Early impact of the COVID-19 pandemic on promotion of infant activity, strength and communication: A qualitative exploration.
Fostering physical activity, muscle strengthening and communication skills in diverse environments are vital to ensuring healthy infant development; however, promotion of these skills may be impacted by the COVID-19 pandemic. Therefore, the purpose of this study was to explore healthcare workers, parents and childcare providers' perceptions of the pandemic's influence on how they engage with infants to promote physical activity, muscle strength and communication. 37 subjects (12 = parents; 12 = childcare providers, 13 = healthcare workers) participated in a semi-structured interview. Data were analyzed via an inductive content analysis. The majority of caregivers identified concerns related to: limitations in social interactions (especially masks impacting communication), lack of access to peer modeling, fewer opportunities for physical exploration, and a need for creative activities in diverse environments (e.g., home/childcare) for infant development during and after the pandemic. Caregivers are concerned about the role COVID-19 is having on infant development. Additional resources on how to promote infant physical activity, muscle strength and communication despite challenges associated with the COVID-19 pandemic are needed.


CCR9 inhibition does not interfere with the development of immune tolerance to oral antigens.
Recent literature indicates that mice deficient in the chemokine receptor CCR9 (CCR9(-/-) mice) are unable to generate oral tolerance. The present report describes how such inability can be overcome by increasing the dose of oral antigen. Pharmacological inhibition of CCR9 did not affect the generation of oral tolerance, regardless of antigen dose. These results highlight the inadequacy of genetic deletion of CCR9 when predicting the effects of pharmacological CCR9 inhibition on intestinal biology.


A geological perspective of plastic pollution.
The Anthropocene, the most recent geologic time division, marks humanity's profound impact on Earth. Amidst debates, the Anthropocene Working Group recommended its inclusion in the International Chronostratigraphic Chart (ICC). This period is characterized by the mid-20th century Great Acceleration Event Array (GAEA), which includes widespread presence of pollutants such as radionuclides, organochlorine pesticides, PCBs, and plastic production. The Anthropocene concept should raise public awareness of these threats, with plastic pollution being a primary concern. Plastics are now pervasive and serve as a marker for the Anthropocene Epoch or Age. Understanding their entry into the geological record requires considering the "Plastic Geological Cycle," which encompasses extraction, production, use, disposal, degradation, fragmentation, accumulation, and lithification. This cycle reveals the transformation of plastics into new forms of pollution characteristic of the Anthropocene. With 91 % of discarded plastics never recycled, they accumulate in the environment and enter the geological record through processes like photodegradation, thermal stress, and biodegradation. The proposed Plasticene stage within the Anthropocene is defined by the post-World War II surge in plastic production and their incorporation into sedimentary processes and rocks. The study of plastics in the geologic record serves as a warning of their negative impacts and highlights the urgency of addressing plastic pollution for a sustainable future.


Linking data-driven innovation to firm performance: a theoretical framework and case analysis.
This paper examines the impact of data-driven innovation (DDI) on firm performance, based on an exploratory case study of a manufacturing firm in China's textile and apparel industry. It explores the influence of various contextual variables on the firm's DDI and suggests ways to enhance DDI and thereby firm performance. Extending the literature on DDI, the paper proposes and validates a theoretical framework that incorporates the influence of various contextual factors on firms' DDI. The findings show that (1) individual context is associated with DDI; (2) organizational context is associated with DDI; and (3) DDI is associated with firm performance. This paper extends our understanding of how firm performance can be improved through DDI and shows that DDI should match a firm's contextual environment. The online version contains supplementary material available at 10.1007/s10479-022-05038-y.


Short-term versus long-term rainfall time series in the assessment of potable water savings by using rainwater in houses.
The main objective of this article is to assess the possibility of using short-term instead of long-term rainfall time series to evaluate the potential for potable water savings by using rainwater in houses. The analysis was performed considering rainfall data from 1960 to 1995 for the city of Santa Bárbara do Oeste, located in the state of São Paulo, southeastern Brazil. The influence of the rainfall time series, roof area, potable water demand and percentage rainwater demand on the potential for potable water savings was evaluated. The potential for potable water savings was estimated using computer simulations considering a set of long-term rainfall time series and different sets of short-term rainfall time series. The ideal rainwater tank capacity was also assessed for some cases. It was observed that the higher the percentage rainwater demand and the shorter the rainfall time series, the larger the difference between the potential for potable water savings and the greater the variation in the ideal rainwater tank size. The sets of short-term rainfall time series considered adequate for different scenarios ranged from 1 to 13 years depending on the roof area, percentage rainwater demand and potable water demand. The main finding of the research is that sets of short-term rainfall time series can be used to assess the potential for potable water savings by using rainwater, as the results obtained are similar to those obtained from the long-term rainfall time series.


Solubilized ibuprofen: evaluation of onset, relief, and safety of a novel formulation in the treatment of episodic tension-type headache.
To evaluate the relative efficacy of a new solubilized formulation of ibuprofen compared with acetaminophen caplets. This double-blind, randomized, parallel group study evaluated 154 subjects taking a single dose of solubilized ibuprofen, 400 mg; acetaminophen, 1000 mg; or placebo for the relief of episodic tension-type headache. Time to relief was measured using a stopwatch, and overall efficacy was measured using traditional categorical pain and relief scales. Ibuprofen capsules (liquigel), 400 mg, were significantly faster than both acetaminophen, 1000 mg, and placebo for all time-to-relief measures. Ibuprofen liquigel had a median time to first perceptible pain relief of 39 minutes compared with 47 minutes for acetaminophen and 113 minutes for placebo. For median time to meaningful relief, ibuprofen liquigel had a time of 39 minutes compared with 53 minutes for acetaminophen and more than 180 minutes for placebo (P</=.02 for both measures). In addition, ibuprofen liquigels demonstrated significantly superior overall analgesic efficacy compared with acetaminophen, 1000 mg, for the relief of episodic tension-type headache. Both active treatments had a side effect profile similar to placebo. Although several other studies have demonstrated the overall analgesic superiority of ibuprofen to acetaminophen, this study demonstrated that the liquigel formulation also provides a clinically relevant advantage for time to analgesic effects.


mRNA-activated DNAzyme nanoprobe for tumor cell precise imaging and gene therapy.
A novel Au-nucleic acid nanoprobe, catalyzed by mRNA, has been developed for live cell imaging and precise treatment of tumor cells. This nanoprobe exhibits the remarkable ability to differentiate between tumor cells and normal cells through live cell mRNA imaging, while selectively inducing apoptosis in tumor cells.


Diagnostic evaluation of an in-house developed single-tube, duplex, nested IS6110 real-time PCR assay for rapid pulmonary tuberculosis diagnosis.
To perform a prospective evaluation on the diagnostic performance of an in-house developed, duplex nested IS6110 real-time Polymerase-Chain-Reaction (PCR) assay (IS6110-qPCR assay) for rapid pulmonary TB diagnosis. A total of 503 sputum specimens were prospectively collected from July 2016 to November 2016. Diagnostic accuracy and optimal cut-off Cycle-threshold (Ct) value for IS6110-qPCR assay was determined by Receiver Operating Characteristic (ROC) curve. Using the optimal cut-off Ct, diagnostic performance of IS6110-qPCR assay was assessed with reference to both bacteriological and clinical information. Meanwhile, limit of detection (LOD) was calculated using Mycobacterium tuberculosis H37Rv as reference strain. ROC curve analysis of IS6110-qPCR assay showed a high Area Under the Curve (AUC) value (0.948) with optimal Ct value at 24.140. Prospective analysis of IS6110-qPCR assay with cut-off Ct = 24.140 showed a high overall sensitivity and specificity of 97.2% and 99.7%, respectively. No cross reactivity was observed among all non-tuberculous mycobacteria specimens in this study. LOD analysis on MTB-spiked sputum showed an average detection limit of 5.0 CFU/mL at Ct = 23.18 (±SD, 0.57). IS6110-qPCR assay is a highly accurate and cost-effective assay developed for primary screening of suspected TB cases, which is particularly suitable for regions with limited resources but high TB burden.


CT and arteriography in cerebral ischemia. A preliminary note.
Sixty patients with cerebral ischemia were studied by both CT and angiography. The results are: 1. Thrombosis of the internal carotid artery: CT shows a hypodensity lateral to the frontal horn. 2. Thrombosis of the middle cerebral artery: the hypodensity occupies the convexity of the frontal, parietal, and temporal lobes. 3. In thrombosis of the posterior cerebral artery there is an occipital hypodensity, while in thrombosis of the vertebral artery the hypodensity occupies a cerebellar hemisphere. 4. Circulatory disturbances without occlusion of the major cerebral vessels: there is a disproportion between the serious CT lesion and paucity of the angiographic findings.


Glutathione peroxidase 4 participates in secondary brain injury through mediating ferroptosis in a rat model of intracerebral hemorrhage.
Oxidative stress plays an important role in secondary brain injury (SBI) after intracerebral hemorrhage (ICH), but the underling mechanism has not been fully elucidated. Recently, the antioxidant enzyme glutathione peroxidase 4 (GPX4), has attracted increasing attention due to its ability to degrade reactive oxygen species (ROS) which are the major indicator of oxidative stress; However, the role of GPX4 in ICH has not been reported. This study was designed to investigate the changes in protein levels, as well as potential role and mechanism of GPX4 in SBI following ICH using a Sprague-Dawley (SD) rat model of ICH induced by autologous blood injection into the right basal ganglia. Firstly, GPX4 protein levels in the brain were reduced gradually and bottomed out at 24 h after ICH, compared with the Sham group. Secondly, genetic-overexpression of GPX4 effectively increased level of GPX4 in the brain, and clearly relieved neuronal dysfunction, brain edema, blood brain barrier (BBB) injury, oxidative stress and inflammation after ICH. In contrast, inhibiting GPX4 with a specific pharmacological inhibitor or genetic knockdown exacerbated SBI after ICH. Finally, Ferrostatin-1, a chemical inhibitor of ferroptosis, was used to explore the role of ferroptosis in brain injury after ICH. The results suggest that inhibiting ferroptosis can significantly alleviate SBI after ICH. In summary, our work indicated that GPX4 contributes to SBI following ICH by mediating ferroptosis. Therefore, inhibiting ferroptosis with specific inhibitors or upregulation of GPX4 may be a potential strategy to ameliorate brain injury induced by ICH.


Parental separation at birth and depression in adulthood: a long-term follow-up of the Finnish Christmas Seal Home Children.
Early separation of a child from the mother has been considered a risk factor for later depression. We investigated the association between very early separation and depression in adulthood in a unique dataset. The index cohort consisted of 3020 subjects born in 1945-1965 in Finland, isolated from their family due to tuberculosis in the family and placed in special nurseries, immediately after birth, for an average time of 7 months. Those subjects alive at 1 January, 1971 were identified. For every index subject two reference subjects were chosen, the matching criteria being sex, year of birth and place of birth. Data on depression were obtained from the Finnish Hospital Discharge Register by the end of year 1998. In males, 4.2% of the index subjects and 2.6% (Adjusted Rate Ratio RR 1.7, 95% CI 1.3-2.3) of the reference subjects had been treated in hospital due to a depressive episode. In females the respective figures were 3.9% for index subjects and 3.6% (RR 1.1, 95% CI 0.8-1.5) for reference subjects. The index subjects had an elevated risk for hospital treated depression in adulthood. One explanation may be that the very early temporal separation from the mother at birth may have unfavourable effects on later psychological development. On the other hand, separation from the parents at birth was not found to be strongly associated with severe adulthood depression.


[The benefits of home visits for peritoneal dialysis patients].
Peritoneal dialysis is exclusively an extrarenal purification technique performed in the patient's own home. The patient is either autonomous, or assisted by a private nurse or a member of his or her family. The nursing team at the center where the patient is being cared for organizes home visits to meet the patient and his or her family in their living environment. These visits provide an opportunity to review compliance with protocols and maintain the partnership with the patient. The team at the Caen Normandy university center for kidney disease shares its experience in this area of care.


The signal transduction pathway that mediates the effect of interleukin-1 beta on the Na+-K+-ATPase in LLC-PK1 cells.
IL-1beta reduces the activity and protein expression of Na(+)-K(+)-ATPase in rat kidney cells. The aim of the present study was to elucidate the signalling pathway involved, using the LLC-PK(1) cell line. In these cells IL-1beta caused a time and concentration-dependent decrease in the protein expression of the Na(+)-K(+)-ATPase. Inhibition of extracellular signal-regulated kinase (ERK), nuclear factor-kappaB (NF-kappaB) and cyclooxygenase (COX), but not p38 mitogen-activated kinase (MAPK), abolished the effect of the cytokine on the pump. The activation of NF-kappaB by IL-1beta was maximal at 20 min and declined thereafter. Inhibition of the transcription factor by pyrrolidinediethyldithiocarbamate (PDTC) down-regulated the ATPase. The effects of IL-1beta on the pump and NF-kappaB were prevented by the COX inhibitor indomethacin. Exogenous PGE(2) reduced protein expression of the ATPase within 15 min, even in presence of an ERK inhibitor. It is concluded that IL-1beta stimulates the mitogen and extracellular signal regulated protein kinase kinase/extracellular signal regulated protein kinase (MEK/ERK) pathway. This activates NF-kappaB, thus leading to increased COX-2 expression and PGE(2) release. PGE(2) in turn inhibits NF-kappaB and reduces the protein expression of Na(+)-K(+)-ATPase.


Evidence of pathogenicity for the leaky splice variant c.1066-6T>G in ATM.
Mild clinical phenotypes of ataxia-telangiectasia (variant A-T) are associated with biallelic ATM variants resulting in residual function of the ATM kinase. At least one regulatory, missense, or leaky splice site mutation resulting in expression of ATM with low level kinase activity was identified in subjects with variant A-T. Studies on the pathogenicity of the germline splicing ATM variant c.1066-6T>G have provided conflicting results. Using whole-exome sequencing, we identified two splice site ATM variants, c.1066-6T>G; [p.?], and c.2250G>A, [p.Ile709_Lys750del], in a compound heterozygous state in a 27-year-old woman who had been diagnosed as having congenital ocular motor apraxia type Cogan in her childhood. Reappraisal of her clinical phenotype revealed consistency with variant A-T. Functional analyses showed reduced expression of ATM protein and residual activity of the ATM kinase at a level consistent with variant A-T. Our results provide evidence for pathogenicity of the leaky ATM splice site variant c.1066-6T>G.


Economic analysis of two models of low-risk maternity care: a freestanding birth center compared to traditional care.
Costs were compared for two models of maternity care for low-risk pregnant women: a freestanding birth center (FSBC) and a medical model of care (MC). Sixty-nine subjects were enrolled in the FSBC group and 77 in the MC. In the FSBC group, prenatal costs were higher (mean difference $751, p </=.001) and childbirth care was less expensive ($1472, p </=.01). When costs for the entire maternity care episode were summed, there were no differences between groups ($6087 vs. $6803). Sensitivity analysis demonstrated that the FSBC could be more cost-effective than MC if it increased its volume.


Review of the Gauromydas giant flies (Insecta, Diptera, Mydidae), with descriptions of two new species from Central and South America.
Gauromydas Wilcox, Papavero & Pimentel, 1989 are giant flies, and include the largest fly known, G. heros (Perty, 1833). This genus was originally erected to group four Neotropical species, namely G. apicalis (Wiedemann, 1830), G. autuorii (d'Andretta, 1951), G. heros, and G. mystaceus (Wiedemann, 1830). As with most of the remaining Mydidae, adults of Gauromydas are very rarely collected. We here describe two new species of Gauromydas (G. mateus sp. nov. and G. papaveroi sp. nov.) discovered in entomological collections, including specimens unstudied for up to eight decades. We also provide revised diagnoses for the remaining four species of Gauromydas, along with a new key and new distribution records for the genus.


In vitro tetracycline susceptibility of Chlamydia trachomatis in clinical specimens.
A novel approach to determine the tetracycline susceptibility of Chlamydia trachomatis directly from specimens without cell culture propagation and adaptation has been explored. Out of a total of 1290 genital specimens from a sexually transmitted disease clinic, 211 (16.4%) were positive for C. trachomatis. A tetracycline concentration of 0.032 microgram/ml completely inhibited the appearance of inclusions in all of the 211 positive specimens. Of the positive specimens, 120 (56.9%) and 18 (8.5%) respectively showed the presence of 1 to 9 and 100 or more inclusions per microtiter well in antibiotic free medium. Other antibiotics are being tested in the same manner.


Perinatal methadone exposure and its influence on the behavioral ontogeny of rats.
The ontogeny of spontaneous motor and sensorimotor behaviors were evaluated daily from postnatal days 2 to 19 in rats maternally exposed to methadone (5 mg/kg) throughout gestation and/or lactation. In the methadone-treated groups, the age at which a specific behavior initially appeared for any group member and the ages at which 50% and a maximal (usually 100%) number of animals demonstrated a particular behavior was often delayed several days in comparison to controls. In addition, the time interval between the age of initial appearance and maximal achievement of a positive response was protracted. Rats subjected to methadone during either gestation or lactation exhibited the most retarded behavioral development. This study demonstrates that the timetable of behavioral maturation is altered in preweaning rats perinatally exposed to methadone, with the degree of response dependent on the timing and duration of opioid treatment. In addition, these results provide a functional correlate to our earlier observations of macroscopic and neurochemical changes in the brains of methadone-treated offspring.


New asymptomatic ischemic lesions on diffusion-weighted imaging after cerebral angiography.
We investigated the frequency of new lesions on diffusion-weighted imaging (DWI) after conventional cerebral angiography (CAG) in acute stroke patients and associated factors. Fifty-six acute stroke patients with CAG and 55 stroke patients without CAG (controls) underwent DWI twice, within 48 h before and after CAG, and within 48 h and 7 days after onset, respectively. The frequency of new DWI lesions was then compared between the two groups. Next, we divided the CAG group patients into two groups according to the presence of new DWI lesions after CAG (Positive and Negative groups), and the factors associated with new DWI lesions were investigated by multivariate logistic regression analysis. New DWI lesions were more often observed in the CAG group than the Control group (43% versus 31%, p=0.192). In the CAG group, mean fluoroscopy time was longer in the Positive group than the Negative group (26.5 min versus 14.9 min, p<0.001). Sensitivity and specificity analysis demonstrated a fluoroscopy time of 17 min to discriminate the Positive and Negative groups. Multivariate logistic regression analysis demonstrated that a fluoroscopy time of over 17 min was independent factor associated with new DWI lesions after CAG (OR, 9.4, 95% CI 1.8 to 48.6, p=0.0078). New DWI lesions were more often seen in patients with CAG than without CAG. However, the difference in number of DWI abnormalities did not reach statistical significance. In CAG patients, fluoroscopy time appears to be an independent factor associated with new DWI lesions.


Structural organization of rat ribosomal genes restriction endonuclease analysis of genomic and cloned ribosomal DNAs.
Structural organization of the rat ribosomal repeating unit was studied using hybridization of blotted restriction fragments of total rat DNA with alpha-32P-labeled cDNA probe synthesized on the 18S and 28S rRNAs. A detailed restriction endonuclease map was constructed, the 18S and 28S rRNA genes mapped and the sizes of the rat ribosomal repeating units determined. Considerable site heterogeneity of rat rDNA was revealed in both nontranscribed and external transcribed spacers. Recombinant phages containing the whole set of transcribed regions and a considerable part of a nontranscribed spacer of the rDNA were selected from the rat gene library. The restriction maps of the cloned rDNA fragments are in good agreement with the map constructed by Southern's technique, add to this map and support the existence of site heterogeneity in ribosomal repeating units. Proximal to the 3'-end of the 28S rRNA gene an internally repetitive region was found, each repeating unit being equal to approx. 150 bp. The site for transcription initiation was mapped 4.0-4.5 kb upstream from the 5'-end of the 18S rRNA gene. Frequently reiterated interspersed sequences were found in the nontranscribed spacer at approx. 2-3 kb distance from both ends of the transcribed region.


Hypertension, a Neglected Disease in Rural and Urban Areas in Moramanga, Madagascar.
Hypertension is one of the main risk factors of cardiovascular diseases. In Madagascar, studies on hypertension in urban and rural communities are scarce. The aim of this study was to determine the prevalence of hypertension and identify associated risk factors in adults living in a health and demographic system in Moramanga, Madagascar. The study included people aged 15 years old and above living in a health and demographic system in Moramanga. A household census was performed in 2012 to enumerate the population in 3 communities in Moramanga. In addition to the questionnaire used in the initial census, a standardized questionnaire and blood pressure were taken twice after 5 and 10 minutes of rest. In urban areas, heights and weights were also measured to calculate the body mass index. There were 3621 and 4010 participants respectively in rural and urban areas. Prevalence of hypertension in rural population was 27.0% (IC95% [25.6-28.5]) and 29.7% (IC95% [28.3-31.1]) in urban population. Among hypertensive subjects, 1.7% (17/979) and 5.3% (64/1191) were on antihypertensive treatment for at least 1 month before the survey in rural and urban population, respectively. In rural areas, increasing age (65 years and older vs 18-25 years OR = 11.81, IC95% [7.79-18.07]), giving more than 3 positive responses to the usual risks factors of hypertension (OR = 1.67, IC95% [1.14-2.42]) and singles in comparison with married people (OR = 1.61, IC95% [1.20-2.17]) were associated to hypertension in a logistic regression model. In urban areas, increasing age (65 years and older vs 18-25 years OR = 37.54, IC95% [24.81-57.92]), more than 3 positive responses to the usual risks of hypertension (OR = 3.47, IC95% [2.58-4.67]) and obesity (OR = 2.45, IC95% [1.56-3.87]) were found as risk factors. Hypertension is highly prevalent in rural areas although it is significantly less treated. As a result, a major epidemic of cardiovascular diseases is at risk in Madagascar's progressively aging society.


Inactivation of Escherichia coli and Shigella in acidic fruit and vegetable juices by peroxidase systems.
To study the bactericidal properties of the lactoperoxidase (LPER)-thiocyanate and soybean peroxidase (SBP)-thiocyanate systems at low pH, their efficiency for inactivation of Escherichia coli and Shigella in acidic fruit and vegetable juices, their effect on colour stability of the juices and interaction with ascorbic acid. Three-strain cocktails of E. coli and Shigella spp. in selected juices were supplemented with the LPER or SBP system. Within 24 h at 20 degrees C, the LPER system inactivated both cocktails by > or = 5 log10 units in apple, 2-5 log10 units in orange and < or = 1 log10 unit in tomato juices. In the presence of SBP, browning was significant in apple juice and white grape juice, slight in pink grape juice and absent in orange or tomato juice. Ascorbic acid protected E. coli and Shigella against inactivation by the LPER system, and peroxidase systems significantly reduced the ascorbic acid content of juices. Our results suggest a different specificity of LPER and SBP for SCN-, phenolic substrates of browning and ascorbic acid in acidic juices. The LPER system appeared a more appropriate candidate than the SBP system for biopreservation of juices. This work may open perspectives towards the development of LPER or other peroxidases as biopreservatives in acidic foods.


Cerebrospinal fluid pressure is decreased in primary open-angle glaucoma.
To compare cerebrospinal fluid (CSF) pressure in patients with primary open-angle glaucoma (POAG) with that in nonglaucomatous patients. Case-control study. Thirty-one thousand, seven hundred and eighty-six subjects underwent lumbar puncture (LP) between 1996 and 2007 at the Mayo Clinic, Rochester, Minnesota. Of these, 28 patients who had POAG and 49 patients who did not have POAG were analyzed. Retrospective review of medical records. Comparison of the 2 groups and factors associated with CSF pressure were analyzed by univariate and multivariate analyses. Demographics (age and gender), medical history, medication use, indication for LP, intraocular pressure (IOP), optic disc cup-to-disc ratio, visual field assessment, and CSF pressure. The mean CSF pressure +/- standard deviation was 13.0+/-4.2 mmHg in nonglaucoma patients and 9.2+/-2.9 mmHg in POAG patients (P<0.00005). The CSF pressure was lower in POAG patients regardless of indication for LP or age. Linear regression analysis showed that cup-to-disc ratio correlated independently with IOP (P<0.0001), CSF pressure (P<0.0001), and the translaminar pressure difference (P<0.0001). Multivariate analysis demonstrated that larger cup-to-disc ratio (P<0.0001) was associated with lower CSF pressure. Cerebrospinal fluid pressure is significantly lower in POAG patients compared with that in nonglaucomatous controls. These data support the notion that CSF pressure may play an important contributory role in the pathogenesis of POAG.


High-dose preoperative external beam and intraoperative irradiation for locally advanced pancreatic cancer.
To analyze results of high-dose preoperative external beam irradiation followed by surgical exploration and intraoperative radiation therapy in patients with unresectable pancreatic cancer. From December 1983 through December 1990, 27 patients with primary unresectable but localized pancreatic adenocarcinoma received high-dose (50 to 54 Gy) external beam irradiation with or without concomitant bolus 5-fluorouracil followed by surgical exploration and intraoperative electron beam irradiation (20 Gy) at the Mayo Clinic. Local control was achieved in 21 of 27 (78%) patients. Actuarial local control at 1, 2, and 5 years was 86%, 68%, and 45%, respectively. In 19 (70%) of the 27 patients, distant metastasis developed, and peritoneal or liver progression (or both) was found in 14 (52%). The actuarial distant metastasis rate at 2 and 5 years was 69% and 83%, respectively. Median survival from the date of diagnosis was 14.9 months. Actuarial 2- and 5-year overall survival was 27% and 7%, respectively. These survival rates are higher (p = 0.001) than the 6% and 0% actuarial 2- and 5-year survival observed in 56 patients who underwent intraoperative radiation therapy followed by postoperative high-dose external beam treatment at our institution. Administering the full component of external beam irradiation before exploration and intraoperative radiation therapy may be more appropriate because it allows better patient selection. Unfortunately, altered patient selection was not effective in decreasing the relative risk of abdominal failure. Because effective systemic chemotherapy does not currently exist, whole abdominal irradiation alone or in combination with chemotherapy warrants evaluation.


Testing night vision goggles in a dark outside environment.
People with degenerative retinal diseases such as retinitis pigmentosa, may have adequate day vision but suffer from poor night vision. We have tested newly developed night vision goggles (NVG) to help these patients overcome their night blindness, thereby promoting more opportunities for normal activities at night or in the dark. A total of 42 subjects with night blindness due to retinitis pigmentosa, choroideremia, cone rod dystrophy, or Bardet Biedl syndrome were recruited and clinically examined (visual acuity, visual field, and contrast sensitivity). Using an experienced mobility trainer, we tested binocular NVG on the subjects in two locations: a dark room and a 1 to 2 h outside course at night that provided different levels of difficulties (i.e., obstacles, brightness, and contrast). The assessment of which patients benefited from the NVG was predominantly based on the subjective evaluation of the mobility trainer, followed by their graded responses on two questionnaires. Based on the evaluation of the mobility trainer, 23 (61%) of the 42 subjects experienced improved mobility and orientation with the NVG outdoors, and 19 (39%) subjects did not. The ophthalmic data demonstrated that a visual acuity better than 20/100 and a visual field > 5 degrees (Goldmann perimetry III4) is necessary to benefit from NVG usage. In addition, subjective responses on increased mobility and independence were positively correlated with successful NVG testing. Night vision goggles have the ability to improve poor night vision in subjects with visual acuity > 20/100 and a visual field > or = 5 degrees (Goldmann: III4). In so doing, NVG can help overcome the obstacles experienced by many people suffering from night blindness. NVG, therefore, have the potential to greatly improve quality of life.


Visual attention modulates reading acquisition.
The processing of letters within strings is challenging for beginning readers. Letter identification is affected by visual similarity, loss of information with eccentricity and interference from nearby letters. In contrast, visual attention enhances letter identification. We here explored whether visual attention resources for multi-element processing, as measured through tasks of visual attention span prior to literacy instruction, predicted reading fluency performance one year later. One hundred and twenty-four mainstream children were assessed in kindergarten on their visual attention span abilities, phonological awareness, letter-name knowledge, early literacy knowledge, verbal short-term memory and non-verbal IQ. The participants' reading performance was measured at the end of grade 1 using tasks of irregular word, pseudo-word and text reading. Results from regression analyses showed that kindergarteners' VA span predicted reading fluency for text, irregular words and pseudo-words one year later, after controlling for age, non-verbal IQ, phonological skills, letter name knowledge and early literacy skills. Path analyses carried out to estimate the differential contribution of VA span to the different reading skills revealed a stronger contribution for pseudo-word reading than irregular word or text reading at the end of Grade 1. These results suggest that pre-reading visual attention resources contribute to later reading fluency, whatever the reading subskills and whatever the reading context (words in isolation or in sentences), with higher involvement to pseudo-word reading. We propose a new conceptual model of the role of visual attention in reading acquisition and argue that many aspects of the models are already supported by available findings.


Priming stimulation of locus coeruleus facilitates memory retrieval in the rat.
Rats were trained to run a linear maze for food reinforcement. During the 5-week retention interval, they were implanted under electrophysiological control with fine stimulating electrodes aimed at the nucleus locus coeruleus (LC). When tested 5 weeks after training, control rats showed forgetting in that they made significantly more errors at the test trial than at the last training trial. Low-level stimulation of LC immediately before the test alleviated the forgetting in that this group made significantly fewer errors than the non-stimulated group on two successive days. The results are taken as behavioral evidence of a role for noradrenergic projections from LC in memory and attention.


Bone marrow transplantation in the management of childhood cancer.
Bone marrow transplantation has become a curative therapy for selected children with leukemia and offers promise as a treatment for certain childhood solid tumors. Complications such as graft-versus-host disease, interstitial pneumonia, and recurrent malignancy continue to affect many patients. As these are overcome, and as methods for T-cell depletion and marrow purging are developed that extend the scope of bone marrow transplantation, it will become an even more significant therapy for childhood malignancy.


Immunology of human warts.
Rapid advances have occurred in the characterization of human papilloma virus (HPV) types applying the new advanced techniques of restriction endonuclease analysis and molecular hybridization to human wart virus. Human papilloma virus can no longer be viewed as a single, homogeneous virus producing all varieties of clinical warts. At least three antigenically heterogeneous HPV types have been associated with common and plantar warts. Two additional HPV types have been found in patients with epidermodysplasia verruciformis. Condylomata acuminata and laryngeal papillomas contain viruses which are also distinct from the preceding viruses and may represent additional HPV types. This antigenic heterogeneity of HPV has important implications concerning the immunology of human warts which have not been taken into account in most previously published studies. Both antibody and cell-mediated responses may be seen in patients with active warts, but many patients with warts have no demonstrable immune reactions. The role of immunity in wart regression remains poorly understood. Nevertheless, the increased frequency of warts in patients receiving immunosuppressive drugs and with immune deficiency states and the immunologic alterations which occur in patients with regressing or cured warts compared to patients with active warts, particularly the increased frequency of cell-mediated responses and antibodies specific for viral antigens, support a possible role for immunity in the resolution of warts. The evidence to date, however, does not prove that immune mechanisms are directly responsible for the elimination of warts.


New shore bug (Hemiptera, Heteroptera, Saldidae) from the Early Cretaceous of China with phylogenetic analyses.
A new genus with a new species of Saldidae, Brevrimatus pulchalifergen. et sp. n., is described and illustrated. The fossil specimen was found from the Early Cretaceous Yixian Formation of Duolun County, Inner Mongolia, China. Phylogenetic analyses within Saldidae were performed, and the results indicate Brevrimatus pulchalifergen. et sp. n. should be assigned to the subfamily Chiloxanthinae.


Ultrabroad Microwave Absorption Ability and Infrared Stealth Property of Nano-Micro CuS@rGO Lightweight Aerogels.
Developing ultrabroad radar-infrared compatible stealth materials has turned into a research hotspot, which is still a problem to be solved. Herein, the copper sulfide wrapped by reduced graphene oxide to obtain three-dimensional (3D) porous network composite aerogels (CuS@rGO) were synthesized via thermal reduction ways (hydrothermal, ascorbic acid reduction) and freeze-drying strategy. It was discovered that the phase components (rGO and CuS phases) and micro/nano structure (microporous and nanosheet) were well-modified by modulating the additive amounts of CuS and changing the reduction ways, which resulted in the variation of the pore structure, defects, complex permittivity, microwave absorption, radar cross section (RCS) reduction value and infrared (IR) emissivity. Notably, the obtained CuS@rGO aerogels with a single dielectric loss type can achieve an ultrabroad bandwidth of 8.44 GHz at 2.8 mm with the low filler content of 6 wt% by a hydrothermal method. Besides, the composite aerogel via the ascorbic acid reduction realizes the minimum reflection loss (RLmin) of - 60.3 dB with the lower filler content of 2 wt%. The RCS reduction value can reach 53.3 dB m2, which effectively reduces the probability of the target being detected by the radar detector. Furthermore, the laminated porous architecture and multicomponent endowed composite aerogels with thermal insulation and IR stealth versatility. Thus, this work offers a facile method to design and develop porous rGO-based composite aerogel absorbers with radar-IR compatible stealth.


Characterization of prickle isoform-specific pk pk1 and pk sple1 mutations in Drosophila melanogaster.
We used paired-end next generation sequencing (NGS) to characterize the classic isoform-specific pk pk1 and pk sple1 mutations of the prickle gene in Drosophila melanogaster . Here we provide evidence that these previously reported null mutations are caused by either a tirant transposon insertion into the 5' UTR of pk pk1 or a premature stop codon in the second exon of pk sple1 . Additional likely benign missense mutations were identified in both mutant isoforms.


Comparative evaluation of oral and dermal cypermethrin exposure on antioxidant profile in Bubalus bubalis.
Cypermethrin, a type II synthetic pyrethroid insecticide, @ 0.5mg/kg/day for 14 consecutive weeks produced mild signs of toxicity in buffalo calves. Significant changes were observed in various antioxidant parameters in blood. There was a marked increase in the extent of lipid peroxidation (33.9%) and enzymic activity of glutathione peroxidase (6.7%), superoxide dismutase (35.0%), catalase (43.7%), glutathione-S-transferase (64.4%), glutathione reductase (36.7%) and glucose-6-phosphate dehydrogenase (32.1%). A significant decrease in blood glutathione (16.7%), total antioxidant activity (45.4%) and vitamin E (40.8%) was observed and no significant effect was found on blood selenium levels. However, the extent of lipid peroxidation (42%) and the depletion of glutathione (28.8%) was greater after dermal sub-acute toxicity of cypermethrin (0.25%) for 14 consecutive days. Similarly, it was observed that the incline in the enzymic activity of glutathione peroxidase (29.7%), superoxide dismutase (38.3%) and glutathione reductase (38.3%) was higher in dermally cypermethrin exposed animals. Thus, the present investigation contemplates that oxidative stress is the important mechanisms involved in cypermethrin-induced toxicity and the oxidative insult produced by dermal route is more severe as compared to oral intoxication.


Characterisation of a nucleo-adhesome.
In addition to central functions in cell adhesion signalling, integrin-associated proteins have wider roles at sites distal to adhesion receptors. In experimentally defined adhesomes, we noticed that there is clear enrichment of proteins that localise to the nucleus, and conversely, we now report that nuclear proteomes contain a class of adhesome components that localise to the nucleus. We here define a nucleo-adhesome, providing experimental evidence for a remarkable scale of nuclear localisation of adhesion proteins, establishing a framework for interrogating nuclear adhesion protein functions. Adding to nuclear FAK's known roles in regulating transcription, we now show that nuclear FAK regulates expression of many adhesion-related proteins that localise to the nucleus and that nuclear FAK binds to the adhesome component and nuclear protein Hic-5. FAK and Hic-5 work together in the nucleus, co-regulating a subset of genes transcriptionally. We demonstrate the principle that there are subcomplexes of nuclear adhesion proteins that cooperate to control transcription.


Clinical relevance of quality of life outcome in cochlear implantation in postlingually deafened adults.
To evaluate the benefits of cochlear implantation in postlingually deafened adults and estimate the clinical relevance of these benefits. Prospective intervention study. Tertiary referral hospital. Forty-four postlingually deafened adults. Cochlear implantation with a Clarion CII HiFocus 1 or HiRes 90K. The Health Utility Index Mark II (HUI2) and Nijmegen Cochlear Implant Questionnaire were administered to quantify health-related QoL (HRQoL); utilities were obtained from the HUI2 and time trade-off instrument. Speech perception scores were analyzed. Patient factors were correlated with postimplant HRQoL and speech perception scores. Clinical significant benefit was estimated using the minimal clinically significant difference (MID) and effect size (ES). The results show a significant improvement in HRQoL and speech perception (p < 0.001). The improvement in HRQoL is mainly obtained in the first months after implantation and is largest in the categories concerning physical functioning (hearing). A shorter duration of deafness (p = 0.003) and higher educational level (p = 0.015) were significant predictors of better speech perception. Cochlear implantation proved to be a cost-effective procedure. By using the MID and ES, we found important clinical improvements on 6 health domains of the Nijmegen Cochlear Implant Questionnaire and on the sensation domain of the HUI2 in most patients; all but 1 of the ESs were large. Cochlear implants have a large and significant positive impact on HRQoL and speech perception and are cost-effective. These improvements are clinically relevant as measured by the MID.


Best practice in brachytherapy.
The 2020 recommendations for good brachytherapy procedures ("Recorad") are updated based on the 2016 article. This new brachytherapy article took into account recent data published in the literature as well as international recommendations. The different brachytherapy steps are successively described from the treatment preparation (brachytherapy technique prescription; procedure and material, dedicated images for planification, dose distribution analysis and validation) to the end of the procedure as well as post-treatment surveillance.


A randomized controlled comparison of guided self-help cognitive behavioral therapy and behavioral weight loss for binge eating disorder.
We performed a randomized controlled study to test the relative efficacy of guided self-help (gsh) cognitive-behavioral therapy (CBTgsh) and behavioral weight loss treatment (BWLgsh) treatments for binge eating disorder (BED). To provide an additional partial control for non-specific influences of attention, a third control (CON) treatment condition was included. We tested the treatments using a guided self-help approach given the promising results from initial studies using minimal therapist guidance. Ninety consecutive overweight patients (19 males, 71 females) with BED were randomly assigned (5:5:2 ratio) to one of three treatments: CBTgsh (N=37), BWLgsh (N=38), or CON (N=15). The three 12-week treatment conditions were administered individually following guided self-help protocols. Overall, 70 (78%) completed treatments; CBTgsh (87%) and CON (87%) had significantly higher completion rates than BWLgsh (67%). Intent-to-treat analyses revealed that CBTgsh had significantly higher remission rates (46%) than either BWLgsh (18%) or CON (13%). Weight loss was minimal and differed little across treatments. The findings suggest that CBT, administered via guided self-help, demonstrates efficacy for BED, but not for obesity. The findings support CBT administered via guided self-help as a first step in the treatment of BED and provide evidence for its specific effects.


Optimization of agro-residues as substrates for Pleurotus pulmonarius production.
The "replacing wood by grass" project can partially resolve the conflict between mushroom production and balancing the ecosystem, while promoting agricultural economic sustainability. Pleurotus pulmonarius is an economically important edible and medicinal mushroom, which is traditionally produced using a substrate consisting of sawdust and cottonseed hulls, supplemented with wheat bran. A simplex lattice design was applied to systemically optimize the cultivation of P. pulmonarius using agro-residues as the main substrate to replace sawdust and cottonseed hulls. The effects of differing amounts of wheat straw, corn straw, and soybean straw on the variables of yield, mycelial growth rate, stipe length, pileus length, pileus width, and time to harvest were demonstrated. Results indicated that a mix of wheat straw, corn straw, and soybean straw may have significantly positive effects on each of these variables. The high yield comprehensive formula was then optimized to include 40.4% wheat straw, 20.3% corn straw, 18.3% soybean straw, combined with 20.0% wheat bran, and 1.0% light CaCO3 (C/N = 42.50). The biological efficiency was 15.2% greater than that of the control. Most encouraging was the indication that the high yield comprehensive formula may shorten the time to reach the reproductive stage by 6 days, compared with the control. Based on the results of this study, agro-residues may be used as a suitable substitution for sawdust and cottonseed hulls as the main cultivation substrates of P. pulmonarius. These results provide a theoretical basis for the "replacing wood by grass" project on edible mushroom cultivation.


Commodity culture: tropical health and hygiene in the British Empire.
Before heading to a 'tropical' region of the Empire, British men and women spent considerable time and effort gathering outfit believed essential for their impending trip. Ordinary items such as soap, clothing, foodstuffs and bedding became transformed into potentially life-saving items that required the fastidious attention of any would-be traveller. Everyone from scientists and physicians to missionaries and administrators was bombarded by relentless advertising and abundant advice about the outfit needed to preserve health in a tropical climate. A closer look at this marketing exercise reveals much about the way people thought about tropical people, places, health and hygiene and how scientific and commercial influences shaped this Imperial commodity culture.


Thrombin and histamine rapidly stimulate the phosphorylation of the myristoylated alanine-rich C-kinase substrate in human umbilical vein endothelial cells: evidence for distinct patterns of protein kinase activation.
Human alpha-thrombin and histamine each stimulates protein phosphorylation in human umbilical vein endothelial cells (HUVEC). We have identified the most prominent of these phosphoproteins by immunoprecipitation as the human homolog of the widely distributed myristoylated alanine-rich C-kinase substrate (MARCKS). Stimulation by 0.1-10 U/ml of alpha-thrombin produces a time-dependent, sustained (plateau 3-5 min) level of MARCKS phosphorylation. MARCKS phosphorylation requires thrombin catalytic activity but not receptor binding and is also seen in response to stimulation by a peptide, TR (42-55), that duplicates a portion of the thrombin receptor tethered ligand created by thrombin proteolytic activity. One micromolar histamine, like alpha-thrombin, produces sustained phosphorylation of MARCKS (plateau 3-5 min). In contrast, 100 microM histamine results in rapid but transient MARCKS phosphorylation (peak 1-3 min). HUVEC treated with 100 microM histamine for 5 min can be restimulated by alpha-thrombin but not fresh histamine, suggesting that the histamine receptor was desensitized. MARCKS phosphorylation can also be induced by several exogenous protein kinase C (PKC) activators and both alpha-thrombin- and histamine-induced MARCKS phosphorylation are inhibited by the PKC antagonist staurosporine. However, while prolonged PMA pretreatment ablates histamine-induced MARCKS phosphorylation, the ability of thrombin to induce MARCKS phosphorylation is retained. These findings provide evidence for agonist-specific pathways of protein kinase activation in response to thrombin and histamine in HUVEC.


Labeling interacting configurations through an analysis of excitation dynamics in a resonant photoemission experiment: the case of rutile TiO2.
A detailed study of resonant photoemission at Ti L(2,3) edges of insulating rutile TiO(2-x) thin film is presented. Pure TiO(2) resonating structures, defect-related resonances, resonant Raman-Auger and normal LVV Auger emissions are tracked, including an unpredicted two-hole correlated satellite below the non-bonding part of the valence band. The analysis of excitation dynamics unambiguously addresses the origin of these features and, in particular, the extent of charge transfer effects on the Ti-O bonding in the valence band of rutile, disclosing further applications to the more general case of, formally, d(0) oxides.


A microwave promoted and Lewis acid catalysed solventless approach to 4-azasteroids.
The preparation of 3-oxo-4-azasteroid from A-nor-3,5-secosteroid-3-oic acid is described in a solventless condition catalysed by Lewis acid under microwave irradiation. We utilized urea as an environmentally benign source for the generation of ammonia for the aza cyclization reaction.


Retail Nutrition Programs and Outcomes: An Evidence Analysis Center Scoping Review.
As nutrition-related diseases contribute to rising health care costs, food retail settings are providing a unique opportunity for registered dietitian nutritionists (RDNs) to address the nutritional needs of consumers. Food as Medicine interventions play a role in preventing and/or managing many chronic conditions that drive health care costs. The objective of this scoping review was to identify and characterize literature examining Food as Medicine interventions within food retail settings and across consumer demographics. An electronic literature search of 8 databases identified 11,404 relevant articles. Results from the searches were screened against inclusion criteria, and intervention effectiveness was assessed for the following outcomes: improvement in health outcomes and cost-effectiveness. One-hundred and eighty-six papers and 25 systematic reviews met inclusion criteria. Five categories surfaced as single interventions: prescription programs, incentive programs, medically tailored nutrition, path-to-purchase marketing, and personalized nutrition education. Multiple combinations of intervention categories, reporting of health outcomes (nutritional quality of shopping purchases, eating habits, biometric measures), and cost-effectiveness (store sales, health care dollar savings) also emerged. The intervention categories that produced both improved health outcomes and cost-effectiveness included a combination of incentive programs, personalized nutrition education, and path-to-purchase marketing. Food as Medicine interventions in the food retail setting can aid consumers in navigating health through diet and nutrition by encompassing the following strategic focus areas: promotion of health and well-being, managing chronic disease, and improving food security. Food retailers should consider the target population and desired focus areas and should engage registered dietitian nutritionists when developing Food as Medicine interventions.


What issues are data scientists talking about? Identification of current data science issues using semantic content analysis of Q&A communities.
Because of the growing involvement of communities from various disciplines, data science is constantly evolving and gaining popularity. The growing interest in data science-based services and applications presents numerous challenges for their development. Therefore, data scientists frequently turn to various forums, particularly domain-specific Q&A websites, to solve difficulties. These websites evolve into data science knowledge repositories over time. Analysis of such repositories can provide valuable insights into the applications, topics, trends, and challenges of data science. In this article, we investigated what data scientists are asking by analyzing all posts to date on DSSE, a data science-focused Q&A website. To discover main topics embedded in data science discussions, we used latent Dirichlet allocation (LDA), a probabilistic approach for topic modeling. As a result of this analysis, 18 main topics were identified that demonstrate the current interests and issues in data science. We then examined the topics' popularity and difficulty. In addition, we identified the most commonly used tasks, techniques, and tools in data science. As a result, "Model Training", "Machine Learning", and "Neural Networks" emerged as the most prominent topics. Also, "Data Manipulation", "Coding Errors", and "Tools" were identified as the most viewed (most popular) topics. On the other hand, the most difficult topics were identified as "Time Series", "Computer Vision", and "Recommendation Systems". Our findings have significant implications for many data science stakeholders who are striving to advance data-driven architectures, concepts, tools, and techniques.


Axoplasmic incorporation of amino acids in a myelinated fiber exceeds that of its soma: a radioautographic study.
The axoplasmic incorporation of amino acids was studied in the giant Mauthner axon to determine its magnitude, to estimate the half-life of the resulting material, and to establish whether or not it undergoes transport. The incorporation of labeled leucine, lysine, and proline was followed by radioautography. The tracers were injected away from the cell body, either in the floor of the IV ventricle or into the spinal cord. Radioautographic reaction on the Mauthner somata was barely discernible. However, at the site of injection, for survivals to 5.6 days, a peak of reaction was observed on the Mauthner axoplasm, with a sharp and symmetric decrement in both central and distal directions; the intensity of the peak decreased with survival (14% at 5.6 days). In intact fibers, the intensity of the reaction was 1.4% compared with that over the Nissl substance of neighboring somata; by contrast, in severed fibers whose axoplasm had been directly exposed to the tracers the reaction rose to 4.1%. At early times, the intensity of the response of the axoplasm as a function of survival of the fish did not have a lag time. In high-resolution radioautograms, most of the grains overlay the ground axoplasm. Cycloheximide depressed the reaction over the fiber open to the extracellular space by 55% whereas only by 20% over the intact fiber. Adsorption of free amino acids or their binding to tRNA were ruled out as a cause of the radioautographic response. Our results indicated that incorporation of amino acids into macromolecules of the Mauthner fiber occurred locally, and its magnitude over the whole axoplasm was estimated to be one order of magnitude larger than that occurring in the soma. The bulk of the material resulting from this incorporation did not undergo transport and survived some days. We suggest that the amino acids were incorporated by a ribosomal mechanism.


Calcium-induced Ca2+ release from sarcoplasmic reticulum of pigs susceptible to malignant hyperthermia. The effects of halothane and dantrolene.
Calcium-induced calcium release and halothane-induced calcium release from pig sarcoplasmic reticulum (SR) were studied. The SR prepared from pigs susceptible to malignant hyperthermia (MH) was shown to release calcium at a much lower level of calcium content than in normal pig SR. The concentration above which halothane can release calcium is 40 microM for both MH-SR and normal SR, although the latter required a high calcium content to demonstrate the calcium release. Dantrolene was shown to inhibit the halothane-induced calcium release. Results suggest that SR plays an important role in pathogenesis of MH.


Inhibitory control of local excitatory circuits in the guinea-pig hippocampus.
1. Exposure to the gamma-aminobutyric acid antagonist, picrotoxin, causes the discharge of hippocampal pyramidal cells to become synchronized. Synaptic mechanisms underlying the development of synchrony were investigated by recording from pairs of cells in the CA3 region of guinea-pig hippocampal slices. 2. Picrotoxin suppressed unitary inhibitory synaptic events. It appeared not to affect monosynaptic excitatory connections. Picrotoxin revealed latent excitatory connections in seven out of twenty-one dual recordings from burst-firing cells. 3. Post-synaptic events revealed by picrotoxin were elicited rarely by single action potentials. They were evoked with mean latencies of at least 8 ms and with more than 30% failures of transmission by bursts of three or more action potentials. They were suppressed by increasing extracellular Ca2+. They were considered to be mediated by polysynaptic excitatory pathways. 4. Polysynaptic excitatory post-synaptic potentials (e.p.s.p.s) had a smooth rising phase with time-to-peak of 15-40 ms and a falling phase of similar duration. Their amplitude was 2-3 mV at membrane potentials close to -70 mV. This shape was similar to that of summed e.p.s.p.s evoked by a burst of three to six action potentials at monosynaptic connections between CA3 cells. 5. One cell could evoke excitatory synaptic events in more than one follower cell, suggesting that axon collaterals mediating recurrent excitation were divergent. More than one polysynaptic excitatory pathway could exist between two cells. 6. We examined the role of recurrent excitatory synapses in the development of synchrony. As inhibition was suppressed by picrotoxin, simultaneous excitatory synaptic events appeared in recordings from pairs of cells. They occurred rhythmically at intervals of 0.5-3 s and grew in amplitude with time. Synchronous neuronal discharges were observed when the threshold for action potential generation was exceeded. 7. Firing induced in one cell could sometimes evoke a sequence of post-synaptic events in another cell as inhibition was suppressed. Initially, no connection was detected. On adding picrotoxin, a polysynaptic e.p.s.p. was revealed and with time longer-latency components were recruited to the synaptic event. The amplitude of later components grew until firing threshold was reached. 8. We suggest that synchronous firing develops due to the loss of inhibitory control over the spread of firing between CA3 pyramidal cells via divergent, polysynaptic, recurrent excitatory pathways.


Ecotoxicological effect of grounded MV River Princess on the intertidal benthic organisms off Goa.
The ecotoxicological effects of oil spill from the grounded vessel MV River Princess on the intertidal benthic organisms of Sinquerim-Candolim beach at Goa were investigated. An intertidal expanse of 1 km on either side of the grounded vessel was selected to evaluate the concentration of total petroleum hydrocarbon (TPH) in the sediment and its effects on the composition, abundance and diversity of micro-, meio- and macrobenthos. TPH in the intertidal sediment ranged from 7.8 to 89 microg g(-1) (mean 35.44+/-26.35 SD). Microbenthos comprised of microalgae, protozoans and juvenile forms of meiobenthos. Apart from juvenile nematodes, which were abundant, Coscinodiscus spp., Navicula spp., and Nitzschia spp. representing microalgae were also observed in microbenthic samples. Meiobenthos was represented by 13 taxa and their total density ranged between 92 and 1057 nos. 10 cm(-2). Maximum meiobenthic abundance of 1057 nos. 10 cm(-2) was observed at Sinquerim. Nematodes were the dominant meiobenthic taxa followed by turbellarians and harpacticoid copepods. The macrobenthos was numerically dominated by polychaetes, followed by crustaceans whereas bivalve molluscs were less represented. There was substantial increase in the petroleum concentration in the beach sediment compared to the previously reported values and highest TPH (89 microg g(-1) sediment) values were in the vicinity of the grounded vessel. The polychaete/amphipod ratio and cumulative and partial dominance abundance-biomass curves showed significant negative impact of TPH on macrofauna. The benthic community structure also showed measurable changes, as there was significant decrease (60%) in the number of species. Given that the microalgal counts were low in sediment, it is assumed that the intertidal meiofauna was possibly using oil-degrading bacteria as alternate food source. In conclusion, the results reported here suggest that the grounded ore carrier is not only detrimental to the beach community, that may take longer time for recovery, but also affects the beach morphology which may have long-term impact on local fishery.


Stepwise 5' DNA end-specific resection of DNA breaks by the Mre11-Rad50-Xrs2 and Sae2 nuclease ensemble.
To repair DNA double-strand breaks by homologous recombination, the 5'-terminated DNA strands must first be resected to produce 3' overhangs. Mre11 from Saccharomyces cerevisiae is a 3' → 5' exonuclease that is responsible for 5' end degradation in vivo. Using plasmid-length DNA substrates and purified recombinant proteins, we show that the combined exonuclease and endonuclease activities of recombinant MRX-Sae2 preferentially degrade the 5'-terminated DNA strand, which extends beyond the vicinity of the DNA end. Mechanistically, Rad50 restricts the Mre11 exonuclease in an ATP binding-dependent manner, preventing 3' end degradation. Phosphorylated Sae2, along with stimulating the MRX endonuclease as shown previously, also overcomes this inhibition to promote the 3' → 5' exonuclease of MRX, which requires ATP hydrolysis by Rad50. Our results support a model in which MRX-Sae2 catalyzes 5'-DNA end degradation by stepwise endonucleolytic DNA incisions, followed by exonucleolytic 3' → 5' degradation of the individual DNA fragments. This model explains how both exonuclease and endonuclease activities of Mre11 functionally integrate within the MRX-Sae2 ensemble to resect 5'-terminated DNA.


Insulin receptor kinase domain autophosphorylation regulates receptor enzymatic function.
We have studied a series of insulin receptor molecules in which the 3 tyrosine residues which undergo autophosphorylation in the kinase domain of the beta-subunit (Tyr1158, Tyr1162, and Tyr1163) were replaced individually, in pairs, or all together with phenylalanine or serine by in vitro mutagenesis. A single-Phe replacement at each of these three positions reduced insulin-stimulated autophosphorylation of solubilized receptor by 45-60% of that observed with wild-type receptor. The double-Phe replacements showed a 60-70% reduction, and substitution of all 3 tyrosine residues with Phe or Ser reduced insulin-stimulated tyrosine autophosphorylation by greater than 80%. Phosphopeptide mapping each mutant revealed that all remaining tyrosine autophosphorylation sites were phosphorylated normally following insulin stimulation, and no new sites appeared. The single-Phe mutants showed insulin-stimulated kinase activity toward a synthetic peptide substrate of 50-75% when compared with wild-type receptor kinase activity. Insulin-stimulated kinase activity was further reduced in the double-Phe mutants and barely detectable in the triple-Phe mutants. In contrast to the wild-type receptor, all of the mutant receptor kinases showed a significant reduction in activation following in vitro insulin-stimulated autophosphorylation. When studied in intact Chinese hamster ovary cells, insulin-stimulated receptor autophosphorylation and tyrosine phosphorylation of the cellular substrate pp185 in the single-Phe and double-Phe mutants was progressively lower with increased tyrosine replacement and did not exceed the basal levels in the triple-Phe mutants. However, all the mutant receptors, including the triple-Phe mutant, retained the ability to undergo insulin-stimulated Ser and Thr phosphorylation. Thus, full activation of the insulin receptor tyrosine kinase is dependent on insulin-stimulated Tris phosphorylation of the kinase domain, and the level of autophosphorylation in the kinase domain provides a mechanism for modulating insulin receptor kinase activity following insulin stimulation. By contrast, insulin stimulation of receptor phosphorylation on Ser and Thr residues by cellular serine/threonine kinases can occur despite markedly reduced tyrosine autophosphorylation.


Assessing glycaemic variability with continuous glucose monitoring system before and after continuous subcutaneous insulin infusion in people with Type 1 diabetes.
We evaluated glycaemic variability with continuous glucose monitoring system in 31 people with Type 1 diabetes mellitus using multiple daily injections initially and after switching to continuous subcutaneous insulin infusion. There was a significant improvement in HbA1c, mean glucose, standard deviation of mean glucose and in hyperglycaemic excursions with CSII.


[Antidepressant effect of L-tryptophan in male rats with dysbalance thyreoid hormones].
The activity of L-tryptophan was studied on young male rats in depressive state caused by thyreoid hormone dysbalance. The immobilization time in the Porsolt forced swim test in thyreoidectomized rats was significantly increased in comparison to the intact control. The replacement therapy with triiodothyronin (T3) reduced the level of depressed behavior to the initial value. Chronic administration of L-tryptophan significantly decreased the total immobilization time in all the test groups, irrespective of the hormonal state. However, the effect of L-tryptophan was more pronounced in T3-treated rats.


Antithrombotic therapy use at discharge and 1 year in patients with atrial fibrillation and acute stroke: results from the AVAIL Registry.
Current American Heart Association/American Stroke Association guidelines identify warfarin use as a class IA indication in patients with atrial fibrillation (AF) and ischemic stroke (IS) or transient ischemic attack (TIA). However, few studies have examined factors associated with long-term antithrombotic therapy use in IS/TIA patients with AF. We utilized the Get With The Guidelines-Stroke national quality improvement registry and the Adherence eValuation After Ischemic Stroke Longitudinal (AVAIL) Registry to examine patterns of antithrombotic use at discharge and at 12 months in IS/TIA patients with AF. A multivariate logistic regression model was developed to identify predictors of warfarin use in this patient population at 12 months. Of the 2460 IS/TIA patients, 291 (11.8%) had AF, of which 5.5% of patients were discharged on aspirin alone, 49.1% on warfarin alone, 1.4% on clopidogrel alone, 34.7% on warfarin plus aspirin, 2.1% on aspirin plus clopidogrel, and 1.0% on aspirin plus clopidogrel plus warfarin. Paradoxically, there was a decrease in the rate of warfarin use in patients with a CHADS2 score>3. The only factor associated with warfarin use at 12-month follow-up was male gender (adjusted odds ratio, 2.27; confidence interval, 1.22-4.35; P=0.01). Overall, the use of warfarin therapy is high at discharge in IS/TIA patients with AF; however, there was a decrease in the rate of warfarin use in patients with a CHADS2 score>3. Compared to women, men were more likely to be on warfarin at 1 year after the index stroke event. Therefore, opportunities exist to improve antithrombotic use in all IS/TIA patients with AF.


Performance of Severe Acute Respiratory Syndrome Coronavirus 2 Real-Time RT-PCR Tests on Oral Rinses and Saliva Samples.
Access to rapid and accurate detection of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is essential for controlling the current global pandemic of coronavirus disease 2019. In this study, the use of oral rinses (ORs) and posterior oropharyngeal saliva as an alternative to swab collection methods from symptomatic and asymptomatic health care workers for the detection of SARS-CoV-2 RNA by RT-PCR was evaluated. For saliva samples, the overall agreement with oropharyngeal swabs was 93% (Ƙ = 0.84), with a sensitivity of 96.7% (95% CI, 83.3%-99.8%). The agreement between saliva and nasopharyngeal swabs was 97.7% (Ƙ = 0.93), with a sensitivity of 94.1% (95% CI, 73.0%-99.7%). ORs were compared with nasopharyngeal swabs only, with an overall agreement of 85.7% (Ƙ = 0.65), and a sensitivity of 63% (95% CI, 46.6%-77.8%). The agreement between a laboratory-developed test based on the CDC RT-PCR and two commercial assays, the Xpert Xpress SARS-CoV-2 and the Cobas SARS-CoV-2, was also evaluated. The overall agreement was >90%. Finally, SARS-CoV-2 RNA in saliva samples was shown to be stable, with no changes in viral loads over 24 hours at both room temperature and 4°C. Although the dilution of SARS-CoV-2 in ORs precluded its acceptability as a sample type, posterior oropharyngeal saliva was an acceptable alternative sample type for SARS-CoV-2 RNA detection.


Chemical defense production in Lotus corniculatus L. II. Trade-offs among growth, reproduction and defense.
Ecological trade-offs between growth, reproduction and both condensed tannins and cyanogenic glycosides were examined in Lotus corniculatus by correlating shoot (leaves and stem) size and reproductive output with chemical concentrations. We found that cyanide concentration was not related to shoot size, but that condensed tannin concentrations were positively correlated with shoot size; larger plants contained higher tannin concentrations. Both tannin and cyanide concentrations were depressed when plants produced fruits. Defense costs change as plants mature and begin to reproduce. These trade-offs indicate that cost of defense chemical production cannot be predicted merely on the basis of molecular size, composition or concentration.


Based on functional and histopathological correlations: is diffusion kurtosis imaging valuable for noninvasive assessment of renal damage in early-stage of chronic kidney disease?
To evaluate the potential of 3 T magnetic resonance diffusion kurtosis imaging (DKI) in assessing the renal damage in early-stage of chronic kidney disease (CKD) patients with normal or slightly changed functional index, using histopathology as reference standard. 49 CKD patients and 18 healthy volunteers were recruited in this study. CKD patients were divided into two groups based on estimated glomerular filtration rate (eGFR): Study group I (eGFR ≥ 90 ml/min/1.73 m2 [n = 20]) and Study group II (eGFR < 90 ml/min/1.73 m2 [n = 29]). DKI was performed in all participants. The DKI parameters (mean kurtosis [MK], mean diffusivity [MD], fractional anisotropy [FA]) of renal cortex and medulla were measured. The differences of parenchymal MD, MK and FA values among the different groups were compared. The correlations between DKI parameters and clinicopathological characteristics were assessed. Diagnostic performance of DKI to assess renal damage in early-stage of CKD was analyzed. The cortex MD and MK showed significant difference among three groups (P < 0.05): trend of cortex MD: Study group II < Study group I < control group; trend of cortex MK: control group < Study group I < Study group II. The cortex MD and MK and medulla FA were correlated with eGFR and Interstitial fibrosis/Tubular atrophy score (0.3 < r < 0.5). Cortex MD and MK yielded an AUC of 0.752 for differentiating healthy volunteers from CKD patients with eGFR ≥ 90 ml/min/1.73 m2. DKI shows potential in non-invasive and multi-parameter quantitative assessment of renal damage in early-stage of CKD patients and provide additional information for changes in renal function and histopathology.


Struvite crystallization induced the discrepant transports of antibiotics and antibiotic resistance genes in phosphorus recovery from swine wastewater.
Struvite (MgNH4PO3·6H2O) crystallization is one of important methods of phosphorus recovery from wastewater. As to livestock wastewater, the high-strength occurrence of antibiotics and antibiotic resistance genes might induce struvite recovery to spread antibiotic resistance to the environment. However, limited information has been reported on the simultaneous transport of antibiotics and ARGs in struvite recovery. In the present study, tetracyclines (TCs) and tetracyclines antibiotic resistance genes (ARGs) were selected as the targeted pollutants, and their discrepant residues in struvite recovery from swine wastewater were investigated. TCs and ARGs were obviously detected, with their contents of 4.88-79.5 mg/kg and 6.99 × 107-2.14 × 1011 copies/g, notably higher than those of TCs 0.550-1.94 mg/kg and ARGs 3.98 × 104-5.66 × 107 copies/g obtained from synthetic wastewater. The correlational relationship revealed that predominant factors affecting TCs and ARGs transports were different. Results from network analyses indicated that among the total edges, the negative correlations between TCs and ARGs predominately occupied 18.0%. The redundancy analysis revealed that mineral components in the recovered products, including struvite, K-struvite and amorphous calcium phosphate, coupling with organic contents, displayed insignificant roles on TCs residues, where heavy metals exerted positive and remarkable functions to boost TCs migration. Unexpectedly, mineral components and heavy metals did not displayed significant promotion on ARGs transport as a whole.


Comparative cost-analysis of two different chronic care facilities for end-stage renal disease patients.
To investigate the cost and quality of life associated with the first specialized chronic care facility for disabled dialysis patients. A case controlled study in dialysis patients admitted to a specialized chronic dialysis unit (RCDU). The study compares the cost of care in a specialized chronic care facility with that of a tertiary hospital. All dialysis patients with severe chronic disability, resident in Greater Toronto, who were unable to be discharged into the community and who were admitted to the RCDU in the first year of the program. Chronic care and rehabilitation services in a specialized dialysis unit. Costs are expressed as $Cdn per patient year. Quality of life scores were measured using SIP and SF-36 questionnaires. The data show a saving of $37,022 Cdn over the 618 day study period with care in the RCDU compared with that of a tertiary hospital. Quality of life measures show no difference in scores. We conclude that this preliminary report confirms a cost benefit of a specialized chronic care dialysis unit.


Influence of age, ability, and angle on pupils' judgments of size of angles.
80 subjects of 11 to 14 years were tested with 8 cards on which were printed angles between 0 degrees and 180 degrees, and on the Raven's Progressive Matrices Test and the Schonell R4 Reading Test. Significant differences on performance were found in relation to age and ability variables and as between angle sizes 0 degrees--90 degrees and 90 degrees--180 degrees.


Distinct families of Z-line targeting modules in the COOH-terminal region of nebulin.
To learn how nebulin functions in the assembly and maintenance of I-Z-I bands, MYC- and GFP- tagged nebulin fragments were expressed in primary cultured skeletal myotubes. Their sites of incorporation were visualized by double staining with anti-MYC, antibodies to myofibrillar proteins, and FITC- or rhodamine phalloidin. Contrary to expectations based on in vitro binding studies, none of the nebulin fragments expressed in maturing myotubes were incorporated selectively into I-band approximately 1.0-micrometer F-alpha-actin-containing thin filaments. Four of the MYC/COOH-terminal nebulin fragments were incorporated exclusively into periodic approximately 0.1-micrometer Z-bands. Whereas both anti-MYC and Rho-phalloidin stained intra-Z-band F-alpha-actin oligomers, only the latter stained the pointed ends of the polarized approximately 1.0-micrometer thin filaments. Z-band incorporation was independent of the nebulin COOH-terminal Ser or SH3 domains. In vitro cosedimentation studies also demonstrated that nebulin SH3 fragments did not bind to F-alpha-actin or alpha-actinin. The remaining six fragments were not incorporated into Z-bands, but were incorporated (a) diffusely throughout the sarcoplasm and into (b) fibrils/patches of varying lengths and widths nested among normal striated myofibrils. Over time, presumably in response to the mediation of muscle-specific homeostatic controls, many of the ectopic MYC-positive structures were resorbed. None of the tagged nebulin fragments behaved as dominant negatives; they neither blocked the assembly nor induced the disassembly of mature striated myofibrils. Moreover, they were not cytotoxic in myotubes, as they were in the fibroblasts and presumptive myoblasts in the same cultures.


Aryl hydrocarbon receptor (AHR), integrating energy metabolism and microbial or obesity-mediated inflammation.
Aryl hydrocarbon receptor (AHR) has been characterized as multifunctional sensor, integrator and ligand-activated transcription factor of the bHLH/PAS family. Regulation of inflammatory diseases and energy metabolism are among the putative functions of AHR. Challenges in AHR research include marked species differences, and cell, tissue and context dependence of AHR functions. The commentary is focused on AHR's role in the integration between energy expenditure and microbial and non-infectious inflammation, the latter exemplified by obesity-mediated nonalcoholic fatty liver disease. One of the mechanisms controlling energy-consuming inflammation is represented by a signalsome that is involved in retinoic acid-triggered neutrophil differentiation and regulation of the NADPH oxidase complex (NOX). Established signalsome components are AHR, CD38, multiple protein kinases and adaptors. To prevent chronic inflammatory diseases, the complex interplay between a range of inflammatory responses and energy expenditure must be precisely regulated. Surviving an infection requires both pathogen clearance and tissue protection from inflammatory damage. Defenses are energy-consuming anabolic programs. Therefore, anti-inflammatory, catabolic tolerance programs by metabolic reprogramming of macrophages have evolved. Therapeutic options of AHR agonists to reduce chronic inflammatory diseases are discussed.


MAKO robot-assisted total knee arthroplasty cannot reduce the aggravation of ankle varus incongruence after genu varus correction ≥ 10°: a radiographic assessment.
The objective of this study was to investigate the ankle alignment alterations after the correction of knee varus deformity in MAKO robot-assisted total knee arthroplasty (MA-TKA). A retrospective analysis was conducted for 108 patients with TKA from February 2021 to February 2022. Patients were divided into two groups based on MAKO robot involvement during the procedure: the MA-TKA group (n = 36) and the conventional manual total knee arthroplasty (CM-TKA) group (n = 72). The patients were divided into four subgroups according to the degree of surgical correction of the knee varus deformity. Seven radiological measurements were evaluated pre and post-surgery: mechanical tibiofemoral angle (mTFA), mechanical lateral distal femoral angle (mLDFA), medial proximal tibial angle (MPTA), lateral distal tibial angle (LDTA), tibial plafond inclination angle (TPIA), talar inclination angle (TIA), and tibiotalar tilt angle (TTTA). TTTA is a quantitative representation of the extent of ankle incongruence. The number of mTFA, mLDFA, and MPTA outliers in the MA-TKA group was significantly lower compared to the CM-TKA group (P<0.05). Knee varus deformity was properly corrected and the mechanical axis was restored in all patients, regardless of the treatment group. Only for varus corrections ≥ 10° did TTTA change significantly (p < 0.01) and ankle varus incongruence aggravate post-operation. The ΔTTTA correlated negatively with ΔTFA (r=-0.310,P = 0.001) and correlated positively with ΔTPIA (r = 0.490,P = 0.000). When the varus correction was ≥ 7.55°, the probability of ankle varus incongruence exacerbation increased 4.86-fold. Compared with CM-TKA, MA-TKA osteotomy showed more precision but was unable to reduce post-operation ankle varus incongruence. When the varus correction ≥ 10°, ankle varus incongruence aggravated, while when the varus correction ≥ 7.55°, the probability of ankle varus incongruence increased 4.86-fold. This may occasion the pathogenesis of ankle pain following TKA.


MR Imaging of the Musculoskeletal System Using Ultrahigh Field (7T) MR Imaging.
MR imaging is an indispensable instrument for the diagnosis of musculoskeletal diseases. In vivo MR imaging at 7T offers many advantages, including increased signal-to-noise ratio, higher spatial resolution, improved spectral resolution for spectroscopy, improved sensitivity for X-nucleus imaging, and decreased image acquisition times. There are also however technical challenges of imaging at a higher field strength compared with 1.5 and 3T MR imaging systems. We discuss the many potential opportunities as well as the challenges presented by 7T MR imaging systems and highlight recent developments in in vivo research imaging of musculoskeletal applications in general and cartilage, skeletal muscle, and bone in particular.


Modulation of nociception and pain-evoked neurobehavioral responses by levetiracetam in a craniotomy pain model.
Traditional and novel analgesic modalities have been extensively tested for post-craniotomy pain management, yet the role of newer antiepileptic drugs in this area remains obscure. This study investigates the impact of levetiracetam (LEV) on pain modulation and neurobehavioral performance in a craniotomy model. Fifty-six Wistar rats were randomly assigned into seven groups: no intervention (CTRL), administration of placebo or LEV with no further intervention (PBO and LEV, respectively), and sham-operation or craniotomy in placebo (PBO-SHAM and PBO-CR, respectively) or LEV-treated rats (LEV-SHAM and LEV-CR, respectively). Pain was assessed by the rat grimace scale before, and at 8 and 24 h after craniotomy, following intraperitoneal injections of LEV (100 mg/kg twice daily) or normal saline two consecutive days before and on the craniotomy day. Elevated plus-maze and olfactory social memory tests were performed at 24- and 48 h post-craniotomy, respectively. Upon testing conclusion blood samples were collected for cytokines estimation. Levetiracetam administration enhanced antinociception in sham and craniotomy groups. In the elevated plus-maze test, LEV-CR rats spent more time in investigating open arms and performed more open arm entries than PBO-SHAM and PBO-CR animals. The olfactory test revealed no between-groups difference in acquisition time during first contact with a juvenile rat, while LEV-CR rats spent less time to recognize the same juvenile rat compared to PBO-SHAM and PBO-CR groups. Furthermore, LEV-treatment attenuated cortisol, interleukin-6 and TNF-a release, in sham and craniotomy animals. In conclusion, preemptive use of LEV decreases nociception, improves pain-evoked behavior and attenuates stress response in rats subjected to craniotomy.


Laparoscopic adjustable gastric banding for morbid obesity in a patient with situs inversus totalis.
Laparoscopic surgery with situs inversus may pose particular challenges to the surgeon. We discuss a case of undiagnosed situs inversus totalis in a morbidly obese patient undergoing laparoscopic adjustable gastric banding (LAGB). The patient was a 29-year-old male with a body mass index (BMI) of 56. There was no prior knowledge of his situs inversus totalis, which was only discovered during laparoscopy at the time of surgery. The operative challenges are discussed. LAGB was performed successfully without complication. Postoperative imaging confirmed dextrocardia and situs inversus totalis, as well as correct gastric band position. However, there has been subsequent gastric band erosion and eventual band removal. We discuss the appropriateness of LAGB in this group of patients.


Trends in cardiovascular burden and mortality among adults with prediabetes in the US, 1999-2018.
Trends in cardiovascular disease (CVD) risk factors and mortality have been reported among US adults with diabetes, but not among those with prediabetes. This study aimed to examine and compare the trends in CVD risk factors and mortality in US adults with diabetes and prediabetes. In this serial, cross-sectional study, medical records of prediabetic patients from the National Health and Nutrition Examination Survey (NHANES) among adults aged 18 years or older were retrospectively reviewed. Data on 17,193 individuals including 7803 with diabetes and 9390 with prediabetes were analyzed from 1999-2000 to 2017-2018. A similar non-linear trend in the mean blood pressure (p = .991) and plasma fasting glucose (p = .068) was observed among the population with diabetes and prediabetes. The mean hemoglobin A1c decreased from 7.5% to 7.1% in diabetes and the trend was different from that in prediabetes (p = .004). Among both groups, a significant decline in the mean total cholesterol was identified while there was a difference in the trend (p = .003). The prevalence of hypertension remained largely the same for diabetes and it declined from 59.8% to 48.8% for prediabetes (p = .044). The prevalence of dyslipidemia increased from 40.4% to 53.5% in diabetes and it remained stable for prediabetes. The all-cause mortality decreased from 148.2 to 93.6 per 10,000 person-years between 1999-2006 and 2007-2014 in prediabetes and heart diseases mortality remained unchanged. In the US from 1999 to 2018, the adults with prediabetes had different secular trends in the mean hemoglobin A1c and the prevalence of hypertension and dyslipidemia compared to those with diabetes. There was a significant reduction in all-cause mortality from 1999 to 2014 for the population with prediabetes. However, heart diseases mortality remained stable among them.


Effect of the duration of macular edema on clinical outcomes in retinal vein occlusion treated with dexamethasone intravitreal implant.
To assess the effect of duration of macular edema (ME) on clinical outcomes after treatment with dexamethasone intravitreal implant 0.7 mg (Ozurdex; Allergan, Inc, Irvine, CA) in patients with ME following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO). Post hoc analysis of pooled data from 2 randomized, controlled trials. Patients with vision loss resulting from ME of 6 weeks' duration or more after BRVO or CRVO (n = 690). The relationship between ME duration at the time of first treatment and treatment outcomes was assessed using logistic regression. Other factors potentially associated with ME duration or patient outcomes were adjusted for in the analyses. The proportion of patients achieving at least 15 letters improvement in best-corrected visual acuity (BCVA) or at least 200-μm or more reduction in central retinal thickness 6 or 12 months after the first treatment with dexamethasone intravitreal implant 0.7 mg. In the 6-month analysis, each 1-month increase in ME duration was associated with a significantly lower likelihood of achieving a BCVA improvement of 15 letters or more (odds ratio [OR], 0.88; 95% confidence interval [CI], 0.83-0.94; P<0.001) or a CRT reduction of 200-μm or more (OR, 0.91; 95% CI, 0.86-0.97; P<0.01) 6 months after treatment. In the 12-month analysis, increased ME duration was associated with a significantly lower likelihood of achieving BCVA improvement of 15 letters or more improvement in BCVA (OR, 0.85; 95% CI, 0.76-0.95; P<0.01) 12 months after treatment; duration was not significantly associated with the likelihood of a CRT reduction of 200-μm or more at 12 months. In general, the effect of ME duration on outcomes was stronger and statistically significant in BRVO patients, but weaker and not statistically significant in CRVO patients. In eyes with retinal vein occlusion, longer ME duration at the time of first treatment with the dexamethasone intravitreal implant 0.7 mg was associated with a significantly lower likelihood of achieving clinically meaningful improvements in vision or CRT 6 or 12 months after treatment. This suggests that prompt treatment for retinal vein occlusion, particularly BRVO, may be associated with improved clinical outcomes. Proprietary or commercial disclosure may be found after the references.


Proteinase-like peptidase activities in malignant and non-malignant gastric tissue.
Activities of several proteinase-like peptidases have been determined in homogenates of malignant tissue, non-malignant tissue adjacent to the tumour (A-NM) and non-malignant tissue distant to the tumour (D-NM) from 17 patients undergoing surgery for histologically confirmed gastric malignancies. In homogenates of malignant tissues the activities of collagenase, cathepsin B, cathepsin (B+L), cathepsin H and cathepsin D were significantly higher than in D-NM tissues. By contrast, the levels of plasminogen activator were significantly lower in malignant tissues than in the D-NM tissues. Furthermore, the activities of collagenase-like and the cysteine-proteinase-like peptidases in the A-NM tissues were lower than in malignant tissues but higher than in the D-NM tissues. Separation of full-thickness non-malignant tissues into mucosal and seromuscular layers revealed significantly higher activities in the former. The elevated levels of these proteinase-like peptidases in homogenates of gastric cancer tissue suggests an important role for these enzymes in tumour invasion.


Coagulopathy of disseminated neuroblastoma.
We performed coagulation studies in 16 patients with advanced neuroblastoma. Four of these patients had major hemorrhagic or thromboembolic complications. Abnormal coagulation screening tests were seen in all patients with active metastatic disease. We also measured plasma fibrinopeptide A, a sensitive measure of intravascular thrombin generation. Increased concentrations of fibrinopeptide A were found in each patient studied with active metastatic disease. Coagulopathy is a frequent finding in metastatic neuroblastoma and may cause severe morbidity. Laboratory studies suggesting either hyper- or hypocoagulability are frequent findings.


Comparing functional metabolic effects of marginal and sufficient selenium supply in sheep.
This study was performed to characterise key data of long-term ovine Se metabolism and to work out the best biomarker of Se status. An upgrade from marginal (<0.05 mg Se/kg diet, 'Se-') to sufficient (0.2mg Se/kg diet, 'Se+') nutritional Se supply using sodium selenite was monitered biweekly by analysing Se concentration, glutathione peroxidase (Gpx) activity and routine biochemistry in blood/serum over 2 years. Se, Cu, Zn, cytosolic Gpx and thioredoxin reductase (TrxR) activity were measured in the liver (biopsies/post-mortem). Se, Gpx, TrxR, glutathione-S-transferase-alpha (aGST) and iodothyronine deiodinase (Dio1) were analysed in the kidney, heart muscle and thyroid. Relative mRNA expression of hepatic aGST1 and Gpx1 was determined. Improvement of Se supply strongly increased serum and liver Se concentration within 10 and 20 days, respectively followed by a plateau. Whereas the achievement of a maximum whole blood Gpx activity was reached after 3 months, serum Gpx3 activity increased with high variations. Hepatic Gpx activity reached a maximum during days 100-200, decreasing thereafter. Distinct group differences in Se and cytosolic Gpx activity were evident in all organs (except Se in kidney). TrxR and Dio1 activity was affected only in the liver. The Se- sheep showed an ongoing decrease in serum Se concentration within 2 years, whereas liver Se remained almost unaffected. High relative Gpx1 mRNA expression in the Se+ group was consensual to high hepatic Gpx activity. Relative mRNA expression of hepatic aGST1 was higher in the Se- sheep. Clinical signs and abnormalities in routine biochemistry were absent. In summary, the best biomarker of Se deprivation and nutritional Se upgrade, respectively was Se in serum. Moreover, hepatic Se concentrations reliably reflected the upgrade of Se supply within days. Whole blood Gpx reacts slowly depending on newly formed erythrocytes restricting its diagnostic use. Vital organs are affected by Se deficiency due to a decrease of cytosolic Gpx activity attenuating the antioxidative system. Cellular up-regulation of aGST1 mRNA expression in the Se- group is assumed to partially compensate for the decreased antioxidant defence due to a loss in Gpx activity. This sheep model appears advantageous for long-term studies on sub-clinical metabolic effects in experimental modifiable nutritional Se supply.


An evaluation of tinidazole as single-dose therapy for the treatment of Trichomonas vaginalis.
Fifty patients suffering from Trichomonas vaginalis infection were treated with a single dose of four 500 mg tablets of tinidazole; 41 patients returned for follow-up, and 39 of these were judged to be cured by the results of microscopic examination and culture of vaginal secretion.


Translation and validation of the Arabic version of the General Medication Adherence Scale (GMAS) in Saudi patients with chronic illnesses.
The study aimed to translate and validate the Arabic version of General Medication Adherence Scale (GMAS) in Saudi patients with chronic diseases. A multi-center cross sectional study was conducted for a month in out-patient wards of hospitals in Khobar, Dammam, Makkah, and Madinah, Saudi Arabia. Patients were randomly selected from a registered patient pools at hospitals and the item-subject ratio was kept at 1:20. The tool was assessed for factorial, construct, convergent, known group and predictive validities as well as, reliability and internal consistency of scale were also evaluated. Sensitivity, specificity, and accuracy were also evaluated. Data were analyzed using SPSS v24 and MedCalc v19.2. The study was approved by concerned ethics committees (IRB-129-25/6/1439) and (IRB-2019-05-002). A total of 282 responses were received. The values for normed fit index (NFI), comparative fit index (CFI), Tucker Lewis index (TLI) and incremental fit index (IFI) were 0.960, 0.979, 0.954 and 0.980. All values were >0.95. The value for root mean square error of approximation (RMSEA) was 0.059, i.e., <0.06. Hence, factorial validity was established. The average factor loading of the scale was 0.725, i.e., >0.7, that established convergent validity. Known group validity was established by obtaining significant p-value <0.05, for the associations based on hypotheses. Cronbach's α was 0.865, i.e., >0.7. Predictive validity was established by evaluating odds ratios (OR) of demographic factors with adherence score using logistic regression. Sensitivity was 78.16%, specificity was 76.85% and, accuracy of the tool was 77.66%, i.e., >70%. The Arabic version of GMAS achieved all required statistical parameters and was validated in Saudi patients with chronic diseases.


Dental attendance among low-income women and their children following a brief motivational counseling intervention: A community randomized trial.
This study tested a behavioral intervention to increase dental attendance among rural Oregonian low-income women and their children. It utilized a multi-site, single-blind, randomized trial design. Four hundred women were randomized into one of four conditions to receive prenatal or postpartum motivational interviewing/counseling (MI) or prenatal or postpartum health education (HE). Counselors also functioned as patient navigators. Primary outcomes were dental attendance during pregnancy for the mother and for the child by age 18 months. Attendance was obtained from the Oregon Division of Medical Assistance Programs and participant self-report. Statewide self-reported utilization data were obtained from the Oregon Pregnancy Risk Assessment Monitoring System (PRAMS). Maternal attendance was 92% in the prenatal MI group and 94% in the prenatal HE group (RR = 0.98; 95% CI = 0.93-1.04). Children's attendance was 54% in postpartum MI group and 52% in the postpartum HE group (RR = 1.03; 95% CI = 0.82-1.28). Compared to statewide PRAMS, attendance was higher during pregnancy for study mothers (45% statewide; 95% CI = 40-50%) and for their children by 24 months (36% statewide; 95% CI = 27-44%). MI did not lead to greater attendance when compared to HE alone and cost more to implement. High attendance may be attributable to the counselors' patient navigator function. ClinicalTrials.gov Identifier NCT01120041.