Attenuation of epithelial-mesenchymal transition via SGLT2 inhibition and diabetic cataract suppression by dapagliflozin nanoparticles treatment.
Chronic hyperglycemia triggers overproduction of AKR1B1 (aldo-keto reductase family 1 member B) and receptor for advanced glycation end product (RAGE), which causes epithelial-mesenchymal transition (EMT) in the lens epithelial cells (LECs) of diabetic mellitus (DM) cataracts. However, it is unclear whether EMT in LECs is related to abnormal increase of SGLT2. Sodium glucose cotransporter 2 (SGLT2) inhibitor, also known as dapagliflozin (Dapa) can be used to treat diabetes. Here, we examined how Dapa or nano eye-drops (DapaN) reduce EMT in LECs of DM cataracts. The nano eye-drop provides an ophthalmic treatment that suppressed diabetic cataract progression and improved potency with reduced side effects. SD rats were injected with streptozocin (STZ) (65 mg/kg, ip), nano-Dapa drops (0.456 mg/10 ml/eye) or Dapa (1.2 mg/kg/day) treatment for 6-12 weeks. Immunofluorescence staining was used for protein quantification of RAGE, SGLT2, N-cadherin and E-cadherin in the LECs of rats. In this study, Dapa applies nanotechnology-based delivery system and it contains polyvinylpyrrolidone (PVP) and HPBCD. Dapa showed therapeutic effect on DM cataracts, wherein it targeted EMT biomarker, E-cadherin. The nano-Dapa drops or oral Dapa inhibited SGLT2, suppressed AKR1B1 expression, decreased AcSOD2- and RAGE-induced EMT in diabetic cataracts. Our findings suggest that nanotechnology-based Dapa eye drops (Dapa-PVP-HPBCD) can effectively improve solubility of Dapa in aqueous solution. Taken together, results suggest that the SGLT2-mediated DM cataract therapy may involve the AKR1B1-RAGE-AcSOD2-EMT pathway. The nano eye drops and Dapa show potential beneficial effects for cataract prevention. This study conveys new insights into cataract treatment and supplementation of nano-Dapa drops shows promising result in preventing diabetic cataracts.


Perspectives of nanofibrous wound dressings based on glucans and galactans - A review.
Wound healing is a complex and dynamic process that needs an appropriate environment to overcome infection and inflammation to progress well. Wounds lead to morbidity, mortality, and a significant economic burden, often due to the non-availability of suitable treatments. Hence, this field has lured the attention of researchers and pharmaceutical industries for decades. As a result, the global wound care market is expected to be 27.8 billion USD by 2026 from 19.3 billion USD in 2021, at a compound annual growth rate (CAGR) of 7.6 %. Wound dressings have emerged as an effective treatment to maintain moisture, protect from pathogens, and impede wound healing. However, synthetic polymer-based dressings fail to comprehensively address optimal and quick regeneration requirements. Natural polymers like glucan and galactan-based carbohydrate dressings have received much attention due to their inherent biocompatibility, biodegradability, inexpensiveness, and natural abundance. Also, nanofibrous mesh supports better proliferation and migration of fibroblasts because of their large surface area and similarity to the extracellular matrix (ECM). Thus, nanostructured dressings derived from glucans and galactans (i.e., chitosan, agar/agarose, pullulan, curdlan, carrageenan, etc.) can overcome the limitations associated with traditional wound dressings. However, they require further development pertaining to the wireless determination of wound bed status and its clinical assessment. The present review intends to provide insight into such carbohydrate-based nanofibrous dressings and their prospects, along with some clinical case studies.


Function of the cytoskeleton in gravisensing during spaceflight.
Since astronauts and cosmonauts have significant bone loss in microgravity we hypothesized that there would be physiological changes in cellular bone growth and cytoskeleton in the absence of gravity. Investigators from around the world have studied a multitude of bone cells in microgravity including Ros 17/2.8, Mc3T3-E1, MG-63, hFOB and primary chicken calvaria. Changes in cytoskeleton and extracellular matrix (ECM) have been noted in many of these studies. Investigators have noted changes in shape of cells exposed to as little as 20 seconds of microgravity in parabolic flight. Our laboratory reported that quiescent osteoblasts activated by sera under microgravity conditions had a significant 60% reduction in growth (p<0.001) but a paradoxical 2-fold increase in release of the osteoblast autocrine factor PGE2 when compared to ground controls. In addition, a collapse of the osteoblast actin cytoskeleton and loss of focal adhesions has been noted after 4 days in microgravity. Later studies in Biorack on STS-76, 81 and 84 confirmed the increased release of PGE2 and collapse of the actin cytoskeleton in cells grown in microgravity conditions, however flown cells under 1 g conditions maintained normal actin cytoskeleton and fibronectin matrix. The changes seen in the cytoskeleton are probably not due to alterations in fibronectin message or protein synthesis since no differences have been noted in microgravity. Multiple investigators have observed actin and microtubule cytoskeletal modifications in microgravity, suggesting a common root cause for the change in cell architecture. The inability of the 0 g grown osteoblast to respond to sera activation suggests that there is a major alteration in anabolic signal transduction under microgravity conditions, most probably through the growth factor receptors and/or the associated kinase pathways that are connected to the cytoskeleton. Cell cycle is dependent on the cytoskeleton. Alterations in cytoskeletal structure can block cell growth either in G1 (F-actin microfilament collapse), or in G2/M (inhibition of microtubule polymerization during G2/M-phase). We therefore hypothesize that microgravity would inhibit growth in either G1, or G2/M.


The effect of the Americans with Disabilities Act on economic well-being of men with disabilities.
This paper estimates the effect of the Americans with Disabilities Act (ADA) on the economic well-being of working-age (20-62) men with disabilities by fitting a fixed-effects model to the U.S. Survey of Income and Program Participation (SIPP) panel data. This paper constructs a new and alternative measure of disability utilizing rich information on limitations to functional activities (FA), activities of daily living (ADL), and instrumental activities of daily living (IADL). The new objective measure of disability identifies a larger group of people as being disabled than conventional self-reported measure. Probability of employment for disabled men fell 5.8% compared to nondisabled men significantly at the 5% level. Log-real-wages of men with disabilities fell 5.3% relative to men without disabilities significantly at the 10% level.


Complete Genome Sequence of Paenibacillus polymyxa SQR-21, a Plant Growth-Promoting Rhizobacterium with Antifungal Activity and Rhizosphere Colonization Ability.
Here we report the complete genome sequence of a plant growth-promoting rhizobacterium (PGPR), Paenibacillus polymyxa SQR-21, which consists of one circular chromosome of 5,828,438 bp with 5,024 coding sequences (CDS). The data presented highlight multiple sets of functional genes associated with its plant-beneficial characteristics.


Nursing comes of age in South Korea--with an American Maryknoller's help.
Maryknoll Sister Patricia Conroy devoted 20 years to the nursing profession in South Korea. Through her work with the Maryknoll Junior College of Nursing in Busan and with the Korean Nurses Association she was instrumental in changing the traditional, Western-oriented nursing curriculum to a course of study more suited to South Korea's present community health needs.


Acute Intestinal Obstruction: A 1-Year Prospective Audit into Causes.
Intestinal obstruction is a common general surgical emergency with high morbidity and mortality. Its aetiology varies widely between and within geographic regions, with gender, age, and time. Obstructed inguinal hernia is still considered the most common cause of intestinal obstruction in Sub-Saharan Africa and other low-income countries, but its incidence appears to be on the decrease as other causes of intestinal obstruction become more common in a particular society. To examine the spectrum of causes of intestinal obstruction in a tertiary hospital in southern Nigeria and compare the results with earlier studies in the region and Nigeria. A cross sectional, single-hospital study of adults diagnosed with and having clinical and radiological features of acute intestinal obstruction. Seventy patients were enrolled in the study, comprising of 35 (50%) males and 35 (50%) females, M:F = 1:1. The mean patient age was 44.8 years. Two peak age incidences of intestinal obstruction were observed in the 36-45 and 56-65 years age groups. Post-operative adhesion 13 (18.5%), obstructed external abdominal hernia 13 (18.5%), colonic cancer 11 (16%), and intussusception seven (10%) were the primary causes of intestinal obstruction. Obstructed inguinal hernia was commonly encountered in males while adhesions and colonic cancers were common in females. Obstructed external abdominal hernias and post-operative adhesion are at par as the main primary causes of intestinal obstruction. Colon cancer and intussusception are increasingly causing more obstructions.


Cardiac allograft vasculopathy in a long-term follow-up after heart transplantation: Role of remnant cholesterol in residual inflammation.
Cardiac allograft vasculopathy (CAV) is a major prognosis limiting factor in heart transplantation (HTx). Disease development and progression are influenced by multiple determinants, but the role of remnant cholesterol (RC) in CAV has not yet been investigated. Therefore, the present study aimed to assess the prevalence of CAV in a very long-term follow-up after orthotopic HTx and to examine the role of RC in residual inflammation despite secondary prevention. Herein, is a retrospective analysis of patient data collected at the last follow-up visit in an outpatient setting. Additionally, RC levels were calculated based upon cholesterol profile. The study population consisted of 184 patients with a mean follow-up of 15.0 ± 6.8 years. More than 40% of the overall cohort had CAV at last follow-up. The mean RC was 27.1 ± 14.7 mg/dL. Patients with CAV had significantly elevated RC despite intensified statin treatment (p = 0.018). A positive correlation was observed between RC and interleukin-6 as a marker of residual inflammation. Elevated RC and prolonged follow-up emerged as significant factors related to CAV in a multivariate analysis (odds ratio [OR] 2.9, 95% confidence interval [CI] 1.5-5.5, p = 0.001 and OR 3.3, 95% CI 1.4-7.7, p = 0.006, respectively), whereas mycophenolate mofetil was inversely associated with CAV (OR 0.4, 95% CI 0.2-0.9, p = 0.034). Remnant cholesterol has proinflammatory properties and is associated with CAV development in HTx. Thus, RC should be concerned as an additional tool for risk assessment.


Human biomonitoring of microplastics and health implications: A review.
Microplastics (MPs) are plastic particles (<5 mm) ubiquitous in water, soil, and air, indicating that humans can be exposed to MPs through ingestion of water and food, and inhalation. This review provides an overview of the current human biomonitoring data available to evaluate human exposure and health impact of MPs. We compiled 91 relevant studies on MPs in human matrices and MPs toxicological endpoints to provide evidence on MPs distribution in the different tissues and the implications this can have from a health perspective. Human exposure to MPs has been corroborated by the detection of MPs in different human biological samples including blood, urine, stool, lung tissue, breast milk, semen and placenta. Although humans have clearance mechanisms protecting them from potentially harmful substances, health risks associated to MPs exposure include the onset of inflammation, oxidative stress, and DNA damage, potentially leading to cardiovascular and respiratory diseases, as well as cancer, as suggested by in vitro and in vivo studies. Based on compiled data, MPs have been recurrently identified in different human tissues and fluids, suggesting that humans are exposed to MPs through inhalation and ingestion. Despite differences in MPs concentrations appear in exposed and non-exposed people, accumulation and distribution pathways and potential human health hazards is still at an infant stage. Human biomonitoring data enables the assessment of human exposure to MPs and associated risks, and this information can contribute to draw management actions and guidelines to minimize MP release to the environment, and thus, reduce human uptake.


Do different types of stress differentially alter behavioural and neurobiological outcomes associated with depression in rodent models? A systematic review.
Cataloguing the effects of different types of stress on behaviour and physiology in rodent models has not been comprehensively attempted. Here, we systematically review whether chronic exposure to physical stress, psychosocial stress, or both types of stress can induce different behavioural and neurobiological outcomes in male and female rodents. We found that physical stress consistently increased depressive-like behaviour, impaired social interaction and decreased body weight, while psychosocial stress consistently increased both anxiety- and depressive-like behaviour, impaired social interaction and learning and memory, increased HPA axis activity, peripheral inflammation and microglial activation, and decreased hippocampal neurogenesis in male rodents. Moreover, we found that the combined effect of both stress types resulted in a more severe pathological state defined by increased anxiety- and depressive-like behaviour, impaired social interaction and learning and memory, increased HPA axis activity and central inflammation, and reduced hippocampal neurogenesis and neural plasticity in male rodents. Phenotypes for females were less consistent, irrespective of the type of stress exposure, on account of the limited number of studies using females. This review highlights that the type of stress may indeed matter and will help animal researchers to more appropriately choose a stress/depression model that fits their research purposes.


Plasma Kynurenine to Tryptophan Ratio Is Not Associated with Undernutrition in Adults but Reduced after Nutrition Intervention: Results from a Community-Based Study in Bangladesh.
Infections and persistent immunological activation are linked to increased kynurenine (KYN) and the KYN-to-Tryptophan (TRP) or KT ratio and may be critical factors in undernutrition. We sought to determine the association between the KT ratio and adult malnutrition, as well as investigate if nutritional supplementation had any influence on the decrease of the KT ratio. A total of 525 undernourished adults aged 18-45 years were recruited and provided a nutrition intervention for 60 feeding days. TRP and KYN concentrations were determined from plasma samples using LC-MS/MS. At baseline, the median (interquartile range (IQR)) TRP, KYN and KT ratios were 24.1 (17.6, 34.3) µmol/L, 0.76 (0.53, 1.18) µmol/L and 30.9 (24.5, 41.7), respectively. Following intervention, the median (IQR) KYN and KT ratios were significantly reduced to 0.713 (0.46, 1.12) µmol/L and 27.5 (21.3, 35.8). The KT ratio was found to be inversely linked with adult BMI (coefficient: -0.09; 95% CI: -0.18, 0.004; p-value = 0.06) but not statistically significant. Additionally, Plasma CRP was correlated positively, while LRP1 was inversely correlated with the KT ratio. Our data suggest that in Bangladeshi adults, the KT ratio is not related to the pathophysiology of malnutrition but correlated with inflammatory and anti-inflammatory biomarkers, and the ratio can be reduced by a nutrition intervention.


Novel thiophenyl C-aryl glucoside SGLT2 inhibitors as potential antidiabetic agents.
Novel thiophene C-aryl glucoside SGLT2 inhibitors were designed and synthesized. Two different types of thiophene derivatives were readily prepared. Among the compounds tested, ethylphenyl at the distal ring 71p showed the best in vitro inhibitory activity in this series to date (IC(50)=4.47 nM) against SGLT2.


Effectiveness of Aromatherapy for Relief of Pain, Nausea, and Vomiting after Percutaneous Nephrolithotomy: A Randomized Controlled Trial.
Postoperative pain, nausea, and vomiting are common side effects of percutaneous nephrolithotomy. Nowadays, non-pharmacological and complementary therapies have been noticed. Therefore, a study was conducted to determine the effectiveness of lavender and clary sage on the pain, nausea, and vomiting after percutaneous nephrolithotomy. This is a randomized clinical trial study on 79 patients undergoing percutaneous nephrolithotomy. Patients were randomly divided into three groups of lavender aromatherapy (n = 27), clary sage aromatherapy (n = 26), and a control group (n = 26). Each of the intervention groups received the inhalation aromatherapy immediately and 3 and 6 h after the operation. Pain, nausea, and emetic episodes in patients of the three groups were measured before the intervention and 30 min after each intervention using a visual analog scale and checklist. Pain decreased significantly in the clary sage aromatherapy group. Nausea had a downward trend in the two groups of aromatherapy. The lavender aromatherapy group had the lowest incidence of emetic episodes compared to the other groups. Regarding the annoying pain, nausea, and vomiting after percutaneous nephrolithotomy for patients, and taking into account the complications of drug therapy, the use of complementary non-pharmacological methods can help increase the comfort of patients.


Clostridium perfringens type A enterotoxin induces release of noradrenaline from the neurosecretory PC12 cell line.
Clostridium perfringens type A enterotoxin(500 ng/ml) induced extensive release of noradrenaline (1/3-2/3 of the total cell content) from PC12 cells in 2-4 min in the presence, but not the absence of extracellular Ca2+. Cells treated with toxin in the absence of Ca2+ released noradrenaline promptly on subsequent addition of Ca2+ to the medium. The amount of noradrenaline released depended on the concentrations of both Ca2+ and toxin in the medium (ED50, 0.3 mM and 420 ng/ml respectively). Ca2+ could be replaced by Ba2+ or Sr2+, and Mn2+ or Co2+, which are Ca2+ channel blockers, did not inhibit the release of the transmitter. These findings are discussed in relation to the systemic effects of enterotoxin.


Injuries in a 1-day recreational cycling tour: Bike New York.
To describe injuries during a 1-day urban cycling tour. During the May 1996 "Bike New York" tour, we monitored EMS calls to identify injuries in a cohort of helmeted cyclists shielded from traffic. We collected demographic information from entry records, injury data from ambulance call reports, and follow-up on transported patients from telephone interviews with emergency physicians. Data were summarized using proportions, relative risks (RRs), 95% confidence intervals (CIs), and chi2 RESULTS: Approximately 28,000 cyclists participated, of which 23,502 (84%) were officially registered. Sixty-eight percent of registered bicyclists were male, and 92% were between 18 and 55 years old. Of the 140 EMS calls made during the tour, 136 (97%) involved participants; this yielded an injury incidence of 5 per 1,000 riders, or 12 to 13 per 100,000 person-miles. Injury was more common among younger cyclists (RR=1.4 for age </=35 years versus age >35 years; 95% CI, 1.0 to 2.0; P <.05), and possibly women (RR=1.3; 95% CI,.9 to 1.8; P =.11). Injuries were mostly minor, but there were 7 concussions and 6 clavicle fractures; none of the 140 injuries was fatal. Thirty-eight calls resulted in ED transport, and 5 of these patients were admitted. Although EMS units were evenly distributed along the route, most EMS calls occurred in only 3 of the 7 zones (P <.001). Injuries during the largest 1-day US cycling tour were uncommon. More data are needed to determine the relative importance of injury risk factors. Data collection during mass events may help guide distribution of EMS personnel.


Anti-apoptotic effects of diosgenin on ovariectomized hearts.
The anti-apoptotic effects of diosgenin, a steroid saponin, on hearts in female with estrogen deficiency have been less studied. This study aimed to evaluate the anti-apoptotic effects of diosgenin on cardiac widely dispersed apoptosis in a bilateral ovariectomized animal model. A total of 60 female Wistar rats, aged 6-7 months, were divided into the sham-operated group (Sham), bilateral ovariectomized rats for 2 months, and ovariectomized rats administered with 0, 10, 50, or 100 mg/kg diosgenin daily (OVX, OVX 10, OVX 50, and OVX 100, respectively) in the second month. The excised hearts were analyzed by H&E staining, TUNEL(+) assays and Western Blot. Cardiac TUNEL(+) apoptotic cells, the levels of Fas ligand, Fas death receptors, Fas-associated death domain, active caspase-8, and active caspase-3 (FasL/Fas-mediated pathways) as well as the levels of Bax, Bad, Bax/Bcl2, Bad/p-Bad, cytosolic Cytochrome c, active caspase-9, and active caspase-3 (mitochondria-initiated pathway) were increased in OVX compared with Sham group but those were decreased in OVX 50 compared with OVX. Diosgenin appeared to prevent or suppress ovariectomy-induced cardiac FasL/Fas-mediated and mitochondria-initiated apoptosis. These findings might provide one of the possible therapeutic approaches of diosgenin for potentially preventing cardiac apoptosis in women after bilateral ovariectomy or women with estrogen deficiency.


Preventive ear care for dogs and cats.
Prevention of ear disease in dogs and cats depends on early detection of factors that predispose these animals to otitis externa. This article reviews the conditions and diseases that place the dog and cat at risk for otitis externa. Routine care of the ears is discussed, and otoscopic examination and techniques for cleaning the external auditory canals are described. Avoidance of potentially harmful therapeutic procedures and irritating or ototoxic pharmacologic substances is emphasized.


[Monitoring techniques in cytomegalovirus infection in solid organ transplant recipients].
The availability of antiviral drugs for cytomegalovirus (CMV) in clinical practice, along with advances in methods of laboratory diagnosis, has substantially alleviated the negative effects of CMV infection in solid organ transplant recipients. Nevertheless, CMV continues to be a significant cause of morbidity and mortality in these patients. Virological monitoring plays a crucial role in controlling these negative consequences. Several diagnostic techniques are now available but not all are applicable in the transplant setting, nor are they all suitable for different clinical situations. Selection of a particular method depends on the clinical objective, the technical profile of the test and the possibilities of the laboratory. Serological tests are useful during pretransplant evaluation of both donor and candidates, the most suitable for this purpose being those that detect IgG antibodies. After transplantation, methods for determining CMV viral load are the cornerstone of diagnosis, prognosis (e.g., as a guide for preemptive therapy), and antiviral treatment monitoring, as well as a first alert on the emergence of drug resistant mutants. The pp65 antigenemia test remains useful as a measure of CMV viral load, but molecular assays are progressively replacing antigenemia in most laboratories because of technical issues. Despite advances in methodological standardization, no reference breakpoint values for viral load interpretation are available, and each center should obtain these values based on their own experience.


Effects of radiation on inherited sterility in the European grapevine moth (Lobesia botrana).
The sterile insect technique (SIT) is an alternative, environmentally friendly method for controlling insect pests. In the Lepidoptera, a low dose of gamma irradiation causes inherited sterility (SIT-IS), leading to full sterility in females but only partial sterility in males, which successfully compete with wild males for mates. This study examined the effect of a low radiation dose (150 Gy) on the fitness parameters of male and female Lobesia botrana, a polyphagous and major pest of vineyards found in the Middle East, Europe and the Americas. Irradiation of the pupae did not affect their emergence rate, flight ability out of a cylinder, male response to sex pheromone in a field cage or male or female mating success. A major effect of irradiation was observed in the significantly reduced number of irradiated females' offspring reaching pupation, and as a consequence a limited number of F2 offspring. The effect of irradiation on male partial sterility (also called inherited sterility) was reflected in the male-biased sex ratio of F1 offspring of irradiated males, the reduced number of F1 offspring and the very low number of F2 descendants. This study demonstrates the feasibility of controlling L. botrana using SIT-IS. Adding this method to the arsenal of environmentally friendly tools to control this pest may assist in further reducing the use of insecticides on edible crops.


Latest hypertension research to inform clinical practice in Asia.
Despite the challenges associated with the coronavirus pandemic, the last 2 years have been active periods for hypertension research and initiatives in Asia. There are new hypertension guidelines from the World Health Organization that can be interpreted and applied locally. This is also the case for data from the latest Blood Pressure Lowering Treatment Trialists' Collaboration meta-analysis, which showed that greater reductions in systolic blood pressure (BP) are associated with lower risks of cardiovascular events. The randomized controlled Strategy of Blood Pressure Intervention in the Elderly Hypertensive study and the Salt Substitute and Stroke Study provide local data to inform practice. Other initiatives to help reduce high salt intake in Asia are also underway. Both drug-resistant and nocturnal hypertension are appropriate areas of focus in Asia, and there are an increasing number of pharmacological and non-pharmacological treatment options for these conditions. Digital therapeutics to promote uptake and implementation of lifestyle interventions are showing promise, and other digital-based strategies such as telemedicine, wearable BP monitors to detect beat-by-beat BP and artificial intelligence will no doubt become integral parts of future strategies to reduce the burden of hypertension and hypertension-related disease. A number of initiatives from the Hypertension Cardiovascular Outcome Prevention and Evidence in Asia Network and Japanese Society of hypertension are underway, and there is good reason for optimism regarding the ongoing and future management of hypertension in Asia based on these and the active research activities in the region.


Metagenomic profiling of ammonia- and methane-oxidizing microorganisms in two sequential rapid sand filters.
Elevated concentrations of ammonium and methane in groundwater are often associated with microbiological, chemical and sanitary problems during drinking water production and distribution. To avoid their accumulation, raw water in the Netherlands and many other countries is purified by sand filtration. These drinking water filtration systems select for microbial communities that mediate the biodegradation of organic and inorganic compounds. In this study, the top layers and wall biofilm of a Dutch drinking water treatment plant (DWTP) were sampled from the filtration units of the plant over three years. We used high-throughput sequencing in combination with differential coverage and sequence composition-based binning to recover 56 near-complete metagenome-assembled genomes (MAGs) with an estimated completion of ≥70% and with ≤10% redundancy. These MAGs were used to characterize the microbial communities involved in the conversion of ammonia and methane. The methanotrophic microbial communities colonizing the wall biofilm (WB) and the granular material of the primary rapid sand filter (P-RSF) were dominated by members of the Methylococcaceae and Methylophilaceae. The abundance of these bacteria drastically decreased in the secondary rapid sand filter (S-RSF) samples. In all samples, complete ammonia-oxidizing (comammox) Nitrospira were the most abundant nitrifying guild. Clade A comammox Nitrospira dominated the P-RSF, while clade B was most abundant in WB and S-RSF, where ammonium concentrations were much lower. In conclusion, the knowledge obtained in this study contributes to understanding the role of microorganisms in the removal of carbon and nitrogen compounds during drinking water production. We furthermore found that drinking water treatment plants represent valuable model systems to study microbial community function and interaction.


Suppression of CpG-ODN-mediated IFNα and TNFα response in human plasmacytoid dendritic cells (pDC) by cannabinoid receptor 2 (CB2)-specific agonists.
Plasmacytoid dendritic cells (pDC) compose 0.2-0.5% of circulating leukocytes but play a significant role in mounting host immune responses. Elevated and chronic activation of pDC are implicated in autoimmune disease like systemic lupus erythematosus and rheumatoid arthritis. Δ9-tetrahydrocannabinol (THC) is a well characterized cannabinoid with potent anti-inflammatory activity, but acceptance of THC as a treatment for autoimmune disorders has been hindered due to psychotropic activity. The psychotropic effects of THC are mediated through cannabinoid receptor 1 (CB1) expressed in the central nervous system while the immunomodulatory effects of THC result from THC binding to CB1 and CB2 on immune cells. Synthetic CB2-selective agonists have been developed to explore immune modulation by cannabinoids in the absence of psychotropic effects. The goal of these studies was to determine if the CB2-selective agonists, JWH-015 and JWH-133, have comparable efficacy to THC in modulating IFNα and TNFα responses by primary human pDC. Treatment with JWH-133 and JWH-015 inhibited CpG-induced IFNα and TNFα responses by pDC. Further, the phosphorylation of IRF7, TBK1, NFκB, and IKKγ, key events in pDC activation, were suppressed by THC, JWH-133, and JWH-015. Likewise, the phosphorylation of AKT at the S473 and T308 residues were differentially modulated by treatment with THC and both JWH compounds. Collectively, these results demonstrate the potential for CB2 targeted therapeutics for treatment of inflammatory conditions involving aberrant pDC activity.


[Psychopathological and hormonal manifestations of alcoholic intoxication and emotional stress in monkeys].
Ethological approach to studying mature P. hamadryas and M. mulatta males has revealed a wide spectrum of changes in individual and zoosocial behaviour in response to the administration of different alcohol doses and stress stimuli. It has been established that neuroendocrine basis for the depression of psychic and locomotor activities developing in conditions of alcohol intoxication and emotional stress is an extremely high release of catecholamines and the increase of glucocorticoid secretion accompanied by a sharp decrease in androgen products. It should be noted that the exposure to stress stimuli during consumption of small alcohol doses intensifies depression-like stress-induced behaviour of monkeys.


Chest PET/MRI in Solid Cancers: Comparing the Diagnostic Performance of a Free-Breathing 3D-T1-GRE Stack-of-Stars Volume Interpolated Breath-Hold Examination (StarVIBE) Acquisition With That of a 3D-T1-GRE Volume Interpolated Breath-Hold Examination (VIBE) for Chest Staging During Whole-Body PET/MRI.
Whole-body positron emission tomography/magnetic resonance imaging (WB-PET/MRI) is increasingly used in oncology. However, chest staging remains challenging. To compare the diagnostic performance of a free-breathing 3D-T1-GRE stack-of-stars volume interpolated breath-hold examination (StarVIBE) with that of a 3D-T1-GRE volume interpolated breath-hold examination (VIBE) during WB-PET/MRI for chest staging. Retrospective, cohort study. One hundred and twenty-three patients were referred for initial staging of solid cancer, 46 of whom had pulmonary nodules and 14 had pulmonary metastasis. Free-breathing 3D-T1-GRE stack-of-stars (StarVIBE) and Cartesian 3D-T1-GRE VIBE at 3.0 T. Image quality was assessed using a 4-point scale and using the signal-to-noise ratio (SNR) of lung parenchyma and contrast-to-noise ratio (CNR) of pulmonary nodules. Diagnostic performances of both sequences were determined by three independent radiologists for detection of pulmonary nodules, lymph node involvement, and bone metastases using chest CT, pathology, and follow-up as reference standards. Paired Student's t-test; chi-squared; Fisher's exact test. A P value <0.05 was considered statistically significant. StarVIBE quality was judged as better in 34% of cases and at least equivalent to VIBE in 89% of cases, with significantly higher quality scores (4 [4-4] vs. 3 [3-4], respectively). SNR and CNR values were significantly higher with StarVIBE (8 ± 1.3 and 9.7 ± 4.6, respectively) than with VIBE (1.8 ± 0.2 and 5.5 ± 3.3, respectively). Compared to VIBE, StarVIBE showed significantly higher sensitivity (73% [95% CI 62-82] vs. 44% [95% CI 33-55], respectively) and specificity (95% [95% CI 88-99] vs. 67% [95% CI 56-77]) for pulmonary nodules detection and significantly higher sensitivity (100% [95% CI 89-100] vs. 67% [95% CI 48-82], respectively) for detection of lymph node involvement. Sensitivities for bone metastases detection were not significantly different (100% [95% CI 88-100] vs. 82% [95% CI 63-94], P = 0.054). Owing to improved SNR and CNR and spatial resolution, a free-breathing 3D stack-of-stars T1-GRE sequence improves chest staging in comparison with standard 3D-T1-GRE VIBE and may be integrated in WB-PET/MRI acquisitions for initial staging of solid cancer. 3 TECHNICAL EFFICACY: Stage 2.


A sulfate reducing bioreactor controlled by an electrochemical system enables near-zero chemical treatment of metallurgical wastewater.
Metallurgical wastewaters are characterized by a low pH (<4), high concentrations of sulfate (15 gSO42- L-1), and metal(loid)s. Current treatment requires the consumption of chemicals such as alkali and high levels of waste sludge generation. In this study, we have shown that combining water electrolysis and sulfate reducing bioreactors enables the in-situ generation of base and H2, eliminating the need for base and electron donor addition, resulting in the near-zero treatment of metallurgical wastewater. By extracting cations from the effluent of the system to the bioreactor, the bioreactor pH could be maintained by the in-situ production of alkali. The current for pH control varied between 112-753 mol electrons per m³ wastewater or 5-48 A m-2 electrode area. High concentrations of sulfate in the influent and addition of CO2 increased the current required to maintain a steady bioreactor pH. On the other hand, a high sulfate reduction rate and increased influent pH lowered the current required for pH control. Moreover, the current efficiency varied from 14% to 91% and increased with higher pH and cation (Na+, NH4+, K+, Mg2+, Ca2+) concentrations in the middle compartment of the electrochemical cell. The salinity was lowered from 70-120 mS cm-1 in the influent to 5-20 mS cm-1 in the system effluent. The energy consumption of the electrochemical pH control varied between 10 and 100 kWh m-3 and was affected by the conductivity of the wastewater. Industrial wastewater was treated successfully with an average energy consumption of 39 ± 7 kWh m-3, removing sulfate from 15 g SO42- L-1 to 0.5 ± 0.5 g SO42- L-1 at a reduction rate of 20 ± 1 gSO42- L-1 d-1..Metal(loid)s such as As, Cd, Cu, Pb, Te, Tl, Ni and Zn were removed to levels of 1-50 µg L-1.


A thermal stereoscope for surface reconstruction of the diabetic foot.
We have constructed a thermal stereoscope utilizing three digital SLR cameras and an infrared camera for rapid surface reconstruction of diabetic foot geometry and temperature distribution. A structured light pattern is projected on to the foot to provide approximately 2500 reconstructed points. The reconstructed point cloud is then fitted to a finite element model, producing root mean squared errors of less than 0.4 mm.


Glycemic Control Among People With Diabetes in Ontario: A Population-Based Cross-Sectional Study.
Our aim in this study was to determine the distribution of glycated hemoglobin (A1C) in the Ontario diabetes population and identify subgroups with a high risk of poor glycemic control. In this cross-sectional study, we used real-world clinical data linked with health-care administrative data to identify all people with prevalent diabetes on December 31, 2019. We then identified their most recent A1C result during the year. The distribution of A1C was assessed, and the proportion of those with an A1C of >8.0% was determined, stratified by various sociodemographic and clinical characteristics. In the population of 1,009,938 individuals with diabetes, mean ± standard deviation A1C was 7.2±1.4%, with 43.4% of them having an A1C of >7.0% and 19.0% with an A1C of >8.0%. Younger age, remote location of residence, longer diabetes duration and other surrogates for diabetes severity were associated with poor control. The mean A1C among people with diabetes in Ontario was 7.2%, but nearly 20% had an A1C of >8%. There were notable disparities in glycemic control that identified several high-risk groups, including younger people, people with longer disease duration and people living in remote areas. Better clinical and policy approaches are needed to improve diabetes care for these populations.


Control of ketogenesis from amino acids. III. In vitro and in vivo studies on ketone body formation lipogenesis and oxidation of tyrosine by rats.
Ketone body formation from tyrosine was studied in rat liver in vitro with special references to the activities of tyrosine aminotransferse (EC 220.127.116.11) and p-hydroxyphenylpyruvate hydroxylase (EC 18.104.22.168). Liver was obtained from rats which had been given a high protein diet or cortisol to induce various levels of tyrosine aminotransferase. The enzyme activities of the preparations were plotted against the amounts of ketone body formed from tyrosine. It was found that over a low range of tyrosine aminotransferase activities, activity was proportional to the amount of ketone body formed. However, above this range, ketone body formation ceased to increase and p-hydroxyphenylpyruvate started to accumulate. This inhibition of ketone body formation and accumulation of the p-hydroxyphenylpyruvate could be prevented by addition of ascorbate. These results suggest that the primary factor regulating metabolism of tyrosine in vitro is tyrosine aminotransferase and when the activity of this is high so that it is no longer rate limiting, p-hydroxyphenylpyruvate hydroxylase becomes the rat limiting step because its activity is inhibited by the accumulation of p-hydroxyphenylpyruvate. For in vivo studies rats were given a high protein diet or cortisol to induce various levels of tyrosine aminotransferase and then injected with a tracer dose of [U- or 1- 14C]tyrosine. Then their respiratory 14CO2 and the incorporation of 14C into total lipids of liver were measured. The amounts of radioactivity in CO2 and lipids were found to be proportional to the tyrosine aminotransferase activity and were not affected by the free tyrosine concentration in the liver. After injection of [U- 14C]acetate the radioactivities in CO2 and lipids were not proportional to the tyrosine aminotransferase activity. These results indicate that the enzyme activity also regulates tyrosine metabolism in vivo. In vivo studied gave no evidence of the participation of p-hydroxyphenylpyruvate hydroxylase in regulation of tyrosine metabolism.


Haplotype characterization of transcribed ovine major histocompatibility complex (MHC) class I genes.
The ovine major histocompatibility complex (MHC) remains poorly characterized compared with those of other livestock species. Molecular genetic analysis of the bovine MHC has revealed considerable haplotype and allelic diversity that earlier serological analysis had not detected. To develop cellular and molecular tools to support development of vaccines against intracellular pathogens of sheep, we have undertaken a molecular genetic analysis of four distinct ovine MHC haplotypes carried by two heterozygous Blackface rams. We have identified 12 novel class I transcripts and used a class I sequence-specific genotyping system to assign each of these transcripts to individual haplotypes. Using a combination of phylogenetic analysis, haplotype and transcript expression data, we identified at least four distinct polymorphic class I MHC loci, three of which appear together in a number of combinations in individual haplotypes. The haplotypes were further characterized at the highly polymorphic Ovar-DRB1 locus, allowing selection of the progeny of the two founder rams for the establishment of an MHC-defined resource population.


Renin-angiotensin system blockers affect cognitive decline in Parkinson's disease: The PPMI dataset.
To explore the potential clinical effects of renin-angiotensin system blocker (RASB, angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs)) in patients from the Parkinson's Progress Marker Initiative (PPMI) study database. One hundred and seven untreated, newly diagnosed PD patients with hypertension, from the PPMI were included. We measured cognitive performance, biomarkers in CSF, and magnetic resonance imaging (MRI) during the five follow-up years for patients exposed or not to renal-angiotensin system blockers. Sixteen PD patients with hypertension underwent [18F]florbetaben positron emission tomography (PET) scanning. SUVRs of region of interest (ROI) were calculated and compared within different groups. Treatment with ARBs but not ACEIs improved global cognitive function evaluated by MoCA score in PD patients with hypertension compared to other hypertensive medicines up to 5 years follow up. Specifically, ARBs improved visuospatial, memory, executive abilities, processing speed attention test scores in PD. There was no significant impact of ARBs on α-syn, tau, Aβ in CSF. RASBs reduced [18F] florbetaben uptake in cortex and subcortex nuclei in the brain. These results show potential protective effect with ARBs in cognitive impairment of parkinson's disease with hypertension.


Glycogen metabolism in the rat visceral yolk sac. I. Glycogen content and gestational age.
The glycogen content of the rat visceral yolk sac was determined between 13.5 and 20.5 days of gestation by the best available colorimetric method. The concentration of glycogen in the tissue increased ten-fold between 13.5 and 18.5 days, to reach a value similar to that for mammalian muscle, but then decreased by 50 per cent between 18.5 and 20.5 days. Determination of the iodine-iodide spectra and fractionation of the glycogen particles by a novel sodium citrate centrifugation method indicated broad similarities between the structures of glycogen particles, isolated by a mild phenol-water method, from the yolk sac and the liver of the rat. However, the proportion of 'high'-molecular-weight glycogen in the yolk sac increases between 18.5 and 20.5 days, as a result of the preferential loss of 'low'-molecular-weight glycogen, so that at term the proportion approaches that found in liver glycogen.


A novel method in the removal of impacted mandibular third molar: buccal drainage.
Food impaction after impacted mandibular third molar extraction is a serious problem that should not be ignored. Incomplete suturing of the distal incision in the conventional method is the main cause of food impaction and delayed wound healing. The present study introduces a novel suture and drainage technology that requires hermetic suturing of the distal incision and rubber drainage for buccal drainage. 76 patients with horizontally/mesially impacted third molars (bilateral) were enrolled in this prospective study. An impacted tooth on one side of each patient was extracted by occlusal drainage using the conventional method, whereas the other side tooth was extracted by buccal drainage using the novel method. The differences in wound healing, facial swelling, bleeding and dry socket between the two sides of each patient were compared postoperatively, and the trends for patient selection of the surgical method were also compared. The results indicated that buccal drainage had obvious advantages in wound healing and reduced the risk of postoperative bleeding, and most patients preferred this technique; there were no significant differences in postoperative facial swelling or pain. Thus, buccal drainage can solve the problem of long-term food impaction induced by traditional incision postoperatively and is worthy of clinical promotion.


The Arabidopsis B-BOX protein BBX25 interacts with HY5, negatively regulating BBX22 expression to suppress seedling photomorphogenesis.
ELONGATED HYPOCOTYL5 (HY5) is a basic domain/leucine zipper (bZIP) transcription factor, central for the regulation of seedling photomorphogenesis. Here, we identified a B-BOX (BBX)-containing protein, BBX25/SALT TOLERANCE HOMOLOG, as an interacting partner of HY5, which has been previously found to physically interact with CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1). BBX25 physically interacts with HY5 both in vitro and in vivo. By physiological and genetic approaches, we showed that BBX25 is a negative regulator of seedling photomorphogenesis. BBX25 and its homolog BBX24 regulate deetiolation processes and hypocotyl shade avoidance response in an additive manner. Moreover, genetic relationships of bbx25 and bbx24 with hy5 and cop1 revealed that BBX25 and BBX24 additively enhance COP1 and suppress HY5 functions. BBX25 accumulates in a light-dependent manner and undergoes COP1-mediated degradation in dark and light conditions. Furthermore, a protoplast cotransfection assay showed that BBX24 and BBX25 repress BBX22 expression by interfering with HY5 transcriptional activity. As HY5 binds to the BBX22 promoter and promotes its expression, our results identify a direct mechanism through which the expression of BBX22 is regulated. We suggest that BBX25 and BBX24 function as transcriptional corepressors, probably by forming inactive heterodimers with HY5, downregulating BBX22 expression for the fine-tuning of light-mediated seedling development.


Life cycle variation and regulation of macronuclear DNA content in Tetrahymena thermophila.
The mean DNA content of G2 macronuclei varies during the life cycle of the ciliate Tetrahymena thermophila. Early in the life cycle the mean is about 130 C; later it is about 94 C. In hybrids between strains A and B the decrease from 130 C to 94 C usually began after 60 fissions after conjugation. In B X B clones the decrease was complete by 50 fissions. The data suggest that there may be a genetic difference between strains A and B with respect to the onset of the decrease in DNA content. The downward regulation of the mean DNA content appears to be related to the mechanism which removes the variance in macronuclear DNA content which is added to macronuclei by unequal macronuclear division. Unequal macronuclear division regularly occurs at all stages of the life cycle, with larger macronuclei tending to divide more unequally. In the absence of regulation, unequal macronuclear division would constantly add variance to G1 macronuclei and their range would continue to increase. Analysis of the variances of G1 and G2 macronuclei suggests that at all stages of the life cycle the added variance is removed by acting upon nuclei which become too small or too large. According to this model, macronuclei with smaller amounts of DNA are regulated upward by an extra macronuclear S phase, while larger amounts are regulated downward by chromatin extrusion and the skipping of macronuclear S. The mean DNA content appears to change during the life cycle because the thresholds at which macronuclei become too small or too large are readjusted. It is postulated that these thresholds are a function of gene dosage.


Genetic variability in response to dietary calcium.
Supplemental dietary calcium has been shown to reduce blood pressure in spontaneously hypertensive rats while restricted calcium diets cause an elevation in blood pressure. This latter nutrient effect has been enhanced by modest sodium restriction and is associated with a reduction in serum ionized calcium concentration. To determine whether alterations of dietary calcium and sodium have a similar influence on blood pressure in genetically normotensive rats, Fisher 344, Wistar Furth, and ACI rats were fed either a low (0.1%) calcium, low (0.25%) sodium diet or normal (1.0%) calcium, normal sodium (0.45%) diet from 4 weeks of age through 29 weeks of age. Indirect measurements of systolic blood pressure showed that only the Fisher 344 rats consistently responded to the low calcium/low sodium diets with an elevation of blood pressure. There was considerable variation in serum electrolytes across strains in the normal diets but all three strains experienced a reduction in ionized calcium and an elevation in phosphorus and magnesium on the restricted diets. In the Fisher 344 rats there were significant (p less than .05) inverse correlations among systolic blood pressure and serum ionized and total calcium concentrations and positive correlations among systolic blood pressure, phosphorus, and magnesium. There was no significant correlation between serum electrolytes and blood pressure in the other two strains. The data indicate that there is genetic variability in the blood pressure response to alterations in dietary calcium and sodium. The pattern of change in serum electrolytes across strains suggests that diet-induced alterations of serum electrolytes, specifically calcium, are not necessarily predictive of a pressor response. It would appear that some other calcium-sensitive physiological process involved in blood pressure regulation must respond differentially to calcium availability across strains.


Monitoring indoor air quality using smart integrated gas sensor module (IGSM) for improving health in COPD patients.
Technology advancement, industrialisation, and globalisation have been significant reasons for air pollution outdoors and indoors. It may surprise us that we spend about 80% of our time indoors breathing toxic, stale, polluted air, making us sluggish and fretful. In contrast to outdoor air, indoor air does not recycle consistently. It traps and builds pollutants from wood and coal stoves, furniture and building materials, paints and solvents, cigarette smoke, and cleaning supplies. The prolonged exposure to these hidden pollutants can prompt respiratory disorders such as lung disease, pneumonitis, asthma, pulmonary hypertension, and chronic obstructive pulmonary disease (COPD). It is enduring and is not curable, which has been a threat to humanity for ages. COPD's major cause is airborne particulate matter and other toxic compounds emitted from indoor and outdoor sources. Outdoor air pollution can be controlled only by acquiring changes in the vast population, wherein for indoor, every individual may create a major impact on improving air purity, thereby promoting health. The proposed design model for monitoring indoor air quality was tested in a normal and stimulating environment where we live. Parameters tested included temperature, humidity, amount of PM2.5, and the concentration of CO, CO2, and NH3. These parameters were monitored for five to 6 h per day for 8 days. Results indicate that the total air quality lies in the moderate range. Further study will be helpful to utilise this module as an effective Indoor air quality (IAQ) monitoring system. HIGHLIGHTS: • A simple, effective, inexpensive integrated gas sensor module (IGSM) has been proposed in this study to monitor the indoor air quality index (IAQI). • Indoor air quality was tested in a normal and stimulating environment for 8 days. • The integrated gas sensor module (IGSM) was composed of sensors in series, and the outputs for the respective parameter were measured easily. • Among the parameters tested, CO and PM2.5 lie in the moderate range, while other pollutants within the normal range reveal that the tested air quality is moderate.


Dry eye syndrome in benign essential blepharospasm.
To determine the significance of dry eye syndrome in benign essential blepharospasm. Retrospective consecutive case series. One hundred and forty-four patients (288 eyes) with benign essential blepharospasm. All subjects had Schirmer I tear tests. Those scores were analysed as a function of patient age, sex, and blepharospasm severity. Individual Schirmer-test scores in both eyes of all patients. A total of 144 eligible subjects (mean age±SD: 68.3±11.5 years; 76% females) were evaluated. Benign essential blepharospasm was significantly associated with female sex (P=0.0044). The mean Schirmer-test value was 5.9±7.5 (median: 2.5) mm; it was <15mm for 86.8% of the patients and <10mm for 75%, with no difference observed between men and women (P=0.27). Dry-eye syndrome severity was not correlated with age at diagnosis, for men (r=-0.22, P=0.22) or women (r=-0.067, P=0.49), or benign essential blepharospasm severity (P=0.15), but was strongly associated with benign essential blepharospasm independently of age, sex or blepharospasm intensity. Dry-eye syndrome and benign essential blepharospasm are strongly linked, independently of age, sex or BEB severity, and should be considered for the diagnosis of benign essential blepharospasm. The useful symptomatic treatment of dry eye will not cure the blepharospasm or the ocular pain, and specific treatment for blepharospasm is required, i.e., quarterly injections of botulinum toxin A into the orbicularis oculi muscle.


Implementation of a pan-European ecosystem and an interoperable platform for Smart and Healthy Ageing in Europe: An Innovation Action research protocol.
As life expectancy continues to increase in most EU Member States, smart technologies can help enable older people to continue living at home, despite the challenges accompanying the ageing process. The Innovation Action (IA) SHAPES 'Smart and Healthy Ageing through People Engaging in Supportive Systems' funded by the EU under the Horizon 2020 Research and Innovation Programme (grant agreement number 857159) attends to these topics to support active and healthy ageing and the wellbeing of older adults. This protocol article outlines the SHAPES project's objectives and aims, methods, structure, and expected outcomes. SHAPES seeks to build, pilot, and deploy a large-scale, EU-standardised interoperable, and scalable open platform. The platform will facilitate the integration of a broad range of technological, organisational, clinical, educational, and social solutions. SHAPES emphasises that the home is much more than a house-space; it entails a sense of belonging, a place and a purpose in the community. SHAPES creates an ecosystem - a network of relevant users and stakeholders - who will work together to scale-up smart solutions. Furthermore, SHAPES will create a marketplace seeking to connect demand and supply across the home, health and care services. Finally, SHAPES will produce a set of recommendations to support key stakeholders seeking to integrate smart technologies in their care systems to mediate care delivery. Throughout, SHAPES adopts a multidisciplinary research approach to establish an empirical basis to guide the development of the platform. This includes long-term ethnographic research and a large-scale pan-European campaign to pilot the platform and its digital solutions within the context of seven distinct pilot themes. The project will thereby address the challenges of ageing societies in Europe and facilitate the integration of community-based health and social care. SHAPES will thus be a key driver for the transformation of healthcare and social care services across Europe.


Ecophysiological studies on the utilization of food in the paddy field grasshopper Oxya velox.
The paddy field grasshopper Oxya velox fed ad libitum on fresh leaves of the grass Digitaria is reared in the laboratory from hatching to death. A female grows to a maximum size of 218±40 mg wet weight on the 240th day, while a male attains a maximum of 132±17 mg weight on the 149th day. Total food intake amounts to 1341 and 557 mg dry grass for a single female and a single male respectively. Feeding rate averages 167 mg wet grass/g wet weight of grasshopper/day. Assimilation efficiency amounts to 27% in both sexes. Unassimilable faeces amount to 1 g for a female and 0.4 g for a male. About 32% of the assimilated food is used for total growth in either sex. Exuviae amount to 4% and 5% of the assimilated food in the female and the male respectively. The average amount of (dry) body substance used for reproduction is 82 mg in fertilized and 10 mg in the parthenogenetic female. A fertilized female consumes more food than a virgin. A female produces 3.5, egg pods on a average, each containing about 4 eggs. About 14% of the assimilated food energy is required for reproduction by a female and 3% by a male. At death the male contains 26% and the female 12% of the assimilated food energy respectively. The energy budget of O. velox is discussed in comparisn with that of Bombyx mori, a lepidopteran.


Chemical facility risks to natural flooding hazards in the United States.
Toxic release inventory (TRI) facilities contain chemicals, most must be kept in process equipment, otherwise leaks are possible. An analysis of the National Flood Hazard Layer and TRI facilities within ArcGIS. The national analysis included TRI facilities intersecting the 100-year floodplain based on the National Flood Hazard Layer. The frequency which TRI facilities are impacted by flooding was analyzed with federal declarations data. We were able to determine what percentage of each state's facilities fall into the floodplain and calculate and assign a risk number to each state.


Pharmacological inhibition of protease-activated receptor-2 reduces crescent formation in rat nephrotoxic serum nephritis.
Glomerular crescent formation is a hallmark of rapidly progressive forms of glomerulonephritis. Thrombosis and macrophage infiltration are features of crescent formation in human and experimental kidney disease. Protease-activated receptor-2 (PAR-2) is a G-protein coupled receptor that links coagulation and inflammation. This study investigated whether pharmacological inhibition of PAR-2 can suppress glomerular crescent formation in rat nephrotoxic serum nephritis (NTN). Disease was induced in Wistar Kyoto rats by immunisation with sheep IgG followed by administration of sheep nephrotoxic serum. Rats (n = 8/group) received the PAR-2 antagonist (GB88, 10 mg/kg/p.o.), vehicle or no treatment starting 3 days before nephrotoxic serum injection and continuing until day 14. Vehicle and untreated rats developed thrombosis and macrophage infiltration in the glomerular tuft and Bowman's space in conjunction with prominent crescent formation. Activation of JNK signalling and proliferation in parietal epithelial cells was associated with crescent formation. GB88 treatment significantly reduced crescent formation with a substantial reduction in glomerular thrombosis, reduced macrophage infiltration in Bowman's space, and reduced activation of parietal epithelial cells. However, GB88 did not protect against the development of proteinuria, renal function impairment, inflammation or tubular cell damage in the NTN model. In conclusion, PAR-2 plays a specific role in glomerular crescent formation by promoting glomerular thrombosis, macrophage accumulation in Bowman's space and activation of parietal epithelial cells.


IgA nephropathy relapse following COVID-19 vaccination treated with corticosteroid therapy: case report.
The flare of immune-mediated disease following coronavirus disease of 2019 (COVID-19) vaccination is a rare adverse event following immunization. De novo, as well as relapsing IgA nephropathy (IgAN) cases, have been reported following either mRNA-1273 (Moderna) or BNT162b2 (Pfizer-BioNTech) vaccination. To our knowledge, the majority of IgAN relapses did not result in severe acute kidney injury (AKI) and resolved spontaneously. This is a case of a 54-year-old female with a previous diagnosis of IgAN who developed IgAN relapse following the second dose of Moderna vaccine. Gross hematuria developed 2 days after vaccination, which was accompanied by significant AKI. Kidney biopsy showed mild tubular atrophy and IgA staining in mesangium without crescent formation. Significant improvement in serum creatinine (Cr) was observed on day 10 after initiating prednisone. Cr came back to normal within 3 months after initiating corticosteroid. COVID-19 vaccination is associated with a flare of IgAN that may cause significant AKI. Steroid therapy is associated with recovery. IgAN flare after COVID-19 vaccination should be closely monitored to elucidate any adverse effect associated with the novel vaccine.


Internet use in the bariatric surgery patient population.
Many patients rely on the Internet for gathering medical information. Bariatric patients appear to explore the Internet for information regarding weight loss surgery. This investigation studied the hypothesis that Internet use is common among the bariatric population. From Oct 1 to Dec 31, 2003, every patient who visited our bariatric clinic was asked to fill out a questionnaire. This survey contained questions concerning use of the Internet and E-mail. Of the 127 respondents, 89% owned a computer, had Internet access, and had an E-mail address. 85% of the patients had searched the Internet for bariatric information, and 98% of these patients (91/93) found the information useful. Of the patients who had access to the Internet, 36% searched for information about the hospital, 40% about the clinic, and 54% about the surgeon. Most of the patients believed that all doctors and all clinics should be available via E-mail (88% and 92% respectively). Most patients who come to a bariatric clinic are Internet savvy. It is helpful for bariatric surgeons and clinics to post information about themselves on the Internet and to be available via E-mail.


Expression of recombinant mouse sperm protein sp56 and assessment of its potential for use as an antigen in an immunocontraceptive vaccine.
Recombinant mouse sp56 protein was produced for testing as an antigen in an immunocontraceptive vaccine. The coding sequence for the mature sp56 protein was cloned into the bacterial expression system pFLAG using a PCR-based method on mouse testis cDNA. Polyclonal antisera were raised in mice against affinity purified recombinant sp56 fusion protein (sp56FLAG) or an artificial sp56 peptide fused to a carrier protein (KLH) and shown to cross-react to a protein band of 75 kD in detergent extracts of mouse sperm by Western immunoblot analysis under reducing conditions. The antisera to sp56FLAG also immunolocalized over the entire acrosome of mouse sperm. Female BALB/c mice were immunized intraperitoneally with sp56FLAG in a fertility trial with 20 microg sp56FLAG in Freund's Complete Adjuvant and boosted three to five times with 20 microg sp56FLAG in Freund's Incomplete Adjuvant. Litter sizes of sp56FLAG-treated mice were significantly smaller than control-treated animals after five boosts.


Identification of a novel GR-ARID1a-P53BP1 protein complex involved in DNA damage repair and cell cycle regulation.
ARID1a (BAF250), a component of human SWI/SNF chromatin remodeling complexes, is frequently mutated across numerous cancers, and its loss of function has been putatively linked to glucocorticoid resistance. Here, we interrogate the impact of siRNA knockdown of ARID1a compared to a functional interference approach in the HeLa human cervical cancer cell line. We report that ARID1a knockdown resulted in a significant global decrease in chromatin accessibility in ATAC-Seq analysis, as well as affecting a subset of genome-wide GR binding sites determined by analyzing GR ChIP-Seq data. Interestingly, the specific effects on gene expression were limited to a relatively small subset of glucocorticoid-regulated genes, notably those involved in cell cycle regulation and DNA repair. The vast majority of glucocorticoid-regulated genes were largely unaffected by ARID1a knockdown or functional interference, consistent with a more specific role for ARID1a in glucocorticoid function than previously speculated. Using liquid chromatography-mass spectrometry, we have identified a chromatin-associated protein complex comprising GR, ARID1a, and several DNA damage repair proteins including P53 binding protein 1 (P53BP1), Poly(ADP-Ribose) Polymerase 1 (PARP1), DNA damage-binding protein 1 (DDB1), DNA mismatch repair protein MSH6 and splicing factor proline and glutamine-rich protein (SFPQ), as well as the histone acetyltransferase KAT7, an epigenetic regulator of steroid-dependent transcription, DNA damage repair and cell cycle regulation. Not only was this protein complex ablated with both ARID1a knockdown and functional interference, but spontaneously arising DNA damage was also found to accumulate in a manner consistent with impaired DNA damage repair mechanisms. Recovery from dexamethasone-dependent cell cycle arrest was also significantly impaired. Taken together, our data demonstrate that although glucocorticoids can still promote cell cycle arrest in the absence of ARID1a, the purpose of this arrest to allow time for DNA damage repair is hindered.


Preparation of electrospun nanofibers with desired microstructures using a programmed three-dimensional (3D) nanofiber collector.
The traditional electrospinning process produces dense two-dimensional (2D) nanofiber (NF) sheets that limit cell infiltration and proliferation. Our previous study demonstrated that 3D NF sheets could be formed on an NF collector surface mounted with multiple movable needles through the corona discharge. In this study, we developed a programmed electrospun 3D NF collector. It can precisely control the moving speed of NF collector during electrospinning; thereby fabricating 3D NFs with desired microstructures (pore size, pore volume, and interconnectivity). Four types of polycaprolactone (PCL) 3D NF matrices with different microstructures can be obtained concurrently on the NF collector surface, which are set by different forward moving speed of the NF collector device: NF-zero (no move, as control), NF-low (0.085 mm/min), NF-mid (0.158 mm/min) and NF-high (0.232 mm/min). A linear increase of the NF sheet thickness (from 0.21 mm to 0.91 mm) was recorded with accelerating collector movement. Quantitative analysis using scanning electron microscopy (SEM), micro-computed tomography (μ-CT), and confocal laser scanning microscopy (CLSM) showed a monotonic increase of pore size and porosity with the increase of collector moving speeds. The collector movement also impacted the crystallinity and mechanical properties of the NFs. When prepared at high collector speed, the NFs showed improved proliferation and differentiation (p < .05) of pre-osteoblastic MC3T3 cells compared to the NFs from the static collector. A programmed NF collector device allows for the reproducible, precise and continuous fabrication of 3D NFs with tailorable geometry and microstructures. This simple, controllable, one-step process could promote the clinical translation of electrospun NFs in tissue engineering and regenerative medicine.


Hemispherectomy for catastrophic epilepsy in infants.
To report our experience with hemispherectomy in the treatment of catastrophic epilepsy in children younger than 2 years. In a single-surgeon series, we performed a retrospective analysis of 18 patients with refractory epilepsy undergoing hemispherectomy (22 procedures). Three different surgical techniques were performed: anatomic hemispherectomy, functional hemispherectomy, and modified anatomic hemispherectomy. Pre- and postoperative evaluations included extensive video-EEG monitoring, magnetic resonance imaging, and positron emission tomography scanning. Seizure outcome was correlated with possible variables associated with persistent postoperative seizures. The Generalized Estimation Equation (GEE) and the Barnard's exact test were used as statistical methods. The follow-up was 12-74 months (mean, 34.8 months). Mean weight was 9.3 kg (6-12.3 kg). The population age was 3-22 months (mean, 11.7 months). Thirteen (66%) patients were seizure free, and four patients had >90% reduction of the seizure frequency and intensity. The overall complication rate was 16.7%. No deaths occurred. Twelve (54.5%) of 22 procedures resulted in incomplete disconnection, evidenced on postoperative images. Type of surgical procedure, diagnosis categories, persistence of insular cortex, and bilateral interictal epileptiform activity were not associated with persistent seizures after surgery. Incomplete disconnection was the only variable statistically associated with persistent seizures after surgery (p<0.05). Hemispherectomy for seizure control provides excellent and dramatic results with a satisfactory complication rate. Our results support the concept that early surgery should be indicated in highly selected patients with catastrophic epilepsy. Safety factors such as an expert team in the pediatric intensive care unit, neuroanesthesia, and a pediatric epilepsy surgeon familiar with the procedure are mandatory.


Hepatic metabolism of heme in rats after exposure to benzene, gasoline and kerosene.
delta-Aminolevulinic acid (ALA) synthetase, delta-ALA dehydratase and heme oxygenase activities were studied in the liver of albino rats, 3 and 20 h after i.p. administration of benzene, gasoline, and kerosene. delta-ALA synthetase activity was increased markedly after benzene administration, while gasoline and kerosene treated groups showed decreased enzyme activity. Inhibition of delta-ALA dehydratase activity was observed in all three groups, but heme oxygenase activity was unchanged.


CRISPR-Cas9-mediated seb1 disruption in Talaromyces pinophilus EMU for its enhanced cellulase production.
Filamentous fungi are working horses for industrial enzyme production. Combinatory approaches, such as random mutagenesis and rational genetic engineering, were adopted to improve their enzyme productivity. The filamentous fungus Talaromyces pinophilus EMU is a hyper cellulase-producing filamentous fungus obtained through random mutagenesis. This study further enhanced its cellulase production through the disruption of seb1 gene, which encodes Seb1, a transcription factor that binds to the stress response element (STRE) and regulates a variety of cellular processes. Gene seb1 was cloned from strain T. pinophilus EMU and disrupted using CRISPR-Cas9 technology. The seb1-disruptants (TpΔseb1 strains) showed distinct morphology from its parent strain. They presented a hyphal branching phenotype with decreased transcription levels of rhoA and ras1 genes involved in hyphal branching. Furthermore, TpΔseb1 strains displayed lower cell biomass, higher specific protein content, and 20%-40% enhancement in filter paper cellulase (FPase) activity, however, insignificant changes in the transcription levels of cbh1 and bgl1 genes involved in cellulase production. Through this study, we confirmed that seb1 gene disruption in T. pinophilus EMU caused more hyphal branching, reduced cell growth, increased protein secretion, and enhanced cellulase production. In addition, we successfully established the CRISPR-Cas9 genome-editing platform in T. pinophilus EMU.


A Study on Efficacy of Differences in Speech Therapy Duration in Vocal Outcomes of Benign Lesions of Vocal Cords After Conventional Microlaryngeal Surgery.
Introduction: Benign laryngeal lesions usually disrupt the microstructure in the vocal cords causing hoarseness of voice. This study analyses the success rate of voice therapy and factors contributing to better outcomes in surgical treatment of benign vocal fold lesions. Methods: Forty consecutive patients with benign vocal cord lesions complying with the inclusion and exclusion criteria were enrolled and divided into two groups A and B, such that one received speech therapy post surgery for 6 weeks and the other received speech therapy for 12 weeks respectively. Preoperatively all the patients were evaluated by voice fatigue index, GRBAS scale and videolaryngoscopy. Vocal fold relaxation exercises were given preoperatively for patients of both groups. After undergoing conventional microlaryngeal excision surgery, both groups of patients underwent subjective analysis by voice fatigue index, perceptual analysis by GRBAS scale and videolaryngoscopy in regular intervals. Speech therapy was started after 1 week of complete voice rest post operatively and patients were followed up at the end of 1 week, 2 months and 4 months from the date of surgery. Results: There is no statistical difference in characteristics of patients between the two groups. Improvement in the Voice fatigue index and GRBAS scale score is statistically the same in groups A and B. Conclusion: Speech therapy is an important part of voice rehabilitation following microlaryngeal surgery. The misconception that longer speech therapy duration leads to better outcomes did not hold true in this study. Speech therapy postoperatively with proper voice hygiene practices is sufficient to obtain a near normal voice. The online version contains supplementary material available at 10.1007/s12070-023-03780-8.


Observations on peritumoral oedema in meningioma. Part II: Mechanisms of oedema production.
Meningiomas occurring in 160 patients were studied in relation to oedema production using computerised tomography. Statistically significant positive correlations with oedema production were found with tumours of large surface area, anterior parasagittal position, prominent vascularity, involving dural sinuses, and with short clinical history. Significant negative correlations were found with small tumour size and the presence of calcification. It is considered that hydromechanical factors predominate in oedema production with meningioma.


Sister Mary Joseph's nodule originating from endometrial carcinoma incidentally detected during surgery for an umbilical hernia: a case report.
Umbilical metastasis (Sister Mary Joseph's nodule) is rare. It is encountered in 1-3% of patients with intra-abdominal and/or pelvic malignancy, with gastric carcinoma being the commonest origin in men and ovarian carcinoma-in women. Only 27 cases of Sister Mary Joseph's nodule originating from endometrial carcinoma have previously been documented in the literature. In a 51-year-old woman, a Sister Mary Joseph's nodule coexisting with a large fibroid uterus was incidentally detected during surgery for suspected strangulated umbilical hernia. Subsequent laparotomy confirmed endometrial carcinoma metastasizing to the umbilical region. This is the 28th case reported in the literature of Sister Mary Joseph's nodule originating from endometrial carcinoma and the first case of Sister Mary Joseph's nodule originating from endometrial carcinoma incidentally detected during surgery for umbilical hernia. Surgeons should be aware of the possibility of Sister Mary Joseph's nodule coexisting with an umbilical hernia.


Chemical and physical changes during storage of differently packed biscuits formulated with sunflower oil.
Various innovative materials are already present on the market, but there is scarce knowledge on their performances when used in real food system. In this study, two innovative packaging materials were investigated for the evaluation during storage of biscuits formulated with sunflower oil and compared to a traditional one. To this aim, three different flexible and composite film containing a metalized plastic layer and a paper layer were used. The control included orientated polypropylene (OPP), while the innovative materials contained poly-lactic acid or OPP with a pro-oxidant additive, ethylene vinyl acetate. The physical (moisture, water activity, hardness/crispness) and chemical (peroxide value, conjugated dienes and trienes, and hexanal and nonanal formation) changes of biscuits were monitored during accelerated storage (35 °C and 50% of relative humidity for 105 days). Packaging materials did not have significant impact on textural quality of biscuits. Instead remarkable differences were observed during storage in the evolution of different lipid oxidation compounds, moisture content and water activity among differently packed biscuits. A new ecofriendly packaging showed the best performances in terms of physico-chemical quality of biscuits. The obtained results provide useful information for industrial application.


Diclofenac sodium. A reappraisal of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy.
Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) advocated for use in painful and inflammatory rheumatic and certain non-rheumatic conditions. It is available in a number of administration forms which can be given orally, rectally or intramuscularly. Conveniently, dosage adjustments are not required in the elderly or in those patients with renal or hepatic impairment. The drug has a relatively short elimination half-life, which limits the potential for drug accumulation. In numerous clinical trials the efficacy of diclofenac is equivalent to that of the many newer and established NSAIDs with which it has been compared. As an analgesic it has a fast onset and long duration of action. When administered intramuscularly it is at least comparable to, and frequently superior to, many narcotic and spasmolytic combinations in renal and biliary colic. Extensive clinical experience has been gained with diclofenac, clearly establishing its safety profile. It is well tolerated compared with other NSAIDs and rarely produces gastrointestinal ulceration or other serious side effects. Thus, diclofenac can be considered as one of the few NSAIDs of 'first choice' in the treatment of acute and chronic painful and inflammatory conditions.


Direct Oral Anticoagulants vs Vitamin K Antagonists in Left Ventricular Thrombi: A Systematic Review and Meta-analysis.
There is increasing interest in direct oral anticoagulants (DOACs), given their safety and convenience in atrial fibrillation, compared with vitamin K antagonists (VKAs). However, the use of DOACs in left ventricular (LV) thrombi is considered off-label, with current guidelines recommending VKAs. The aim of this meta-analysis was to compare the safety and efficacy of DOACs to VKAs in the management of LV thrombi. A systematic search was conducted for studies published between January 1, 2009 and January 31, 2021 in PubMed, Embase, and CENTRAL. Included studies compared DOACs to VKAs for the treatment of LV thrombi and reported on relevant outcomes. Odds ratios (ORs) were pooled with a random-effects model. Sixteen cohort studies and 2 randomized controlled trials were identified, which included 2666 patients (DOAC = 674; VKA = 1992). Compared with VKAs, DOACs were associated with a statistically significant reduction in stroke (OR 0.63, 95% confidence interval [CI] 0.42-0.96; P = 0.03; I 2 = 0%). There were no significant differences in bleeding (OR 0.72, 95% CI 0.50-1.02; P = 0.07; I2 = 0%), systemic embolism (OR 0.77, 95% CI 0.41-1.44; P = 0.41; I2 = 0%), stroke or systemic embolism (OR 0.83, 95% CI 0.53-1.33; P = 0.45; I2 = 33%), mortality (OR 1.01, 95% CI 0.64-1.57; P = 0.98; I2 = 0%) or LV thrombus resolution (OR 1.29, 95% CI 0.83-1.99; P = 0.26; I2 = 56%). Within the context of low-quality evidence, there was a statistically significant reduction in stroke among those treated with DOACs, without an increase in bleeding. There were no significant differences in systemic embolism, stroke or systemic embolism, mortality, or LV thrombus resolution, suggesting that DOACs may be a reasonable option for treatment of LV thrombi.


Development of a potential primary method for protein quantification via electrospray differential mobility analysis.
Accurate protein quantification is the basis for establishing the metrological traceability of in vitro diagnostics or drug products. In this study, we established and validated a potential primary method for protein quantification based on electrospray-differential mobility analysis coupled with a condensation particle counter (ES-DMA-CPC). The analytical performance of this method was assessed using the certified reference material NIMCmAb, and the uncertainty of measurement was evaluated. The method was applied to the quantification of three other protein reference materials and one highly purified protein, including myoglobin, bovine serum albumin, IgG monoclonal antibody, and one highly purified fibrinogen, with a molecular weight range between 17 kDa and 340 kDa. In addition, when compared with isotope dilution mass spectrometry (IDMS) and UV‒VIS spectrophotometry approaches, the ES-DMA-CPC method showed good agreement with IDMS method for the quantification of these protein reference materials. Our proposed method provided an accurate quantification of proteins, especially those with large molecular weights. Moreover, our method could be a potential primary method for protein quantification and serve as a complement to IDMS method.


Impact of COVID-19 and restricted self-help group attendance on drinking behavior among people with alcohol use disorder: Results of a nationwide cross-sectional survey.
Concerns regarding symptom severity and the risk of relapse among people seeking recovery from alcohol use disorder (AUD) have been raised since the onset of the COVID-19 pandemic. Owing to preventive measures implemented during the pandemic (social distancing or lockdown), self-help group (SHG) meetings were restricted. However, the impact of deprivation of onsite recovery meetings on drinking behavior and risk among SHG members with AUD remains unclear. We examined the proportion of SHG members who reported drinking and their reasons for drinking during the early stages of the pandemic and the effect of nonattendance at onsite recovery meetings on drinking behavior during the early pandemic period, stratified by gender. A national cross-sectional survey of Japanese SHG members was conducted to measure self-reported alcohol consumption, sociodemographic characteristics, AUD diagnosis, treatment status, SHG meeting attendance, membership duration, psychological distress, and health-related variables. Of 6478 SHG members, 2955 (male: n = 2678; female: n = 277; response rate: 46.7%) responded, and the responses were analyzed using a gender-stratified multivariate logistic regression model. Most participants reported having abstained from alcohol use, while 6% of the respondents reported having consumed alcohol during the early stages of the pandemic. The proportion of "drinkers" among women (10.5%) was significantly higher than that among men (5.9%; p = 0.012). Through multivariate model analysis, the factors associated with drinking during the pandemic were identified as psychological distress (among men and women) and not attending onsite recovery meetings (among men). Conversely, a longer duration of SHG membership was associated with less drinking during the pandemic for both genders. Most SHG members appear to have remained abstinent during the early stages of the COVID-19 pandemic. However, psychological distress in both genders and the inability to attend recovery meetings among men may have influenced drinking behavior.


A Phase 2a, Double-Blind, Placebo-controlled Randomized Trial of Inhaled TLR9 Agonist AZD1419 in Asthma.
Rationale: To examine the potential of TLR9 (Toll-like receptor 9) activation to modulate the type 2 immune response in asthma.Objectives: To evaluate efficacy and safety of AZD1419, an inhaled TLR9 agonist, in a phase 2a, randomized, double-blind trial.Methods: Adult patients with asthma with a history of elevated eosinophils (>250 cells/μl) were randomized 1:1 to receive 13 once-weekly doses of inhaled AZD1419 (1, 4, or 8 mg; n = 40) or placebo (n = 41). Inhaled corticosteroids and long-acting β2-agonist were tapered down and then discontinued. The last four doses of AZD1419 were given without maintenance medication, followed by a 40-week observation period. Primary endpoint was time to loss of asthma control (LOC).Measurements and Main Results: AZD1419 induced a T-helper cell type 1-type IFN response with a sustained reduction in markers of type 2 inflammation. However, there were no statistically significant differences between AZD1419 and placebo for time to LOC, proportion of patients with LOC, changes in Asthma Control Questionnaire-five-item version, exacerbations, reliever use, FEV1, peak expiratory flow, or fractional exhaled nitric oxide (FeNO). LOC was predicted by an early rise in FeNO in 63% of patients. Despite withdrawal of maintenance treatment, 24 patients completed the study without LOC; AZD1419 n = 11, placebo n = 13. Adverse events were balanced across groups, with no deaths or serious adverse events judged as causally related to AZD1419.Conclusions: AZD1419 was safe and well tolerated but did not lead to improved asthma control, despite reducing markers of type 2 inflammation. Results suggest that a novel accelerated step-down approach based on FeNO is possible for patients with well-controlled asthma.


Differentiation of peste des petits ruminants and rinderpest viruses by neutralisation indices using hyperimmune rinderpest antiserum.
Six field isolates believed to be rinderpest viruses and 2 known strains of peste des petits ruminants (PPR) viruses were titrated in the presence of normal rabbit serum and with hyperimmune rinderpest antiserum prepared in rabbits. The known PPR viruses had indices less than 10 whereas 4 of the suspect field isolates had indices greater than a hundred. Two suspect field isolates had indices less than 20; both were collected from small ruminant wild life and are probably PPR viruses.


Isoprene in urban Atlantic forests: Variability, origin, and implications on the air quality of a subtropical megacity.
Biosphere-atmosphere interactions play a key role in urban chemistry because of biogenic volatile organic compound (BVOC) emissions. Of the BVOC, isoprene is the most emitted compound; however, it also has anthropogenic origins in urban areas. In this study, we aimed to investigate the spatio-temporal variability and atmospheric impacts of biogenic and anthropogenic isoprene in the subtropical megacity of São Paulo (MASP), Brazil. Several measurement campaigns were conducted in three different urban Atlantic forests (Matão, PEFI, and RMG), and an urban background site (IAG); this equated to a total of 268 samples for the 2018-2019 period. For all sampling points, daytime average concentrations of isoprene were two to three times higher during the rainy season (IAG: 1.75 ± 0.93 ppb; Matão: 0.87 ± 0.35 ppb; PEFI: 0.50 ± 0.30 ppb; RMG: 0.37 ± 0.18 ppb), than those observed during the dry season (IAG: 0.46 ± 0.24 ppb; Matão: 0.31 ± 0.17 ppb; PEFI: 0.17 ± 0.11 ppb; RMG: 0.11 ± 0.07 ppb). Average isoprene concentrations were similar to those observed in other places worldwide, with the exception of the Amazon forest. Our results indicate differences in isoprene concentrations between sites, suggesting that environmental conditions such as the urban heat island and vegetation types, may play a role in spatial variability. Estimates of the isoprene fraction indicated that the biogenic fraction (85%) surpassed the anthropogenic fraction during the rainy season. By contrast, the anthropogenic fraction (52%) exceeded the biogenic fraction during dry periods. These fractions have an impact on potentially forming secondary pollutants gaseous (ozone formation potential: 7.19-33.32 μg m-3), and aerosols (secondary organic aerosols formation potential: 0.41-1.88 μg m-3). These results highlight the role of biogenic isoprene and its potential impact on urban air quality in subtropical megacities; this requires further investigation under future climate change scenarios.


An invasive zone in human liver cancer identified by Stereo-seq promotes hepatocyte-tumor cell crosstalk, local immunosuppression and tumor progression.
Dissecting and understanding the cancer ecosystem, especially that around the tumor margins, which have strong implications for tumor cell infiltration and invasion, are essential for exploring the mechanisms of tumor metastasis and developing effective new treatments. Using a novel tumor border scanning and digitization model enabled by nanoscale resolution-SpaTial Enhanced REsolution Omics-sequencing (Stereo-seq), we identified a 500 µm-wide zone centered around the tumor border in patients with liver cancer, referred to as "the invasive zone". We detected strong immunosuppression, metabolic reprogramming, and severely damaged hepatocytes in this zone. We also identified a subpopulation of damaged hepatocytes with increased expression of serum amyloid A1 and A2 (referred to collectively as SAAs) located close to the border on the paratumor side. Overexpression of CXCL6 in adjacent malignant cells could induce activation of the JAK-STAT3 pathway in nearby hepatocytes, which subsequently caused SAAs' overexpression in these hepatocytes. Furthermore, overexpression and secretion of SAAs by hepatocytes in the invasive zone could lead to the recruitment of macrophages and M2 polarization, further promoting local immunosuppression, potentially resulting in tumor progression. Clinical association analysis in additional five independent cohorts of patients with primary and secondary liver cancer (n = 423) showed that patients with overexpression of SAAs in the invasive zone had a worse prognosis. Further in vivo experiments using mouse liver tumor models in situ confirmed that the knockdown of genes encoding SAAs in hepatocytes decreased macrophage accumulation around the tumor border and delayed tumor growth. The identification and characterization of a novel invasive zone in human cancer patients not only add an important layer of understanding regarding the mechanisms of tumor invasion and metastasis, but may also pave the way for developing novel therapeutic strategies for advanced liver cancer and other solid tumors.


Economic issues in access to medications: schizophrenia treatment in England.
Mental health problems and the services to address them are currently receiving more attention in the UK than ever. Mental health care in England--indeed, across the UK--is experiencing a much needed transformation. It is therefore highly pertinent to examine the patterns of psychotropic medication use, given their intended links to recovery, rehabilitation, and reintegration, as well as to explore the economic and other factors that appear to influence those patterns. These are the aims of this paper. Our attention will be primarily focused on England. What this analysis shows is that given a higher profile by government, including additional funding (although not really benefiting differentially compared to other parts of the health service) and the first national service framework, it is possible to see changes in service patterns, access and (to a degree) outcomes. These changes are occurring at a time when new classes of psychotropic medication are being introduced in a range of therapeutic areas, contributing to the relatively rapid growth of take-up but also raising questions about appropriateness, effectiveness, cost-effectiveness and equity.


Clinical assessment of solid phase immunoadsorbent assay of human prostatic acid phosphatase.
A new solid phase immunoenzyme assay for human prostatic acid phosphatase was tested in clinical practice. Clearly elevated levels of prostatic acid phosphatase (PAP) were found with advancing age and even more so in patients with benign prostatic hyperplasia (BPH). In patients with localized carcinoma of the prostate there was no elevation of levels above those observed in patients with BPH. When lymph node metastases were found at staging lymphadenectomy, the preoperative level of prostatic acid phosphatase was elevated in 7 of 12 cases. Good response to hormone treatment of metastatic carcinoma of the prostate was indicated by decrease of PAP-levels to normal. Rising levels often preceded the clinical manifestation of progression.


Should a matched sibling donor still be considered the primary option for allogeneic hematopoietic cell transplantation in patients over 50 years of age with myelodysplastic syndrome?
Human leukocyte antigen (HLA)-matched sibling donors (MSDs) are the preferred choice for allogeneic hematopoietic cell transplantation (HCT). However, as myelodysplastic syndrome (MDS) is most frequently diagnosed in the elderly, MSDs are also likely to be of advanced age. It is unclear whether an MSD should be considered the primary choice for allogeneic HCT in elderly patients with MDS. We retrospectively compared survival and other outcomes in 1787 patients with MDS over 50 years of age and receiving allogeneic HCT between 2014 and 2020, using either MSD (n = 214), 8/8 allele-matched unrelated donor (MUD) (n = 562), 7/8 allele-MUD (n = 334), or unrelated cord blood (UCB) (n = 677) in Japan. In multivariate analysis, compared to MSD transplants, the risk of relapse was significantly lower following 8/8MUD transplants (hazard ratio [HR], 0.74; P = 0.047), whereas non-relapse mortality was significantly higher following UCB transplants (HR, 1.43; P = 0.041). However, donor type did not determine overall survival, disease-free survival, or graft-versus-host disease (GVHD)-free, relapse-free survival, but chronic GVHD-free, relapse-free survival was better after UCB (HR, 0.80; P = 0.025) and 8/8MUD (HR, 0.81; P = 0.032) compared to MSD transplants. Our study demonstrated that MSDs are not superior to alternative HCT methods, such as 8/8MUD, 7/8MUD, or UCB, in this population.


Vibrational analysis of α-cyanohydroxycinnamic acid.
In the present study, a comparative Raman vibrational analysis of alpha-cyano-4-hydroxycinnamic acid (4CHCA) and its derivative, alpha-cyano-3-hydroxycinnamic acid (3CHCA), was performed. The Raman spectra of the 4CHCA and 3CHCA in solid form were obtained and analyzed to determine differences between the two structurally similar derivatives. For comparison, the CHCA derivatives cyanocinnamic acid (CCA) and coumaric acid (CA) were also studied. The plausible vibrational assignments were made and matched with those obtained theoretically using density functional theory (DFT) based method employing a 6-31 g basis set. The computational wavenumbers obtained were in good agreement with the observed experimental results. This was the first reported Raman study of CCA, 3CHCA and 4CHCA.