Effects of the COVID-19 pandemic on maternal and perinatal health service utilisation and outcomes in Mozambique: an interrupted time series analysis.
To measure the effects of the COVID-19 pandemic on maternal and perinatal health services and outcomes in Mozambique. This is an observational study analysing routine service delivery data using interrupted time series analysis. We used 43 months of district-level panel data with April 2020 as the point of interruption, adjusting for seasonality and population growth to analyse service utilisation outcomes. The 222 public health facilities in Nampula Province, Mozambique, from January 2018 to July 2021. The change in the number of antenatal care (ANC) visits and facility deliveries, and the change in the rate of adverse birth outcomes at pandemic onset and over time compared with expected levels and trends, respectively. There were no significant disruptions to ANC at pandemic onset. Following this, there was a significant monthly increase of 29.8 (18.2-41.4) first ANC visits and 11.3 (5.5-17.2) ANC visits within the first trimester per district above prepandemic trends. There was no significant change in the number of fourth ANC visits completed. At the onset of COVID-19, districts experienced a significant decrease of 71.1 (-110.5 to -31.7) facility deliveries, but the rate then increased significantly above prepandemic trends. There was no significant increase in any adverse birth outcomes during the pandemic. Conversely, districts observed a significant monthly decrease of 5.3 uterine rupture cases (-9.9 to -0.6) and 19.2 stillbirths (-33.83 to -4.58) per 100 000 facility deliveries below prepandemic trends. There was a significant drop of 23.5 cases of neonatal sepsis/100 000 facility deliveries per district at pandemic onset. Despite pandemic interference, Nampula Province saw no disruptions to ANC, only temporary disruptions to facility deliveries and no increases in adverse birth outcomes. ANC visits surprisingly increased, and the rates of uterine rupture, stillbirth and neonatal sepsis decreased, suggesting that Nampula Province may offer insights about health system resilience.


Primary carcinoid tumor of the liver: A case report.
A53-year-old woman was hospitalized with a hepatic tumor that had been detected on health-screening ultrasonography. Laboratory data showed no marked findings: HBs-Ag and HCV-Ab were negative, and levels of serum AFP, PIVKA-II, CEA, and CA 19-0 were within their normal ranges. Ultrasonogram showed a hyperechoic circle concentric with and inside of a hypoechoic mass in the right hepatic lobe. The tumor appeared isodense with the surrounding liver in unenhanced CT, but enhanced CT showed a low density mass. A celiac arteriogram revealed a hypervascular tumor. The resected tumor measured 20×15 mm. Microscopic findings showed a carcinoid tumor that was positive for Grimelius stain. Further examination of the lung, gastrointestinal tract, and other organs found no primary carcinoid tumor. The patient has been well and free from tumor of the liver or elsewhere for the 7 years since her operation. We therefore considered this lesion to have been a primary carcinoid tumor of the liver. Only 14 cases of this disease have ever been reported in Japan. This report includes a review of the literature on the imaging of this rare tumor.


Effect of the National Diabetes Prevention Program on Weight Loss for English- and Spanish-Speaking Latinos.
To study the effect of the National Diabetes Prevention Program (NDPP) on weight loss in Latinos. No-control, cohort study comparing Latino and non-Hispanic white (NHW) participants. A health-care system. Five hundred sixty-seven Latino and 175 NHW patients who enrolled in the NDPP. A total of 45.2% of Latinos selected the Spanish-language NDPP. The NDPP is a nationwide translation of a clinical trial and seeks to prevent diabetes through weight loss in a yearlong group program. Independent variables included ethnicity, class language, and number of sessions attended. Main outcomes were initial attendance, number of sessions attended, and weight loss. Multivariate logistic regression and analysis of covariance were used to determine differences in NDPP outcomes by ethnicity, language, and number of sessions attended. Mean attendance was 8.60 of 22 sessions. Each session was associated with 0.30% (±0.02; P < .001) body weight loss. Latinos were half as likely to attend as NHWs, odds ratio 0.52 ( P < .001). Latino attendees came to 2.67 ± 0.63 ( P < .001) fewer sessions than NHWs. There were no weight loss differences by ethnicity after controlling for attendance. Outcomes did not differ among Latinos in the English- and Spanish-language NDPP. Latinos appeared to benefit less from the NDPP compared to NHWs, likely due to lower attendance rates. Further efforts are needed to support their participation.


The potential risk of using historic claims to set bundled payment prices: the case of physical therapy after lower extremity joint replacement.
One of the most significant challenges of implementing a multi-provider bundled payment contract is to determine an appropriate, casemix-adjusted total bundle price. The most frequently used approach is to leverage historic care utilization based on claims data. However, those claims data may not accurately reflect appropriate care (e.g. due to supplier induced demand and moral hazard effects). This study aims to examine variation in claims-based costs of post-discharge primary care physical therapy (PT) utilization after total knee and hip arthroplasties (TKA/THA) for osteoarthritis patients. This retrospective cohort study used multilevel linear regression analyses to predict the factors that explain the variation in the utilization of post-discharge PT after TKA or THA for osteoarthritis patients, based on the historic (2015-2018) claims data of a large Dutch health insurer. The factors were structured as predisposing, enabling or need factors according to the behavioral model of Andersen. The 15,309 TKA and 14,325 THA patients included in this study received an average of 20.7 (SD 11.3) and 16.7 (SD 10.1) post-discharge PT sessions, respectively. Results showed that the enabling factor 'presence of supplementary insurance' was the strongest predictor for post-discharge PT utilization in both groups (TKA: β = 7.46, SE = 0.498, p-value< 0.001; THA: β = 5.72, SE = 0.515, p-value< 0.001). There were also some statistically significant predisposing and need factors, but their effects were smaller. This study shows that if enabling factors (such as supplementary insurance coverage or co-payments) are not taken into account in risk-adjustment of the bundle price, they may cause historic claims-based pricing methods to over- or underestimate appropriate post-discharge primary care PT use, which would result in a bundle price that is either too high or too low. Not adjusting bundle prices for all relevant casemix factors is a risk because it can hamper the successful implementation of bundled payment contracts and the desired changes in care delivery it aims to support.


Uridine diphosphate galactose 4-epimerase. Alkylation of enzyme-bound diphosphopyridine nucleotide by p-(bromoacetamido)phenyl uridyl pyrophosphate, an active-site-directed irreversible inhibitor.
When UDP-galactose 4-epimerase is inactivated by p-(bromoacetamido)phenyl uridyl pyrophosphate (BUP), the diphosphopyridine nucleotide (DPN) associated with this enzyme as a tightly bound coenzyme cannot be reduced by substrates or by UMP-activated reduction by glucose. Upon acid denaturation of the inactivated enzyme, the DPN released corresponded to 15-30% of that released from the native enzyme. When the enzyme is inactivated by [14C]BUP, about 80% of the radioactivity bound at the active site is released from the protein upon acid denaturation. When epimerase-[3H]DPN is inactivated with [14C]BUP, the 3H and 14C released from the protein upon denaturation of the complex cochromatograph on DEAE-Sephadex. Experiments with [nicotinamide-4-3H]DPN and [adenine-2,8-3H]DPN show that it is the adenine ring that is alkylated. The data suggest that the adenine ring of DPN in epimerase-DPN may be oriented near the glycosyl-binding subsite of this enzyme. Since the nicotinamide ring must also be near this site, it appears that the DPN may not be in an extended conformation when it is bound at the active site of UDP-galactose 4-epimerase from Escherichia coli.


Impact of the first 5 years of a national abdominal aortic aneurysm screening programme.
The Abdominal Aortic Aneurysm (AAA) Screening Programme was introduced by the National Health Service (NHS) in England to reduce the rate of death from ruptured AAA in men. The programme commenced in 2009 and was implemented completely across the country in April 2013. The aim was to review the first 5 years of the programme, looking specifically at compliance and early outcome. Men aged 65 years were invited for a single abdominal ultrasound scan. Data were entered into a bespoke database (AAA SMaRT). This was a planned analysis after the first 5 years of the programme. The summation analysis involved the first 700 000 men screened, and the first 1000 men with a large AAA referred for possible treatment. The prevalence of AAA (aortic diameter larger than 2·9 cm) in 65-year-old men was 1·34 per cent. Mean uptake was 78·1 per cent, but varied from 61·7 to 85·8 per cent across the country. Based on the Index of Multiple Deprivation, uptake was 65·1 per cent in the most deprived versus 84·1 per cent in the least deprived areas. Of the first 1000 men referred for possible treatment of a large AAA (greater than 5·4 cm), the false-positive rate was 3·2 per cent. Some 870 men underwent a planned AAA intervention (non-intervention rate 9·2 per cent), with seven deaths (perioperative mortality rate 0·8 per cent). The processes in the NHS AAA Screening Programme are effective in detecting and treating men with AAA.


HTLV-2 infection in Manaus, Brazil: first description of HTLV-2c subtype in an urban area of the Western Amazon region.
We investigated the prevalence of human T-cell lymphotropic virus types 1 and 2 (HTLV-1/2) infection in patients with hematological diseases from the western Amazon region of Brazil. Samples from 306 patients were submitted for the molecular diagnosis of HTLV-1/2 infection by real time PCR (qPCR), with amplification, sequencing, and phylogenetic analysis of the long terminal repeat (LTR) region. A 29-year-old male carrier of sickle cell anemia with a history of multiple blood transfusions was diagnosed with the HTLV-2c subtype. This study describes the first known occurrence of HTLV-2c in the urban area of Brazil's western Amazon region.


[Significance of the correlation between follicle-stimulating and luteinizing components in the pregnant mare serum--relevance to results of biotechnical regulation of reproduction].
Full assessment of the correlation between follicle-stimulating and luteinising components in PMS is of greatest importance to progress in bio-engineering action to regulate reproduction processes. Biological tests ought to be developed that are of high specificity and convenient applicability to practice conditions. Studies into the components of "raw" PMS will enable high-economy and specific use of such serum in animal husbandry.


A prospective cohort study of the impact of outpatient Intensive Cardiac Rehabilitation on depression and cardiac self-efficacy.
To evaluate whether an Intensive Cardiac Rehabilitation (ICR) program improves depression and cardiac self-efficacy among patients with a qualifying cardiac diagnosis. Prospective, longitudinal cohort design. Single-center, tertiary referral, outpatient cardiac rehabilitation center. Patients with a qualifying diagnosis for ICR. Outpatient ICR. Mental health, as assessed using the Patient Health Questionnaire-9 (PHQ-9) and cardiac self-efficacy using the Cardiac Self-Efficacy (CSE) scale. Of the 268 patients included (median age 69 y, 73% men), 70% had no depressive symptoms at baseline (PHQ-9 score <5). PHQ-9 scores improved in the overall sample (p < 0.0001), with greater improvements among patients with mild depressive symptoms at baseline (-4 points, p < 0.001) and those with moderate to severe depressive symptoms at baseline (-5.5 points, p < 0.001). Cardiac self-efficacy improved overall, and the two subsections of the cardiac self-efficacy questionnaire titled, "maintain function" and "control symptoms" improved (all p < 0.001). Participation in an outpatient ICR program is associated with fewer depressive symptoms and greater cardiac self-efficacy among patients with CVD who qualify for ICR. The improvement in depression was greatest for those with moderate to severe depressive symptoms.


Presence and distribution of insect-associated and entomopathogenic fungi in a temperate pine forest soil: An integrated approach.
For decades entomopathogenic fungi have garnered interest as possible alternatives to chemical pesticides. However, their ecology outside of agroecosystems demands further study. We assessed the diversity and abundance of entomopathogenic and insect-associated fungi at a loblolly pine forest in North Carolina, USA using culture-dependent and next-generation sequencing libraries. Fungi were isolated using Galleriamellonella larvae, as well as from soil dilutions plated on a selective medium. Isolates were identified using Sanger sequencing of the ITS and LSU rRNA gene regions, and represented 36 OTUs including Metarhizium, Lecanicillium, and Paecilomyces. Additionally, we assessed the chitinolytic potential of isolates and found widespread, variable ability to degrade chitin within and between genera. Phylogenetic analyses resolved several isolates to genus, with some forming clades with other insect-associated taxa, as well as with fungi associated with plant tissues. Saprophytes were widely distributed in soil, while entomopathogens were less abundant and present primarily in the top two cm of the soil. The similarity between culture-dependent and next-generation sequencing results demonstrates that both methods can be used concurrently in this system to study the ecology of entomopathogenic fungi.


Arabidopsis immune-associated nucleotide-binding genes repress heat tolerance at the reproductive stage by inhibiting the unfolded protein response and promoting cell death.
Plants are vulnerable to heat stress, especially during reproductive development. The heat shock response (HSR) in the cytosol and nucleus, as well as the unfolded protein response (UPR) in the endoplasmic reticulum (ER), are two mechanisms that enable plants to survive heat stress. Excessive heat or ER stresses lead to cell death when the UPR cannot repair stress damage, but the means by which cell survival or death is determined remains unclear. In this study, we used a genome-wide association study (GWAS) to identify that a cluster of five Immune-associated nucleotide-binding protein (IAN) genes (IAN2 to IAN6) is responsible for variation in heat tolerance at the reproductive stage in Arabidopsis thaliana. These IAN genes have both unique and overlapping functions in the negative regulation of heat tolerance, and their loss of function singly or in combination confers increased heat tolerance, measured by a lower number of barren siliques and a higher seedling survival rate under heat. The loss of rice IAN1 gene function also leads to enhanced heat tolerance, suggesting a conserved function of plant IANs. Transcriptome analysis revealed enhanced expression of HSR and UPR genes, as well as reduced cell death, under heat and ER stress in the mutant of IAN6, a major effect member in Arabidopsis. Furthermore, the IAN proteins were found to promote cell death induced by heat stress, ER stress, and cell death-inducing molecules. Thus, the Arabidopsis IAN genes repress heat tolerance, probably through the HSR and UPR and by enhancing the cell death pathway. The IAN2 to IAN6 proteins are partially localized to the ER, suggesting a direct role in the UPR and UPR-mediated cell death. In addition, a natural IAN6 variant from more heat-tolerant Arabidopsis accessions confers greater heat tolerance and induces less cell death compared with the natural variant from less heat-tolerant accessions. The heat-tolerant IAN6 variant is associated with a higher maximum temperature of the warmest month at its collection sites compared with the heat-sensitive variant. Taken together, these results reveal an important role of Arabidopsis IAN2 to IAN6 genes in the regulation of the HSR, UPR, and cell death, and suggest that their natural variations have adaptive functions in heat tolerance.


The in-capillary DPPH-capillary electrophoresis-the diode array detector combined with reversed-electrode polarity stacking mode for screening and quantifying major antioxidants in Cuscuta chinensis Lam.
An in-capillary 2, 2-diphenyl-1-picrylhydrazyl (DPPH)-CE-the DAD (in-capillary DPPH-CE-DAD) combined with reversed-electrode polarity stacking mode has been developed to screen and quantify the active antioxidant components of Cuscuta chinensis Lam. The operation parameters were optimized with regard to the pH and concentration of buffer solution, SDS, β-CDs, organic modifier, as well as separation voltage and temperature. Six antioxidants including chlorogenic acid, p-coumaric acid, rutin, hyperin, isoquercitrin, and astragalin were screened and the total antioxidant activity of the complex matrix was successfully evaluated based on the decreased peak area of DPPH by the established DPPH-CE-DAD method. Sensitivity was enhanced under reversed-electrode polarity stacking mode and 10- to 31-fold of magnitude improvement in detection sensitivity for each analyte was attained. The results demonstrated that the newly established in-capillary DPPH-CE-DAD method combined with reversed-electrode polarity stacking mode could integrate sample concentration, the oxidizing reaction, separation, and detection into one capillary to fully automate the system. It was considered a suitable technique for the separation, screening, and determination of trace antioxidants in natural products.


Bilateral anterior and posterior scleritis in a patient with acute myelogenous leukemia.
To report a novel case of bilateral anterior and posterior scleritis in a patient with acute myelogenous leukemia (AML). A 69-year-old African American man was admitted to the hospital for relapse of AML. After admission, but prior to induction of chemotherapy, the patient developed ocular redness and proptosis. The diagnosis of bilateral anterior and posterior scleritis was made following an ophthalmic examination, infectious and autoimmune lab work-up, and neuroimaging. The patient was administered immunosuppressive therapy, clinically monitored, and initiated on chemotherapy for AML relapse. About one week later, the patient showed clinical improvement and resolution of the scleritis and proptosis. Scleritis may present during AML relapse, and it may be due to a paraneoplastic syndrome or a reactive anti-leukemic inflammatory response. Clinicians should monitor patients with AML relapse for symptoms such as ocular redness, proptosis, pain, photophobia, and decreased vision, which may indicate development of scleritis.


Infectious bursal disease virus-induced activation of JNK signaling pathway is required for virus replication and correlates with virus-induced apoptosis.
The Jun NH2-terminal kinase (JNK) which serves as an important component of cellular signal transduction pathways has been shown to regulate many viral infections. The present study demonstrated for the first time that infectious bursal disease virus (IBDV), the causative agent of a highly contagious disease in chickens, can activate JNK1/2 pathway in IBDV-infected cells dependent upon viral replication. IBDV-induced JNK1/2 activation causes its downstream target c-Jun phosphorylation, which kinetically paralleled JNK1/2 activation. Investigations into the mechanism of JNK1/2 regulation revealed that inhibition of JNK1/2 activation leads to reduced viral progeny release, which is associated with decreased viral transcription and lower virus protein expression, and thereby limiting apoptotic cell death as evidenced by blockage of Bax activation, cytochrome c release, and caspase activation. These data suggest that the JNK pathway plays an important role in the IBDV replication and contributes to virus-mediated changes in host cells.


High-school seniors' college enrollment goals: Costs and benefits of ambitious expectations.
High school students with high long-term educational expectations attain higher levels of education than those with lower expectations. Less studied is the role of students' short-term college enrollment expectations for the year after high school graduation. The purpose of the current study was to examine the costs and benefits of ambitious short-term expectations and the impact of falling short of these expectations on mental health, motivation, and educational outcomes. Over 1000 youth with expectations to attend college were surveyed during their senior year of high school, one year later, and four years later. Participants who did not achieve their short-term expectations had lower educational attainment four years later but were not less satisfied with their educational progress. The negative consequences of falling short of one's expectations were restricted to individuals with less ambitious short-term expectations. Thus, the benefits of ambitious short-term expectations for youth may outweigh the costs.


Naphthodithiophenediimide-Bithiopheneimide Copolymers for High-Performance n-Type Organic Thermoelectrics: Significant Impact of Backbone Orientation on Conductivity and Thermoelectric Performance.
The development of n-type conjugated polymers with high electrical conductivity (σ) has continued to pose a massive challenge in organic thermoelectrics (OTEs). New structural insights into the charge-carrier transport are necessitated for the realization of high-performance OTEs. In this study, three new n-type copolymers, named pNB, pNB-Tz, and pNB-TzDP, consisting of naphthodithiophenediimide (NDTI) and bithiopheneimide (BTI) units, are synthesized by direct arylation polymerization. The backbone orientation is altered by incorporating thiazole units into the backbone and tuning the branching point of the side chain. The alteration of the backbone orientation from face-on to bimodal orientation with both face-on and edge-on fractions significantly impacts the σ and the power factors (PFs) of the polymers. As a result, pNB-TzDP, with the bimodal orientation, demonstrates a high σ of up to 11.6 S cm-1 and PF of up to 53.4 µW m-1 K-2 , which are among the highest in solution-processed n-doped conjugated polymers reported so far. Further studies reveal that the bimodal orientation of pNB-TzDP introduces 3D conduction channels and leads to better accommodation of dopants, which should be the key factors for the excellent thermoelectric performance.


The posterior capsule and phacoemulsification.
1. The discission rate for 268 patients with intact posterior capsules with a 32-month follow-up in 43%. 2. The discission rate for 160 patients with intact posterior capsules and IOL implants with a 20-months follow-up in 20%. 3. To open or not open the posterior capsule at the time of surgery should be decided by the surgeons using these consistent statistics.


[Pertussis vaccine coverage in postpartum women].
Since July 2006, it has been recommended to give a booster of a pertussis vaccine to women just after delivery, if they have received their last dose more than 10 years before. The aim of this study was to evaluate the pertussis vaccine coverage in a cohort of women just after delivery. All patients (n=31) hospitalized in postpartum unit on the 15th September 2006 were included in the study. They were submitted a questionnaire and medical records available in the department were reviewed. The vaccination coverage was not indicated in any medical records. Only six patients claimed they knew their pertussis vaccination status (less than five years: two patients, between five and 10 years: two patients, more than 10 years: two patients). Two patients had their vaccination booklet. The pertussis vaccine coverage is probably very low. The information about pertussis vaccine status in postpartum women is not available currently because it is not recorded by medical team and is unknown by patients themselves. An effort in educating obstetricians and corrective actions are necessary if we want the recent vaccine schedule to be followed.


Mineral content and blood parameters of dying brown trout (Salmo trutta L.) exposed to acid and aluminum in soft water.
1. Whole body mineral content and blood parameters were monitored in dying brown trout exposed to acid (pH 4.5) and aluminium (12 mumol l-1) at low external calcium concentration (20 mumol l-1). 2. Fish surviving the treatment had elevated haematocrit, low plasma sodium levels, and low whole body sodium and potassium content. 3. Dying trout had haematocrit and plasma sodium levels similar to treatment survivors, but whole body mineral content was unaffected and moisture content increased. 4. Death was probably caused by redistribution of fluid from the extracellular compartment to the intracellular compartment.


Weight ratio of the lungs and pleural effusion to the spleen in the diagnosis of drowning.
An accurate and reliable method of diagnosing death by drowning is an important requirement in forensic autopsies. In this study, we compared the weight ratio of the lungs and pleural effusion to the spleen for 55 cases of drowning (37 males, 18 females), 36 cases of mechanical asphyxiation (16 males, 20 females), and 26 cases of acute cardiac death (19 males, 7 females). In the case of the males, there were significant differences in the weight of the spleen and the total weight of the lungs and pleural effusion between drowning and the other causes of death; however, there was no such significant difference in the females. We observed significant differences in the lungs and pleural effusion/spleen weight ratio between drowning and the other causes of death for both sexes. Therefore, these findings suggest that the ratio may be a useful index to accurately diagnose death by drowning, while ruling out mechanical asphyxiation and acute cardiac death in forensic autopsies.


Microbial approaches for pharmaceutical wastewater recycling and management for sustainable development: A multicomponent approach.
A microbial-driven approach for effluent treatment, recycling, and management of Pharmaceutical and Personal Care Products (PPCPs) has been undertaken to mitigate the menace of water contamination. Bioremediation processes are mainly considered the first preference in pharmaceutical wastewater recycling and management. PPCPs are reported as one of the primary sources of emerging contaminants in various water matrices, which raises concern and requires efficient management. Their widespread utilization, persistently high level, and resistance to breaking down make them one of the potentially dangerous compounds causing harm to the ecosystem. Continually increasing PPCPs level PPCPs contaminants in water bodies raised concern for human health as they can produce potential risks with harmful and untoward impacts on our health. PPCPs are composed of multiple diverse compounds used by humans and animals, which include biopharmaceuticals, vitamins and nutritional supplements, antibiotics, counter-prescription drugs, cosmetics products, and unused pharmaceutical products. Personal care products are found to be bioaccumulative, reduce water quality and potentially impact ecological health. However, continual exposure to PPCPs in aquatic organisms, impacts their endocrine function disruption, gene toxicity, and antibiotic resistance. Decreased water quality may result in an outbreak of various water-borne diseases, which could have acute or long-term health complications and may result in an outbreak of various water-borne diseases, which could have acute or long-term effects on public and community health. Polluted water consumption by humans and animals produces serious health hazards and increased susceptibility to water-borne diseases such as carcinogenic organic or inorganic contaminants and infectious pathogens present in water bodies. Many water resource recovery facilities working on various conventional and advanced methods involve the utilization of microbes for filtration and advanced oxidation processes. Therefore, there is an immense need for bioremediation techniques facilitated by mixed cultures of bacteria, algae, and other microbes that can be used as an alternative approach for removing pharmaceutical content from effluent. This review highlights the various sources of PPCPs and their impacts on soil and water bodies, resulting in bioaccumulation. Different techniques are utilized to detect PPCPs, and various control strategies imply controlling, recycling, and managing waste.


Hypertonicity-responsive ubiquitin ligase RNF183 promotes Na, K-ATPase lysosomal degradation through ubiquitination of its β1 subunit.
We previously reported that RNF183, a member of the RING finger (RNF) protein family, is specifically expressed in the renal collecting duct and that RNF183 mRNA is induced by the activity of nuclear factor of activated T cells 5 (NFAT5), which regulates the transcription of essential proteins for adaptation to hypertonic conditions. The renal medulla is the only tissue that is continuously hypertonic; therefore, RNF183 possibly plays an important role in adaptation to continuous hypertonic conditions. However, the mechanism of how cells adapt to long-term hypertonicity via RNF183 remains unclear. In this study, the Na, K-ATPase α1 subunit was identified as a candidate substrate of RNF183 by the BirA proximity-biotinylation technique. The Na, K-ATPase α1 subunit acts as an ion transporter along with the Na, K-ATPase β1 subunit at the plasma membrane. We confirmed that RNF183 interacted with both α1 and β1 subunits; however, we found that RNF183 ubiquitinated only the β1 subunit, not the α1 subunit. Furthermore, RNF183 translocated both α1 and β1 subunits from the plasma membrane to lysosomes. In addition, the expression levels of α1 and β1 subunits in HEK293 cells stably expressing RNF183 were significantly decreased compared with mock control cells, and were restored by siRNA-mediated knockdown of RNF183. Moreover, in RNF183-expressing cells, chloroquine treatment increased the protein levels of the α1 and β1 subunits. Therefore, our results suggest that Na, K-ATPase α1 and β1 subunits are degraded in lysosomes by RNF183-mediated ubiquitination of β1 subunit.


Occipital lobe epilepsy with fear as leading ictal symptom.
Ictal fear is a semiological feature which is commonly associated with mesial temporal lobe epilepsy. Here, we describe fear as a leading symptom in cryptogenic occipital lobe epilepsy. In a patient with negative MRI findings, intracranial EEG recordings documented a strict correlation between habitual ictal anxiety attacks and both spontaneous and stimulation-induced epileptic activity in a right occipital epileptogenic area with subsequent spreading to the symptomatogenic zone in the amygdala. Circumscribed occipital topectomy led to seizure freedom. Episodes of non-epileptic fear ceased shortly afterwards. This report provides insight into pathways of propagation of epileptic activity, illustrates different etiologies of pathologic fear and underlines the importance of ictal EEG recordings.


Correlation tests between relative light unit and colony forming unit for improving adenosine triphosphate bioluminescence analysis in bacterial consolidation treatments on palaeontological heritage.
In this article bacterial carbonate mineralization treatments are proposed as a novel strategy for decayed fossils and palaeontological heritage conservation; specifically, by means of inoculation of Myxococcus xanthus, a bacterium of proven effectiveness in ornamental stone bioconsolidation. Bioconsolidation treatments can be very effective, stable, nontoxic, environmentally friendly, and chemically compatible with fossil heritage. The method reproduces what nature has been doing for millennia with fossils that have been permineralized by bacterial calcium carbonate precipitation. There is, however, some concern that bacterial inoculation could lead to the growth of undesirable microbiota, which could subsequently damage the fossil substrate. Because of this, the use of bacteria on heritage items must be meticulously monitored and analysis strategies should be carried out to detect bacteria viability during and after treatments. For this purpose, adenosine triphosphate assay is proposed in this article as a fast, affordable, portable, and easy-to-use system for conservators. as ATP assay results are relative and difficult to relate to colony forming unit, this study aims to improve their applicability by examining the correlation between ATP analysis and total viable bacteria count in the specific case of M. xanthus. This research provides reference and correlatable data to obtain an approximate estimation of M. xanthus viable bacterial colonies based on relative light unit data.


Compression-induced hexa-to-tetra phase transition of confined germanene.
Via molecular dynamics (MD) simulations we find the existence of the new allotrope of two-dimensional (2D) germanene, i.e. 2D tetra-germanene (tetra-Ge) which contains entirely tetragons. We compress 2D hexa-germanene (hexa-Ge) step by step over a broad density range at constant temperature and hexa-tetra Ge phase transition occurs. We find that the compression of hexa-Ge at 2000 K (not far above the melting point of hexa-Ge) leads to the formation of tetra-Ge with the highest quality. Atomic structure of the obtained tetra-Ge at 300 K is analyzed in details. Although fraction of tetragons in the tetra-Ge is very high (larger than 0.99), some defects are found in addition to the skew tetragons. Due to containing almost entirely tetragons, tetra-Ge may exhibit new behaviors unlike those of the hexa-Ge. Subsequent studies in this direction for 2D tetra-Ge. In addition, first-principles calculations under density functional theory confirm the existence of stable tetra-Ge.


Philothermal and chemotactic locomotion of leukocytes. Method and results.
A newly developed technique for quantitating the locomotion of polymorphonuclear leukocyte (PMN) populations in temperature gradients has revealed that PMNs accumulate toward higher temperatures. The experiments yield measurements of the numbers of cells that adhere to glass and migrate from a cell suspension through a liquid/gel meniscus into a glass/agarose interface, and of their spatial distribution at subsequent time intervals. Cell locomotion was investigated as a function of the magnitude, sign, and temporal variation of the temperature gradient, the cell concentration in the source suspension, and the presence or absence of chemoattractant gradients. It was found (1) that a temperature gradient stimulates crossing of the meniscus toward higher temperatures, (2) that only a portion of the cells reverses direction of locomotion in response to reversal of the temperature gradient after the cells have traversed the meniscus, and (3) that the distribution of cells in the migration space depends on cell concentration, suggesting that the dynamics of PMN locomotion depend on cell-cell interactions.


[Genital sites of giant-cell arteritis].
Temporal arteritis is one of the localisation of the giant cell arteritis. The involvement of the female genital tract had been rarely reported with only 16 cases in the literature. We report 3 cases revealed by a tumor of the genital tract. Histologic features are found in the vessels of ovaries, fallopian tubes and myometrium. Only one patient had symptoms suggestive of temporal arteritis.


A sub-analysis of multi-center planning radiosurgery for intracranial metastases through automation (MC-PRIMA) comparing UK and international centers.
A sub-analysis of the MC-PRIMA study was performed to compare the plan quality of stereotactic radiosurgery (SRS) to multiple brain metastases (MBM) between UK and other international centres. Six centres from the UK and nineteen from other international centres autoplanned using Multiple Brain Mets™ (AutoMBM; Brainlab, Munich, Germany) software for a five MBM study case from a prior planning competition that was originally organized by the Trans-Tasmania Radiation Oncology Group (TROG). Twenty-three dosimetric metrics and the resulting composite plan score per the TROG planning competition were compared between the UK and other international centres. Planning experience and planning time from each planner were recorded and statistically compared. Planning experiences between two groups are equal. Except for mean dose to the hippocampus, all other 22 dosimetric metrics were comparable between two groups. The inter-planner variations in these 23 dosimetric metrics and the composite plan score were also statistically equivalent. Planning time is slightly longer in the UK group (mean = 86.8 min) with a mean difference of 50.3 min. AutoMBM effectively achieves standardization of the plan quality of SRS to MBM within UK and further against the other international centres. Significant planning efficiency gain by AutoMBM both among the UK and other international centres may help to increase the capacity of SRS service by alleviating the clinical and technical loadings.


Restructuring of DNA sequences in the germline genome of Oxytricha.
Most genes in the germline genome of hypotrichous ciliates are crippled by the presence of interrupting sequences. Some genes are additionally impaired because their sequences are in disorder. These gene defects are corrected when germline chromosomal DNA sequences are amplified, cut, spliced, reordered, and eliminated to produce somatic DNA.


Why retroperitoneal lymphadenectomy for testicular tumors?
Most patients with seminoma can be managed successfully with irradiation after a high inguinal orchiectomy. Since anaplastic seminoma has a high predilection for dissemination adjuvant chemotherapy with an alkylating agent, such as L-phenylalanine mustard, is advised. There is much more controversy regarding the management of patients with non-seminomatous tumors. Because lymphangiography has an accuracy of about 90 per cent the justification of a retroperitoneal lymphadenectomy for staging purposes is no longer valid. Irradiation of the retroperitoneal and pelvic lymph nodes in a good survival rate for patients with clinical stages I and II diseases. It is anticipated that with limited resection in selected stage IIB patients and with the judicious use of elective or adjuvant chemotherapy the results in these patients may be improved further. The morbidity associated with retroperitoneal lymphadenectomy is no longer justified since equally effective alternative approaches with lower morbidity rate are available.


Affinity-based release of polymer-binding peptides from hydrogels with the target segments of peptides.
Peptides with affinities for the target segments of polymer hydrogels were identified by biological screening using phage-displayed peptide libraries, and these peptides exhibited an affinity-based release capability from hydrogels. The results from cell culture assays demonstrated the sustained anticancer effects of the drug-conjugated peptides that were released from the hydrogels.


Hip muscle activity in people with hip-related pain compared to asymptomatic controls: A systematic review.
Altered hip and thigh muscle activity have been observed across a spectrum of articular hip pathologies, including hip osteoarthritis, femoroacetabular impingement syndrome, and labral pathology. No systematic reviews have examined muscle activity associated with hip pathology and hip-related pain across the life span. A greater understanding of impairments in hip and thigh muscle activity during functional tasks may assist in the development of targeted treatment strategies. We conducted a systematic review using the PRISMA guidelines. A literature search was performed in five databases (MEDLINE, CINAHL, EMBASE, Sports Discuss, and PsychINFO). Studies were included that (i) investigated people with hip-related pain (femoroacetabular impingement syndrome, labral tears) or hip osteoarthritis; and (ii) reported on muscle activity using electromyography of hip and thigh muscles during functional tasks such as walking, stepping, squatting, or lunging. Two independent reviewers performed data extraction and assessed risk of bias using a modified version of the Downs and Black checklist. Non-pooled data demonstrated a limited level of evidence. Overall, differences in muscle activity appeared to be more prevalent in people with more advanced hip pathology. We found that impairments in muscle activity in those with intra-articular hip pathology measured using electromyography were variable but appeared to be greater in severe hip pathology (e.g., hip OA).


An evidenced-based scoring index to determine the periodontal prognosis on molars.
This retrospective study evaluates and assigns scores to six prognostic factors and derives a quantitative scoring index used to determine the periodontal prognosis on molar teeth. Data were gathered on 816 molars in 102 patients with moderate-to-severe periodontitis. The six factors evaluated (age, probing depth, mobility, furcation involvement, smoking, and molar type) were assigned a numeric score based on statistical analysis. The sum of the scores for all factors was used to determine the prognosis score for each molar. Only patients with all first and second molars at the initial examination qualified for the study. All patients were evaluated a minimum of 15 years after treatment. The post-treatment time ranged from 15 to 40 years and averaged 24 years. When the study was completed, 639 molars survived (78%), and, of those surviving molars, 588 survived and were periodontally healthy (92%). In molars with lower scores (scores 1-3), the 15-year survival rates ranged from 98% to 96%. In molars with middle scores (scores 4-6), the 15-year survival rates ranged from 95% to 90%, and, for molars with higher scores (scores 7-10), the survival rates ranged from 86% to 67%. The present results indicate that the periodontal prognosis of molars diagnosed with moderate-to-severe periodontitis can be calculated using an evidence-based scoring index.


[New evidence in the secondary prevention of thromboembolic disease].
The risk of recurrent venous thromboembolism is nearly 40% of all patients after 10 years of follow up. The risk is higher in patients with permanent risk factors, who should receive indefinite anticoagulation with acenocoumarol or warfarin, except cancer patients who should receive lower doses of low molecular weight heparin The remaining patients should receive a 3-month course of treatment, after which the need to continue this treatment should be reevaluated. The decision to continue should be individually tailored and balanced against hemorrhagic risk. Determination of D-dimer values at the end of treatment and the presence of residual vein thrombosis or right ventricular dysfunction could be useful to identify patients at low risk of recurrence, who can safely discontinue anticoagulation. The emergence of new oral anticoagulants has opened up a new scenario for secondary prevention in the next few years.


Association of V227A PPARalpha polymorphism with altered serum biochemistry and alcohol drinking in Japanese men.
Peroxisome proliferator-activated receptor (PPAR) alpha plays a major role in alcoholic liver disease in rodents. The two-fold objective of our study was to determine the presence of PPARalpha polymorphisms and their frequencies in Japanese populations and then to evaluate the effects of any alleles on metabolic parameters and alcohol drinking. Analysis of coding SNP in PPARalpha was performed in 706 Japanese men; from these subjects 655 men were further studied after exclusion criteria were applied. PPARalpha-V227A, which has not been reported in Europe and North America as a major polymorphism, was discovered with the frequency of 0.05. PPARalpha-L162V was found in European and North American populations, but not in Japanese, thus confirming the ethnic differences in PPARalpha allele frequencies. The A227 allele was associated with increased serum concentrations of gamma glutamyltranspeptidase. In non-drinkers, the total cholesterol (TC) levels were significantly lower in those having the PPARalpha-V227A polymorphism. In drinkers, however, it was comparable among V227A polymorphisms, and conversely higher in those having both A227 and aldehyde dehydrogenase 2 (ALDH2) variants when further divided according to the ALDH2 polymorphism. Significant interactions between PPARalpha-V227A polymorphism and drinking were also found for TC, triglyceride levels and AST/ALT ratios. These results suggest that the activity of the A227 allele without drinking may be higher than in wild-type allele, but its activity may become lower during drinking habits. PPARalpha-V227A is a major polymorphism in the Japanese population, and its activity may be greater compared to wild-type, but decreased by alcohol drinking.


Synergistic pathogenic effects of combined mouse monoclonal anti-desmoglein 3 IgG antibodies on pemphigus vulgaris blister formation.
Pemphigus vulgaris (PV) is an autoimmune blistering disease caused by anti-desmoglein 3 (Dsg3) IgG antibodies. Previously, we generated an active mouse model for PV by adoptive transfer of splenocytes from immunized or naive Dsg3(-/-) mice. In this study, we isolated 10 anti-Dsg3 IgG mAbs (NAK-series) from PV model mice generated by transfer of naive Dsg3(-/-) splenocytes. We characterized their epitopes using domain-swapped and point-mutated Dsg1/Dsg3 molecules and examined their pathogenic activities in blister formation in three different assays. In a passive transfer model using neonatal mice, eight of 10 NAK mAbs showed pathogenic activity when injected together with half the minimum pathogenic dose of anti-Dsg1 IgG autoantibodies from pemphigus foliaceus (PF) patients. None of the mAbs could induce the PV phenotype when individual hybridoma clones were inoculated by peritoneal injection into adult Rag2(-/-) mice. NAK mAbs displayed a range of potency in an in vitro dissociation assay using primary cultured mouse keratinocytes. Interestingly, when multiple hybridoma clones recognizing different epitopes were inoculated in combination, recipient mice developed the PV phenotype. In vitro dissociation assays confirmed that combined NAK mAbs had synergistic pathogenic effects. These findings indicate that although an individual anti-Dsg3 IgG is not sufficient to cause blistering in adult mice, several together can induce the PV phenotype. These mAbs will provide a valuable tool to investigate the molecular mechanisms of blister formation, mimicking the effects of the polyclonal IgG antibodies found in patients.


Mechanism of VKORC1 and VKORC1L1 signaling in the effects of sodium dehydroacetate on coagulation factors in rat hepatocytes.
Sodium dehydroacetate (Na-DHA) is widely used as an antibacterial and preservative additive in food and cosmetics. Previously, we reported that repeated oral administration of Na-DHA induces coagulation disorders, and inhibited liver vitamin K epoxide reductase complex subunit 1 (VKORC1) and VKORC1-like protein 1 (VKORC1L1) in rats. However, the effects of Na-DHA on coagulation factors in rat hepatocytes and the mechanism of VKORC1 and VKORC1L1 signaling in that process are unclear. Here, we constructed stable Vkorc1 and Vkorc1l1 overexpressing cell lines using lentiviruses and transfected small interfering RNAs into buffalo rat liver BRL3A cells for Vkorc1 and Vkorc1l1 overexpression and silencing, respectively. After treatment with 5 mmol/L Na-DHA for 24 h, VKORC1 and VKORC1L1 expression levels were detected by real-time PCR and western blotting. Vitamin K (VK) and factor IX (FIX) contents were detected using enzyme linked immunosorbent assays. We observed that Na-DHA inhibited VKORC1 and VKORC1L1 expression levels and reduced VK and FIX levels in rat hepatocytes. Overexpression or silencing of Vkorc1 and Vkorc1l1 increased or decreased, respectively, the production and secretion of VK and FIX in rat hepatocytes, and alleviated or aggravated the inhibitory effects of Na-DHA on VKORC1 and VKORC1L1 expression levels. Taken together, the results indicated that both VKORC1 and VKORC1L1 signaling play regulatory roles in the effects of Na-DHA on coagulation factors in rat hepatocytes.


Prioritising risk mitigation strategies for environmentally sustainable clothing supply chains: Insights from selected organisational theories.
Recent outbreak of COVID-19 pandemic has provided strong impetus to supply chain resilience research. In a volatile and uncertain business environment, resilience can be incorporated by developing and implementing effective risk mitigation strategies. In this research, risk mitigation strategies for environmentally sustainable clothing supply chain have been prioritised by considering their efficacy to mitigate various risks. Twelve risks and thirteen mitigation strategies, identified through literature review and experts' opinion, are considered as decision criteria and alternatives respectively. Fuzzy Technique for Order Preference by Similarity to Ideal Solutions (fuzzy TOPSIS) is implemented under a group decision making scenario for prioritising the strategies. Developing supply chain agility; multiple green sourcing and flexible capacities; adoption of green practices; building trust, coordination and collaboration; and alignment of economic incentives and revenue sharing are found to be dominant risk mitigation strategies for environmentally sustainable clothing supply chain. These strategies have been viewed through the lens of resource dependence, change management and transaction cost theories. Organisation desirous to build resilience in their supply chain can prioritise the risk mitigation strategies and adopt a portfolio of strategies based on the outcome of this research.


New protocol for in-house management of computer assisted orthognathic surgery.
The aim of this study was to evaluate retrospectively the accuracy of a protocol for completely in-house, computer-assisted, orthognathic surgery, generating resin printed intermediate surgical guides. A retrospective, observational study was made on a cohort of 15 patients treated consecutively from September 2017 to May 2019, who underwent bimaxillary orthognathic surgery planned with the same 3-dimensional program and whose surgical intermediate splints were obtained with the same all-in-house protocol. Virtual planned surgical movements were compared with the real surgical outcome. The differences were not significant for eight of the 12 variables considered. The p values, calculated with the Wilcoxon signed rank test, were evenly distributed and ranged from p=0.001 to p=0.820. Significant differences were reported in four measurements: angle between sella-nasion plane and a line connecting the incisal edge and the apex of the root of the most prominent incisor (U1-SN) (p=0.001), angle between Frankfort plane and a line connecting the incisal edge and the root apex of the most prominent upper incisor (p=0.008), dental midline discrepancies (p=0.006), and occlusal plane tilt (U1-FH) (p=0.001), basically due to intraoperative settings. The 3-dimensional resin printed surgical guides were shown to be a reliable alternative to the commercial ones and showed high rate of accuracy for most of the variables assessed. Four out of 12 of these showed significant errors, but two of them were only minimal discrepancies with no clinical implications.


Structural analyses of β2-glycoprotein I: is there a circular conformation?
Antiphospholipid antibodies targeting β2-glycoprotein I (β2GPI) cause thrombosis and pregnancy morbidity in antiphospholipid syndrome (APS) patients. How these antibodies recognize β2GPI remains controversial. This study aimed to elucidate the structure of β2GPI and evaluate how pathogenic anti-domain I (DI) antibodies recognize it in human plasma. β2GPI was made recombinant and purified from human plasma using different protocols. Structural and functional analyses were conducted using orthogonal techniques, namely, electron microscopy, size-exclusion chromatography, single-molecule Förster resonance energy transfer, and microfluidic diffusional sizing. Electron microscopy and size-exclusion chromatography showed that the structure of β2GPI produced recombinantly and purified from plasma is elongated, even when subjected to conditions previously reported to favor circularization. Single-molecule Förster resonance energy transfer analyses of β2GPI labeled at positions 88 in DII and 278 in DV showed that these residues are located >90 Å apart, consistent with an elongated form. They also documented that the distance between these 2 residues did not change when the protein was reconstituted in human plasma. Microfluidic diffusional sizing documented that β2GPI binds with moderate affinity to a prototypical anti-DI antibody targeting the epitope G40-R43 despite being elongated. Circulating β2GPI is elongated and, therefore, fully capable of binding to anti-DI antibodies. Binding of β2GPI to negatively charged phospholipids drives autoantibody recognition by increasing the local concentration of the antigen and not by dramatically changing its conformation. These findings clarify the structural properties of β2GPI, which have important implications for understanding APS pathogenesis and the development of APS diagnostics and therapeutics.


Construction of cubic CaTiO3 perovskite modified by highly-dispersed cobalt for efficient catalytic degradation of psychoactive pharmaceuticals.
Sulfate radical mediated advanced oxidation processes (SR-AOPs) have emerged as a promising alternative for emerging contaminants degradation. However, high activity and great stability are commonly difficult to juggle, and the structure-activity correlations are still ambiguous. This study constructed the cubic CaTiO3 perovskite modified by highly-dispersed cobalt for peroxymonosulfate (PMS) activation to improve the specific lattice plane exposure and reduce the metal leaching simultaneously. 98% of amitriptyline (AMT) degradation was achieved within 60 min under the condition of 200 mg/L Co0.1-CTO and 100 mg/L PMS. The results indicated that surface Co2+/Co3+ redox couple and lattice oxygen were responsible for PMS activation, and the evolution of ·OH, SO4·- and 1O2 were revealed. According to density functional theory (DFT) calculations, the highly-dispersed Co on cubic surface effectively captured PMS and promoted electron transfer for the generation of ·OH and SO4·-, while more oxygen atoms exposed on Co0.1-CTO(200) surface facilitated the generation of 1O2. Briefly, this study provides a novel strategy of catalyst synthesis in PMS activation for water treatment.


Medial thinning and atherosclerosis--evidence for involvement of a local inflammatory effect.
Medial attenuation in relation to atherosclerotic plaques is poorly understood. We investigated the potential role of a local inflammatory response. Segments of carotid artery and descending aorta were studied. The samples were grossly normal (n = 10), presented circumscribed atherosclerotic plaques (n = 19) or confluent atherosclerotic lesions (n = 8). Tissues were fixed in formalin or snap frozen in liquid nitrogen. Sections were stained with conventional staining methods and immunohistochemically (smooth muscle cells, macrophages, and T and B lymphocytes). Medial thickness was measured with an ocular micrometer; inflammatory infiltrates and medial vascularization were assessed semiquantitatively. Increasing severity of intimal lesions was accompanied by a significant increase in medial inflammation and vascularization and by a significant decrease in medial thickness. The inflammatory infiltrates in the media consisted of macrophages and T lymphocytes, localized predominantly around vasa vasorum. In advanced atherosclerosis they spread more diffusely. Inflammatory cells of the intimal atheroma also penetrated the media. At sites of inflammation the media contained HLA-DR positive smooth muscle cells with loss of collagen. The media in confluent atherosclerosis was almost devoid of smooth muscle cells, with loss of collagen and focal fibrosis. We postulate that the inflammatory reaction in the media relates to atherosclerosis, has a remodelling effect on medial tissues and may cause medial attenuation.


Correlation of Angina Pectoris and Perfusion Decrease by Collateral Circulation in Single-Vessel Coronary Chronic Total Occlusion Using Myocardial Perfusion Single-Photon Emission Computed Tomography.
To evaluate the perfusion decrease in donor myocardium by collateral circulation and its correlation with angina pectoris in patients with chronic total occlusion (CTO) using myocardial perfusion single-photon emission computed tomography (MPS). Thirty-six patients with single-vessel CTO without any other stenosis were included. All patients underwent MPS and coronary angiography (CAG) within 2 months. Total 72 donor arteries were evaluated for the grades of collaterals to the CTO artery using the Rentrop grading system on CAG. Perfusion defects and perfusion scores in donor and CTO territories were analyzed on MPS. Myocardial perfusion of donor and CTO territories were evaluated according to the presence of angina pectoris and the grades of collateral circulation. When the CTO territory was ischemic, symptomatic patients showed higher summed difference scores in the CTO territory compared to asymptomatic patients (3.5 ± 2.4 vs. 1.5 ± 0.8 for symptomatic and asymptomatic groups respectively; p = 0.034). However, when the CTO territory was nonischemic, symptomatic patients showed higher summed stress scores (SSS, 4.3 ± 2.9 vs. 1.6 ± 1.2; p = 0.032) and summed rest scores (SRS, 4.2 ± 2.5 vs. 1.5 ± 1.1; p = 0.003) in the donor territories. On the per-vessel analysis, perfusion defects in donor territories were more frequent (0 % vs. 53 % vs. 86 % for Rentrop 0, Rentrop 1-2 and Rentrop 3, respectively; p < 0.001) and showed higher SSS (0.0 ± 0.0, 1.3 ± 1.6 and 2.1 ± 1.1 for Rentrop 0, Rentrop 1-2 and Rentrop 3, respectively; p = 0.001) and SRS (0.0 ± 0.0, 1.0 ± 1.4 and 1.7 ± 1.2; p = 0.003) at higher Rentrop grades, but their patterns were variable. Angina pectoris was related to either ischemia of the myocardium beyond CTO or a perfusion decrease in the donor myocardium. The perfusion decrease in donor myocardium positively correlated with the collateral grades.


The Role of Noninvasive Surrogates of Inflammation in Monitoring Pediatric Inflammatory Bowel Diseases: The Old and the New.
Effectiveness of limited available therapies for pediatric inflammatory bowel disease has reached stagnation. Previous non-invasive monitoring strategies have relied upon cumbersome tools to evaluate clinical symptoms and biochemical markers that do not reflect endoscopic activity or respond quickly to treatments. Novel, patient-centric, and highly accurate, monitoring strategies with a focus on intestinal ultrasound for a direct, precise monitoring of activity to achieve disease modification are now possible. Ultimately, research on the optimal tight control monitoring strategies, individualized to each pediatric inflammatory bowel disease patient, are in development and offer a hope to potential therapeutic ceiling breakthrough on the horizon.


The influence of crabs on litter processing in high intertidal mangrove forests in tropical Australia.
Measurements of litter fall and litter removal by crabs, in conjunction with estimates of litter decay by microbes and tidal export of litter from three high-intertidal mangrove forests were made during a year-long study in tropical northeastern Australia. In forests dominated by Ceriops tagal and Bruguiera exaristata, litter standing stocks remained low on the forest floor (mean 6 g·m-2), although litter fall was high; 822 and 1022 g·m-2·y-1, respectively. Sesarmid crabs removed 580 (Ceriops) and 803 (Bruguiera) g·m-2·y-1, or 71 and 79%, of the total annual litter fall from the forest floor. Relative to the rate of litter removal by crabs, microbial turnover of whole, unshredded litter was insignificant, accounting for <1% of annual litter fall. Export of litter by tides was estimated to remove 194 (Ceriops) and 252 (Bruguiera) g·m-2·y-1 or 24 and 25% of annual litter fall. In a forest dominated by Avicenniamarina, in which an ocypodid crab was more abundant than sesarmids, litter standing stocks were higher (mean 84 g·m-2) and crabs removed less litter; 173 g·m-2·y-1 or 33% of the annual litter fall of 519 g·m-2·y-1. Microbial turnover of intact litter was more important in the Avicennia forest (168 g·m-2·y-1 or 32% of annual litter fall), and tides exported 107 g·m-2·y-1 or 21% of litter production. In areas where sesarmid crabs were absent or rare in Ceriops forests, there were significantly higher standing stocks of litter and slower rates of leaf removal. Taking into account the probable assimilation efficiencies of sesarmid crabs feeding on mangrove leaves, we estimate that in Ceriops and Bruguiera forests leaf processing by crabs turns litter over at >75 times the rate of microbial decay alone, thus facilitating the high sediment bacterial productivity in these forests. The importance of litter processing by crabs increases with height in the intertidal in tropical Australia, in contrast to New World mangrove forests, where the reverse is true.


The sex-shift in single disease and multimorbid asthma and rhinitis during puberty - a study by MeDALL.
Cross-sectional studies suggested that allergy prevalence in childhood is higher in boys compared to girls, but it remains unclear whether this inequality changes after puberty. We examined the sex-specific prevalence of asthma and rhinitis as single and as multimorbid diseases before and after puberty onset in longitudinal cohort data. In six European population-based birth cohorts of MeDALL, we assessed the outcomes: current rhinitis, current asthma, current allergic multimorbidity (ie, concurrent asthma and rhinitis), puberty status and allergic sensitization by specific serum antibodies (immunoglobulin E) against aero-allergens. With generalized estimating equations, we analysed the effects of sex, age, puberty (yes/no) and possible confounders on the prevalence of asthma and rhinitis, and allergic multimorbidity in each cohort separately and performed individual participant data meta-analysis. We included data from 19 013 participants from birth to age 14-20 years. Current rhinitis only affected girls less often than boys before and after puberty onset: adjusted odds ratio for females vs males 0.79 (95%-confidence interval 0.73-0.86) and 0.86 (0.79-0.94), respectively (sex-puberty interaction P = .089). Similarly, for current asthma only, females were less often affected than boys both before and after puberty onset: 0.71, 0.63-0.81 and 0.81, 0.64-1.02, respectively (sex-puberty interaction P = .327). The prevalence of allergic multimorbidity showed the strongest sex effect before puberty onset (female-male-OR 0.55, 0.46-0.64) and a considerable shift towards a sex-balanced prevalence after puberty onset (0.89, 0.74-1.04); sex-puberty interaction: P < .001. The male predominance in prevalence before puberty and the "sex-shift" towards females after puberty onset were strongest in multimorbid patients who had asthma and rhinitis concurrently.


Circulating vascular endothelial growth factor receptor 2/pAkt-positive cells as a functional pharmacodynamic marker in metastatic colorectal cancers treated with antiangiogenic agent.
The anti-vascular endothelial growth factor (VEGF) antibody bevacizumab has received considerable attention as a first-line treatment of advanced colorectal cancers. Difficulties associated with effectively monitoring the activity of this drug have prompted us to seek a pharmacodynamic marker suitable for defining the optimum biological dose and schedule of bevacizumab administration against colon cancer in early clinical trials. We evaluated inhibitory effects of bevacizumab on VEGF signaling and tumor growth in vitro and in vivo, and assessed phosphorylation of VEGF receptor 2 (VEGFR2) and downstream signaling in endothelial cells as pharmacodynamic markers using phospho-flow cytometry. We also validated markers in patients with metastatic colorectal cancer (mCRC) treated with bevacizumab-based chemotherapy. In in vitro studies, bevacizumab inhibited proliferation of human umbilical vein endothelial cells in association with reduced VEGF signaling. Notably, bevacizumab inhibited VEGF-induced phosphorylation of VEGFR-2, Akt, and extracellular signal-regulated kinase (ERK). In vivo, treatment with bevacizumab inhibited growth of xenografted tumors and attenuated VEGF-induced phosphorylation of Akt and ERK. The median percentages of VEGFR2 + pAkt + and VEGFR2 + pERK + cells, determined by phospho-flow cytometry, were approximately 3-fold higher in mCRC patients than in healthy controls. Bevacizumab treatment decreased VEGFR2 + pAkt + cells in 18 of 24 patients on day 3. Bevacizumab combined with chemotherapy decreased the number of VEGFR2 + pAkt + cells, reflecting impaired VEGFR2 signaling. Together, these data suggest that changes in the proportion of circulating VEGFR2 + pAkt + cells may be a potential pharmacodynamic marker of the efficacy of antiangiogenic agents, and could prove valuable in determining drug dosage and administration schedule.


The effects of heavy metals on germination and seedling characteristics in two halophyte species in Mediterranean marshes.
The influence of different concentrations (10-2000 μM) of heavy metals (Cu, Mn, Ni, Zn) was analysed in Atriplex halimus and Salicornia ramosissima germination pattern and seedling size. They are two halophyte species that grow in the Estuary of Huelva (Southwest Iberian Peninsula, Spain), one of the most heavy metal-polluted environments in the world. All of the metals tested affected the final germination percentage in A. halimus and only Ni reduced germination in S. ramosissima. The germination rate was unaffected in both species. The study of seedling development shows that S. ramosissima, an intertidal annual species, has a higher tolerance of metals than A. halimus, a bush that inhabits the upper part of the marshes. Taking into account the metal concentrations in the estuary and the effects of these on the seedling development of the species analysed, we conclude that metals might limit plant colonisation in some parts of the marshes.


Intestinal and extra-intestinal cancer in Crohn's disease: follow-up of a population-based cohort in Copenhagen County, Denmark.
To determine the long-term risk of intestinal and extra-intestinal malignancies in Crohn's disease patients in Copenhagen County, Denmark. In Copenhagen County, a strictly population-based cohort of 374 patients with Crohn's disease diagnosed between 1962 and 1987 was followed until 1997 in order to determine the long-term risk of intestinal and extra-intestinal malignancies. Information on cancer occurrence was provided by the Danish National Cancer Registry and confirmed by the examination of hospital files. The observed number of cases was compared with the expected number, calculated from individually computed person-years at risk and 1995 cancer incidence rates for the background population. The risk of small bowel adenocarcinoma was significantly increased, independent of age and gender (standardized morbidity ratio, 66.7; 95% confidence interval, 18.1-170.7). The risk of colorectal cancer was not increased, either in the total group of patients or in patients with colonic Crohn's disease exclusively (standardized morbidity ratio, 1.64; 95% confidence interval, 0.20-5.92). Extra-intestinal cancer did not occur more frequently than expected. This population-based study of patients with Crohn's disease revealed no increase in colorectal cancer risk, possibly due to maintenance treatment with 5-aminosalicylic acid preparations and surgery in treatment failure. In contrast, the risk of small bowel cancer was increased more than 60-fold, but the numbers were small. The risk of extra-intestinal cancer was not increased and no lymphomas were observed.


Swedish physicians' perspectives on work and the medical care system--II: The cases of child and maternal health physicians.
This paper reports the results of focused interviews with child health and maternal health physicians in the public ambulatory care sector of a large Swedish city to describe (1) the organization of their work activities, (2) their perspectives on their work, and (3) their perspectives on the medical care system. Child health physicians (who were attached to a major teaching hospital) practiced in child health clinics for preschoolers and school health clinics. Each physician covered several such settings. Maternal health physicians were attached to local hospitals and practiced full time in maternal health centers. Child health physicians described their work in terms of preventive care, patient care, integration of ambulatory and hospital services, and technological sophistication; they described the system in terms of quality of care, quality of diagnosis and treatment, adequacy of resources, and distribution of services. Maternal health physicians described work in terms of a biophysical orientation, practice independence, relations with hospitals and other specialists, and dependence on nurses; they described the system in terms of technological sophistication, ambulatory and hospital care, and problems of other specialties. Both were more positive about both work and the system than were district general practitioners, and some interpretation is offered.


The influence of precompression on elasticity of thyroid nodules estimated by ultrasound shear wave elastography.
To investigate the influence of variations in resting pressure (precompression) on thyroid ultrasound supersonic shear wave elastography (SWE). Thirty-five normal thyroid glands (Norm), 55 benign hyperplastic nodules (BHN), and 17 papillary thyroid cancers (PTC) in 96 subjects underwent thyroid SWE. Four precompression levels were applied manually by the operator, ranging from A (baseline, 0 % strain) to D (high, 22-30 % strain). SWE results at each precompression level were compared using ANOVA tests with P < 0.05 indicating significance. SWE indices were highest in PTC, followed by BHN and Norm at each precompression level (P < 0.05). All tissue types showed successive increases in SWE results as precompression increased, although the rate was higher for PTC than BHN and Norm (Ps < 0.05). SWE values (kPa) of Norm, BHN, and PTC at baseline precompression (A) were 10.3 ± 3.3, 17.7 ± 7.6, and 22.2 ± 11.9 compared with 21.1 ± 4.2, 42.3 ± 16.0, and 97.6 ± 46.8 at high precompression (D). SWE index differences between precompression levels A and D were 10.8 kPa for Norm, 24.6 kPa for BHN, and 75.4 kPa for PTC. PTCs show greater SWE stiffening than BHN as precompression rises. Precompression effects on thyroid nodules are not negligible and may account for wide discrepancies in published SWE discriminatory performance results for thyroid malignancy. • Increases in resting pressure (precompression) applied by the operator increases thyroid stiffness. • Papillary cancers show greater increases in stiffness (strain hardening) than benign nodules. • Precompression may affect the diagnostic performance of shearwave elastography for thyroid malignancy.


Variable HLA expression on deceased donor lymphocytes: Not all crossmatches are created equal.
Flow cytometric crossmatch tests are used to detect donor-specific antibody and determine eligibility for transplantation. Crossmatch sensitivity is dependent on lymphocyte quality, to include HLA expression on the cell surface. The impact of HLA expression variability on crossmatch reactivity was examined using lymphocytes isolated from different donor types: deceased donor (DD) versus living donor (LD) and tissue sources (blood, spleen, or lymph nodes). HLA class I expression was similar on B cells isolated from LD blood, DD spleen, and DD lymph nodes, but significantly lower on B cells isolated from DD blood (p = 0.0004). In contrast, class II expression on B cells and class I on T cells were significantly higher in LD blood than all DD tissues. Within DD tissues, spleen provided the highest expression of class II on B cells and class I on T cells. HLA expression on B cells, but not T cells, was impacted by memory (CD27+) versus non-memory status. Importantly, HLA expression differences on lymphocytes isolated from the same donor but different tissues impacted crossmatch outcomes. HLA expression is impacted by multiple factors and should be routinely monitored to ensure crossmatch sensitivity and to reconcile crossmatch strength with solid phase HLA antibody analyses.


Somatic Embryogenesis: Still a Relevant Technique in Citrus Improvement.
The genus Citrus contains numerous fresh and processed fruit cultivars that are economically important worldwide. New cultivars are needed to battle industry threatening diseases and to create new marketing opportunities. Citrus improvement by conventional methods alone has many limitations that can be overcome by applications of emerging biotechnologies, generally requiring cell to plant regeneration. Many citrus genotypes are amenable to somatic embryogenesis, which became a key regeneration pathway in many experimental approaches to cultivar improvement. This chapter provides a brief history of plant somatic embryogenesis with focus on citrus, followed by a discussion of proven applications in biotechnology-facilitated citrus improvement techniques, such as somatic hybridization, somatic cybridization, genetic transformation, and the exploitation of somaclonal variation. Finally, two important new protocols that feature plant regeneration via somatic embryogenesis are provided: protoplast transformation and Agrobacterium-mediated transformation of embryogenic cell suspension cultures.


Central action of recombinant interleukin-1 to inhibit acid secretion in rats.
The influence of recombinant human interleukins-1 beta and -1 alpha and rat interleukin-1 beta on gastric acid secretion was investigated in awake rats with pylorus ligation. IC injection of either human interleukin-1 beta, human interleukin-1 alpha, or rat interleukin-1 beta induced a dose-dependent inhibition of gastric acid output. At IC doses less than 100 ng, human interleukin-1 beta was more effective than the other forms or sources of interleukin-1, whereas at higher doses (100-500 ng), human interleukins-1 beta and -1 alpha and rat interleukin-1 beta were equipotent. The inhibitory effect was observed 30 minutes after interleukin-1 injection and maintained throughout the 6-hour experimental period. IC injection of interleukin-1 beta inhibited vagally stimulated gastric acid secretion induced by IC injection of the stable thyrotropin-releasing hormone analogue RX 77368. Indomethacin (1, 5, and 10 mg/kg, IP, -30 minutes) induced a dose-related prevention of the inhibitory effect of IC interleukin-1 beta. IC injection of the corticotropin-releasing factor antagonist alpha-CRF9-41, bilateral adrenalectomy, and noradrenergic blockade with bretylium did not influence the antisecretory effect of interleukin-1. Polypeptide action was not related to changes in circulating gastrin levels. Human interleukin-1 beta injected IV also inhibited gastric acid secretion, but the peripheral dose required to induce a significant effect was 10(3)-fold higher than when given centrally. These results show that IC interleukin-1 beta acts centrally to induce a long-lasting inhibition of gastric acid secretion, and this effect requires the integrity of prostaglandin pathways. These data suggest a possible interaction between the immune and gastrointestinal systems.


Development of tolerance to experimental cardiac allografts in utero.
"Actively acquired tolerance" to foreign cells was described in 1953 by Medawar and colleagues and formed the basis for subsequent efforts in organ transplantation. We have applied these historic principles of intrauterine immune manipulation in a vascularized cardiac allograft model. Allogeneic Lewis-Brown Norway (LBN) splenocytes (0 to 5 x 10(7) cells) were injected intraperitoneally into each fetus of a pregnant Lewis rat at day 14 to 16 of gestation, when T cells are "educated" to distinguish self from foreign. This manipulation causes fetal attrition inversely proportional to the number of cells injected. Heterotopic transplantation using an LBN heart was carried out in each surviving fetus at 6 to 8 weeks of age. Untreated Lewis rats rejected LBN hearts within 7.6 days. Rats receiving LBN splenocytes in utero demonstrated prolongation of graft survival proportional to the number of cells given. Surviving animals exposed to 5 x 10(7) allogeneic cells in utero (n = 4) had graft survivals of 24 to more than 150 days (mean, 88.0 days), significantly longer than control animals (6 to 10 days; mean, 7.6 days; p < 0.02). Significant prolongation of cardiac allograft survival and in some cases complete tolerance can be achieved by intrauterine exposure to allogeneic cells at a critical period of immunologic development. Because many serious cardiac defects amenable to treatment by cardiac transplantation can be detected by ultrasound early in gestation, treatment based on this strategy may become useful in pediatric heart transplantation.


Spectrophotometric determination of dihydralazine in pharmaceuticals after derivatization with 2-hydroxy-1-naphthaldehyde.
A sensitive and selective colorimetric assay has been developed for the determination of dihydralazine. The method is based on the interaction of dihydralazine with an ethanolic solution of 2-hydroxy-1-naphthaldehyde to yield a water-insoluble yellow product, 1,4-bis[(2-hydroxy-1-naphthyl)methylene hydrazine]phthazine. This colour can be quantified spectrophotometrically at 420 nm. The calibration curve was linear between 0.4 and 8 micrograms ml-1 of dihydralazine. The molar absorptivity at 420 nm is 24000 l mol-1 cm-1. The method was successfully applied to the determination of dihydralazine in mixtures containing other drugs (reserpine, hydrochlorothiazide, oxprenolol, xanthinol, rutoside, chlorthalidone and bietaserpine).


Synergistic prognostic value of coronary distensibility index and fractional flow reserve based cCTA for major adverse cardiac events in patients with Coronary artery disease.
Coronary distensibility index (CDI), as an early predictor of cardiovascular diseases, has the potential to complement coronary computed tomography angiography (cCTA)-derived fractional flow reserve (CT-FFR) for predicting major adverse cardiac events (MACEs). Thus, the prognostic value of CT-FFR combined with CDI for MACEs is worth exploring. Patients with a moderate or severe single left anterior descending coronary artery stenosis were included and underwent FFR and CDI analysis based on cCTA, followed up at least 1 year, and recorded MACEs. Multivariate logistic regression analysis was performed to determine independent predictors of MACEs. The area under of receiver operating characteristic (ROC) curve was used to evaluated evaluate the diagnostic performance of CT-FFR, CDI, and a combination of the two. All the vessel-specific data were from LAD. 150 patients were analysed. 55 (37%) patients experienced MACEs during follow-up. Patients with CT-FFR ≤ 0.8 had higher percentage of MACEs compared with CT-FFR > 0.8 (56.3% vs.7.3%, p < 0.05). Patients' CDI was significantly decreased in MACEs group compared with non-MACEs group (p < 0.05). Multivariate analysis revealed that diabetes (p = 0.025), triglyceride (p = 0.015), CT-FFR ≤ 0.80 (p = 0.038), and CDI (p < 0.001) are independent predictors of MACEs. According to ROC curve analysis, CT-FFR combined CDI showed incremental diagnostic performance over CT-FFR alone for prediction of MACEs (AUC = 0.831 vs. 0.656, p = 0.0002). Our study provides initial evidence that combining CDI with CT-FFR shows incremental discriminatory power for MACEs over CT-FFR alone, independent of clinical risk factors. Diabetes and triglyceride are also associated with MACEs.


The effect of continuous pyridostigmine administration on functional (A12) acetylcholinesterase activity in guinea-pig muscles.
Pyridostigmine which causes a reversible inhibition of acetylcholinesterase (AChE), was administered continuously for 6 days to guinea-pigs, via a subcutaneously implanted osmotic pump. This produced 40-50% inhibition of red cell acetylcholinesterase (AChE). Controls were animals treated with saline via pumps, and untreated animals. The activities of the functional A12 molecular form of AChE were compared in diaphragm, extensor digitorum longus (EDL) and soleus muscles in the three animal groups at 6 days. The pumps were removed at 6 days and the A12 AChE activities were determined at various times thereafter As the enzyme separation procedure was lengthy, drug-induced inhibition was no longer present when the enzyme activity was measured. At 6 days, the activity was significantly higher in EDL (over 50% higher) and soleus (over two-fold higher) in pyridostigmine-treated animals than saline-treated animals. In the diaphragm, the activities in pyridostigmine and saline-treated animals were similar but both were significantly (over two-fold) higher than in untreated animals. At 1 day after pump removal (day 7) the activity had declined in all three muscles of the pyridostigmine-treated animals and in the diaphragm of saline-treated animals. Thereafter, in the diaphragm (but not the EDL or soleus) in pyridostigmine-treated animals, there were marked variations in the enzyme activity up to day 20. In saline-treated animals there was a marked transient increase in activity at day 13 in all muscles. The results indicate that the homeostatic control offunctional AChE had been affected in both the pyridostigmine and saline treatment groups.


Atypical empathic responses in adolescents with aggressive conduct disorder: a functional MRI investigation.
Because youth with aggressive conduct disorder (CD) often inflict pain on others, it is important to determine if they exhibit atypical empathic responses to viewing others in pain. In this initial functional magnetic resonance imaging (fMRI) study, eight adolescents with aggressive CD and eight matched controls with no CD symptoms were scanned while watching animated visual stimuli depicting other people experiencing pain or not experiencing pain. Furthermore, these situations involved either an individual whose pain was caused by accident or an individual whose pain was inflicted on purpose by another person. After scanning, participants rated how painful the situations were. In both groups the perception of others in pain was associated with activation of the pain matrix, including the ACC, insula, somatosensory cortex, supplementary motor area and periaqueductal gray. The pain matrix was activated to a specific extent in participants with CD, who also showed significantly greater amygdala, striatal, and temporal pole activation. When watching situations in which pain was intentionally inflicted, control youth exhibited signal increase in the medial prefrontal cortex, lateral orbitofrontal cortex, and right temporo-parietal junction, whereas youth with CD only exhibited activation in the insula and precentral gyrus. Furthermore, connectivity analyses demonstrated that youth with CD exhibited less amygdala/prefrontal coupling when watching pain inflicted by another than did control youth. These preliminary findings suggest that youth with aggressive CD exhibit an atypical pattern of neural response to viewing others in pain that should be explored in further studies.


Cryosurgery in the management of intractable facial pain.
The biological sequelae to the experimental freezing of peripheral nerves have been shown to differ in several respects from those following other types of nerve injury. A clinical application of these effects utilising the extreme low temperature produced by modern cryosurgical equipment is proposed and a preliminary evaluation is made.


Adaptation to low body temperature influences pulmonary surfactant composition thereby increasing fluidity while maintaining appropriately ordered membrane structure and surface activity.
The interfacial surface tension of the lung is regulated by phospholipid-rich pulmonary surfactant films. Small changes in temperature affect surfactant structure and function in vitro. We compared the compositional, thermodynamic and functional properties of surfactant from hibernating and summer-active 13-lined ground squirrels (Ictidomys tridecemlineatus) with porcine surfactant to understand structure-function relationships in surfactant membranes and films. Hibernating squirrels had more surfactant large aggregates with more fluid monounsaturated molecular species than summer-active animals. The latter had more unsaturated species than porcine surfactant. Cold-adapted surfactant membranes displayed gel-to-fluid transitions at lower phase transition temperatures with reduced enthalpy. Both hibernating and summer-active squirrel surfactants exhibited lower enthalpy than porcine surfactant. LAURDAN fluorescence and DPH anisotropy revealed that surfactant bilayers from both groups of squirrels possessed similar ordered phase characteristics at low temperatures. While ground squirrel surfactants functioned well during dynamic cycling at 3, 25, and 37 degrees C, porcine surfactant demonstrated poorer activity at 3 degrees C but was superior at 37 degrees C. Consequently the surfactant composition of ground squirrels confers a greater thermal flexibility relative to homeothermic mammals, while retaining tight lipid packing at low body temperatures. This may represent the most critical feature contributing to sustained stability of the respiratory interface at low lung volumes. Thus, while less effective than porcine surfactant at 37 degrees C, summer-active surfactant functions adequately at both 37 degrees C and 3 degrees C allowing these animals to enter hibernation. Here further compositional alterations occur which improve function at low temperatures by maintaining adequate stability at low lung volumes and when temperature increases during arousal from hibernation.


COVID-19 outbreaks among crew members in non-cruise vessels anchoring in Salvador, Brazil, 2021.
The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected the maritime sector due to virus transmission onboard and traffic restrictions. However, reports of SARS-CoV-2 transmission on board have been mostly restricted to those occurring on cruise ships. To report COVID-19 outbreaks in eight non-cruise vessels and discuss measures to prevent and control the onboard transmission of SARS-CoV-2. We investigated outbreaks of COVID-19 on vessels anchoring in Baía de Todos-os-Santos, Salvador, Brazil, between February and November 2021. Most vessels were cargo ships that had docked several times before anchoring in Salvador (five had docked in ≥ 9 ports). The crew ranged from 22 to 63 members. The infection attack rate on each vessel ranged from 9.7 to 88.9%. The risk of symptomatic infection largely varied among the crew of each vessel (0 to 91.6%). Overall, the risk of developing COVID-19 signs and symptoms was lower among crew members vaccinated (age-adjusted risk ratio: 0.19; 95% confidence interval 0.06-0.65). SARS-CoV-2 variants not previously identified in Salvador were detected (C.14, B.1.617.2 and B.1.351). Despite maritime guidelines to avert COVID-19 on board, outbreaks have happened. The multiple stopovers of non-cruise vessels during their routes may contribute to the spread of SARS-CoV-2 variants worldwide. Reducing the onboard transmission of SARS-CoV-2 depends on joint efforts by the crew and local health authorities and, equally important, achieving high vaccination coverage to prevent infections and illness.


Activation and control of factor VII by activated factor X and thrombin. Isolation and characterization of a single chain form of factor VII.
Factor VII purified as previously described, was found to consist of two polypeptide chains joined by disulfide bridges. We now report the isolation and 200,000-fold purification of a single chain form of Factor VII. This was accomplished by protecting the molecule against proteolysis by including benzamidine during the entire purification. The purification was essentially as previously reported except that barium cirtate was substituted for barium sulfate as an absorbant for Factor VII as it resulted in a 4-fold increase in yield. Single chain Factor VII is rapidly hydrolyzed by Factor Xa in the presence of calcium ions and phospholipids, and by thrombin, to a two-chain form which possesses at least 85 times the Factor VII clotting activity of the single chain species. The two-chain form of the enzyme requires tissue factor in order to activate Factor X. From the observed rates of activation of Factor VII by Xa in the presence of calcium ions and phospholipids, it was calculated that at approximately physiological concentration, Factor VII activity would increase at an initial rate of 20-fold per min; this reaction is sufficiently rapid to constitute a feedback control mechanism. The action of thrombin is approximately 40-fold slower under these conditions. Diisopropylphosphorofluoridate inactivates the single chain and two-chain forms of Factor VII at approximately equal rates. After inhibition, the single chain species could be cleaved but not activated by proteolysis.


Effects of bacterial lipopolysaccharide on the production of colony-stimulating activity in C3H/HeJ mouse long-term bone marrow cultures.
Bacterial lipopolysaccharide (LPS)-induced colony-stimulating activity (CSA) in murine long-term bone marrow culture system was investigated. Bone marrow culture cells of LPS-nonresponsive C3H/HeJ mice responded to LPS in terms of CSA production as efficiently as bone marrow culture cells of LPS-responsive C3H/slc mice. On the other hand, both peritoneal macrophages and bone marrow macrophages from C3H/HeJ mice did not produce CSA in vitro after treatment with LPS. Percoll density gradient separation of adherent layer cells in bone marrow cultures showed that two cell populations were present. One population was nonspecific esterase positive, productive of high CSA to LPS stimulation and light density cells, the other population was nonspecific esterase negative, productive of low CSA to LPS stimulation and high density cells, and CSA production stimulated by LPS in C3H/HeJ mice bone marrow culture cells was mainly attributed to the latter population of cells. These results suggest that CSA production stimulated by LPS in C3H/HeJ mice is regulated by different cell populations, respectively in vivo and in vitro.


Microplastics physicochemical properties, specific adsorption modeling and their interaction with pharmaceuticals and other emerging contaminants.
This review discusses the imminent threat that microplastics (MPs) associated with pharmaceuticals represent to the aquatic environment and public health. We initially focused upon recognizing and stressing that MPs are ubiquitous pollutants. The influence of environmental factors, such as pH, mechanical stress, and photodegradation, are examined, aiming to elucidate how both substances might associate, what are their simultaneous degradation pathways and, to understand the interactions between MPs and pharmaceuticals. Mathematical tools, such as modeling and simulations, are presented in detail, aiming to improve how information is interpreted. Furthermore, it is exhibited that MPs sorption and interaction behavior towards organic contaminants play an important role in understanding its dynamics in the environment, as well as their possible interactions with pharmaceuticals that are summarized. At last, MPs and pharmaceuticals toxicity and bioaccumulation are presented.


An indirect method to assess wrist ligament forces with particular regard to the effect of preconditioning.
A method has been developed to calculate the forces that are developed in the ligaments of a joint specimen during motions. This indirect method is needed since direct measurements fail in the case of small ligaments. As an example the small ligaments of the carpal joint are considered. The rationale of the method is that the force generated in a ligament depends on the amount of strain to which it is subjected and on its material characteristics. In the method presented the lengths of the ligaments are determined in vitro at several joint positions by means of röntgenstereophotogrammetry. The zero-force length and the force-elongation relationship are determined on the same ligaments isolated in a materials testing machine. Over a considerable part of the strain range the measurement errors are relatively small compared to the forces determined, less than 10%. The method is applicable to joints in situations where other measuring methods cannot be used. The present analysis shows, however, that the force values determined are susceptible to preconditioning of the ligaments. In preconditioned ligaments the forces could be up to 50% lower than in the non-preconditioned situation. This suggests that ligament forces may vary considerably in vivo, depending on the extent of preconditioning provoked by a particular function.


Presurgical prognostic factors in carcinoma of the cervix, stages IB and IIA.
Possible prognostic factors in early stage cervical cancer include patient age, tumor size, cell type, differentiation, and channel invasion. In this study each of these factors was evaluated based only on the findings available before surgery, and the observations are compared with patient survival and incidence of node metastases. One hundred consecutive patients with stage IB or IIA cervical cancer treated by primary radical surgery and followed at least 2 years are reported. Disease-free survival was 90% at 2 years and 85% at 5 years; 19% had node metastases. Of the factors studied, only age greater than 50 years was associated with poor prognosis (p less than 0.02 versus age less than 50 years). Only large tumor size was associated with increased node metastases (p less than 0.001 versus medium and small size). Tumor cell type, differentiation, and channel involvement had no bearing on survival or node metastases. Because older age and large tumors appear to be factors of poor prognosis for surgery, and yet it is not clear that these patients fare better with radiotherapy, we suggest a prospective trial of radiotherapy versus surgery for this group.


A facile electrophoretic technique to monitor phosphoenolpyruvate-dependent kinases.
Phosphoenolpyruvate (PEP)-dependent kinases are central to numerous metabolic processes and mediate the production of adenosine triphosphate (ATP) by substrate-level phosphorylation (SLP). While pyruvate kinase (PK, EC: 126.96.36.199), the final enzyme of the glycolytic pathway is critical in the anaerobic synthesis of ATP from ADP, pyruvate phosphate dikinase (PPDK, EC: 184.108.40.206), and phosphoenolpyruvate synthase (PEPS, EC: 184.108.40.206) help generate ATP from AMP coupled to PEP as a substrate. Here we demonstrate an inexpensive and effective electrophoretic technology to determine the activities of these enzymes by blue-native polyacrylamide gel electrophoresis (BN-PAGE). The generation of pyruvate is linked to exogenous lactate dehydrogenase (LDH), and the oxidation of reduced nicotinamide adenine dinucleotide (NADH) coupled to 2,6-dichloroindophenol (DCIP) and iodonitrotetrazolium chloride (INT) results in a formazan precipitate which is easily quantifiable. The selectivity of the enzymes is ensured by including either AMP or ADP and pyrophosphate (PP(i) ) or inorganic phosphate (P(i) ). Activity bands were readily obtained after incubation in the respective reaction mixtures for 20-30 min. Cell-free extract concentrations as low as 20 μg protein equivalent yielded activity bands and substrate levels were manipulated to optimize sensitivity of this analytical technique. High-pressure liquid chromatography (HPLC), two-dimensional (2-D) SDS-PAGE (where SDS is sodium dodecyl sulfate), and immunoblot studies of the excised activity band help further characterize these PEP-dependent kinases. Furthermore, these enzymes were readily identified on the same gel by incubating it sequentially in the respective reaction mixtures. This technique provides a facile method to elucidate these kinases in biological systems.


Neural network predictions of (n,2n) reaction cross-sections at 14.6 MeV incident neutron energy.
In this study, we have estimated the (n,2n) reaction cross-section for 14.6 MeV incident neutron energy by using the artificial neural network (ANN) method. We have also predicted the reaction cross-sections whose experimental data are not available in the literature. For the construction of the present ANN, available experimental data in the literature has been borrowed. The ANN estimations have been compared with the available experimental data and the results from a theoretical calculation and the two commonly used computer codes. According to the results that the ANN results are in good agreement with the experimental data than the codes and this shows that the method can be a powerful tool for the estimation of cross-section data for the neutron-induced reactions. Considering the predictions of the ANN of the cross-sections whose experimental data are not available in the literature, it is seen that they are in line with the trend of the experimental data, but far from the results given by the theoretical calculations and two computer codes.