A genetic polymorphism (rs17251221) in the calcium-sensing receptor gene (CASR) is associated with stone multiplicity in calcium nephrolithiasis.
Calcium nephrolithiasis is one of the most common causes of renal stones. While the prevalence of this disease has increased steadily over the last 3 decades, its pathogenesis is still unclear. Previous studies have indicated that a genetic polymorphism (rs17251221) in the calcium-sensing receptor gene (CASR) is associated with the total serum calcium levels. In this study, we collected DNA samples from 480 Taiwanese subjects (189 calcium nephrolithiasis patients and 291 controls) for genotyping the CASR gene. Our results indicated no significant association between the CASR polymorphism (rs17251221) and the susceptibility of calcium nephrolithiasis. However, we found a significant association between rs17251221 and stone multiplicity. The risk of stone multiplicity was higher in patients with the GG+GA genotype than in those with the AA genotype (chi-square test: P = 0.008; odds ratio = 4.79; 95% confidence interval, 1.44-15.92; Yates' correction for chi-square test: P = 0.013). In conclusion, our results provide evidence supporting the genetic effects of CASR on the pathogenesis of calcium nephrolithiasis.


The eye in the partial trisomy 2q syndrome.
Mandibulofacial dysostosis, mental retardation, skeletal, genital, and ocular malformations occurred in a family with partial trisomy of the long arm of chromosome 2. Translocations of chromatin material from the long arm of chromosome 2 to the short arm of chromosome 9 was balanced in the female carriers of the pedigree but was unbalanced among the males. Ocular signs in the males included uveal coloboma, anterior chamber angle anomalies as in Ringer's syndrome, congenital glaucoma with dislocated lens, exotropia, and blepharoconjunctivitis. These findings were related to an inherited malformation syndrome.


Detection of a Putative TetR-Like Gene Related to Mycobacterium bovis BCG Growth in Cholesterol Using a gfp-Transposon Mutagenesis System.
In vitro transposition is a powerful genetic tool for identifying mycobacterial virulence genes and studying virulence factors in relation to the host. Transposon shuttle mutagenesis is a method for constructing stable insertions in the genome of different microorganisms including mycobacteria. Using an IS1096 derivative, we have constructed the Tngfp, a transposon containing a promoterless green fluorescent protein (gfp) gene. This transposon was able to transpose randomly in Mycobacterium bovis BCG. Bacteria with a single copy of the gfp gene per chromosome from an M. bovis BCG::Tngfp library were analyzed and cells exhibiting high levels of fluorescence were detected by flow cytometry. Application of this approach allowed for the selection of a mutant, BCG_2177c::Tngfp (BCG-Tn), on the basis of high level of long-standing fluorescence at stationary phase. This BCG-Tn mutant showed some particular phenotypic features compared to the wild type strain, mainly during stationary phase, when cholesterol was used as a sole carbon source, thus supporting the relationships of the targeted gene with the regulation of cholesterol metabolism in this bacteria. This approach showed that Tngfp is a potentially useful tool for studying the involvement of the targeted loci in metabolic pathways of mycobacteria.


Flow cytometric analyses of the specific activation of peripheral blood mononuclear cells from healthy donors after in vitro stimulation with a fermented mistletoe extract and mistletoe lectins.
Immunostimulatory properties of mistletoe extracts derived from Viscum album L. (VAL) are well described, demonstrating activation especially of T, T-helper cells and monocytes/macrophages. In order to characterise in detail the communication between different cell populations, we studied mistletoe-induced expression of co-stimulatory signals and their ligands by flow cytometry. Peripheral blood mononuclear cells (PBMC) from 15 healthy controls were incubated for 7 days with a fermented VAL extract. VAL significantly upregulated the expression of the co-stimulatory molecule B7.1 (CD80) on monocytes/macrophages, but not B7.2 (CD86). No significant changes in the expression of either molecules on B cells could be found, suggesting that only monocytes/macrophages act as antigen presenting cells (APCs) in this in vitro system. Purified mistletoe lectins, components of most VAL extracts were also analysed, but did not induce similar responses of monocytes/macrophages. The receptor for B7 molecules, CD28, but not CTLA-4 (CD152), was also found to be significantly enhanced on CD4+ cells after VAL simulation. There was no evidence for activation of a B cell response via the CD40/CD40L pathway. Our data support the concept that stimulation by VAL extracts induces a specific T-helper cell reaction with monocytes/macrophages acting as APCs and purified lectins do not exert the same effects.


The effect of additional core stability exercises on improving dynamic sitting balance and trunk control for subacute stroke patients: a randomized controlled trial.
To examine the effect of core stability exercises on trunk control, dynamic sitting and standing balance, gait, and activities of daily living in subacute stroke patients. A randomized controlled trial. Inpatient rehabilitation hospital in two centres. Eighty patients (mean of 23.25 (±16.7) days post-stroke) were randomly assigned to an experimental group and a control group. Both groups underwent conventional therapy for five days/week for five weeks and the experimental group performed core stability exercises for 15 min/day. The patients were assessed before and after intervention. The Trunk Impairment Scale (Spanish-Version) and Function in Sitting Test were used to measure the primary outcome of dynamic sitting balance. Secondary outcome measures were standing balance and gait as evaluated via Berg Balance Scale, Tinetti Test, Brunel Balance Assessment, Postural Assessment Scale for Stroke (Spanish-Version), and activities of daily living using Barthel Index. The experimental group showed statistically significant differences for all of the total scale scores (P<0.05), except for the sitting section of the Brunel Balance Assessment. The mean (SD) difference between groups in Trunk Impairment Scale total score was 3.40 (±4.12) points, and its subscale dynamic sitting balance was 2.28 (±3.29). The Berg Balance Scale was 14.54 (±18.19) points, and the Barthel Index was 13.17 (±25.27) points. Collectively, these results were in favour of the experimental group. Core stability exercises in addition to conventional therapy improves trunk control, dynamic sitting balance, standing balance, gait and activities of daily living in subacute post-stroke patients.


Glucocorticoids up-regulate constitutive interleukin-10 production by human monocytes.
IL-10 plays an immunosuppressive role in inflammatory responses. Increased plasma levels of IL-10 have been detected in patients under glucocorticoid (GC) therapy, indicating that steroids may exert their suppressive effect, in part, by increasing IL-10 production. The aim was to define possible mechanisms by which steroids up-regulate IL-10 production. To this end, we have analysed ex vivo the effect of GCs on the constitutive production of IL-10 by lymphocytes and cells of myeloid origin. Monocytes and T cells were isolated by a Percoll gradient and B cells were purified by rosetting. Protein and mRNA IL-10 levels were determined by ELISA and by Northern blot, respectively. Monocytes, but not T or B cells, up-regulated the constitutive production of IL-10 following pre-treatment for at least 12 h with physiological doses of dexamethasone (Dex). Up-regulation of IL-10 occurred at both protein and mRNA levels, probably indicating that the effect of Dex was by incrementing gene transcription. Other steroids had similar outcomes, their effects being dose-related, proportional to the steroid potency and totally reversed by the steroid antagonist RU486. Thus, transcript levels of IL-10 were up-regulated by GCs probably through binding of the GC receptor to its specific glucocorticoid response element sequence in the IL-10 promoter. In contrast to monocytes, differentiated immature macrophages and dendritic cells did not vary their constitutive IL-10 production after pre-treatment with Dex. Our results support the fact that steroids up-regulate constitutive IL-10 production by selectively triggering activation signals on monocytes.


Impact of diffusion, ultrafiltration, and posture on total body electrical resistance in patients on hemodialysis.
Monitoring of hydration in patients on hemodialysis (HD) by currently available bioelectrical impedance analysis (BIA) methods is hampered by limited accuracy. This may be caused by changes in total body electrical resistance (TBER) that are induced by processes other than ultrafiltration (UF). To identify these sources of error, we examined the impact of UF, diffusion, and postural change (PC), separately. Extracellular TBER (TBERe) was measured by bioimpedance spectroscopy every 30 min in 23 patients on HD, for 2 h during diffusion-only (DO), followed by 2-h UF-only (UFO). The impact of PC from upright to semi-recumbent position was assessed by a 2-h TBERe measurement on the day after HD. TBERe increased by 23.5 ± 12.4 Ω (P < 0.001) during DO and by 40.0 ± 16.2 Ω (P < 0.001) during UFO. PC, evaluated on a separate day, was associated with an increase in TBERe of 27.6 ± 26.0 Ω (P < 0.001). TBERe changes during DO were mainly attributed to PC and to a lesser extent to electrolyte exchange. Extrapolation of the data to a conventional 4-h HD session indicates that about 32% of the total increase in TBERe is not related to UF. In conclusion, a significant part of the increase in TBER during HD is not related to UF but can be attributed to other processes such as the effects of PC and diffusion-related electrolyte exchange. These factors have to be taken into account when TBER-guided UF is considered.NEW & NOTEWORTHY Current BIA methods have limited accuracy in patients on HD. This may be related to the incorrect assumption that all changes in total body electrical resistance (TBER) are caused by changes in body water volumes. The present study indicates that two-thirds of the change in TBER during a conventional 4-h HD session can be attributed to fluid extraction, and that the remaining part is caused by other processes such as postural change and electrolyte exchange. This may cause volume prediction errors when not recognized.


Management of detrusor-external sphincter dyssynergia.
Detrusor-external sphincter dyssynergia (DSD) is a debilitating problem in patients with spinal cord injury. DSD carries a high risk of complications, and even life expectancy can be affected. The mainstay of treatment is the use of antimuscarinic medication and catheterization, but in those for whom this is not possible external sphincterotomy has been the traditional management route. External sphincterotomy, however, is associated with significant risks, including hemorrhage, erectile dysfunction and the need for repeat procedures, and over the last decade alternatives have been investigated, such as urethral stents and botulinum toxin injection. We present a review of DSD, including the current management strategies and prospects for future treatment.


Dialectics in carrier research: the ADP/ATP carrier and the uncoupling protein.
A concise review is given of the research in our laboratory on the ADP/ATP carrier (AAC) and the uncoupling protein (UCP). Although homologous proteins, their widely different functions and contrasts are stressed. The pioneer role of research on the AAC, not only for the mitochondrial but also for other carriers, and the present state of their structure-function relationship is reviewed. The function of UCP as a highly regulated H+ carrier is described in contrast to the largely unregulated ADP/ATP exchange in AAC. General principles of carrier catalysis as derived from studies on the AAC and UCP are elucidated.


Comparison of binding interaction between β-lactoglobulin and three common polyphenols using multi-spectroscopy and modeling methods.
Tea, coffee and fruit in dairy products are rich in polyphenols. The interaction mechanism between β-lactoglobulin (β-LG) and chlorogenic acid (CGA), ferulic acid (FA) and epigallocatechin-3-gallate (EGCG) was investigated. Fluorescence experiments proved that polyphenols quenched β-LG fluorescence strongly in static mode and EGCG had stronger binding affinity toward β-LG than CGA and FA. The main interaction force of EGCG binding with β-LG was different from CGA and FA. Furthermore, circular dichroism and fourier transform infrared data indicated that polyphenols changed β-LG secondary structure inducing a-helix to β-structures transition. The surface hydrophobicity of β-LG was also changed slightly by them according to surface hydrophobicity and particle size experiments. These results showed that the interaction mechanism of β-LG with phenolic acid esters was different from it with phenolic acids. Besides, polyphenols had impact on the structure and functionality of β-LG, which would be valuable in dairy processing industry.


Reinforcement of reciprocal inhibition by contralateral movements in man.
A reduction of flexor carpi radialis H reflex size was produced by submotor threshold stimulation of the radial nerve. This reduction reflects reciprocal inhibition exerted by the inhibitory IA interneuron. The effects of contralateral movements on IA reciprocal inhibition were studied in eight normal subjects. Active contralateral arm movement appeared to significantly increase the degree of reciprocal inhibition without affecting the unconditioned reflex. A minor enhancement of reciprocal inhibition was also noted after passive mobilization. Results are discussed in terms of contralateral segmental afferent fibers influencing IA interneuronal excitability. They strongly suggest that contralateral muscular IA afferents may reinforce reciprocal inhibition in man.


Amplification of olfactory signals by Anoctamin 9 is important for mammalian olfaction.
Sensing smells of foods, prey, or predators determines animal survival. Olfactory sensory neurons in the olfactory epithelium (OE) detect odorants, where cAMP and Ca2+ play a significant role in transducing odorant inputs to electrical activity. Here we show Anoctamin 9, a cation channel activated by cAMP/PKA pathway, is expressed in the OE and amplifies olfactory signals. Ano9-deficient mice had reduced olfactory behavioral sensitivity, electro-olfactogram signals, and neural activity in the olfactory bulb. In line with the difference in olfaction between birds and other vertebrates, chick ANO9 failed to respond to odorants, whereas chick CNGA2, a major transduction channel, showed greater responses to cAMP. Thus, we concluded that the signal amplification by ANO9 is important for mammalian olfactory transduction.


Properties and localization of phospholipase A2 activity in rat stomach.
In the glandular stomach of rat, phospholipase A2 activity was detected and characterized by the use of sonicated 1-acyl-2-[1-14C]oleoyl-sn-glycero-3-phosphocholine (1 mM in 200 mM glycylglycine buffer/2 mM CaCl2) as substrate. The specific activity was 4.9 X 10(-2) mumol/min per mg protein in the whole glandular stomach homogenate (n = 8). It showed individual variation among rats. The optimal pH was 8.0. The activity was relatively heat-resistant and calcium-dependent. More than 90% of phospholipase A2 activity was located in the corpus and less than 10% was in the antrum. In the corpus wall, which consists of mucosa, submucosa, muscularis externa and serosa, the mucosal part (mucosa and submucosa) contained 80-90% of total activity. The effect of some clinical agents (ulcerogenic and anti-ulcer agents) on the phospholipase A2 activity was examined. The activity in the corpus was inhibited by cimetidine (50% inhibition at 5 X 10(-3) M) and stimulated by indomethacin (50% stimulation at 5 X 10(-5) M). Cetraxate hydrochloride (10(-6)-10(-3) M), 16,16-dimethylprostaglandin E2 (10(-7)-10(-4) M) and dexamethasone (10(-7)-10(-3) M) had no effect.


Evaluation and management of thyroid incidentalomas detected prior to the parathyroid surgery.
We investigated the management of thyroid incidentalomas associated with cases of parathyroid lesions in order to suggest a practical approach to their management from a surgical point of view. 639 patients underwent radiological and ultrasound investigation of the thyroid area because of parathyroid disorders and parathyroidectomy and had at least three years of follow-up. All follow-up data for these cases were investigated from the moment the lesion was detected and up to the last report. Out of 639 cases, incidental or asymptomatic thyroid nodules were found in 179 patients (28%), of which, 22 patients were operated (parathyroidectomy + thyroidectomy) and 157 remained with the nodules. For these patients, the average period of follow-up was 7 years 5 mo. Following the results of the follow-up, 52 patients (33%) were suggested to have surgery of the thyroid gland and 49 were operated (16 total thyroidectomies and 33 hemithyroidectomies). The complications after the second surgery included recurrent laryngeal nerve palsy (n = 3), superior laryngeal nerve palsy (n = 1), permanent hypocalcaemia (n = 8), and surgical damage to the internal jugular vein (n = 1). All complications occurred at the previously operated side of the neck. While surgery remains the management of choice for malignant thyroid incidentalomas, for benign cases, if an asymptomatic thyroid nodule was detected inside the thyroid lobe on the side of planned parathyroidectomy and if the size of the nodule is ˃1.5 cm we suggest combined parathyroidectomy + hemithyroidectomy.


A technic for freezing an extremity in preparation for amputation.
Freezing of an extremity permits delay in amputation, and the time gained can be devoted to such intensive therapy as may be indicated. A safe, efficient, and convenient technic is described.


Impact of pseudoprogression and treatment beyond progression on outcome in patients with non-small cell lung cancer treated with immune checkpoint inhibitors.
Immune checkpoint inhibitors (ICI) have become an important treatment option for non-small cell lung cancer (NSCLC). We aimed to evaluate the clinical impact of pseudoprogression (PsP) and treatment beyond RECIST1.1-defined progressive disease (TBP) on outcome in NSCLC patients treated with ICI. NSCLC patients treated with ICI between Mar 2016 and July 2018 were recruited in a consecutive manner. Response was assessed every 8-12 weeks using RECIST1.1 and iRECIST. Based on iRECIST, PsP was defined as progressive disease (PD) on RECIST1.1 subsequently reset to non-PD categories. Using log-rank test, progression-free survival (PFS) was compared between patients with and without PsP, and overall survival (OS) was compared between patients treated with and without TBP. The impact of TBP on OS was evaluated through multivariate Cox proportional hazard models. Of the 189 patients, seven (3.7%) experienced PsP which mostly occurred approximately 3 months after baseline. The median PFS was significantly longer in patients with PsP (not reached) than those without PsP (3.8 months, P = .02). Among patients who demonstrated PD according to RECIST1.1, median OS was significantly longer in patients with TBP (17.2 months) than those without TBP (7.4 months, P < .001). On multivariate analysis adjusting other covariates, TBP (HR, 0.4; 95% CI, 0.2-0.7) remained as a significant protective factor for mortality. PsP occurred in 3.7% of NSCLC patients under ICI treatment. Based on iRECIST scheme, PsP and TBP may be associated with survival benefit.


Recurrent Anterior Non-necrotizing Scleritis as an Adverse Event of ChAdOx1 nCoV-19 (Vaxzevria) Vaccine.
To describe a case of anterior scleritis related to SARS-CoV-2 vaccine. SARS-CoV-2 vaccines appear safe; however vaccination has triggered thromboembolic events in predisposed patients. A retrospective case report of anterior scleritis in a woman following administration of both ChAdOx1nCoV-19 vaccine doses was studied by complete ophthalmologic examination and complementary tests. The patient has overcome SARS-CoV-2 infection a year prior. Ancillary tests including autoimmune and infectious diseases were negative. The chronology between ChAdOx1nCoV-19 vaccine and the sequential episodes of scleritis may have a cause-and-effect relationship. Ophthalmologists may be aware of scleritis as an ocular manifestation following ChAdOx1nCoV-19 vaccine, in otherwise healthy patients.


Alphafoetoprotein uptake by cloned cell lines derived from a nickel-induced rat rhabdomyosarcoma.
Rat, mouse, pig and chicken alphafoetoproteins (AFP), rat serum albumin and egg albumin, or their fluoresceinated conjugates were added to cultures of several cloned cell lines isolated from a nickel-induced rat rhabdomyosarcoma. The intracellular uptake of assayed proteins was revealed by the indirect immunoperoxidase technique and/or by direct fluorescence microscopy. All the clones examined bound AFP, and all but one internalized the protein. The protein localized in the membrane and the cytoplasm, as well as along straight processes interconnecting cells. Nuclei were always AFP negative. The protein uptake of fluoresceinated conjugates of AFP and serumalbumin was already visible 15 min after incubation and progressed with time to reach a plateau 4-5 h later. Ultrastructural radioautographs of cells incubated with [3H]-AFP (rat) showed protein accumulation in several organelles and particularly in lipid droplets. Parallel to these observations, the intracellular presence of AFP within myofibrillar structures was demonstrated in tongue sections of rat foetuses and neonates. The results presented here provide experimental evidence of the reappearance in cloned cell lines derived from a primary rhabdomyosarcoma of a property pertaining to foetal striated muscle.


Reproductive performance of rabbit females from three paternal lines with a different potential for growth rate and resilience.
A total of 197 nulliparous rabbits (from three paternal lines) were used to test potential strategies to overcome the consequences on reproduction associated with the selection for high growth rate. The R line was selected for growth rate during the growing period for 37 generations, the RF line was founded through a high selection intensity of elite animals of the R line, and the RFLP line, which was obtained by backcrossing RF animals with the LP line (a long-lived productive maternal line, characterised by high resilience). BW, perirenal fat thickness, fertility, daily feed intake, milk yield and blood metabolites of females were controlled from 1st artificial insemination to 3rd parturition. Litter size, litter weight, individual weight and feed ingestion of kits were controlled from birth to weaning. Our results show that RF females were significantly lighter than R and RFLP females throughout the trial (-5.0%; P < 0.05). Furthermore, RF animals had a higher fertility rate than RFLP females, at first cycle (+10.5 percentage points; P < 0.05). However, RFLP had a higher fertility rate than RF females at second cycle (+21.5 percentage points; P < 0.01). On average, RFLP females had higher perirenal fat thickness than R females at parturition (+3.0%; P < 0.05) and higher daily feed intake than of R and RF females during gestation and late lactation (+9.7 and +8.7%, respectively; P < 0.05). RFLP females produced more milk than R and RF females in the two first lactations (+18.5%; P < 0.001). In the first three parturitions, R females delivered fewer kits born alive (-1.7 kits than RF and RFLP; P < 0.05). In addition, R females' blood had a higher concentration of glutamine and glutamate than RFLP (+24 and +22.7%, respectively; P < 0.05). RFLP litters were heavier than both R and RF litters throughout lactation. However, R kits were heavier at birth than RF and RFLP (+7.9%). Results suggest that the foundation of a paternal line using elite animals could generate females with better early reproductive performance. In addition, backcrossing the RF line with a maternal LP line resulted in a genetic line whose females had a different resource allocation strategy to foster reproduction during the studied period.


PPARγ enhances ILC2 function during allergic airway inflammation via transcription regulation of ST2.
Group 2 innate lymphoid cells (ILC2s) represent the major player during hyperresponsive airway inflammation. Peroxisome proliferator-activated receptor-γ (PPARγ) was highly expressed on ILC2 and its potential role in asthma has been suggested. However, the detailed mechanism underlying the effects of PPARγ on ILC2-induced airway inflammation remains to be fully understood. Here we identified PPARγ as a positive regulator of lung ILC2. Expression of PPARγ on ILC2 was dramatically induced upon interleukin-33 (IL-33) challenge. Deficiency of PPARγ in hematopoietic system in mice (PPARγfl/fl Vav1Cre) significantly impaired the function of ILC2 in lung, which led to apparent alleviation of airway inflammation in response to IL-33 or Papain challenge, when compared with those in PPARγfl/fl littermates control. Mechanistic studies identified IL-33 receptor ST2 as a transcriptional target of PPARγ. Overexpression of ST2 rescued the functional defects of ILC2 lacking PPARγ. Collectively, these results demonstrated PPARγ as an important regulator of ILC2 during allergic airway inflammation, which sheds new lights on the importance of PPARγ in asthma.


Synthesis of structurally defined chondroitin sulfate: Paving the way to the structure-activity relationship studies.
Chondroitin sulfate (CS) is one of the major and widespread glycosaminoglycans, a family of structurally complex, linear, anionic hetero-co-polysaccharides. CS plays a vital role in various normal physiological and pathological processes, thus, showing varieties of biological activities, such as anti-oxidation, anti-atherosclerosis, anti-thrombosis, and insignificant immunogenicity. However, the heterogeneity of the naturally occurring CS potentially leads to function unspecific and limits further structure-activity relationship studies. Therefore, the synthesis of CS with well-defined and uniform chain lengths is of major interest for the development of reliable drugs. In this review, we examine the remarkable progress that has been made in the chemical, enzymatic and chemoenzymatic synthesis of CS and its derivatives, providing a broad spectrum of options to access CS of well controlled chain lengths.


Surface Properties of Aqueous Solutions of Poly- (Maleic Acid-Co-Vinyl-n-Alkyl) Potassium Salts.
The surface activity of five potassium salts from poly(maleic acid-co-vinyl-n-alkyl) was studied. The unusual behavior found is attributed to a polymer stabilization process by hydrophobic microdomains in the bulk. Copyright 1999 Academic Press.


Fragmentary pathological myoclonus in NREM sleep.
A 42-year-old patient is reported who presented with marked daytime sleepiness and in whom the only major nocturnal polysomnographic abnormality was intense fragmentary (partial) myoclonus occurring with equal frequency in all stages of NREM sleep associated with some degree of sleep fragmentation. The myoclonus was very brief (less than 150 msec duration), aperiodic and recurred in asynchronous and asymmetrical fashion over the legs, arms and face. It appears unrelated to the clinically similar physiological myoclonus of REM sleep. Other main sleep disorders such as periodic movements, restless leg syndrome, sleep apnea and narcolepsy-cataplexy were excluded by history and polysomnography.


An enzyme immunoassay for the flow cytometer (FEIA).
This report describes the use of a fluorescent activated cell sorter (FACS) in combination with an enzyme immunosorbent assay (EIA). This combination of techniques expands the versatility of the flow cytometer. It introduces a new set of fluorescent enzyme products for antigen detection. These highly substantive fluorescent compounds permit the flow cytometer to quantify cell-EIA reactions and also to delineate subpopulations of cells with different quantities of surface antigens. Because the FEIA product is colored, as well as fluorescent, a simple light microscope may also be used to define the distribution of the label on the cell surface. These techniques have been applied to the examination of antigens on human erythrocytes, human T cell lymphoma cells (H9), and to surface markers on the tissue culture cell line K562.


An algae - Desert snail food chain: Energy flow and soil turnover.
The feeding ecology of adult desert snails (Sphincterochila zonata), inhabiting a loess plain in the Negev Desert, was studied during a 7-year period. Energy flow and soil turnover determinations were made at the individual and population level on the basis of field observations and data derived from laboratory simulations. Sphincterochila zonata were only active on 8-27 winter days annually, otherwise they were dormant. The snails fed exclusively on algae that grew on the soil surface following rain. The mean annual dry-weight biomass of algae was 197.4(±118.1) gr·m-2. The dry weight biomass of snails ranged from 0.02-0.14 gr·m-2. Annual production in the food chain varied substantially from year to year (1-1539 Kj·m-2), but the net annual energy balance of the snails was always positive. Soil crust turnover, resulting from grazing of snails on algae, was estimated at 142 kg·hectare-1 during the study period.The annual magnitude of energy flow and soil turnover is determined by the soil surface moisture regime which in turn, is a function of rainfall patterns. Sphincterochila zonata may serve an important role in Negev ecosystems by dispersing soil algae and altering soil structure. The snails are not subject to substanding predation by rodents but may occasionally serve as an important food source for migrating birds.


Biochemical changes and quality characterization of cold-stored 'Sahebi' grape in response to postharvest application of GABA.
In this study, the effect of γ-aminobutyric acid (GABA) at 0 (control), 20 and 40 mM on maintaining postharvest quality, chilling tolerance and fungal decay of 'Sahebi' grapevine (Vitis vinifera L.) was investigated during 60 days storage at 1 °C. GABA-treated fruits especially at 40 mM showed less weight loss (35%), rachis browning (30%) and decay incident (63%) compared to the control. GABA-induced abscisic acid was linked to lower membrane electrolyte leakage (13%) in treated grapes. Moreover, at the end of 60 days, GABA treatment at 40 mM resulted in higher activities of antioxidant enzymes including superoxide dismutase (50%), catalase (35%), guaiacol peroxidase (65%), and ascorbate peroxidase (47%) and lower malondialdehyde (21%) compared to control samples. The highest soluble sugars and organic acids were related to 40 mM GABA-treated grape clusters. Phenolic compounds (phenolic acids, stilbenes, flavonoids and anthocyanidins) and antioxidant capacity increased in 40 mM GABA-treated grape due to lower polyphenol oxidase activity. Therefore, GABA is recommended for maintaining internal quality and reduction in fungal decay and chilling injury of grapes during postharvest storage.


Increased incidence and recurrence rates of acute diverticulitis in patients with irritable bowel syndrome.
Acute diverticulitis (AD) is commonly diagnosed in outpatient and emergency departments and is associated with severe complications such as perforation and fistula. Symptoms of irritable bowel syndrome (IBS), such as abdominal pain, constipation and diarrhoea, are also common with AD. This study aimed to evaluate the strength of a possible association between IBS and AD. This retrospective study analysed records from Taiwan's National Health Insurance Research Database and involved a total of 25 810 patients, including 12 905 IBS patients diagnosed between 2000 and 2012. The IBS and non-IBS cohorts were matched by propensity score for age, gender, comorbidities and medication, then compared for confounding variables by the chi-square test or Student's t-test. The association between AD and IBS was determined using Cox proportional hazards models. Kaplan-Meier curves assessed the cumulative incidence of AD in IBS patients. The overall incidence of AD was 3.95-fold higher in the IBS cohort than in the non-IBS cohort (63.34 vs 16.02 per 100 000 person-years, respectively) and IBS was an independent risk factor for subsequent diagnosis of AD in multivariate Cox proportional hazards regression model adjusted hazards ratio (aHR = 3.84, 95% CI = 2.29-6.44, P < 0.001) and Kaplan-Meier (log-rank test, P < 0.001) analysis. IBS was also associated with a high recurrence rate of AD (aHR = 8.30, 95% CI = 1.07-64.30, P = 0.04). The epidemiological evidence in this study demonstrates that patients with IBS are associated with a higher incidence of AD and also its recurrence.


Randomized Controlled Trials for the Treatment of Hidradenitis Suppurativa.
Hidradenitis suppurativa (HS) is a chronic, inflammatory, recurrent, debilitating skin disease. Several treatment modalities are available, but most of them lack high-quality evidence. A systematic search was performed to identify all randomized controlled trials for the treatment of HS in order to review and evaluate the evidence. Recommendations for future randomized controlled trials include using validated scores, inclusion of patient rated outcomes, and thorough report of side effects. Evidence for long-term treatment and benefit/risk ratio of available treatment modalities is needed in order to enhance evidence-based treatment in daily clinical practice. Combining surgery with antiinflammatory treatment warrants further investigation.


Effect of paracetamol use on the modification of the development of asthma by reactive oxygen species genes.
Recent studies have identified an increase in the prevalence of asthma associated with paracetamol use. To identify the relationship among asthma, biomarkers, genes, and paracetamol use in preschool children. We undertook a population-based, cross-sectional survey of 933 preschool children. Asthma status was classified according to medical history and asthmatic symptoms. History of paracetamol use in infancy was recorded. Impulse oscillometry, blood tests for eosinophils and total IgE, and genotyping of NAT2, Nrf2, and GSTP1 polymorphisms by TaqMan assay were conducted. Paracetamol use in infancy was associated with an increased risk of treatment for asthma within the previous 12 months. Paracetamol use together with a family history of asthma increased the risk of asthma diagnosis ever, current asthma, and treatment for asthma within the previous 12 months. Gene polymorphisms in NAT2 (rs4271002), Nrf2 (rd6726395), and GSTP1 (rd1695) increased the risk of treatment for asthma within the last 12 months. Eosinophils were significantly elevated in the group with paracetamol use and a family history of asthma; however, the serum total IgE level and IOS did not show any significant difference. Paracetamol use in infancy was significantly associated with increased risk of asthma. The association is more significant in genetically susceptible children, related to antioxidant genes, and the effect may be mediated by eosinophilic inflammation.


Clinical Validation of a Plasma Donor-derived Cell-free DNA Assay to Detect Allograft Rejection and Injury in Lung Transplant.
Lung transplant patients are vulnerable to various forms of allograft injury, whether from acute rejection (AR) (encompassing acute cellular rejection [ACR] and antibody-mediated rejection [AMR]), chronic lung allograft dysfunction (CLAD), or infection (INFXN). Previous research indicates that donor-derived cell-free DNA (dd-cfDNA) is a promising noninvasive biomarker for the detection of AR and allograft injury. Our aim was to validate a clinical plasma dd-cfDNA assay for detection of AR and other allograft injury and to confirm and expand on dd-cfDNA and allograft injury associations observed in previous studies. We measured dd-cfDNA fraction using a novel single-nucleotide polymorphism-based assay in prospectively collected plasma samples paired with clinical-pathologic diagnoses. dd-cfDNA fraction was compared across clinical-pathologic cohorts: stable, ACR, AMR, isolated lymphocytic bronchiolitis, CLAD/neutrophilic-responsive allograft dysfunction (NRAD), and INFXN. Performance characteristics were calculated for AR and combined allograft injury (AR + CLAD/NRAD + INFXN) versus the stable cohort. The study included 195 samples from 103 patients. Median dd-cfDNA fraction was significantly higher for ACR (1.43%, interquartile range [IQR]: 0.67%-2.32%, P = 5 × 10-6), AMR (2.50%, IQR: 2.06%-3.79%, P = 2 × 10-5), INFXN (0.74%, IQR: 0.46%-1.38%, P = 0.02), and CLAD/NRAD (1.60%, IQR: 0.57%-2.60%, P = 1.4 × 10-4) versus the stable cohort. Area under the receiver operator characteristic curve for AR versus stable was 0.91 (95% confidence interval [CI]: 0.83-0.98). Using a ≥1% dd-cfDNA fraction threshold, sensitivity for AR was 89.1% (95% CI: 76.2%-100.0%), specificity 82.9% (95% CI: 73.3%-92.4%), positive predictive value, 51.9% (95% CI: 37.5%-66.3%), and negative predictive value, 97.3% (95% CI: 94.3%-100%). For combined allograft injury area under the receiver operator characteristic curve was 0.76 (95% CI: 0.66-0.85), sensitivity 59.9% (95% CI: 46.0%-73.9%), specificity 83.9% (95% CI: 74.1%-93.7%), positive predictive value, 43.6% (95% CI: 27.6%-59.6%), and negative predictive value, 91.0% (95% CI: 87.9%-94.0%). These results indicate that our dd-cfDNA assay detects AR and other allograft injury. dd-cfDNA monitoring, accompanied by standard clinical assessments, represents a valuable precision tool to support lung transplant health and is appropriate for further assessment in a prospective randomized-controlled study.


Isolation and properties of carboxylesterase P4 from Yersinia pseudotuberculosis.
The carboxylesterase P4 produced by Yersinia pseudotuberculosis was purified 330-fold by gel permeation and DEAE-trisacryl chromatography with a final yield of 21%. The apparent molecular weight, as determined by fast-protein liquid chromatography, was 45 kDa. The hydrolytic activity of esterase P4 was higher with the 1-naphthyl esters than with the 2-naphthyl esters of acetic, propionic and butyric acids. The apparent Km values were identical for 1-naphthyl acetate and 1-naphthyl propionate (0.15 mM). The enzyme was unstable at pH values below 5, but retained 80% of its initial activity after 30 min at 65 degrees C. It was unaffected by EDTA, eserine, tosyl-L-lysine chloromethylketone, iodoacetamide or 4-hydroxymercuribenzoate, but was strongly inhibited by low concentrations of diisopropyl fluorophosphate, suggesting the presence of serine in its active site. The purified enzyme gave a single precipitin line on Ouchterlony double immunodiffusion with homologous antiserum. This antiserum cross-reacted with the esterase bands E3 and E5 of Y. enterocolitica biotype 1, whereas there was no cross-reaction with the esterase bands produced by Y. enterocolitica biotypes 2 to 5, Y. intermedia, Y. frederiksenii, Y. kristensenii or Y. aldovae. The carboxylesterase P4 produced by Y. pestis was physicochemically, biochemically and immunologically indistinguishable from Y. pseudotuberculosis carboxylesterase P4. The latter enzyme and carboxylesterase B of Escherichia coli showed some biochemical similarities, but were antigenically unrelated. Our data confirm the relevance of esterases to phylogenetic and taxonomic studies of Enterobacteria.


Hepatic neoplasms in childhood - a clinicopathologic study.
Primary hepatic tumours are rare in childhood. We observed nine cases between 1976 and 1995, of which eight were hepatoblastomas and one a mesenchymal hamartoma. A male-to-female ratio of 2:1 was noted; 78% of the cases occurred in children below 2 years of age. Five hepatoblastomas were of the pure epithelial type; mesenchymal components encountered in the mixed type were cartilage, bone, and spindle sarcomatous cells.


The heart as a system of coupled nonlinear oscillators.
In various approximations the heart is considered as a system of coupled nonlinear oscillators which are characterized by their phase transition curve (PTC) only. The system exhibits many phenomena which are known from ECG recordings such as multi-level-Wenckebach periodicity, dissociation, induction or removal of a tachycardia by an extrasystole, pseudo-block and the gap phenomenon. All these can be discussed within the model on a quantitative level.


[Clinical Outcomes after Keraring Implantation for Keratoconus Management in Thin Corneas].
The aim of our study was to evaluate the clinical outcomes after Keraring implantation for keratoconus in patients with thin corneas. Ten eyes from 10 patients with keratoconus, who underwent femtosecond laser-assisted Keraring implantation for keratoconus, were included in this retrospective study. Uncorrected visual acuity (UCVA), corrected visual acuity (CDVA), keratometric readings, central corneal thickness and thinnest corneal pachymetry have been evaluated preoperatively and 6 months after the Keraring implantation. UCVA, BCVA and keratometric readings improved at 6 months postoperatively. Our data showed significant keratometric amelioration and visual improvement after Keraring implantation for keratoconus in patients with thin corneas at 6 months postoperatively.


Medical uses of cosmetic colored contact lenses.
To explore the clinical issues surrounding the use of hand-painted contact lenses for medical indications and to assess patient satisfaction with the use of these lenses for an unsightly eye. A questionnaire was sent to all patients visiting the contact lens department of Western Eye Hospital for a colored contact lens fitting during a 1-year period. The questionnaire related to patient satisfaction with the lenses and aspects of wear. Replies were received from 25 of a total of 33 patients. The average wearing time was 11.3 hours per day. Most (88%) patients wore lenses for cosmetic reasons, and 12% wore lenses for cosmetic and refractive purposes. Satisfaction was 76% regarding lens comfort and 88% regarding lens color. Provided lens care is satisfactory and the patient does not have unreasonable expectations, a tinted contact lens can be a useful device. In view of the cost implication, this is a valuable service provided by the hospital.


An evaluation of bias in k-factor analysis.
Randomization and simulation are used to detect bias in k-factor analysis. In nine previously published data sets there is strong evidence of bias. This may result from either non-independence of observations or the arithmetic relationship used to estimate k-factors, which can generate "spurious correlations". Randomization can be used to test for density dependence without bias. This procedure confirms the existence of densitydependent effects in 8 of the 9 populations and 11 of the 16 k-factors previously thought to have density-dependent effects.


Influence of discontinuing feeding degradable cosubstrate on the performance of a fluidized bed bioreactor treating a mixture of trichlorophenol and phenol.
The purpose of our research was to evaluate the effect of eliminating supplementation of sucrose to the reactor influent on the performance of a lab scale partially-aerated methanogenic fluidized bed bioreactor (PAM-FBBR). Two operational stages were distinguished: in the first stage the influent contained a mixture of 120/30/1000 mg/L of 2,4,6-trichlorophenol/phenol/COD-sucrose (TCP/Phe/COD-sucrose); in the second stage only the xenobiotic concentrations were the same 120/30 mg/L of TCP/Phe whereas sucrose addition was discontinued. Removal efficiencies of TCP, Phe, and COD were very high and close for both stages; i.e., η(TCP): 99.9 and 99.9%; η(Phe): 99.9 and 99.9%; η(COD) = 96.46 and 97.48% for stage 1 and stage 2, respectively. Traces of 2,4,6 dichlorophenol (0.05 mg/L) and 4-chlorophenol (0.07-0.26 mg/L) were found during the first 15 days of operation of the second stage, probably due to the adaptation to no co-substrate conditions. Net increase of chloride anion Cl(-) in effluent ranged between 59.5 and 61.5 mg Cl(-)/L that was very close to the maximum theoretical concentration of 62.8 mg Cl(-)/L. PCR-DGGE analysis revealed a richness decrease of eubacterial domain posterior to sucrose elimination from the influent whereas archaeal richness remained almost the same. However, the bioreactor performance was not negatively affected by discontinuing the addition of co-substrate sucrose. Our results indicate that the application of PAM-FBBR to the treatment of groundwaters polluted with chlorophenols and characterized by the lack of easily degradable co-substrates, is a promising alternative for on site bioremediation.


The Effects of Holothurin and Caspofungin on the Vaginal Cell Inflammation Parameters of the Rattus norvegicus Strain Post Induction of Candida albicans.
Candida albicans (C. albicans) is a fungus that causes superficial and invasive candidiasis in its host. Caspofungin, has been widely used as a synthetic antifungal, whereas holothurin has been shown to have potential as a natural antifungal. The purpose of this study was to see how holothurin and caspofungin affected the number of C. albicans's colonies, LDH levels, and the number of inflammatory cells in vagina of Rattus norvegicus. Design of this research is using posttest only with control group design with 48 Rattus norvegicus Wistar strains used in this study were divided into six treatment groups. Each group was divided into three-time intervals of 12, 24, and 48 hours. LDH markers were tested using ELISA, inflammatory cells were counted manually, and the number of colonies was calculated using colonymetry before being diluted with NaCl 0.9% and planted in sabouraud dextrose agar (SDA). According to the findings, inflammatory cells in the treatment of holothurin (48-hours) had an OR of 1.68 CI (-0.79-4.16) P = 0.09 and caspofungin had an OR of 4.18 CI (1.26-9.63) P = 0.09. Meanwhile, LDH in the holothurin (48-hour) treatment obtained OR 348, CI (286-410), P=0.03, and Caspofungin OR 393, CI (277-508), P=0.03. Colonies were obtained with zero numbers in the holothurin treatment (48 hours) and with Caspofungin OR 393, CI (273-508) P=0.00. Holothurin and caspofungin administration reduced the number of C. albicans colonies and the number of inflammatory cells (P 0.05), implying that holothurin and caspofungin could prevent C. albicans infection.


Physicochemical conditions and timing of rodingite formation: evidence from rodingite-hosted fluid inclusions in the JM Asbestos mine, Asbestos, Québec.
Fluid inclusions and geological relationships indicate that rodingite formation in the Asbestos ophiolite, Québec, occurred in two, or possibly three, separate episodes during thrusting of the ophiolite onto the Laurentian margin, and that it involved three fluids. The first episode of rodingitization, which affected diorite, occurred at temperatures of between 290 and 360 degrees C and pressures of 2.5 to 4.5 kbar, and the second episode, which affected granite and slate, occurred at temperatures of between 325 and 400 degrees C and pressures less than 3 kbar. The fluids responsible for these episodes of alteration were moderately to strongly saline (approximately 1.5 to 6.3 m eq. NaCl), rich in divalent cations and contained appreciable methane. A possible third episode of alteration is suggested by primary fluid inclusions in vesuvianite-rich bodies and secondary inclusions in other types of rodingite, with significantly lower trapping temperatures, salinity and methane content. The association of the aqueous fluids with hydrocarbon-rich fluids containing CH4 and higher order alkanes, but no CO2, suggests strongly that the former originated from the serpentinites. The similarities in the composition of the fluids in all rock types indicate that the ophiolite had already been thrust onto the slates when rodingitization occurred.


RGTA-based matrix therapy in severe experimental corneal lesions: safety and efficacy studies.
Corneal alteration potentially leading to ulceration remains a major health concern in ocular surface diseases. A treatment that would improve both the quality and speed of healing and control the inflammation would be of great interest. Regenerating agents (RGTAs) have been shown to stimulate wound healing and modulate undesired fibrosis in various in vivo systems. We investigated the effects of RGTA-OTR4120(®) in a rabbit corneal model in order to assess its potential use in ocular surface diseases. First, we assessed its safety for 7 and 28 days using the Draize test criteria in healthy rabbit eyes; then, we investigated the effect of a single dose (50μl, 5μg) in an alkali-burned cornea model. Daily follow-up of clinical signs of healing was scored, and histology was performed at D7. RGTA was well tolerated; no signs of ocular irritation were observed. In the corneal alkali-burn model, non-RGTA-treated eyes showed inflammatory clinical signs, and histology confirmed a loss of superficial corneal layers with epithelial disorganization, neovascularization and infiltration of inflammatory cells. When compared to NaCl control, RGTA treatment appeared effective in reducing clinical signs of inflammation, enhancing re-epithelialization, and improving histological patterns: edema, fibrosis, neovascularization and inflammation. Three to four layers of epithelial cells were already organized, stroma was virtually unvascularized and keratocytes well implanted in parallel collagen fibers with an overall reorganization similar to normal cornea. RGTA appears to be a promising agent for controlling ocular surface inflammation and promoting corneal healing and was well tolerated. This study offers preclinical information and supports the findings of other (compassionate or pilot) studies conducted in patients with various ocular surface diseases.


Photochemical enhancement of DNA delivery by EGF receptor targeted polyplexes.
Photochemical internalization (PCI) is a physico-chemical targeting method that enables light directed delivery of nucleic acids into cells. The technology is based on photosensitizers that localize in the membranes of endocytic vesicles. A light activation of the photosensitizers induces photochemical reactions that lead to rupture of the vesicular membranes. This results in the release of endocytosed compounds (e.g., nucleic acids) into the cell cytosol. Physico-chemical and biological targeting techniques can be combined to promote efficient and specific gene delivery to target cells. The present protocol describes PCI of epidermal growth factor receptor (EGFR)-targeted DNA polyplexes. The DNA polyplexes made are small (50-100 nm in diameter), and they contain polyethylenimine (PEI) conjugated with the EGF protein as a cell-binding ligand for EGFR-mediated endocytosis and polyethylene glycol (PEG) for masking the polyplex surface charge. PCI of such targeted PEG-PEI/DNA polyplexes enables high and EGFR-specific gene transfer activity in cells. Although describing in detail PCI of DNA polyplexes, the methodology presented in this protocol is also applicable for PCI of other gene therapy vectors (e.g. viral vectors), peptide nucleic acids (PNA), small interfering RNA (siRNA), and for vectors targeted to alternate cell surface receptors. Generally, PCI can be applied whenever 100% survival of the treated cell population is not required.


Network analysis of the relationships between problematic smartphone use and anxiety, and depression in a sample of Chinese college students.
Problematic smartphone use (PSU) is associated with both anxiety and depression. However, the relationships between components of PSU and symptoms of anxiety or depression have not been investigated. Hence, the aim of this study was to closely examine the relationships between PSU and anxiety and depression to identify the pathological mechanisms underpinning those relationships. A second aim was to identify important bridge nodes to identify potential targets for intervention. Symptom-level network structures of PSU and anxiety, and PSU and depression were constructed to investigate the connections between the variables and evaluate the bridge expected influence (BEI) of each node. Network analysis using data from 325 Chinese healthy college students was performed. Five strongest edges appeared within the communities in both the PSU-anxiety and PSU-depression networks. The "Withdrawal" component had more connections with symptoms of anxiety or depression than any other PSU node. In particular, the edges between "Withdrawal" and "Restlessness" and between "Withdrawal" and "Concentration difficulties" were the strongest cross-community edges in the PSU-anxiety network and PSU-depression network, respectively. Furthermore, "Withdrawal" had the highest BEI in the PSU community in both networks. These findings provide preliminary evidence of the pathological pathways linking PSU with anxiety and depression, with "Withdrawal" linking PSU with both anxiety and depression. Hence, "Withdrawal" may be a potential target for preventing and intervening in cases of anxiety or depression.


Changing pattern in the clinical presentation of breast cancer in the absence of a screening program over a period of thirty-three years in Iran.
To survey the proportion of stages at the presentation of the disease without a screening program, among a population of breast cancer patients that is as a representative sample of the country in a distinct period. The population of the current study is found among the female breast cancer patients who were referred to oncology centers in northeastern Iran over a thirty-three-year period from 1980 to 2012. Four thousand patients were divided into three time periods consisting of 521 cases from 1980 to 1990, 1178 cases from 1991 to 2001, and 2302 cases from 2002 to 2012. While there was no difference in the proportions of T1 and T3 tumors, T2 tumors showed an increase (P = 0.001) and T4 tumors a decrease (P = 0.000) during these periods. There was no change in the proportion of stage I, however the proportion of stage II had risen (P = 0.000), while that of stage III (P = 0.002), and stage IV (P = 0.000) had fallen. The study's urban and rural populations experienced a similar trend in this respect, with the exception that the rural population exhibited more striking changes during the study's recent years. After a thirty-three-year follow up on breast cancer in northeastern Iran, it is obvious that this disease is now presented in its earlier stages even in the absence of a screening program. In spite of this, the proportion of T1 disease and those tumors are discovered by a screening program has not significantly changed.


L-Fucose is involved in human-gut microbiome interactions.
L-Fucose is one of the key metabolites in human-gut microbiome interactions. It is continuously synthesized by humans in the form of fucosylated glycans and fucosyl-oligosaccharides and delivered into the gut throughout their lifetime. Gut microorganisms metabolize L-fucose and produce short-chain fatty acids, which are absorbed by epithelial cells and used as energy sources or signaling molecules. Recent studies have revealed that the carbon flux in L-fucose metabolism by gut microorganisms is distinct from that in other sugar metabolisms because of cofactor imbalance and low efficiencies in energy synthesis of L-fucose metabolism. The large amounts of short-chain fatty acids produced during microbial L-fucose metabolism are used by epithelial cells to recover most of the energy used up during L-fucose synthesis. In this review, we present a detailed overview of microbial L-fucose metabolism and a potential solution for disease treatment and prevention using genetically engineered probiotics that modulate fucose metabolism. Our review contributes to the understanding of human-gut microbiome interactions through L-fucose metabolism. KEY POINTS: • Fucose-metabolizing microorganisms produce large amounts of short-chain fatty acids • Fucose metabolism differs from other sugar metabolisms by cofactor imbalance • Modulating fucose metabolism is the key to control host-gut microbiome interactions.


Use of Donor Hearts ≥50 Years Old for Septuagenarians in Heart Transplantation.
The impact of using donors ≥50 years old on heart transplantation outcomes of septuagenarians is unknown, which may have a potential to expand the donor pool. From January 2011 to December 2021, 817 septuagenarians received donor hearts <50 years old (DON<50) and 172 septuagenarians received donor hearts ≥50 years old (DON≥50) in the United Network for Organ Sharing database. Propensity score matching was performed using recipient characteristics (167 pairs). The Kaplan-Meier method and Cox proportional hazards model were used to analyze death and graft failure. The number of heart transplants in septuagenarians has been increasing (54 per year in 2011 to 137 per year in 2021). In a matched cohort, the donor age was 30 years in DON<50 and 54 years in DON≥50. In DON≥50, cerebrovascular disease was the main cause of death (43%), whereas head trauma (38%) and anoxia (37%) were the causes in DON<50 (P < .001). The median heart ischemia time was comparable (DON<50, 3.3 hours; DON≥50, 3.2 hours; P = .54). In matched patients, 1- and 5-year survival rates were 88.0% (DON<50) vs 87.2% (DON≥50) and 79.2% (DON<50) vs 72.3% (DON≥50), respectively (log-rank, P = .41). In the multivariable Cox proportional hazards models, donors ≥50 years old were not associated with death in matched (hazard ratio, 1.05; 95% CI, 0.67-1.65; P = .83) and nonmatched groups (hazard ratio, 1.11; 95% CI, 0.82-1.50; P = .49). The use of donor hearts older than 50 years can be an effective option for septuagenarians, thereby potentially increasing organ availability without compromising outcomes.


Robust microtubule dynamics facilitate low-tension kinetochore detachment in metaphase.
During mitosis, sister chromatids are stretched apart at their centromeres via their attachment to oppositely oriented kinetochore microtubules. This stretching generates inwardly directed tension across the separated sister centromeres. The cell leverages this tension signal to detect and then correct potential errors in chromosome segregation, via a mechanical tension signaling pathway that detaches improperly attached kinetochores from their microtubules. However, the sequence of events leading up to these detachment events remains unknown. In this study, we used microfluidics to sustain and observe low-tension budding yeast metaphase spindles over multiple hours, allowing us to elucidate the tension history prior to a detachment event. We found that, under conditions in which kinetochore phosphorylation weakens low-tension kinetochore-microtubule connections, the mechanical forces produced via the dynamic growth and shortening of microtubules is required to efficiently facilitate detachment events. Our findings underscore the critical role of robust kinetochore microtubule dynamics in ensuring the fidelity of chromosome segregation during mitosis.


A three-dimensional study of organelle interrelationships in regenerating rat liver. 3. Organelles related to bile.
A number of cell structures are described which show a morphological relationship to the bile canaliculi. Two types of peribiliary vesicles are identified: osmication positive ones occurring between the bile canaliculi and the osmicated immature Golgi cisternae and probably deriving from the latter, and osmication negative ones related to MVB, on which they appear as buds. Small coated vesicles are seen attached to this second type. Large lacunae may originate from MVB, as suggested by the MVB-like internal vesicles they may contain. Some stay in luminal continuity with the bile canaliculi. Canalicular coated vesicles are seen as parts of the canalicular plasma membrane and free in the cytoplasm.


Association of glycosylated hemoglobin and outcomes in patients with COVID-19 and pre-existing type 2 diabetes: A protocol for systematic review and meta-analysis.
The impact of glycosylated hemoglobin on mortality in patients with coronavirus disease 2019 (COVID-19) and type 2 diabetes (T2D) remains uncertain. In this study, we aim to assess the effect of pre-hospital blood glucose regulation on patients with COVID-19 and pre-existing T2D. All randomized controlled trials (RCTs) and cohort studies of association of glycosylated hemoglobin and outcomes in patients with COVID-19 and T2D will be included in this review. PubMed, Embase, and CNKI will be searched for relevant literature, up to August 20, 2020 in English and Chinese language. Two reviewers will select trials independently for inclusion and assess trial quality. Two pairs of authors will independently extract information for each included trials. Primary outcomes are death and composite adverse outcomes: the number of participants who died or remained severely disabled. Revman 5.3 will be used for heterogeneity assessment, data synthesis, subgroup analysis, sensitivity analysisa and generating funnel-plots. We will provide practical results about the association of glycosylated hemoglobin and outcomes in patients with COVID-19 and T2D. The stronger evidence about the association of glycosylated hemoglobin and outcomes in patients with COVID-19 and T2D will be provided for clinical practice. PROSPERO CRD42020200574. There is no need for ethical approval, and the review will be reported in a peer-reviewed journal.


Special Issue: Recent Advances in Ionic Liquids.
This special issue on ionic liquids provides a comprehensive overview of recent advances in the field, including their synthesis, characterization, and applications.


The effects of photobiomodulation therapy on mouse pre-osteoblast cell line MC3T3-E1 proliferation and apoptosis via miR-503/Wnt3a pathway.
Photobiomodulation therapy (PBMT) has been demonstrated as regulating osteoblast proliferation. MicroRNAs (miRNAs) are involved in various pathophysiologic processes in osteoblast, but the role of miRNAs in the PBMT-based promotion of osteoblast proliferation remains unclear. This study aimed to investigate the effects of PBMT treatment (3.75 J/cm2) on mouse pre-osteoblast cell line MC3T3-E1 proliferation and apoptosis via the miR-503/Wnt3a pathway; meanwhile, detect the expressions of miR-503 and Wnt3a after PBMT treatment and the role of miR-503 in regulating Wnt signaling molecules Wnt3a, β-catenin, Runx2, apoptotic proteins caspase-3, and Bcl-2 in vitro. The PBMT parameters were as follows: 808 nm continuous wavelength, 0.401 W output power, 0.042 W/cm2 power density, 9.6 cm2 spot size, 36 J energy, 3.75 J/cm2 energy density, 90 s irradiation for three times per 12 h, 14.5 cm distance of the laser source and the angle of divergence of the laser beam was 7°. In our present study, the target relationship was predicted and verified by bioinformatics analysis and luciferase reporter assays. Gene mRNA and protein expressions were examined by qPCR and western blot analysis. The MTT method was used to evaluate the effect of miR-503 on MC3T3-E1 cells proliferation. And cell apoptosis was examined by flow cytometry. The results showed that PBMT treatment reduced the expression of miR-503 and increased the level of Wnt3a (p < 0.01). Bioinformatics analysis and luciferase reporter assays revealed that Wnt3a was a target of miR-503, and Wnt3a was regulated by miR-503. Furthermore, miR-503 was found to functionally inhibit proliferation and promote apoptosis (p < 0.01). And during this process, Wnt3a, β-catenin, Runx2, and Bcl-2 expressions were significantly inhibited (p < 0.01); however, caspase-3 level was upregulated (p < 0.01). These results suggest that miR-503 plays a role in osteoblast proliferation and apoptosis in response to PBMT, which is potentially amenable to therapeutic manipulation for clinical application.


TRAM: a new concept in transport monitoring.
A new monitoring system has been designed to eliminate the need to interrupt monitoring to transport critically ill patients. The key innovation of the system is a self-contained multiparameter signal acquisition and processing module that contains a battery-backed microprocessor and retains monitor setup information when moved from one monitor to another. The module functions in Marquette Series 7010 surgical monitors and bedside monitors and in the new Marquette Transport Remote Acquisition Monitor (TRAM). Lines connecting the patient to the module remain connected. The TRAM module provides continuous, integrated multiparameter monitoring during transport. Monitored parameters include up to four simultaneous ECG leads, two invasive blood pressures, pulse rate, cardiac output and two temperatures (in place of cardiac output).


Electrophysiology and indications for pacing in the '80's.
Newer electrophysiological studies have improved our understanding of the pathogenesis of cardiac arrhythmias. Bradycardias originate either from a dysfunction of impulse formation in the sinoatrial node or from a disturbed conduction of the impulse. Different pathogenetic mechanisms are discussed as causes of tachyarrhythmias: circus movement (re-entry) is primarily due to pathological changes in conduction and refractoriness. Focal impulse formation results from local disturbances of depolarization and repolarization of the cell membrane: increased automaticity, abnormal automaticity, triggered activity. Symptomatic bradycardias still represent the standard indication for cardiac pacing particularly with implantable pacemakers. Based on clinical electrophysiology, various types of pacemakers are available at present: atrial triggered and atrial pacing pacemakers, AV-sequential pacemakers, ventricular demand-pacemakers, stand-by pacemakers, and fixed rate pacemakers. The multiprogrammability of newer pacemaker devices is a very useful tool in avoiding secondary interventions. For antitachycardia pacemaker therapy there are essentially three methods in use: 1. overdrive pacing to prevent re-entry phenomena and automaticity and also to suppress tachyarrhythmias based on increased or abnormal automaticity; 2. competitive stimulation for termination of tachycardias by means of single impulses; and 3. rapid atrial stimulation to convert atrial flutter into atrial fibrillation and consequently to normal sinus rhythm. In very rare cases rapid ventricular stimulation is mandatory. The positive results achieved with temporary stimulation methods have led to the development of permanent (implantable) antitachycardia pacemakers for long-term therapy, which have proven to be a low-risk alternative in drug-resistant tachyarrhythmias.


Posttraumatic stress disorder and relationship functioning: A comprehensive review and organizational framework.
Posttraumatic stress disorder (PTSD) is associated with impairments in relationship functioning. Beyond the abundance of research that has demonstrated this basic link, more recent research has begun to explore possible mediators and moderators of this association. The present paper reviews and synthesizes existing literature in the context of an overarching organizational framework of potential ways in which PTSD impacts relationship functioning. The framework organizes findings in terms of specific elements of PTSD and comorbid conditions, mediators (factors that are posited to explain or account for the association), and moderators (factors that are posited to alter the strength of the association). Specific symptoms of PTSD, comorbid symptoms, and many of the potential mediators explored have extensive overlap, raising questions of possible tautology and redundancy in findings. Some findings suggest that non-specific symptoms, such as depression or anger, account for more variance in relationship impairments than trauma-specific symptoms, such as re-experiencing. Moderators, which are characterized as individual, relational, or environmental in nature, have been the subject of far less research in comparison to other factors. Recommendations for future research and clinical implications of the findings reviewed are also presented.


Bonded amalgam restorations: a comparative study of glass-ionomer and resin adhesives.
This study assessed the effectiveness of a glass-ionomer liner/base (Vitrebond) and two adhesive resins (Amalgambond and Panavia Ex) in bonding amalgam to enamel/dentine cavities in vitro. Restorations placed without any intermediary, or with varnish, served for comparison purposes. Standardised unretentive cavities on the buccal sides of a total of 78 extracted human molar teeth were prepared to receive the restorations. After application of the adhesive materials (without light curing the Vitrebond), the cavities were filled with amalgam (Dispersalloy). Each specimen was stored for 24 hours in distilled water at 37 degrees C. The amalgam restorations were then pulled from the cavities using an Instron machine and the retentive strength values were recorded. The results showed that any of the three adhesive intermediary agents substantially enhanced the retention of the amalgam restorations. The Vitrebond specimens had the highest mean retentive strength value (133 N), followed by Amalgambond (18% lower) and Panavia Ex (38% lower); the difference between the value for the Vitrebond specimens and that for the Panavia Ex specimens was statistically significant. The Vitrebond specimens failed due to gross enamel fractures and a cohesive failure of the glass-ionomer layer. The Amalgambond specimens failed at the resin/amalgam interface, while the Panavia Ex specimens showed enamel fractures and failure at the resin/dentine interface. It appears that Vitrebond has the potential for being an effective amalgam adhesive in vivo.


Pathways linking childhood abuse history and current socioeconomic status to inflammation during pregnancy.
Women who have experienced significant adversities during childhood and adulthood are at risk for excessive inflammation during pregnancy, but the mechanisms are unclear. Using structural equation modeling, we examined pathways from childhood abuse history and current socioeconomic status (SES) to inflammatory markers through indicators of health risk, recent stressors, and psychological distress in 214 women assessed at mid-pregnancy (5-31 weeks gestation). Self-reported data on socioeconomic indicators, childhood trauma history, pre-pregnancy body mass index (BMI), smoking, sleep quality, interpersonal conflict, recent life events, perceived stress, and depressive symptoms were collected, and serum levels of C-reactive protein (CRP) and interleukin (IL)-6 were determined. In separate models, pre-pregnancy BMI, sleep quality, and interpersonal conflict statistically explained the relationship between adversity and inflammation. These three intermediate variables were then entered into a multiple mediation analysis to examine unique effects. Childhood abuse history and current SES both demonstrated significant indirect effects on CRP through pre-pregnancy BMI, and current SES showed a significant indirect effect on IL-6 through all intermediate variables. When examining each indirect pathway individually, pre-pregnancy BMI and interpersonal conflict emerged as parallel pathways by which low current SES leads to elevated IL-6; the indirect pathway through sleep quality was no longer significant. Pre-pregnancy BMI and interpersonal conflict are two independent mechanisms by which adversity is associated with increased inflammation during pregnancy. Women who have been exposed to significant adversity may be at particular risk for obesity, sleep disruption, and interpersonal conflict, with implications for immune dysregulation during pregnancy.


Correction of microtubule defects within Aβ plaque-associated dystrophic axons results in lowered Aβ release and plaque deposition.
The hallmark pathologies of the Alzheimer's disease (AD) brain are amyloid beta (Aβ)-containing senile plaques and neurofibrillary tangles formed from the microtubule (MT)-binding tau protein. Tau becomes hyperphosphorylated and disengages from MTs in AD, with evidence of resulting MT structure/function defects. Brain-penetrant MT-stabilizing compounds can normalize MTs and axonal transport in mouse models with tau pathology, thereby reducing neuron loss and decreasing tau pathology. MT dysfunction is also observed in dystrophic axons adjacent to Aβ plaques, resulting in accumulation of amyloid precursor protein (APP) and BACE1 with the potential for enhanced localized Aβ generation. We have examined whether the brain-penetrant MT-stabilizing compound CNDR-51657 might decrease plaque-associated axonal dystrophy and Aβ release in 5XFAD mice that develop an abundance of Aβ plaques. Administration of CNDR-51657 to 1.5-month-old male and female 5XFAD mice for 4 or 7 weeks led to decreased soluble brain Aβ that coincided with reduced APP and BACE1 levels, resulting in decreased formation of insoluble Aβ deposits. These data suggest a vicious cycle whereby initial Aβ plaque formation causes MT disruption in nearby axons, resulting in the local accumulation of APP and BACE1 that facilitates additional Aβ generation and plaque deposition. The ability of a MT-stabilizing compound to attenuate this cycle, and also reduce deficits resulting from reduced tau binding to MTs, suggests that molecules of this type hold promise as potential AD therapeutics.


Neonatal testicular torsion--a lost cause?
Twenty-four neonates presented with signs of testicular ischaemia over a 13-year period. They had a mean birth weight of 3.706 kg. The right testicle was affected in 13, the left in 9 and there was bilateral torsion in 2 babies. Two babies had no twist in the cord, but the testicles were nonviable macroscopically and microscopically. Twenty-one babies had primary exploration revealing necrotic testes in all patients and they underwent orchidectomies. The other three babies had conservative management and the affected testes had atrophied on follow-up. Sixteen babies had contralateral orchidopexy. Doppler ultrasound scans were reported as normal in 2 of 13 babies who had scans. No testes were salvaged following surgery. The incidence of testicular torsion in the neonatal period was calculated as 6.1 per 100,000 live births. No testis was salvaged following surgery in our series of 24 patients. This dismal outcome underlines that immediate surgical exploration, although commonly performed, rarely saves torted testes.


Radiolabelled monoclonal antibodies (McAb): an alternate approach to the conventional methods for the assessment of cardiomyocyte damage in an experimental brain-death pig model.
The present study was carried out to determine the possible use of cTn-I in the cardiac myofibrillar architecture, as a potential target for in vivo radioimmunodetection of cardiac damage in a brain death pig model. Radioiodination of the anti-cTn-I 5F4 McAb was carried out by lactoperoxidase method. The percentage iodine incorporation achieved was 70-75%. The radioiodinated McAbs were purified on Sephadex G-25 column and characterised by Paper chromatography, Phast Gel electrophoresis and electroimmunoblotting. Radioiodinated anti-cTn-I 5F4 McAbs were employed alongside Pyrophosphate (Tc99m-PPi) and Thallium201 chloride (Tl201) in 24 landrace pigs (brain-dead = 18 & sham-operated = 6). The percentage cardiac uptake of the radiolabelled antibody injected dose was significantly higher in the brain dead animals (0.196%) as compared to that of sham-operated animals (0.11%). Specific in vivo localization of radiolabelled McAbs in the infarcted cardiac tissue was confirmed by computer-aided reconstruction of 3-D images of the isolated heart. The preliminary results of the study revealed preferential uptake of radiolabelled antibody at the site of myocyte damage resulting from artificially induced brain death.


Induction and decay of amino acid transport in the liver. Turnover of transport activity in isolated hepatocytes after stimulation by diabetes or glucagon.
System A-mediated amino acid transport in liver tissue is stimulated by diabetes or by exogenous glucagon. The present report describes the decay process for stimulated System A activity in isolated rat hepatocytes. Transport induced by glucagon, insulin, or spontaneous diabetes (BB/G rats) decayed rapidly after initiation of primary cultures; the estimated half-life was about 1.5 h. In contrast, the stimulated activity in cultured hepatocytes from streptozotocin-diabetic rats had a half-life of about 2.5 h. It is not known if the loss of System A activity is the result of proteolysis or of another form of inactivation. The decay was blocked by either actinomycin or cycloheximide, but was unaffected by leupeptin, methylamine, chloroquine, dinitrophenol, rotenone, or tunicamycin. Studies with cycloheximide and actinomycin suggest the following: 1) within 30 min after initiation of cell cultures, synthesis of the corresponding mRNA for the transport-inactivating protein has begun; 2) the mRNA for transport-inactivating protein is relatively long-lived, but the inactivating protein itself has a half-life of less than 1 h; and 3) actinomycin blocks the decay through inhibition of transport-inactivating protein biosynthesis rather than by protection of the mRNA for the protein responsible for System A activity. A working model for the synthesis and decay of System A activity is presented. Cationic amino acid transport, System y+, was also stimulated severalfold after induction of diabetes or glucagon injection of rats. Systems ASC, X-, and N were enhanced to varying degrees in hepatocytes from diabetic or glucagon-injected rats, but the level of stimulation for each was not as great as that found for Systems A or y+.


Modification of an ELISA-based procedure for affinity determination: correction necessary for use with bivalent antibody.
A recently described procedure for the evaluation of the affinity of monoclonal antibodies [Friguet et al., J. Immun. Meth. 77, 305-319 (1985)] uses an ELISA system to determine the quantity of free antibody present in a mixture of antigen and antibody. However, an intact IgG may bind antigen by either of two binding sites, and an IgG can bind to a solid-phase antigen whether one or two of its binding sites are free. Therefore, this procedure does not directly provide the concn of liganded binding sites, the quantity necessary for calculation of the thermodynamic association constant. A binomial probability distribution relates the fraction of liganded binding sites to the concn of unliganded, singly liganded, and doubly liganded IgG assuming that the binding of each Fab to antigen is independent. Simulated experiments were used to compare the apparent binding characteristics of bivalent IgG and monovalent Fab and to calculate apparent association constants in each case. It was found that the affinity of binding sites on intact IgG was underestimated by a factor of at least 2 and that the error was inversely related to the fraction of liganded binding sites. Binding site affinity of an antibody may be underestimated by several orders of magnitude. On the basis of binomial analysis, it is possible to convert apparent concns of bound IgG to actual concns of liganded binding site resulting in the calculation of valid association constants for intact IgG without alteration of the experimental protocol.


Approaches to the identification of ABAR as an abscisic acid receptor.
Abscisic acid (ABA) is a vital phytohormone that regulates seed maturation and germination, seedling growth, and adaptation to environmental stresses. ABA functions through a complex network of signaling pathways, where the cell response is initiated by an ABA receptor which triggers downstream signaling cascades to induce the final physiological effects. Two classes of technologies may be used for the isolation of ABA receptors. One is the genetic screening for ABA receptor mutants, and another is the biochemical isolation of ABA-binding proteins that are putative ABA receptors. We implemented biochemical approaches, namely, the purification of ABA-binding proteins to identify a putative ABA receptor; this protein was further characterized by a combination of biochemical and reverse genetic approaches. The identified ABA receptor, called ABAR, mediates the responses of plants to ABA in seed germination, postgerminative growth, and stomatal movement. This protein is the H subunit (CHLH) of the magnesium protoporphyrin-IX chelatase (Mg-chelatase) that also plays a key role in both chlorophyll biosynthesis and plastid-to-nucleus signaling. Here, we describe the experimental procedures for the purification of ABA-binding proteins and the identification of the ABA-binding protein, ABAR/CHLH, as an ABA receptor.


The CCL20 and CCR6 axis in psoriasis.
Psoriasis is a TNF-α/IL-23/IL-17A-mediated inflammatory skin disease that causes a significant socioeconomic burden in afflicted patients. IL-17A-producing immune cells, including Th17 cells, are crucial effector cells in the development of psoriasis. IL-17A stimulates epidermal keratinocytes to produce CCL20, which eventually recruits CCR6 + Th17 cells into the lesional skin. Thus, the CCL20/CCR6 axis works as a driving force that prepares an IL-17A-rich cutaneous milieu. In this review, we summarize the current research topics on the CCL20/CCR6 axis and the therapeutic intervention of this axis for psoriasis.


A prospective study of serum adiponectin and regression of metabolic syndrome: The ARIRANG study.
Increased serum adiponectin levels may play a protective role in metabolic syndrome. However, few prospective studies have examined the effect of serum adiponectin in the improvement of metabolic components in subjects with metabolic syndrome. We investigated the association of serum adiponectin levels with the regression of metabolic syndrome in a population-based longitudinal study. A total of 1308 adults (575 men and 733 women) with metabolic syndrome at baseline were examined and followed. Baseline serum adiponectin concentrations were measured by radioimmunoassay. During an average of 2.6 years of follow-up, metabolic syndrome had disappeared in 184 men (29.8%) and 235 women (32.1%). In multivariable adjusted models, the odds ratio (95% confidence interval) for regression of metabolic syndrome comparing the highest to the lowest quartiles of adiponectin levels was 0.93 (0.56-1.53) in men and 2.48 (1.54-4.01) in women. Increased serum adiponectin is a predictor for the regression of metabolic syndrome in women. Adiponectin may have potential therapeutic applications in metabolic disease.


Research on the aerobic granular sludge under alkalinity in sequencing batch reactors: Removal efficiency, metagenomic and key microbes.
Effects of additional alkalinity on the performance of aerobic granular sludge (AGS) in sequencing batch reactors (SBR) performing simultaneous nitrification, denitrification, and phosphorus removal (SNDPR) were evaluated. Results showed that COD and ammonia-N (NH4+-N) were slightly stimulated and remained high and stable with the increase of alkalinity up to 750 mg/L, while denitrification was boosted and total inorganic nitrogen (TIN) removal efficiency increased from 60.46% to 98.62% with an additional alkalinity of 750 mg/L. However, total phosphorus (TP) removal stayed unaffected and efficient. Illumina MiSeq sequencing revealed that microbial diversity and richness shifted mostly with 500 mg/L exterior alkalinity addition. Additional alkalinity altered the bacterial compositions within aerobic granules at various levels and the enrichment of Thiothrix and Acinetobacter was accounted for the promotion of COD and TIN removal.


Antiemetic efficacy of high-dose dexamethasone: randomized, double-blind, crossover study with a combination of dexamethasone, metoclopramide and diphenhydramine.
A double-blind, randomized, crossover study was conducted to compare the efficacy and safety of high-dose dexamethasone (Protocol D) with a combination of dexamethasone, metoclopramide and diphenhydramine (Protocol DMD) in the management of chemotherapy-induced nausea and vomiting in cancer patients. All entered patients had received no prior chemotherapy. During the study chemotherapy was administered on an inpatient basis. The majority of patients (94%) were treated with cytotoxic drugs of significant emetogenic activity and 40% of the study group received cis-platin-containing combinations. Of the 60 evaluable patients, complete antinausea and antivomiting effects of D were observed in 30 (50%) and 34 (57%), respectively and of DMD in 17 (28%) and 26 patients (43%) respectively. The difference was not statistically significant (P = 0.09 and 0.24, respectively). Lack of significant difference between the two regimens was demonstrated irrespective of the administered cytotoxic drugs. The DMD protocol caused more adverse reactions than D. While 27 patients (45%) experienced no side effects from D, only 14 (24%) remained free of complications due to DMD (P = 0.001). Furthermore, DMD produced more sedation, insomnia, headache, diaphoresis, dizziness and diarrhoea than the D regimen. In addition it gave rise to more adverse effects on appetite and activity. Upon direct questioning, 37 patients (62%) expressed a preference for D, 14 (23%) preferred DMD and 9 (15%) found no difference between the two regimens. We conclude that, while the short DMD protocol has an antiemetic activity equivalent in its effectiveness to D, its associated adverse reactions would minimize its usefulness. Therefore, further investigations should be conducted to find a safer and more potent combination of antiemetics suitable for therapy in an outpatient setting.


Neuritic growth cone and ependymal gap junctions in the feline subfornical organ during early development.
Intercellular contacts in the subfornical organ (SFO) of kittens 3, 16, and 29 days old were studied in thin sections and by the freeze-etch method. Gap junctions appeared between growing nerve processes and target cells. The junctions were interspersed between immature synapses lacking mitochondria as well as full pre- and postsynaptic membrane specializations. Gap junctions were seen on filopodia as well as on more mature processes. The morphology of these junctions was typical of those described earlier but they were of small size (0.2-0.3 micron). Gap junctions of peculiar form were also seen between ependymal elements in the SFO at 16 days. These were of large size (0.5-0.8 micron) and were often of segmented character. This segmentation consisted of bands 3-4 particles in width with a center-to-center spacing of 90 nm with particle free corridors between corresponding to the width of about two rows of particles. The margin of the group might be circumscribed by a row of particles. Although gap junctions of large size were seen between ependymal cells in thin section, features corresponding to the particle free corridors have not been observed to date.


A Technique to Reduce the Early Recurrence of Intussusception in Ultrasound-Guided Hydrostatic Reduction.
Ultrasound-guided saline enema is highly successful in treating pediatric intussusception; however, early recurrence-within 48 hours-is possible. This study aimed to explore effective methods of reducing early recurrence. This study included patients aged 0 to 14 years diagnosed with ileocolic intussusception with a symptom duration of <48 hours from January 2019 to March 2021. The patients were divided into control and intervention groups. All patients received successful treatment with ultrasound-guided saline enema; however, in patients treated before January 4, 2020 (control group), the intestinal fluid was drained immediately, and in patients treated after January 4, 2020 (intervention group), the intestinal fluid was drained after 15 minutes of intestinal pressure maintenance. Early recurrence rates of the groups were compared. Ileocolic intussusception was treated successfully by ultrasound-guided saline enema in 231 patients (116, control group;115, intervention group). The early recurrence rate in the intervention group (10%; 95% CI: 4.9-16.5) was numerically lower than that in the control group (19%; 95% CI: 12.3-27.3). No significant difference was observed in the number of recurrences per person between the groups (P = .448). Patients without early recurrence were older (P = .004) and received enemas of a shorter duration (P < .001) and lower pressure (P < .001) than patients without early recurrence. Maintaining reduction pressure for 15 minutes after a successful ultrasound-guided saline enema may reduce the early recurrence of intussusception. A randomized controlled trial is needed because the intervention and control cohorts were most probably incomparable (due to the COVID-19 pandemic).


Bedload sediment transport model for revealing the multi-year trend of polychlorinated biphenyl contamination in the river sediment (Kupa, Croatia).
This article investigated the multi-year polychlorinated biphenyl (PCB) burden of the sediment collected along the Kupa River flow in Croatia using the bedload sediment transport model. Kupa, as the natural border between Croatia and Slovenia, belongs to the water system Krupa (Slovenia) → Lahinja (Slovenia) → Kupa (Croatia) → Sava → Danube → Black Sea. From 1962 to 1985, the total quantity of waste calculated for pure PCBs, released by a capacitor manufacturer into the environment within various locations of the Krupa River in Slovenia, was 70 tons. Krupa River (Slovenia) has become one of the most PCB-polluted rivers in Europe, and consequently, PCBs have been detected in the Kupa River (Croatia). Model application revealed that contamination of the Kupa River (Croatia) started significantly earlier than 1983, when a high concentration of PCB was detected for the first time in the Krupa River (Slovenia), with probably significantly higher sediment concentrations at the upstream boundary of the Kupa. A slow concentration changes and PCB accumulation in the sediment should be expected downstream compared to the upstream boundary, governed mainly by high flow events. The PCBs in sediments from 2020/2021 are markedly different after the Lahinja confluence with Kupa (0.2-0.6 μg kg-1 vs. 1.4-34.3 μg kg-1). Measurements of PCBs in Kupa sediment suggest that the intake of PCB has not yet been completely stopped, which should be confirmed by detailed monitoring in the future. The contamination situation observed in the Kupa River represents an excellent example of the persistency of PCBs in the environment.


Bulbocapnine's ability to antagonize the adrenergic inhibitory action of dopamine and analogs.
Dopamine in the presence of cocaine, 5,6-dihydroxy-2-dimethylaminotetralin (M-7), apomorphine and N,N-dimethyldopamine produced dose dependent inhibition on the heart rate increase due to stimulation of the right cardioaccelerator postganglionic nerves. Inhibitory actions of these compounds were antagonized by bulbocapnine. Also bulbocapnine antagonized the blood pressure increase due to N,N-dimethyldopamine but did not antagonize the pressor response of dopamine.


Sleep ecology, sleep characteristics and behavior problems in young maltreated children: A scoping review.
Behavior problems are highly prevalent in young maltreated children. Their etiology is multifactorial and has been widely documented. Lately, researchers paid increased attention to the role of sleep in non-maltreated children's behavior problems. They showed that poor sleep (e.g., short sleep duration, nocturnal awakenings) increased behavior problems. In addition, an inadequate sleep ecology (e.g., lack of sleep hygiene or bedtime routine) may lead to sleep problems. As maltreated children often live in disorganized environments, this study aims to map knowledge about sleep ecology and sleep characteristics, as well as their associations with behavior problems in young maltreated children from one to five years old. A scoping review was performed according to the PRISMA-SR checklist. Bibliographic databases were searched from 1993 to May 2020. From the 650 studies screened, nine reported results about sleep ecology or sleep characteristics or their associations with behavior problems in young maltreated children. Only one study described their sleep ecology. Eight studies documented or compared sleep characteristics, showing slight differences between maltreated and non-maltreated children (e.g., longer nighttime sleep duration or shorter naps in maltreated children). Four studies revealed associations between sleep characteristics and behavior problems in young maltreated children (e.g., shorter sleep duration was associated with more externalizing behaviors). Literature about sleep ecology, sleep characteristics, as well as with their associations with behavior problems in young maltreated children is scarce. Their sleep ecology especially deserves to be investigated. Longitudinal studies, studies with comparison groups, combining objective and subjective validated sleep measures, and taking into account maltreatment characteristics and children's developmental stage should be pursued.


Patients' experiences of cognitive impairment following critical illness treated in an intensive care unit: A scoping review.
Treatment with modern technology in an intensive care unit has increased critical illness survival. However, many patients are affected by their critical illness for months or years following discharge, as they experience cognitive impairments. Long-term cognitive impairments can severely affect patients' quality of life. Exploring patients' experiences on how and which cognitive impairments affect their everyday lives is important to improve planning of relevant research into interventions that may alleviate the burden of post-intensive cognitive impairments. To review the literature on patients' experiences of cognitive impairment following critical illness treated in an intensive care unit. A systematic search was conducted in PubMed, Cinahl, PsycInfo and Embase in March-May 2021. References and citations in relevant studies were explored. The Covidence tool was used by two independent researchers to identify relevant studies for inclusion. The Mixed Methods Appraisal Tool was used for critical appraisal. The JBI methodology for scoping reviews and the PRISMA-ScR checklist were used (Supporting Information File 1). We identified 11 relevant qualitative and/or quantitative studies. Four themes were found: 'Experiencing poor memory', 'Managing everyday life', 'Unsupported by the healthcare system' and 'Strategies for support in recovery'. Patients used various strategies during their recovery and rehabilitation to regain independence and avoid being a burden. They needed information to support their recovery and rehabilitation; otherwise, they felt unsupported and betrayed by the healthcare system. Patients experienced various cognitive impairments following critical illness in the intensive care unit, affecting and challenging their quality of life and adaption to everyday life. Knowledge gained by exploring patients' experience of cognitive impairments following critical illness in the intensive care unit can contribute to improve clinical practice by targeting and optimising patients' rehabilitation process. No patient or public involvement in this scoping review.


An Excel fitting routine for correcting protein absorption spectra for scatter.
Protein concentrations are often determined in a non-destructive manner by measuring the absorbance at 280 nm. However, light scattering in protein samples can complicate such assessment. We here describe a simple Excel Solver-based fitting routine to correct full protein UV absorption spectra for both Rayleigh and Mie scattering. Using samples displaying various degrees of natural and artificially induced scattering, we show that our multi-wavelength fitting method is not only capable of aiding in the determination of protein concentrations but can also be employed in the spectral analysis of protein structural changes that are accompanied by alterations in scatter intensity.


The effect of Transition to Specialty Practice Programs on Australian emergency nurses' professional development, recruitment and retention.
To date, emergency nursing Transition to Specialty Practice Program (TSPP) evaluations have been single-site observational studies. The aim of this paper was to examine the professional development, recruitment and retention outcomes of Australian emergency nursing TSPPs. An explanatory sequential design was used. Data were collected via online surveys and interviews of emergency Nurse Unit Managers and Nurse Educators. Survey data from EDs with TSPPs and EDs without TSPPs were compared. Qualitative data were analysed using content analysis. Data were collected from 118 EDs, and 13 interviews. TSPPs were offered in 72.1% of EDs. EDs with TSPPs had higher proportions of nurses with postgraduate qualifications (Mdn 28.3% vs. 22.1%, p=0.45) and Clinical Specialists (Mdn 16.4% vs. 6.3%, p=0.04). The median proportion of currently rostered nurses with TSPP completion was 34.2% in EDs with TSPPs introduced in 2000-2005 indicating ED high levels of retention. Emergency nursing TSPPs have had a positive effect on nursing professional development, recruitment and retention. To ensure consistency in outcomes and optimise reliability of emergency nursing skills and knowledge, a national emergency nursing TSPP framework is needed.


Synthesis and biological investigation of tetrahydropyridopyrimidinone derivatives as potential multireceptor atypical antipsychotics.
In the present study, a series of tetrahydropyridopyrimidinone derivatives, possessing potent dopamine D2, serotonin 5-HT1A and 5-HT2A receptors properties, was synthesized and evaluated as potential antipsychotics. Among them, 3-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)-9-hydroxy-2-methyl-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidin-4-one (10d) held the best pharmacological profile. It not only exhibited potent and balanced activities for D2, 5-HT1A, and 5-HT2A receptors, but was also endowed with low activities for α1A, 5-HT2C, H1 receptors and hERG channels, suggesting a low propensity for inducing orthostatic hypotension, weight gain and QT prolongation. In animal models, compound 10d reduced phencyclidine-induced hyperactivity with a high threshold for catalepsy induction. On the basis of its robust in vitro potency and in vivo efficacy in preclinical models of schizophrenia, coupled with a good pharmacokinetic profile, 10d was selected as a candidate for further development.