a birthweight < 3rd centile, without any other major perinatal complications. Compared with the BAER in 36 appropriate-for-gestational age (AGA) term infants, the preterm SGA infants did not show any abnormalities at 21 s(-1) clicks, except for a slight increase in wave III amplitude. At 51 s(-1) clicks, there was an increase in III-V/I-III interval ratio (ANOVA p < 0.05). At 91 s(-1), the I-III interval shortened, whereas the III-V interval and III-V/I-III interval ratio increased (all p < 0.05). Wave V amplitude tended to increase slightly at all repetition rates of clicks used, although this increase did not reach statistical significance. The III-V interval and III-V/I-III interval ratio in the preterm SGA infants at different click rates correlated inversely with occipitofrontal head circumference at the time of testing, i.e. the smaller the head the longer the III-V interval (all p < 0.01). Wave III amplitude at 21 s(-1) also correlated inversely with head circumference (p < 0.01), suggesting that the slight increase in this amplitude in the preterm SGA infants is related to their relatively small head size. There were no major abnormalities in the BAER up to 91 s(-1) clicks at term in preterm SGA infants. The slight increase in III-V interval at high-rate stimulation suggests a subtle degree of central neural dysfunction, which is associated with small head size following IUGR.


Tryptophan fluorescence of (Na+ + K+)-ATPase as a tool for study of the enzyme mechanism.
1. The protein fluorescence intensity of (Na+ + K+)-ATPase is enhanced following binding of K+ at low concentrations. The properties of the response suggest that one or a few tryptophan residues are affected by a conformational transition between the K-bound form E2 . (K) and a Na-bound form E1 . Na. 2. The rate of the conformational transition E2 . (K) leads to E . Na has been measured with a stopped-flow fluorimeter by exploiting the difference in fluorescence of the two states. In the absence of ATP the rate is very slow, but it is greatly accelerated by binding of ATP to a low affinity site. 3. Transient changes in tryptophan fluorescence accompany hydrolysis of ATP at low concentrations, in media containing Mg2+, Na+ and K+. The fluorescence response reflects interconversion between the initial enzyme conformation, E1 . Na and the steady-state turnover intermediate E2 . (K). 4. The phosphorylated intermediate, E2P can be detected by a fluorescence increase accompanying hydrolysis of ATP in media containing Mg2+ and Na+ but no K+. 5. The conformational states and reaction mechanism of the (Na+ + K+)-ATPase are discussed in the light of this work. The results permit a comparison of the behaviour of the enzyme at both low and high nucleotide concentrations.


The ratio of lens thickness to axial length for biometric standardization in angle-closure glaucoma.
Biometric measurements were made by ultrasonography in 44 left eyes of 44 patients with primary angle-closure glaucoma. We defined the ratio between the lens thickness and the axial length (lens thickness/axial length factor) as a representative and unifying unit for biometric assessment of the eye. This factor defined the relationship between the lens, iris, and cornea and thus the status of the angle. Lens thickness/axial length factor values were found to be age dependent and were greater than normal for most age groups with angle-closure glaucoma. The mean normal value was 1.91 +/- 0.44; the mean values for patients in different age groups with angle-closure glaucoma ranged from 1.87 +/- 0.11 to 2.39 +/- 0.17.


Genetic Risk Stratification in Arrhythmogenic Left Ventricular Cardiomyopathy.
Arrhythmogenic left ventricular cardiomyopathy is characterized by early malignant ventricular arrhythmia associated with varying degrees and times of onset of left ventricular dysfunction. Variants in numerous genes have been associated with this phenotype. Here, the authors review the literature on recent cohort studies of patients with variants in desmoplakin, lamin A/C, filamin-C, phospholamban, RBM20, TMEM43, and selected channelopathy genes also associated with structural disease. Unlike traditional sudden cardiac death risk assessment in nonischemic cardiomyopathy, left ventricular systolic function is an insensitive predictor of risk in patients with these genetic diagnoses.


Does the private sector receive an excessive return from investments in health care infrastructure projects? Evidence from the UK.
This paper is concerned with the cost-efficiency of Private Finance Initiatives (PFIs) in the delivery of hospital facilities in the UK. We outline a methodology for identifying the "fair" return on equity, based on the Weighted Average Cost of Capital (WACC) of each investor. We apply this method to assess the expected returns on a sample of 77 contracts signed between 1997 and 2011 by health care provider organisations in the UK. We show that expected returns are in general in excess of the WACC benchmarks. The findings highlight significant problems in current procurement practices and the methodologies by which bids are assessed. To minimise the financial impact of hospital investments on health care systems, a regulatory regime must ensure that expected returns are set at the "fair" rate.


The accuracy of triglyceride-glucose (TyG) index for the screening of metabolic syndrome in adults: A systematic review and meta-analysis.
To investigate the relationship between the triglyceride-glucose (TyG) index, a novel surrogate index of insulin resistance (IR), and metabolic syndrome (MetS) in a systematic review and meta-analysis. Studies that report the TyG index in adult subjects with and without MetS were included. Thirteen observational articles were included in this study, with a total of 49,325 participants. Two different categories of meta-analyses were performed. First, the means of the TyG index were compared in participants with and without MetS. The pooled mean difference (MD) of the TyG index between groups was 0.83 units (CI 95: 0.74-0.92, I2 = 98, P-value < 0.001), and the subgroup analyses showed MD significantly differed based on the MetS diagnostic criteria. The pooled MD were 0.80 units (CI 95: 0.70-0.91, I2 = %88, P-value < 0.001) and 0.82 units (CI 95: 0.79-0.86, I2 = %0, P-value > 0.767) for studies reported data for males and females individual, respectively. Second bivariate diagnostic test accuracy (DTA) meta-analysis was performed and determined that the TyG index's pooled sensitivity and specificity for screening of MetS were 80% (CI95: 75%-84%, I2 = 87%, P-value < 0.001) and 81% (CI95: 77%-84%, I2 = 90.45%, P-value < 0.001), respectively. Summary receiver-operating characteristics (sROC) curves were also plotted with the area under the sROC curve of 0.87 (CI 95: 0.84-0.90). The TyG index is a sensitive and specific index for MetS and may be valuable for MetS screening. CRD42022316209.


Analysis of tissue factor expression in various cell model systems: cryptic vs. active.
Tissue factor (TF) encryption plays an important role in regulating TF coagulant activity. Potential differences in experimental cell model systems and strategies hampered our understanding of the TF encryption mechanisms. To characterize the procoagulant activity status of TF in different cell types, and to determine whether increased TF procoagulant activity following the activation stems from transformation of the cryptic TF to the active form. Simultaneous kinetic analyses of TF-FVIIa activation of FX and FVIIa binding to cell surface TF were performed under identical experimental conditions in fibroblast (WI-38), cancer cell (MDA-231), endothelial cell (HUVEC) and monocytic cell (THP-1) model systems. These data were then utilized to estimate TF coagulant-specific activity and percentages of active and cryptic TF present in these cell types. MDA-231 and WI-38 cells express 10 to 100 times more TF on their cell surfaces compared with perturbed HUVEC and THP-1 cells. TF-specific activity on cell surfaces of MDA-231, WI-38 and THP-1 cells was very similar. Nearly 80-90% of the TF in MDA-231, WI-38 and THP-1 cells was cryptic. A plasma concentration of FVII would be sufficient to bind both active and cryptic TF on cell surfaces. Increased TF activity following cell activation stems from decryption of cryptic TF rather than increasing the coagulant activity of the active TF. Our data demonstrate that TF encryption is not limited to a specific cell type, and unlike previously thought, the majority of the TF expressed in cancer cells is not constitutively procoagulant.


Risk factors associated with unilateral hearing loss.
To analyze the presence of Joint Committee on Infant Hearing (JCIH) risk factors and co-occurring birth defects (CBDs) in children with unilateral hearing loss (UHL). Retrospective review. Statewide registry of universal newborn hearing screen data for all children born in Virginia from 2002 through 2008. The study population comprised 371 children with confirmed UHL. Universal newborn hearing screen status, presence or absence of JCIH risk factors, and CBDs Of the 371 children with confirmed unilateral hearing loss, 362 (97.5%) were identified through a failed universal newborn hearing screen. Of these 362 children, 252 (69.6%) had no JCIH risk factors and 110 (30.3%) had 1 or more risk factor reported. Nine children (2.5%) with 1 or more risk factors passed the universal newborn hearing screen but had later-onset UHL. Craniofacial anomaly was the most commonly reported JCIH risk factor in 48 children (43.6%). A family history of permanent childhood hearing loss was present in 24 children (21.8%). Twenty children (18.2%) had stigmata associated with a syndrome including hearing loss. Of the 110 children with UHL and a JCIH risk factor, additional CBDs were identified in 83 (75.5%). An ear-specific anomaly was most prevalent in 37 infants (44.6%), followed by cardiovascular anomalies in 34 infants (41.0%). Thirty percent of children with confirmed UHL had a JCIH risk factor, most commonly craniofacial anomalies, family history of hearing loss, and stigmata of syndromes associated with hearing loss. However, the absence of JCIH risk factors does not preclude the development of UHL. Further studies assessing the etiology of UHL and risk factor associations are warranted.


Evaluation of medical career-counseling resources across Canada.
North American medical school accreditation requires career counseling. The Memorial University of Newfoundland (MUN) MedCAREERS program was implemented in 2000 before published evidence of efficacy of Canadian medical school career-counseling programs existed. Data were gathered initially through the Canadian Residency Matching Service Post-Match Survey in 2003 and subsequently through the Canadian Graduation Questionnaire from 2006 to 2008. The overall response rate was 61%. Perceived benefits and efficacy of the MUN MedCAREERS Web site and several career-counseling resources were determined along with participation rates encompassing a 6-year period. Most career-counseling resources were perceived as helpful, regardless of participation rate. Our goal was to provide information on an array of career-counseling resources so that Canadian medical schools can avail of appropriate resources and select activities to help students make informed decisions about their specialty choice. Planners of career-counseling activities may wish to consider elements that students find most helpful.


Evidence that a nuclear matrix protein participates in premessenger RNA splicing.
The role of nuclear matrix proteins in premessenger RNA splicing has been investigated using antibodies raised against isolated rat liver nuclear matrix and cross-reactive with a 65-kDa HeLa cell nuclear matrix protein (IGA-65). IGA-65 is an internal nuclear matrix component which can be solubilized as a component of nuclear splicing extracts, by the action of endogenous ribonucleases, EDTA, and DTT during extract preparation. Preincubation of splicing extract with antibodies against IGA-65 (anti-IGA-65) inhibited in vitro splicing of exogenous adenovirus precursor RNA. Furthermore, assembly of precursor RNA into active spliceosome complexes was inhibited by pretreatment of extracts with anti-IGA-65, suggesting a role for IGA-65 during early spliceosome assembly. The IGA-65 present in splicing extracts was distinguishable from known U-snRNP and hnRNP proteins on protein gels. Furthermore, electrophoresis of splicing extract on native gels indicated that IGA-65 was present in protein complexes different from those containing U-snRNPs or hnRNP C protein. The data support identification of complexes containing IGA-65 as nuclear factors involved in pre-mRNA splicing and, by extension, suggest a role for the nuclear matrix during processing in vivo.


GPCR biased ligands as novel heart failure therapeutics.
G protein-coupled receptors have been successfully targeted by numerous therapeutics including drugs that have transformed the management of cardiovascular disease. However, many GPCRs, when activated or blocked by drugs, elicit both beneficial and adverse pharmacology. Recent work has demonstrated that in some cases, the salutary and deleterious signals linked to a specific GPCR can be selectively targeted by "biased ligands" that entrain subsets of a receptor's normal pharmacology. This review briefly summarizes the advances and current state of the biased ligand field, focusing on an example: biased ligands targeting the angiotensin II type 1 receptor. These compounds exhibit unique pharmacology, distinct from classic agonists or antagonists, and one such molecule is now in clinical development for the treatment of acute heart failure.


Anxiolytic effects of the aqueous extract of Uncaria rhynchophylla.
The purpose of this study was to characterize the putative anxiolytic-like effects of the aqueous extract of hooks with stem of Uncaria rhynchophylla using the elevated plus maze (EPM) and the hole-board apparatus in rats and mice. Control rats were treated with an equal volume of saline, and positive control rats with buspirone (1 mg/kg). Single or repeated treatments of the aqueous extract of Uncaria rhynchophylla (200 mg/kg/day, p.o.) for 7 days significantly increased the time-spent and entries into open arms of the EPM, and reduced the time-spent and entries into the closed arms versus saline controls (P<0.05). However, no changes in spontaneous locomotor activity or myorelaxant effects were observed versus saline controls. In the hole-board test, repeated treatment with the aqueous extract of Uncaria rhynchophylla (100 or 200 mg/kg/day, p.o.) significantly increased the number of head-dips (P<0.05). In addition, the anxiolytic-like effects of Uncaria rhynchophylla extract as assessed using the EPM test were abolished by WAY 100635 (0.3 mg/kg, i.p.), a 5-HT(1A) receptor antagonist. These results suggest that Uncaria rhynchophylla is an effective anxiolytic agent, and acts via the serotonergic nervous system.


Pediatric physical therapists' perceptions of their training in assistive technology.
Availability of assistive technology (AT) and federal legislation promoting greater use of AT for children with disabilities have increased substantially. The purpose of this study was to determine the perceived adequacy of previous training in AT, specific training needs, preferred methods of training, and the confidence level of pediatric physical therapists in providing AT. Three hundred eighty pediatric physical therapists responded to a survey questionnaire mailed to a random sample of members of the Section on Pediatrics of the American Physical Therapy Association. The survey was used to determine training needs of therapists in the area of AT, their confidence in delivering AT services, preferred methods of training, and challenges in becoming trained. The therapists reported having less-than-adequate training in AT and a lack of confidence in delivering AT services. They also reported that they would like accessible and affordable training that focuses on funding technology and services, knowledge of specific devices, and assessment and evaluation methods. The findings underscore the need to develop pre-service, in-service, and continuing education training opportunities in AT for providers working with children who have disabilities.


Attention to attention in aphasia - elucidating impairment patterns, modality differences and neural correlates.
It is increasingly acknowledged that patients with aphasia following a left-hemisphere stroke often have difficulties in other cognitive domains. One of these domains is attention, the very fundamental ability to detect, select, and react to the abundance of stimuli present in the environment. Basic and more complex attentional functions are usually distinguished, and a variety of tests has been developed to assess attentional performance at a behavioural level. Attentional performance in aphasia has been investigated previously, but often only one specific task, stimulus modality, or type of measure was considered and usually only group-level analyses or data based on experimental tasks were presented. Also, information on brain-behaviour relationships for this cognitive domain and patient group is scarce. We report detailed analyses on a comprehensive dataset including patients' performance on various subtests of two well-known, standardised neuropsychological test batteries assessing attention. These tasks allowed us to explore: 1) how many patients show impaired performance in comparison to normative data, in which tasks and on what measure; 2) how the different tasks and measures relate to each other and to patients' language abilities; 3) the neural correlates associated with attentional performance. Up to 32 patients with varying aphasia severity were assessed with subtests from the Test of Attentional Performance (TAP) as well as the Test of Everyday Attention (TEA). Performance was compared to normative data, relationships between attention measures and other background data were explored with principal component analyses and correlations, and brain-behaviour relationships were assessed by means of voxel-based correlational methodology. Depending on the task and measure, between 3 and 53 percent of the patients showed impaired performance compared to normative data. The highest proportion of impaired performance was noted for complex attention tasks involving auditory stimuli. Patients differed in their patterns of performance and only the performance in the divided attention tests was (weakly) associated with their overall language impairment. Principal components analyses yielded four underlying factors, each being associated with distinct neural correlates. We thus extend previous research in characterizing different aspects of attentional performance within one sample of patients with chronic post stroke aphasia. Performance on a broad range of attention tasks and measures was variable and largely independent of patients' language abilities, which underlines the importance of assessing this cognitive domain in aphasic patients. Notably, a considerable proportion of patients showed difficulties with attention allocation to auditory stimuli. The reasons for these potentially modality-specific difficulties are currently not well understood and warrant additional investigations.


Assessment of rhizosphere bacterial diversity and composition in a metal hyperaccumulator (Boehmeria nivea) and a nonaccumulator (Artemisia annua) in an antimony mine.
Heavy metal hyperaccumulators are widely used in mining restoration due to their ability to accumulate and transport heavy metals, compared to nonaccumulators. Rhizosphere bacteria in metal hyperaccumulators play a key role in the uptake of heavy metals from soil; however, assessments of the differences of rhizosphere bacteria between metal hyperaccumulators and nonaccumulator are scarce. To understand the difference of bacterial composition between hyperaccumulator and nonaccumulator in rhizosphere, the diversity and composition of rhizosphere bacteria in a metal hyperaccumulator (Boehmeria nivea) and a nonaccumulator (Artemisia annua) grown in the same field in Xikuangshan were evaluated using Illumina Miseq high-throughput sequencing technology. Boehmeria nivea and A. annua had 3926 overlapping OTUs, 19,736 and 17,579 unique OTUs, respectively. Boehmeria nivea had lower Chao1 index, Shannon index and Pielou index than A. annua. The dominant phyla and genera of rhizosphere bacteria in B. nivea and A. annua were similar, but some rhizosphere bacterial communities with heavy metal remediation ability mainly appeared in the rhizosphere of the hyperaccumulator. Compared to A. annua, B. nivea showed a significantly higher relative abundance of rhizosphere bacteria, such as Acidobacteria and Bacteroidete at the phylum level and RB41 at the genus level. Some specific rhizosphere bacteria with the ability to bind metal, such as Leifsonia and Kibdelosporangium, were only found in the rhizosphere of B. nivea. Results indicated that B. nivea, as a metal hyperaccumulator, has a key function in governing metal-resistant rhizosphere bacteria in response to antimony compound pollution stress. Understanding the diversity of rhizosphere bacteria between hyperaccumulators and nonaccumulators is beneficial to formulate strategies to improve metal uptake efficiency by selecting specific plant species and rhizosphere bacteria grown on polluted soil.


Transient Daratumumab-Induced Refractive Shift in Multidrug-Resistant Multiple Myeloma: Case Report and Literature Review.
Daratumumab, an anti-CD38 monoclonal antibody, is worldwide approved for treatment of newly diagnosed and relapsed/refractory multiple myeloma (MM) patients and is available as intravenous or subcutaneous formulations. Intravenous daratumumab is associated with frequent infusion-related reactions, while eye complications, especially refractive shifts, are very rare, with only previously reported cases. Here, we described a rare case of multi-refractory MM who developed transient myopic shift during intravenous daratumumab infusion successfully treated only with cycloplegic collyrium not requiring infusion rate lowering or drug discontinuation. This conservative therapeutic approach allowed termination of induction therapy and autologous hematopoietic stem-cell transplantation resulting in durable complete remission.


Factors Affecting Length of Stay in the Emergency Department in Patients Who Presented with Abdominal Pain.
We aimed to identify factors affecting length of stay in the emergency department in patients who presented with abdominal pain. A retrospective cohort study was conducted from 1 January 2017 to 31 December 2017. The medical records were reviewed from 217 patients older than 15 years with the chief complaint of abdominal pain. The patients were divided into emergency department length of stay (EDLOS) < 4 hours and ≥4 hours. The two groups were compared in terms of baseline characteristics, physical examination, time of presenting, attending physicians, interdepartmental consultations, investigations, ED disposition, final diagnosis, and mortality. The significant factors affecting longer EDLOS were examined using univariate and multivariate analyses by logistic regression. Factors affecting longer EDLOS were age ≥50 (odds ratio (OR) 3.17, 95% confidence interval (CI) 1.36-7.42), interdepartmental consultation ≥2 specialists (OR 71.82, 95% CI 5.67-909.51), blood testing ≥2 rounds (OR 85.6, 95% CI 4.22-1734.6), and ultrasonography (OR 8.28, 95% CI 1.84-37.26). The study found that the statistically significant factors that prolonged EDLOS in patients with the chief complaint of abdominal pain were age, rounds of blood test, interdepartmental consultation, and the need for ultrasonography.


Isolation and characterization of bacteriophages from the human skin microbiome that infect Staphylococcus epidermidis.
Phage therapy might be a useful approach for the treatment of nosocomial infections; however, only few lytic phages suitable for this application are available for the opportunistic pathogen, Staphylococcus epidermidis. In the current study, we developed an efficient method to isolate bacteriophages present within the human skin microbiome, by using niche-specific S. epidermidis as the host for phage propagation. Staphylococcus epidermidis was identified on the forehead of 92% of human subjects tested. These isolates were then used to propagate phages present in the same skin sample. Plaques were observable on bacterial lawns in 46% of the cases where S. epidermidis was isolated. A total of eight phage genomes were genetically characterized, including the previously described phage 456. A total of six phage sequences were unique, and spanned each of the major staphylococcal phage families; Siphoviridae (n = 3), Podoviridae (n = 1) and Myoviridae (n = 2). One of the myoviruses (vB_SepM_BE06) was identified on the skin of three different humans. Comparative analysis identified novel genes including a putative N-acetylmuramoyl-L-alanine amidase gene. The host-range of each unique phage was characterized using a panel of diverse staphylococcal strains (n = 78). None of the newly isolated phages infected more than 52% of the S. epidermidis strains tested (n = 44), and non-S. epidermidis strains where rarely infected, highlighting the narrow host-range of the phages. One of the phages (vB_SepM_BE04) was capable of killing staphylococcal cells within biofilms formed on polyurethane catheters. Uncovering a richer diversity of available phages will likely improve our understanding of S. epidermidis-phage interactions, which will be important for future therapy.


Mechanism of cadmium binding on the cell wall of an acidophilic bacterium.
Under certain conditions bacteria can act as a good biosorbent for different toxic heavy metals. However, no study on this aspect has been reported in case of acidophilic, heterotrophic, Gram-negative Acidiphilium strains, which are mostly resistant to several heavy metals. FTIR, SEM, TEM along with sorption experiments using bacterial cells of Acidiphilium symbioticum H8 were conducted to establish the mechanism of Cd(2+) ion sorption. The anionic functional groups present in the cell envelop were the components primarily responsible for the metal-binding capability of the bacterium. Sorption experiments further confirmed that 248.62 mg of cadmium was adsorbed per gram biomass at pH 6.0. The process can better be explained by Langmuir-Freundlich dual isotherm model. Blocking of the functional groups by chemical modification suggested that the binding of cadmium on the biomass occurs through electrostatic reaction and complex formation. Accumulation of cadmium on the cell envelop was supported by fine structure study.


Transfer Learning of the ResNet-18 and DenseNet-121 Model Used to Diagnose Intracranial Hemorrhage in CT Scanning.
The aim of the study was to verify the ability of the deep learning model to identify five subtypes and normal images in non-contrast enhancement CT of intracranial hemorrhage. A total of 351 patients (39 patients in the normal group, 312 patients in the intracranial hemorrhage group) who underwent intracranial hemorrhage noncontrast enhanced CT were selected, obtaining 2768 images in total (514 images for the normal group, 398 images for the epidural hemorrhage group, 501 images for the subdural hemorrhage group, 497 images for the intraventricular hemorrhage group, 415 images for the cerebral parenchymal hemorrhage group, and 443 images for the subarachnoid hemorrhage group). Based on the diagnostic reports of two radiologists with more than 10 years of experience, the ResNet-18 and DenseNet-121 deep learning models were selected. Transfer learning was used. 80% of the data was used for training models, 10% was used for validating model performance against overfitting, and the last 10% was used for the final evaluation of the model. Assessment indicators included accuracy, sensitivity, specificity, and AUC values. The overall accuracy of ResNet-18 and DenseNet-121 models was obtained as 89.64% and 82.5%, respectively. The sensitivity and specificity of identifying five subtypes and normal images were above 0.80. The sensitivity of the DenseNet-121 model to recognize intraventricular hemorrhage and cerebral parenchymal hemorrhage was lower than 0.80, 0.73, and 0.76, respectively. The AUC values of the two deep learning models were found to be above 0.9. The deep learning model can accurately identify the five subtypes of intracranial hemorrhage and normal images, and it can be used as a new tool for clinical diagnosis in the future.


Basal levels of metabolic activity are elevated in Genetic Absence Epilepsy Rats from Strasbourg (GAERS): measurement of regional activity of cytochrome oxidase and lactate dehydrogenase by histochemistry.
The Genetic Absence Epilepsy Rats from Strasbourg (GAERS) are considered an isomorphic, predictive, and homologous model of human generalized absence epilepsy. It is characterized by the expression of spike-and-wave discharges in the thalamus and cortex. In this strain, basal regional rates of cerebral glucose utilization measured by the quantitative autoradiographic [(14)C]2-deoxyglucose technique display a widespread consistent increase compared to a selected strain of genetically nonepileptic rats (NE). In order to verify whether these high rates of glucose metabolism are paralleled by elevated activities of the enzymes of the glycolytic and tricarboxylic acid cycle pathways, we measured by histochemistry the regional activity of the two key enzymes of glucose metabolism, lactate dehydrogenase (LDH) for the anaerobic pathway and cytochrome oxidase (CO) for the aerobic pathway coupled to oxidative phosphorylation. CO and LDH activities were significantly higher in GAERS than in NE rats in 24 and 28 of the 30 brain regions studied, respectively. The differences in CO and LDH activity between both strains were widespread, affected all brain systems studied, and ranged from 12 to 63%. The data of the present study confirm the generalized increase in cerebral glucose metabolism in GAERS, occurring both at the glycolytic and at the oxidative step. However, they still do not allow us to understand why the ubiquitous mutation(s) generates spike-and-wave discharges only in the thalamocortical circuit.


Subcutaneous teicoplanin in staphylococcal bone and joint infections.
We aimed to describe the use of subcutaneous teicoplanin as an alternative for the treatment of staphylococcal bone and joint infections. A retrospective multicentric cohort (2002-2015) was conducted with patients receiving subcutaneous teicoplanin for a staphylococcal bone and joint infection. Forty patients were assessed. A median loading dose of 9.4 mg/kg/12h (IQR, 6.1-13.1) was administered to 35 patients, subcutaneously for 18 of them. Thirteen of these patients received three injections per week. No excess risk of failure was identified. The trough level was not significantly different between the various routes (p=0.462), and was significantly higher if the loading dose was≥9 mg/kg/injection (p<10-3). The use of subcutaneous teicoplanin seems to be acceptable as an alternative to other routes of administration for antibiotics.


Asymmetrical changes in cerebral blood oxygenation induced by an active standing test in children with postural tachycardia syndrome.
Near-infrared spectroscopy enables recognition of various brain conditions based on certain factors, such as oxygenated hemoglobin (oxy-Hb). Since July 2012, we have been trying to determine the mechanisms of autonomic function in Japanese children with orthostatic intolerance (also called orthostatic dysregulation) in Nihon University Itabashi Hospital in Tokyo, Japan. A total of 23 children aged 7-16 years diagnosed with postural tachycardia syndrome (POTS), a subtype of orthostatic dysregulation, were enrolled in the study. We evaluated the relation between asymmetry in frontal cortex activity and the automatic nervous system and compared oxy-Hb changes in the right and left frontal cortices during an active standing test. We observed that during active standing oxy-Hb decreased in the frontal cortex. The oxy-Hb changes were asymmetrical, with a significantly larger decrease in the left frontal cortex than in the right frontal cortex, suggesting that tachycardia during active standing in POTS patients might be caused by activation of the right frontal cortex, which induces sympathetic nervous system activity.


The influence of L-opsin gene polymorphisms and neural ageing on spatio-chromatic contrast sensitivity in 20-71 year olds.
Chromatic contrast sensitivity may be a more sensitive measure of an individual's visual function than achromatic contrast sensitivity. Here, the first aim was to quantify individual- and age-related variations in chromatic contrast sensitivity to a range of spatial frequencies for stimuli along two complementary directions in color space. The second aim was to examine whether polymorphisms at specific amino acid residues of the L- and M-opsin genes (OPN1LW and OPN1MW) known to affect spectral tuning of the photoreceptors could influence spatio-chromatic contrast sensitivity. Chromatic contrast sensitivity functions were measured in 50 healthy individuals (20-71 years) employing a novel pseudo-isochromatic grating stimulus. The spatio-chromatic contrast sensitivity functions were found to be low pass for all subjects, independent of age and color vision. The results revealed a senescent decline in spatio-chromatic contrast sensitivity. There were considerable between-individual differences in sensitivity within each age decade for individuals 49 years old or younger, and age did not predict sensitivity for these age decades alone. Forty-six subjects (including a color deficient male and eight female carriers) were genotyped for L- and M-opsin genes. The Ser180Ala polymorphisms on the L-opsin gene were found to influence the subject's color discrimination and their sensitivity to spatio-chromatic patterns. The results expose the significant role of neural and genetic factors in the deterioration of visual function with increasing age.


The impact of the COVID-19 pandemic on African American cancer survivors.
Coronavirus disease 2019 (COVID-19) has had profound effects on population health to date. African American cancer survivors are particularly vulnerable to developing severe consequences; therefore, understanding the impact of the virus on this patient population is critical. The Detroit Research on Cancer Survivors cohort is a unique effort to understand the determinants of poor outcomes in African American cancer survivors. To date, more than 4500 cancer survivors and nearly 950 primary caregivers have been enrolled; participation includes a survey and the collection of biospecimens, medical records, and tumor tissue. Beginning in the spring of 2020, a supplemental survey focusing on the impact of COVID-19 was offered to enrolled participants. The analysis included 890 survivors. Nearly all survivors (>99%) reported changes in their daily activities in an effort to reduce the risk of infection. More than 40% of the survivors reported some disruption in their access to medical care. A substantial proportion of the survivors (>40%) reported feeling anxious, depressed, and/or isolated during the COVID-19 pandemic. Approximately 40% of the patients reported changes in health behaviors shown to negatively affect survivorship outcomes (physical inactivity, smoking, and alcohol use) as a result of the pandemic. The influence of the COVID-19 pandemic on African American cancer survivors is substantial: it has affected both their physical and mental health. Coupled with changes in health behaviors, these factors will likely affect outcomes in this high-risk patient population, and this makes further study and interventions necessary to mitigate the long-term impact of the pandemic on cancer outcomes.


Sulfate reducing bacterial community and in situ activity in mature fine tailings analyzed by real time qPCR and microsensor.
Sulfate reducing bacteria (SRB) play significant roles in anaerobic environments in oil sands mature fine tailings (MFTs). Hydrogen sulfide (H2S) is produced during the biological sulfate reduction process. The production of toxic H2S is one of the concerns because it may hinder the landscape remediation efficiency of oil sands tailing ponds. In present study, the in situ activity and the community structure of SRB in MFT and gypsum amended MFT in two settling columns were investigated. Combined techniques of H2S microsensor and dissimilatory sulfite reductase β-subunit (dsrB) genes-based real time quantitative polymerase chain reaction (qPCR) were applied to detect the in situ H2S and the abundance of SRB. A higher diversity of SRB and more H2S were observed in gypsum amended MFT than that in MFT, indicating a higher sulfate reduction activity in gypsum amended MFT; in addition, the activity of SRB varied as depth in both MFT and gypsum amended MFT: the deeper the more H2S produced. Long-term plans for tailings management can be assessed more wisely with the information provided in this study.


Irreversible injury in anoxic hepatocytes precipitated by an abrupt increase in plasma membrane permeability.
Using low-light digitized video microscopy, the onset, progression, and reversibility of anoxic injury were assessed in single hepatocytes isolated from fasted rats. Cell-surface bleb formation occurred in three stages over 1-3 h after anoxia. Stage I was characterized by formation of numerous small blebs. In stage II, small blebs enlarged by coalescence and fusion to form a few large terminal blebs. Near the end of stage II, cells began to swell rapidly, ending with the apparent breakdown of one of the terminal blebs. Breakdown of the bleb membrane initiated stage III of injury and was coincident with a rapid increase of nonspecific permeability to organic cationic and anionic molecules. On reoxygenation, stages I and II were fully reversible, and plasma membrane blebs were resorbed completely within 6 min of reoxygenation without loss of viability. Stage III, however, was not reversible, and no morphological changes occurred on reoxygenation. The results indicate that onset of cell death owing to anoxia is a rapid event initiated by a sudden increase of nonspecific plasma membrane permeability caused by rupture of a terminal bleb. Anoxic injury is reversible until this event occurs.


[The cerebral hemodynamics in patients with humeroscapular periarthritis under the influence of decimeter waves and deresinated naphthalan].
110 patients with scapulohumeral periarthritis of vertebrogenic origin were exposed to decimetric waves or received salt-free naphthalan. There were also patients who got combined treatment with decimetric waves and salt-free naphthalan. REG recorded positive shifts in cerebral hemodynamics due to these factors utilization.


Ferromagnetic ordering and metamagnetism in malonate bridged 3D diamond-like and honeycomb-like networks: [Cu(mal)(DMF)]n and [[Cu(mal)(0.5pyz)].H2O]n (mal = Malonate Dianion, DMF = N,N-dimethylformamide, pyz = Pyrazine).
Two three-dimensional (3D) malonate bridged networks, [Cu(mal)(DMF)](n) (1) and [[Cu(mal)(0.5pyz)].H(2)O](n) (2), have been synthesized in H(2)O-DMF solution. Compound 1 exhibits ferromagnetic ordering below 2.6 K (T(c)), and 2 displays a metamagnetic behavior below 3.2 K (T(N)).


Hypersensitivity to 35% carbon dioxide in patients with adult separation anxiety disorder.
Adults with panic disorder (PD) and children with separation anxiety disorder (CSAD) show higher reactivity to CO(2). Our hypothesis was patients with adult separation anxiety disorder (ASAD) would show similar hypersensitivity to CO(2). In the present study, we determined whether sensitivity to CO(2) was enhanced in adult patients with separation anxiety disorder with no history of panic attacks. Patients with PD (n=38), adult separation anxiety disorder (ASAD) patients with no history of panic attacks (n=31), and healthy subjects (n=40) underwent a 35% CO(2) inhalation challenge procedure. Baseline and post-inhalation anxiety were assessed with the Acute Panic Inventory, Visual Analog Scale, and Anxiety Sensitivity Index-3 (ASI-3). As hypothesized the rate of CO(2)-induced panic attacks was significantly greater in PD and ASAD patient groups (55.3% and 51.6% respectively) than healthy comparison group (17.5%). Nine (69.2%) of 13 patients in PD group who have ASAD concurrent with PD had a CO(2)-induced panic attack. ASI-3 total scores were not different between PD and ASAD groups and both were significantly higher than controls. However, anxiety sensitivity did not predict the occurrence of panic attacks. The researchers were not blind to the diagnosis and there was no placebo arm for comparison. Besides, parameters of respiratory physiology were not evaluated. ASAD was associated with CO(2) hypersensitivity quite similar to PD. This finding partly unfolds the complex relationship of 'CSAD, PD, and CO(2) hypersensitivity' and indicates that CO(2) hypersensitivity and separation anxiety extend together beyond childhood.


Generating binomial coefficients in a row of Pascal's triangle from extensions of powers of eleven.
Sir Isaac Newton noticed that the values of the first five rows of Pascal's triangle are each formed by a power of 11, and claimed that subsequent rows can also be generated by a power of 11. Literally, the claim is not true for the 5 t h row and onward. His genius mind might have suggested a deep relation between binomial coefficients and a power of some integer that resembles the number 11 in some form. In this study, we propose and prove a general formula to generate the values in any row of Pascal's triangle from the digits of ( 1 0 ⋯ 0 ︸ Θ zeros 1 ) n . It can be shown that the numbers in the cells in n t h row of Pascal's triangle may be achieved from Θ + 1 partitions of the digits of the number ( 1 0 ⋯ 0 ︸ Θ zeros 1 ) n , where Θ is a non-negative integer. That is, we may generate the number in the cells in a row of Pascal's triangle from a power of 11, 101, 1001, or 10001 and so on. We briefly discuss how to determine the number of zeros Θ in relation to n, and then empirically show that the partition really gives us binomial coefficients for several values of n. We provide a formula for Θ and prove that the ( n + 1 ) t h row of Pascal's triangle is simply Θ + 1 partitions of the digits of ( 1 0 ⋯ 0 ︸ Θ zeros 1 ) n from the right.


A quantitative analysis of the effect of continuity of care on 30-day readmission and in-hospital mortality among patients with acute ischemic stroke.
Continuity of care is a core element of high-quality patient care in a primary care setting and one of a national priority. To assess and quantify the impact of continuity of care on 30-day readmissions, 30-day inpatient mortality, and hospital length of stay (LOS), among hospitalized patients with acute ischemic stroke disease. Observational retrospective cohort (n = 356,134) using a 2.75% random sample (n=1,036,753) from the State of Florida Agency for Health Care Administration (AHCA) database from 2006 to 2016. We assessed continuity of care using an integrated continuity of care CoC score, calculated by merging three standard indices of continuity of care - Bice-Boxerman Continuity of Care Index (COCI), Herfindahl Index (HI), and Usual Provider of Care (UPC) Index via a Principal Component Analysis (PCA). We measured 30-day hospital readmissions, 30-day inpatient mortality, and LOS. Our analysis revealed that hospital LOS was significantly affected by CoC. The statistically significant average treatment effect (ATEs), expressed in risk difference (RD), ranged between 0.27 [95%CI: (0.07, 0.48)] and 1.0 day [95%CI: (0.57, 1.43)]. A similar trend was observed for 30-day readmission (ATEs ranging from 0.0067 [95%CI: (0.0002, 0.0132) to 0.0071 [95%CI: (0.0005, 0.0136)]), and inpatient mortality (ATEs ranging from 0.0006 [95% confidence interval (CI): (0.0001, 0.0012)] to 0.0007 [95%CI: (0.0001, 0.0012)]). Our findings suggest a strong association between continuity of care and clinical outcomes. Continuity of care leads to a reduction in mortality, rehospitalization, and hospital length of stay.