A verbal descriptor incremental pain scale developed by South African Tswana-speaking patients with low back pain.
Measuring pain in patients whose home language is not English can be difficult as there may not be a scale available in their home language. Scales devised in other countries may also not be accurate after translation. The aim of this study was to develop and test a new verbal pain descriptor scale in a Tswana-speaking population in South Africa with low back pain. Two separate Tswana-speaking groups (20 males and 20 females) of patients with low back pain were asked to describe each of four categories of pain: mild, moderate, severe and worst. They then voted and descriptions obtaining more than 70% of the vote were taken to the next round of voting with both groups together. A final scale of one description for each category of pain (Tswana Verbal Pain Descriptor Scale - TVPDS) for both males and females was tested on a sample of 250 patients with low back pain and against three other non-verbal pain scales. All items on the final scale were approved by at least 70% of both male and female participants. The scores for the TVPDS correlated well with present pain perception (r = 0.729, p < 0.0001) measured on the numerical visual analogue scale. The TVPDS correlated well with the Wong-Baker FACES Pain Rating Scale (r = 0.695, p < 0.0001) and the Pakistani Coin Pain Scale (r = 0.717, p < 0.0001). The TVPDS has the potential to be a useful clinical scale but more testing in other languages is still required. This pain scale has the potential to be a useful scale to use for Tswana-speaking persons with low back pain and could also be useful for persons of other languages, if translated.


Entropic Uncertainty for Two Coupled Dipole Spins Using Quantum Memory under the Dzyaloshinskii-Moriya Interaction.
In the thermodynamic equilibrium of dipolar-coupled spin systems under the influence of a Dzyaloshinskii-Moriya (D-M) interaction along the z-axis, the current study explores the quantum-memory-assisted entropic uncertainty relation (QMA-EUR), entropy mixedness and the concurrence two-spin entanglement. Quantum entanglement is reduced at increased temperature values, but inflation uncertainty and mixedness are enhanced. The considered quantum effects are stabilized to their stationary values at high temperatures. The two-spin entanglement is entirely repressed if the D-M interaction is disregarded, and the entropic uncertainty and entropy mixedness reach their maximum values for equal coupling rates. Rather than the concurrence, the entropy mixedness can be a proper indicator of the nature of the entropic uncertainty. The effect of model parameters (D-M coupling and dipole-dipole spin) on the quantum dynamic effects in thermal environment temperature is explored. The results reveal that the model parameters cause significant variations in the predicted QMA-EUR.


Myotonic dystrophy type 1 presenting as male infertility.
Myotonic dystrophy 1 (DM1) is a multi-system disorder characterized by endocrine defects that include testicular and tubular atrophy, oligospermia and azoospermia, and increased follicle-stimulating hormone levels. We describe a rare case of DM1 presenting as infertility in a 29-year-old man.


Land uses in cities and their impacts on the water quality of urban freshwater blue spaces in the Pampean region (Argentina).
Freshwater blue spaces (FBS), such as ponds, are key elements of the urban landscape and are under strong anthropogenic pressure. Land-use types and diversity may exert a negative or positive impact on FBS' water quality depending on their nature and arrangement. The information available in this respect is remarkably scarcer for water bodies in the Global South than for the north. Thus, we aim to identify and quantify the land-use types in a 500-m buffer zone of urban ponds in the Pampean region (Argentina) to assess their impact on water quality. We based our study on 15 FBS located in neighborhoods of Buenos Aires province during cold and warm seasons. We analyzed physical, chemical, and biological variables, and estimated water conditions by means of water quality indexes (WQIs) and quality guidelines. We quantified the dominant land-use type and the diversity of uses in the ponds' buffer zones, and evaluated their relationships with WQIs. Our results showed that WQIs were negatively related to a high proportion of residential areas in the adjacent zone, while positively to recreational ones. The diversity of land uses did not influence the water quality. We propose a new WQIpond with fewer key response variables, and as sensitive as the currently used WQIobjetive. We conclude that water quality from urban ponds in the Pampean region can be affected by dominant land-use type in the adjacent area but also the quality of their water supply sources (superficial and/or underground), clandestine wastewater discharges, and non-point pollution.


Responses of an AV universal (DDD) pulse generator (Cordis 233D) to programmed single ventricular extrastimuli.
To evaluate factors playing a role in initiation and perpetuation of pacemaker-mediated tachycardias (PMTs), 22 consecutive patients with symptomatic conduction disorders were studied after implantation of an AV universal (DDD) pulse generator (Cordis 233D). Patients were divided into two groups, depending upon the presence or absence of ventriculo-atrial (VA) conduction during electrophysiological study (EPS) performed before pacemaker implantation. PMTs could be initiated in six of eight patients of Group I and in none of 14 patients of Group II. Initiation and perpetuation of PMTs during DDD pacing were dependent upon the capacity of the patient to conduct ventricular premature beats (VPBs) and subsequent paced ventricular beats retrogradely to the atria, and upon three programmable parameters of the pulse generator (AV delay period, upper rate limit, tachycardia response). Programmed single ventricular extrastimulation demonstrated that: (1) merely the presence of VA conduction during EPS, although necessary, was not sufficient to induce PMTs after DDD pacemaker implantation; (2) VPBs introduced late rather than early in the cardiac cycle initiated PMTs in a different way; (3) the initiation of PMTs could be prevented during study by adjusting the programmable parameters (AV delay period, upper rate limit, tachycardia response); (4) one of the two available tachycardia responses of the pulse generator (gradual fall-back response) was able to terminate and initiate PMTs consistently. These observations helped in understanding the responses of the Cordis 233D pulse generator to ventricular premature beats. They indicate that additional refinement of the pulse generator is necessary to solve the problem of PMT.


Striatal degeneration in glutaric acidaemia type II.
A girl of first cousin parents presented in the 1st year of life with a progressive neurological disease with muscle weakness and hypotonia, accompanied later by dystonia. Investigations, including gas chromatography of urine, showed no abnormality. Autopsy showed marked neuronal loss and gliosis in the putamen and globus pallidus. The activity of glutaryl-CoA dehydrogenase in cultured fibroblasts was normal, but the activity of electron transfer flavoprotein was markedly diminished. Retrospective study of urine by capillary gas chromatography/mass spectrometry showed small amounts of glutaric and other organic acids. This is the first report of striatal degeneration in association with glutaric acidaemia type II. The neuropathological changes were milder than those in glutaric acidaemia type I.


[Analysis of in-hospital morbidity and mortality of colorectal cancer and accuracy of POSSUM models for mortality risk].
To develop the modified P-POSSUM equation and the modified Cr-POSSUM equation and compare their performances with POSSUM in forecasting in-hospital morbidity and mortality of colorectal cancer. Data of 903 patients undergone operation of colon and rectal cancers from 1992 to 2005 in our department were enrolled in this study. ROC curve was applied to judge the differentiation ability of each score. Model goodness-or-fit was tested by the Hosmer-Lemeshow statistic and subgroup analysis was performed by the ratio of observed to expected deaths (O:E ratio). A 70:30 percent split-sample validation technique was adopted for model development and testing. Stepwise logistic regression was used to develop the modified P-POSSUM and the modified Cr-POSSUM. Their performance in validating sample, colonic cancer sample, rectal cancer sample, elective surgery sample, emergency surgery sample, curative surgery sample and palliative surgery sample was tested by ROC curve, Hosmer-Lemeshow statistic and O:E ratio. The modified P-POSSUM showed good discrimination in all samples except the emergency surgery and palliative surgery. The predicted mortality of modified P-POSSUM was very close to the observed mortality. However, the modified Cr-POSSUM showed good discrimination in all samples except the palliative surgery. The predicted mortality was higher than the observed mortality, but still within the 95% confidence interval (CI) of the observed mortality. Both the modified models offered better accuracy than the P-POSSUM. The modified P-POSSUM and the modified Cr-POSSUM model provide an accurate prediction of inpatient mortality in Chinese colorectal cancer patients.


Chronobiological aspects of adult-onset Crohn disease.
To study the time course of Crohn disease and its signs. To compare the results with the world literature and draw conclusions for practice. Fifty-six patients were studied retrospectively: 31 males aged 19-48 years with disease duration 1-8 years, and 25 females aged 21-65 with disease duration 1-13 years. The disease was active (Crohn disease activity index > 150) in 25 patients and inactive in 31. Plasma levels of interleukin-6 (normal upper value 8 pg/ml) were investigated with radioimmunoassay. Bone mineral density was measured as the T-score (normal range between -1 and 0 standard deviations) in the forearm using dual-energy X-ray absorptiometry. The seasonality of births of the patients in relation to the total Slovak population and seasonality of severity of three important disease signs were examined with Halberg cosinor regression. The dependence of the signs on age and duration of disease was evaluated using quadratic regression. Results are presented as 95% confidence intervals (for means) and 95% tolerance intervals (for individuals). The level of statistical significance was set at alpha = 0.05. Significant seasonality in births was found: decreased frequency in May-June and increased frequency in September-January. Significant spring elevation of interleukin-6 levels, accompanied by significant spring rise of the disease activity index and by decrease of bone density, is described. Among patients with active disease, interleukin-6 levels significantly increased up to the age of 41 years, whereas linear increase of disease activity during aging was on the borderline level of significance in the same subgroup. No significant age trend was encountered in T-score for either subgroup. The same was true for interleukin-6 and disease activity versus duration. Significant decrease in T-score paralleled disease duration up to seven years in the subgroup with active disease. The course of Crohn disease is influenced by time, including the seasons of the year. However, this does not find full agreement in the world literature, probably because of geographic, socioeconomic and epidemiologic differences, as well as varying approaches in method. In practice, regular monitoring of the time course is necessary in provision of appropriately timed treatment.


Association between the serum level of vitamin D and systemic sclerosis in a Chinese population: a case control study.
Several autoimmune diseases have been associated with reduced vitamin D levels. However, the serum level of vitamin D in Chinese systemic sclerosis (SSc) patients have not been reported. The aim of this study was to evaluate the serum levels of vitamin D in Chinese SSc patients and analyze the association between vitamin D and SSc. 25-hydroxy vitamin D 125 I RIA kit was applied to evaluate the serum levels of vitamin D in 60 SSc patients and 60 healthy controls from Anhui Provincial Hospital, China. The data of epidemiological and clinical characteristics of SSc patients were also collected. The serum levels of vitamin D were significantly lower in SSc patients than that in healthy controls (26.51 ± 6.27 vs. 36.29 ± 14.24 ng/mL, P < 0.001). The ratio of pulmonary involvement in vitamin D insufficiency patients was higher than that in normal vitamin D patients, but the difference missed statistical significance. The differences in other aspects were not statistically significant in the two groups. Serum levels of vitamin D in patients with SSc were lower than that in healthy controls. Further studies are needed to determine whether vitamin D supplement could provide some positive effects.


Minimizing Variance in Gastroschisis Management Leads to Earlier Full Feeds in Delayed Closure.
Limited guidance exists regarding appropriate timing for feed initiation and advancement in gastroschisis. We hypothesized that implementation of a gastroschisis management protocol would allow for standardization of antibiotic and nutritional treatment for these patients. We conducted a retrospective comparison of patients with simple gastroschisis at two pediatric hospitals before and after initiation of our gastroschisis care protocol. Complicated gastroschisis and early mortality were excluded. The control group extended from January 2012 to January 2014 and the protocol group from July 2014 to July 2016. Variables of interest included time to feed initiation, time to goal feeds, length of stay, and National Surgical Quality Improvement Program-defined complications. We performed a subgroup analysis for primary versus delayed gastroschisis closure. Statistical analyses, including F-tests for variance, were conducted in Prism. Forty-seven patients with simple gastroschisis were included (control = 22, protocol = 25). Protocol compliance was 76% with no increase in complication rates. There was no difference in length of stay or time from initiation to full feeds overall between the control and protocol groups. However, neonates who underwent delayed closure reached full feeds significantly earlier, averaging 9 d versus 15 d previously (P = 0.04). For infants undergoing delayed closure, the time to full feeds in this group now appears to match that of patients undergoing primary closure, indicating that delayed closure should not be a reason for slower advancement. Additional studies are needed to assess the impact of earlier full enteral nutrition on rare complications and rates of necrotizing enterocolitis.


Oxygen toxicity induces apoptosis in neuronal cells.
1. A high oxygen atmosphere induced apoptosis in cultured neuronal cells including PC12 cells and rat embryonic cortical, hippocampal, and basal forebrain neurons associated with DNA fragmentation and nuclear condensation. 2. The sensitivity of CNS neurons to a high-oxygen atmosphere was the following order; cortex > basal forebrain > hippocampus. 3. Cycloheximide and actinomycin-D inhibited the apoptosis, indicating that it depends on new macromolecular synthesis. In contrast, cultured postnatal CNS neurons were resistant to oxidative stress. 4. Neurotrophic factors such as nerve growth factor (NGF), fibroblast growth factor (FGF), and epidermal growth factor (EGF) blocked the apoptosis induced by a high-oxygen atmosphere.


The effect of religion on the perception of health states among adults in the United Arab Emirates: a qualitative study.
Investigate how religion may affect the perception of health states among adults in the United Arab Emirates and the implications for research on self-reported health and quality of life and the use of values in cost-effectiveness analysis. Qualitative analysis of short-structured interviews with adult Emiratis carried out by a market research agency.The COREQ criteria have been used where appropriate to guide the reporting of our findings. Participants were recruited from shopping malls and other public places in the cities of Al Ain and Abu Dhabi. Two hundred adult Emiratis broadly representative of the Emirati population in terms of age and gender. Eighty one per cent of participants said that their perception of health states was influenced by their spiritual or religious beliefs. The two overarching themes that seemed to explain or classify these influences were 'fatalism' and 'preservation of life'. Subthemes included powerlessness to change what is preordained by God, fear of disability (particularly diminished mobility) and appreciation of health and life and the requirement to look after one's health. A final theme was that of acceptance, with respondents expressing a willingness to endure suffering and disability with patience in the expectation of rewards in the hereafter. Our results emphasise the need for further work to establish locally relevant value sets for Muslim majority countries in the Middle East and elsewhere for use in health technology assessment decision-making, rather than relying on value sets from other regions.


Zebrafish and cardiac toxicology.
Model systems are a mainstay in toxicological research. Zebrafish are rapidly becoming an important model organism for studying vertebrate development. The advantages of zebrafish: short reproductive cycle, production of numerous transparent, synchronously developing embryos, low cost, and standardization make zebrafish an attractive model for toxicologists as well. The use of these fish to study heart development has moved forward very rapidly, laying the groundwork for studying the effects of chemicals on cardiac development and function. Here we describe approaches that can be used to study cardiac toxicity in developing zebrafish, focusing on examples where zebrafish embryos have been especially useful in understanding the impact of specific toxicants on heart development and function.


Clash of the Cytokine Titans: counter-regulation of interleukin-1 and type I interferon-mediated inflammatory responses.
Over the past decades the notion of 'inflammation' has been extended beyond the original hallmarks of rubor (redness), calor (heat), tumor (swelling) and dolor (pain) described by Celsus. We have gained a more detailed understanding of the cellular players and molecular mediators of inflammation which is now being applied and extended to areas of biomedical research such as cancer, obesity, heart disease, metabolism, auto-inflammatory disorders, autoimmunity and infectious diseases. Innate cytokines are often central components of inflammatory responses. Here, we discuss how the type I interferon and interleukin-1 cytokine pathways represent distinct and specialized categories of inflammatory responses and how these key mediators of inflammation counter-regulate each other.


Clearance of effusion material from the attic space--an experimental study in the rat.
Rat serum with Evan's blue added as a tracer was instilled into the attic through a pars flaccida perforation in rats. At intervals the drainage of the effusion-like material was observed through a hole in the tympanic bulla. The distribution of ciliary cells was studied in the middle ear using light microscopic and scanning electronmicroscopic techniques. It was noted that the effusion material was propelled from the attic to the inlet of the Eustachian tube mainly by hydrostatic forces. It is also concluded that this mechanism might apply in Homo sapiens and that the drainage position of the head may be of importance in preventing and treating otitis media with effusion (OME).


Family factors mediate discrimination related stress and externalizing symptoms in rural Latino adolescents.
Externalizing disorders are more prevalent in rural than urban settings and account for disproportionately high mental health service costs for rural adolescents. Although cultural stressors such as discrimination have been associated with externalizing problems in ethnic minority youth broadly, this relationship is understudied in Latinos, particularly those in rural settings. Further, though the associations of family processes such as familism and family conflict have been studied in relation to youth externalizing symptoms, whether these processes change in the face of adolescent discrimination stress remains unknown. A moderated multiple mediation model was used to examine the association between perceived discrimination, externalizing symptoms, and the indirect effect of family factors (familism, and family conflict) in a large sample (n = 455) of rural Latino youth. We also evaluated whether indirect and direct effects of discrimination on externalizing symptoms differed in boys versus girls. Familism and family conflict each independently mediated the relationship between discrimination related stress and externalizing symptoms. However, discrimination had a direct effect on externalizing symptoms for boys only. In girls, this association held only when family factors were accounted for. Post-hoc analyses reveal that the moderating effect of sex on discrimination is driven by differences in rule-breaking behavior, as opposed to aggressive behavior. Findings suggest that discrimination is associated with changes in the family environment which in turn invoke elevated risk for externalizing problems. Further, family-focused interventions that address externalizing problems may be especially effective for adolescent girls.


Cardiovascular Outcomes in Patients With Biopsy-proven Alcohol-related Liver Disease.
Patients with alcohol-related liver disease (ALD) frequently have risk factors for cardiovascular disease (CVD), but their long-term risk of CVD is not well-known, especially considering the competing risk of death from liver-related causes. It is further unknown if any excess risk varies across histological subgroups. We investigated the risk of CVD outcomes in 3488 persons with ALD and an available liver biopsy in Sweden between 1969 and 2016, compared with a matched reference population (n = 15,461). Administrative coding from national diagnostic and histopathology registers were used to define exposures and outcomes. Competing risk regression, taking non-CVD death into account and adjusting for potential confounders, was used to estimate subdistribution hazard ratios for incident CVD up until Dec 31, 2019. At baseline, patients with ALD had a median age of 58 years, 64% were men, and 2039 (58%) had cirrhosis on histology. The incidence rate of CVD was 35.6 per 1000 person-years in ALD compared with 19.0 per 1000 person-years in reference individuals. ALD was associated with a 2-fold increased short-term risk for CVD compared with matched reference individuals (subdistribution hazard ratio during the first year after diagnosis, 2.29; 95% confidence interval, 1.79-2.95), but this risk decreased with time. Incidence rates of CVD were comparable across histological subgroups (ranging from 27.4 CVD cases per 1000 person-years in those with normal histology to 39.2 cases per 1000 person-years in those with cirrhosis). Persons with biopsy-proven ALD have increased rates of CVD across histological subgroups compared with matched reference individuals, particularly just after ALD diagnosis. Active surveillance of modifiable CVD risk factors should be considered by clinicians treating patients with ALD.


Challenges to hypertension and diabetes management in rural Uganda: a qualitative study with patients, village health team members, and health care professionals.
The prevalence of hypertension and diabetes are expected to increase in sub-Saharan Africa over the next decade. Some studies have documented that lifestyle factors and lack of awareness are directly influencing the control of these diseases. Yet, few studies have attempted to understand the barriers to control of these conditions in rural settings. The main objective of this study was to understand the challenges to hypertension and diabetes care in rural Uganda. We conducted semi-structured interviews with 24 patients with hypertension and/or diabetes, 11 health care professionals (HCPs), and 12 community health workers (known as village health team members [VHTs]) in Nakaseke District, Uganda. Data were coded using NVivo software and analyzed using a thematic approach. The results replicated several findings from other settings, and identified some previously undocumented challenges including patients' knowledge gaps regarding the preventable aspects of HTN and DM, patients' mistrust in the Ugandan health care system rather than in individual HCPs, and skepticism from both HCPs and patients regarding a potential role for VHTs in HTN and DM management. In order to improve hypertension and diabetes management in this setting, we recommend taking actions to help patients to understand NCDs as preventable, for HCPs and patients to advocate together for health system reform regarding medication accessibility, and for promoting education, screening, and monitoring activities to be conducted on a community level in collaboration with village health team members.


Comparative effects of ascobin and glutathione on copper homeostasis and oxidative stress metabolism in mitigation of copper toxicity in rice.
Copper (Cu) pollution of agricultural land is a major threat to crop production. Exogenous chemical treatment is an easily accessible and rapid approach to remediate metal toxicity, including Cu toxicity in plants. We compared the effects of ascobin (ASC; ascorbic acid:citric acid at 2:1) and glutathione (GSH) in mitigation of Cu toxicity in rice. Plants subjected to Cu stress displayed growth inhibition and biomass reduction, which were connected to reduced levels of chlorophylls, RWC, total phenolic compounds, carotenoids and Mg2+ . Increased accumulation of ROS and malondialdehyde indicated oxidative stress in Cu-stressed plants. However, application of ASC or GSH minimized the inhibitory effects of Cu stress on rice plants by restricting Cu2+ uptake and improving mineral balance, chlorophyll content and RWC. Both ASC and GSH pretreatments reduced levels of ROS and malondialdehyde and improved activities of antioxidant enzymes, suggesting their roles in alleviating oxidative damage. A comparison on the effects of ASC and GSH under Cu stress revealed that ASC was more effective in restricting Cu2+ accumulation (69.5% by ASC and 57.1% by GSH), Ca2+ and Mg2+ homeostasis, protection of photosynthetic pigments and activation of antioxidant defence mechanisms [catalase (110.4%), ascorbate peroxidase (76.5%) and guaiacol peroxidase (39.0%) by ASC, and catalase (58.9%) and ascorbate peroxidase (59.9%) by GSH] in rice than GSH, eventually resulting in better protection of ASC-pretreated plants against Cu stress. In conclusion, although ASC and GSH differed in induction of stress protective mechanisms, both were effective in improving rice performance in response to Cu phytotoxicity.


Schizophrenia and the COVID-19 pandemic: A narrative review from the biomedical perspective.
The outbreak of the Coronavirus Disease 2019 (COVID-19) pandemic in 2020 caused a rapid worsening of global mental health. Patients with severe mental disorders, including schizophrenia, are at higher risk of being infected. The neuroinvasive potential of the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) has been confirmed. The aim of this article was to present a narrative and comprehensive review of multidimensional associations between schizophrenia and COVID-19 with special emphasis on common biological pathways. Online searches were performed in the PubMed database and covered the publication period until September 17, 2022. Search terms included "psychosis", "schizophrenia", "inflammation" and "COVID-19". Viewed as a neuroinflammatory state, schizophrenia shares several neurobiological mechanisms with the COVID-19. Environmental stress, common comorbidities of schizophrenia and adverse effects of antipsychotic treatment are associated with the higher severity and mortality of the COVID-19. Additionally, more frequent relapses of psychosis have been observed, and might be related to lower treatment adherence. In the context of clinical manifestation, higher level of negative symptoms has been identified among patients with schizophrenia during the pandemic. Improvements in mental health care policy and treatment adjustment are necessary to protect people with schizophrenia who are the population that is particularly vulnerable to the consequences of the COVID-19 pandemic. Future research will show if prenatal infection with the SARS-CoV-2 increases a risk of psychosis.


Purification and characterization of a novel lipase from the digestive glands of a primitive animal: the scorpion.
Higher animal's lipases are well characterized, however, much less is known about lipases from primitive ones. We choose the scorpion, one of the most ancient invertebrates, as a model of a primitive animal. A lipolytic activity was located in the scorpion digestive glands, from which a scorpion digestive lipase (SDL) was purified. Pure SDL, a glycosylated protein, has a molecular mass of 50 kDa, it presents the interfacial activation phenomenon. It was found to be more active on short-chain triacylglycerols than on long-chain triacylglycerols. SDL is a serine enzyme and possesses one accessible sulfhydryl group which is not essential for the catalysis. Among the NH2-terminal 33 residues, a 17 amino acids sequence shows similarities with sequence of Drosophila melanogaster putative lipase. Interestingly, neither colipase, nor bile salts were detected in the scorpion hepatopancreas. This indicates that colipase evolved in vertebrates simultaneously with the appearance of an exocrine pancreas and a true liver which produces bile salts. Furthermore, polyclonal antibodies directed against SDL failed to recognise the classical digestive lipases. Altogether, these results suggest that SDL is a member of a new group of digestive lipases belonging to invertebrates.


Quantification of FAM20A in human milk and identification of calcium metabolism proteins.
FAM20A, a recently discovered protein, is thought to have a fundamental role in inhibiting ectopic calcification. Several studies have demonstrated that variants of FAM20A are causative for the rare autosomal recessive disorder, enamel-renal syndrome (ERS). ERS is characterized by defective mineralization of dental enamel and nephrocalcinosis suggesting that FAM20A is an extracellular matrix protein, dysfunction of which causes calcification of the secretory epithelial tissues. FAM20A is a low-abundant protein that is difficult to detect in biofluids such as blood, saliva, and urine. Thus, we speculated the abundance of FAM20A to be high in human milk, since the secretory epithelium of lactating mammary tissue is involved in the secretion of highly concentrated calcium. Therefore, the primary aim of this research is to describe the processes/methodology taken to quantify FAM20A in human milk and identify other proteins involved in calcium metabolism. This study used mass spectrometry-driven quantitative proteomics: (1) to quantify FAM20A in human milk of three women and (2) to identify proteins associated with calcium regulation by bioinformatic analyses on whole and milk fat globule membrane fractions. Shotgun MS/MS driven proteomics identified FAM20A in whole milk, and subsequent analysis using targeted proteomics also successfully quantified FAM20A in all samples. Combination of sample preparation, fractionation, and LC-MS/MS proteomics analysis generated 136 proteins previously undiscovered in human milk; 21 of these appear to be associated with calcium metabolism. Using mass spectrometry-driven proteomics, we successfully quantified FAM20A from transitional to mature milk and obtained a list of proteins involved in calcium metabolism. Furthermore, we show the value of using a combination of both shotgun and targeted driven proteomics for the identification of this low abundant protein in human milk.


Review of diagnosis, differential diagnosis, and management of retroperitoneal lymphangioma.
Lymphatic malformation (LM) is the currently preferred term for what was previously known as lymphangioma. Retroperitoneal LMs are extremely rare, benign, cystic masses that arise from lymphatic vessels. They can be challenging to diagnose because they resemble other retroperitoneal cystic tumors. The development of treatment strategies for rare diseases, including retroperitoneal LM, requires the acquisition of new knowledge to enhance our understanding of the disease progression. Therefore, we present an update regarding fundamental and advanced issues associated with retroperitoneal LM. This review describes the epidemiology, histopathology, biomedicine, clinical manifestations, radiological features, differential diagnosis, and management of this lesion.


Therapeutic opportunities to prevent post-traumatic arthritis: Lessons from the natural history of arthritis after articular fracture.
An estimated 12% of patients seeking surgical intervention for symptomatic arthritis have an etiology of post-traumatic arthritis (PTA). The onset of PTA is rapid in the setting of articular fracture (AF). The investigation began with development of a murine model of a closed AF that develops PTA. In the process of characterizing this model a technique was developed for assessing quantitative synovial fluid biomarker concentrations. The work began with observations of the natural history of PTA development in the C57BL/6 strain of mice. A species of mice (MRL/MpJ) was found that is protected from PTA after AF. Further work identified key differences between mouse strains that did and did not develop PTA. This knowledge led to an intervention based on anti-cytokine (interleukin 1 receptor antagonist, (IL-1Ra) delivery in the C57BL/6 strain of mice that successfully prevented PTA following AF. This success in preventing PTA in the murine model has elucidated several important clinical implications: 1) Pro-inflammatory cytokines play an important role in the development of PTA after joint injury, 2) Pharmacologic intervention can lessen the severity of PTA after an AF, and 3) The murine AF model of joint injury provides a novel means of studying mechanisms of PTA development.


Correction: Bartha et al. How to Measure Adherence to a Mediterranean Diet in Dental Studies: Is a Short Adherence Screener Enough? A Comparative Analysis. Nutrients 2022, 14, 1300.
The authors would like to make a correction in a recently published paper [...].


Neonatal hyperbilirubinemia and the risk of febrile seizures and childhood epilepsy.
The aim of the study was to estimate the association between newborn children treated with phototerapy for hyperbilirubinemia and the subsequent risk of febrile seizures or epilepsy in early childhood. We conducted a follow-up study of singleton children (N=70 230) born between February 1998 and May 2003 from the Danish National Birth Cohort (DNBC). Information on exposure to phototherapy for hyperbilirubinemia was obtained from a questionnaire in the DNBC. Information on epilepsy and febrile seizures were obtained from the Danish National Hospital Registry (DNHR). Cox proportional hazard regression model was used to calculate hazard ratios (HRs) with 95% confidence intervals (CI). Newborns treated with phototherapy for hyperbilirubinemia had a higher risk of developing epilepsy in early childhood (HR: 1.66, 95% CI: 1.23-2.24) but not febrile seizures (HR: 1.04, 95% CI: 0.86-1.27). The increases risk of epilepsy were only present for boys (HR: 1.98, 95% CI: 1.40-2.78) not for girls (HR: 1.14, 95% CI: 0.64-2.02) CONCLUSION: Phototherapy for hyperbilirubinemia in newborns was associated with an increased risk of epilepsy for males in early childhood. No excess risk was seen with febrile seizures.


Superiority of PLK-2 as α-synuclein phosphorylating agent relies on unique specificity determinants.
Phosphorylation of α-synuclein at Ser-129 is of crucial relevance to Parkinson's disease and related synucleinopathies. Here we provide biochemical evidence that PLK2 and to a lesser extent PLK3 are superior over CK2, as catalysts of Ser-129 phosphorylation both in full length α-synuclein and in a peptide reproducing the C-terminal segment of the protein. By using substituted peptides we also show that the sequence surrounding Ser-129 is optimally shaped for undergoing phosphorylation by PLK2, with special reference to the two acidic residues at positions n-3 (Glu-126) and n+2 (Glu-131) whose replacement with alanine abrogates phosphorylation.


Delay-dependent guaranteed-cost control based on combination of Smith predictor and equivalent-input-disturbance approach.
This paper presents a new system configuration and a design method to improve control performance for a system with an input time delay and disturbances. The equivalent-input-disturbance approach is extended to handle a time-delay system. It is combined with the Smith predictor to reject disturbances. A delay-dependent stability condition is devised in terms of a matrix inequality by using the free-weighting matrix approach. The gain of the observer is designed by applying the cone complementary linearization method to the matrix inequality. A numerical example demonstrates the validity of the method.


[Radiation-induced cutaneous hamartoma in a patient with Cowden syndrome. Clinical evidence for heterozygosity].
A 56-year-old woman had typical features of Cowden syndrome in the form of hamartomas involving the skin, lips, and oral mucosa. At the age of 48, a mastectomy was performed for adenocarcinoma with a regional metastasis, and X-ray treatment was applied to the left axilla. Subsequently the patient developed approximately 30 skin-colored nodules surrounding the irradiated axillary region within several months. Histopathological examination of one of these lesions showed characteristic features of sclerotic fibroma. The multiple radiation-induced fibrous hamartomas observed may be best explained by multiple events of loss of heterozygosity (LOH), because molecular studies in other patients with Cowden syndrome have shown that both benign and malignant tumors originate from LOH. The X-ray treatment would have induced LOH in many cells, giving rise to either homo- or hemizygosity for the Cowden mutation.


An entropy-based measure of hydrologic complexity and its applications.
Basin hydrologic response is a function of soil moisture distributional featuresAn information-based dimensionless index of hydrologic complexity is appliedThe complexity index characterizes soil moisture distributional features.


[Environmental chemical pollution and toxic risk for humans: the particular role of organochlorine pesticides].
There is an increasing concern about environmental exposure to multiple chemicals and adverse changes in reproductive development, function, or behaviour in wildlife. The major group of environmental chemicals, such as organochlorine pesticides, polychlorinated biphenyls (PCBs) and other xenoestrogens are currently known to have estrogenic effects in vertebrates or fishes. Recent studies suggest that past exposure to such estrogenic compounds may affects the risk of developing breast cancer, precocious puberty, or impaired fertility in man.


Effect of central serotonin depletion on blood pressure and the renin system in rats.
In the present study we examined the effect of depletion of central nervous system serotonin by 5,7-dihydroxytryptamine on blood pressure in male Wistar rats. We also analyzed the relationship between the serotonergic and renin-angiotensin systems. Blood pressure was determined before and after intracisternal administration of 5,7-dihydroxytryptamine, 200 micrograms in saline with 1 mg/ml ascorbic acid (n = 9). Control rats (n = 8) received intracisternal vehicle. Before sacrifice, blood and cerebrospinal fluid samples were obtained. The brain was dissected in several areas. Serotonin, norepinephrine, angiotensinogen, and reninlike concentrations were determined in the brain parenchyma; angiotensinogen concentration was evaluated in cerebrospinal fluid and plasma samples; plasma renin activity was also measured. Treatment produced a significant decrease in blood pressure (-10 mm Hg; p less than 0.025) and, simultaneously, a high depletion of serotonin stores in the studied central areas (p less than 0.001), except in the cerebral cortex. Reninlike concentration was increased in the medulla oblongata (p less than 0.005) and the brainstem (p less than 0.02) after 5,7-dihydroxytryptamine treatment. Angiotensinogen concentration was decreased in the hypothalamus and elevated in the spinal cord. Angiotensinogen concentration in cerebrospinal fluid, plasma angiotensinogen concentration, and plasma renin activity did not change with treatment. Serotonin concentration in the cerebrospinal fluid remained unchanged, while the 5-hydroxyindoleacetic acid level was diminished (-47%; p less than 0.001). Intracisternal administration of 5,7-dihydroxytryptamine produced a hypotensive effect in normal rats and several modifications of the renin-angiotensin complex, suggesting a relationship between the monoaminergic and peptidergic systems.


Measurement of microbial numbers and biomass contained in thermophilic anaerobic reactors.
This paper describes the determination of the microbial population in terms of the number, biomass, and composition of single- and two-phase, laboratory-scale thermophilic (55 degrees C) anaerobic reactors under steady-state conditions. Epifluorescence microscopy with 4',6-diamidine-2-phenylindole (DAPI) as fluorochrome was used to determine the total number of microorganisms in the reactors, and autofluorescence microscopy was used to determine the total methanogenic bacteria populations. The results obtained by the direct count methods were compared to the quantity of biomass contained in the system, which was determined by volatile suspended solids. The concentration of acidogenic bacteria was estimated by subtraction of the autofluorescence results from those of the DAPI epifluorescence microscopy. The viable bacterial population was determined by plating techniques using an anaerobic chamber. The total bacterial and methanogenic populations of single-stage digesters increase when the hydraulic retention time decreases; nevertheless, the percentages of the principal bacterial groups (acidogenic and methanogenic) remain constant at 87% and 13%, respectively. In the two-stage reactors, the percentages of the acidogenic and methanogenic groups are 99% and 26% of the total population in the acidogenic and methanogenic reactors, respectively. In the single-stage reactors, biomass determinations can be used to estimate microbial concentrations, and vice versa, as there is a high positive correlation between microorganism concentration and biomass. The syntrophic relationship between the bacteria involved in the anaerobic process is a possible explanation for the low values of viable population obtained in the reactors studied. Nevertheless, there is a high correlation between direct counts by epifluorescence microscopy and viable plate counts for the combined system studied.


Transforming growth factor beta activates protein kinase C in microvessels isolated from immature rat brain.
We investigated the activation of protein kinase C in microvessels isolated from rat brain. We found that unstimulated kinase activity in microvessels from immature animals is soluble while that from adults is particulate. The tumor promoter, phorbol 12-myristate 13-acetate, and the diacylglycerol analog, 1-oleoyl-2-acetyl-sn-glycerol, caused the redistribution of protein kinase C activity to the membrane fraction in microvessels from immature rats. Exposure to transforming growth factor beta resulted in similar redistribution of kinase activity. To our knowledge, this is the first report of an effect of transforming growth factor beta on protein kinase C. The kinase activity in microvessels from adult animals was unaffected by exposure to these agonists. We suggest that protein kinase C activation promotes differentiation of the brain microvasculature. Transforming growth factor beta may mediate this process.


Self-Reported Pre-Pandemic Physical Activity and Likelihood of COVID-19 Infection: Data from the First Wave of the CoCo-Fakt Survey.
To investigate the potential protective role of exercise on the odds of COVID-19 infection in unvaccinated contact persons (CPs) who were at higher risk of infection due to confirmed contact with infected persons. Before the onset of the vaccination campaign, the first wave of the CoCo-Fakt online survey was conducted with SARS-CoV-2-positive persons and their confirmed contacts who were isolated/quarantined between 1 March 2020 and 9 December 2020. Within this analysis, 5338 CPs were included and divided into those who subsequently tested positive (CP-P) and those who remained negative (CP-N). We assessed demographics as well as pre-pandemic lifestyle characteristics including physical activity (PA; type, frequency, time, intensity; duration clustered as 'below PA guidelines', 'meeting PA guidelines', and 'above PA guidelines'; intensity clustered as 'low intensity' and 'moderate-to-vigorous intensity') and sedentary behaviour. A greater percentage of CP-Ns reported being active before the pandemic compared to CP-Ps (69% vs. 63%; p = .004). Moreover, CP-Ns reported higher PA duration (164.1 min/week vs. 143.2 min/week; p = .038) and higher PA intensities than CP-Ps (67% vs. 60% moderate-to-vigorous intensity, 33% vs. 40% low intensity; p = .003). Adjusting for age, sex, socioeconomic status, migration background, and pre-existing chronic diseases, the odds of infection were negatively associated with exercise (yes/no) (Nagelkerke R2 = 1.9%), PA levels above PA guidelines (Nagelkerke R2 = 2.0%), and PA intensity (Nagelkerke R2 = 1.8%). Due to the beneficial effects of PA on the odds of infection, an active lifestyle should be promoted especially during possible subsequent pandemics (while taking into account necessary hygiene measures). Moreover, inactive and chronically ill persons should be especially encouraged to adopt a healthier lifestyle.


[Body mass changes during pregnancy and concentration of insulin and neuropeptide Y in women with regard to the BMI].
Obesity poses a serious problem to human population as it increases the risk of diabetes, hypertension, metabolic syndrome. In pregnancy obesity increases the frequency of its complications. The main aim of the study was to estimate the increase of body mass and insulin and neuropeptide Y concentrations in pregnant women. The changes of body mass and BMI in women before pregnancy and before delivery and the concentrations of insulin and neuropeptide Y in blood were estimated. The increase of body mass and BMI during the pregnancy period was higher in the group with high body mass and I stage obesity and increase of insulin concentration depended on increase of the body mass. Higher concentration of NPY was found in the group of women with normal body mass and obese if compared to stages II and III of obesity No correlation between insulin increase and concentration of NPY was found. In most pregnant women body mass gain is excessive and leads to obesity of different stages. Insulin concentration increases as BMI increases. Neuropeptide Y concentration in the obese women group was lower than in the normal weight group.


Comparing community detection algorithms in psychometric networks: A Monte Carlo simulation.
Identifying the correct number of factors in multivariate data is fundamental to psychological measurement. Factor analysis has a long tradition in the field, but it has been challenged recently by exploratory graph analysis (EGA), an approach based on network psychometrics. EGA first estimates a network and then applies the Walktrap community detection algorithm. Simulation studies have demonstrated that EGA has comparable or better accuracy for recovering the same number of communities as there are factors in the simulated data than factor analytic methods. Despite EGA's effectiveness, there has yet to be an investigation into whether other sparsity induction methods or community detection algorithms could achieve equivalent or better performance. Furthermore, unidimensional structures are fundamental to psychological measurement yet they have been sparsely studied in simulations using community detection algorithms. In the present study, we performed a Monte Carlo simulation using the zero-order correlation matrix, GLASSO, and two variants of a non-regularized partial correlation sparsity induction methods with several community detection algorithms. We examined the performance of these method-algorithm combinations in both continuous and polytomous data across a variety of conditions. The results indicate that the Fast-greedy, Louvain, and Walktrap algorithms paired with the GLASSO method were consistently among the most accurate and least-biased overall.


Complete Genomic Sequence of an Agarolytic Pseudoalteromonas Species Isolated from Deep Seawater.
We report the complete genomic sequence of the agarolytic bacterium Pseudoalteromonas sp. strain MM1, recovered from deep seawater. The genome has two circular chromosomes with sizes of 3,686,652 bp and 802,570 bp and GC contents of 40.8 and 40.0%, and it carries 3,967 protein-coding sequences, 24 rRNA genes, and 103 tRNA genes.


Self-experimentation, ethics and efficacy.
Much fundamental progress in medicine and, more broadly, in medical sciences has required or benefited from self-experiments. This review provides a definition of self-experiments in which experimenters themselves are subjects for their research, and it considers the logical steps which such experiments require. Lay, medical and scientific communities are often unaware of the contributions and the full range of outcomes from self-experiments. Hence, some implications for ethics committees are explored.


Host-Pathogen Interactions after Lung Transplant: Are Cystic Fibrosis Patients Unique?
The impact of Pseudomonas aeruginosa airway colonization on lung allografts is not entirely clear. In this issue of Cell Reports Medicine, Dugger et al.1 identify distinct clinical outcomes and lung allograft biology in recipients with and without cystic fibrosis.


Optimizing the Immunogenicity of HIV Vaccines by Adjuvants - NIAID Workshop Report.
This report summarizes the highlights of a workshop convened by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), on April 4-5, 2022, to provide a discussion forum for sharing insights on the current status, key challenges, and next steps to advance the current landscape of promising adjuvants in preclinical and clinical human immunodeficiency virus (HIV) vaccine studies. A key goal was to solicit and share recommendations on scientific, regulatory, and operational guidelines for bridging the gaps in rational selection, access, and formulation of clinically relevant adjuvants for HIV vaccine candidates. The NIAID Vaccine Adjuvant Program working group remains committed to accentuate promising adjuvants and nurturing collaborations between adjuvant and HIV vaccine developers.


Programming Injectable DNA Hydrogels Yields Tumor Microenvironment-Activatable and Immune-Instructive Depots for Augmented Chemo-Immunotherapy.
Injectable hydrogels have attracted increasing attention for promoting systemic antitumor immune response through the co-delivery of chemotherapeutics and immunomodulators. However, the biosafety and bioactivity of conventional hydrogel depots are often impaired by insufficient possibilities for post-gelling injection and means for biofunction integration. Here, an unprecedented injectable stimuli-responsive immunomodulatory depot through programming a super-soft DNA hydrogel adjuvant is reported. This hydrogel system encoded with adenosine triphosphate aptamers can be intratumorally injected in a gel formulation and then undergoes significant molecular conformation change to stimulate the distinct release kinetics of co-encapsulated therapeutics. In this scenario, doxorubicin is first released to induce immunogenic cell death that intimately works together with the polymerized cytosine-phosphate-guanine oligodeoxynucleotide (CpG ODN) in gel scaffold for effectively recruiting and activating dendritic cells. The polymerized CpG ODN not only enhances tumor immunogenicity but minimizes free CpG-induced splenomegaly. Furthermore, the subsequently released anti-programmed cell death protein ligand 1 (aPDL1) blocks the corresponding immune inhibitory checkpoint molecule on tumor cells to sensitize antitumor T-cell immunity. This work thus contributes to the first proof-of-concept demonstration of a programmable super-soft DNA hydrogel system that perfectly matches the synergistic therapeutic modalities based on chemotherapeutic toxicity, in situ vaccination, and immune checkpoint blockade.


Effect of pore geometry on the fatigue properties and cell affinity of porous titanium scaffolds fabricated by selective laser melting.
Porous titanium scaffolds with different unit cell type (tetrahedron and octahedron) and pore size (500 µm and 1000 µm) were fabricated by selective laser melting (SLM), and the effects of unit cell type and pore size on their fatigue properties and cell affinity were studied. The fatigue properties were performed by static and dynamic mechanical testing, while the cell affinity was evaluated in vitro with mouse osteoblast cells. It was found that octahedron scaffolds exhibited superior static mechanical properties, longer fatigue lives and higher fatigue strength in comparison to those of tetrahedron ones. As expected, scaffolds with 1000 µm pore resulted in lower compressive properties and shorter fatigue lives compared to those with 500 µm pore. The differences were analyzed based on the unit cell structure, porosity, and manufacturing imperfections. Scanning electron microscopy (SEM) and immunofluorescence showed that cells spread better on octahedron scaffolds than those on tetrahedron ones. Meanwhile, the scaffolds with 1000 µm pore were more suitable for cell attachment and growth within the same unit cell owing to higher porosity. The comparison of different pore geometry on the mechanical and biological property provided further insight into designing an optimal porous scaffold.


Spermatogenesis after scrotal reconstruction.
Objective. To explore the effect of scrotal reconstruction following avulsion on spermatogenesis. Methods. Three patients were followed-up after having their scrotums reconstructed. Two scrotums were reconstructed by skin flap. Another patient's testicles were buried in thigh pockets. The follow-up continued from 3 months to 4 years after operation, and we examined the sperm quality, sexual function, sexual hormone, and testis biopsy. Results. The follow-up data showed that the spermatogenesis was not altered in the early stage (up to three months), but was substantially abnormal in the late stage (after two years). Conclusions. Using the thick skin flaps, or burying the testicle for scrotum reconstruction are not recommended for patients who wish to remain fertile.


Assessment of MRI issues at 3-Tesla for metallic surgical implants: findings applied to 61 additional skin closure staples and vessel ligation clips.
Metallic skin closure staples and vessel ligation clips should be tested at 3-Tesla to characterize MRI issues in order to ensure patient safety. Therefore, metallic surgical implants were assessed at 3-Tesla for magnetic field interactions, MRI-related heating, and artifacts. A skin closure staple (Visistat Skin Stapler, staple, Polytetrafluoroethylene, PTFE, coated 316L/316LVM stainless steel; Teleflex Medical, Durham, NC) and a vessel ligation clip (Hemoclip Traditional, stainless steel; Teleflex Medical, Durham, NC) that represented the largest metallic sizes made from materials with the highest magnetic susceptibilities (i.e., based on material information) among 61 other surgical implants (52 metallic implants, 9 nonmetallic implants) underwent evaluation for magnetic field interactions, MRI-related heating, and artifacts using standardized techniques. MRI-related heating was assessed by placing each implant in a gelled-saline-filled phantom with MRI performed using a transmit/receive RF body coil at an MR system reported, whole body averaged SAR of 2.9-W/kg for 15-min. Artifacts were characterized using T1-weighted, SE and GRE pulse sequences. Each surgical implant showed minor magnetic field interactions (20- and 27-degrees, which is acceptable from a safety consideration). Heating was not substantial (highest temperature change, ≤ 1.6°C). Artifacts may create issues if the area of interest is in the same area or close to the respective surgical implant. The results demonstrated that it would be acceptable for patients with these metallic surgical implants to undergo MRI at 3-Tesla or less. Because of the materials and dimensions of the surgical implants that underwent testing, these findings pertain to 61 additional similar implants.


Structure and flexibility of the endosomal Vps34 complex reveals the basis of its function on membranes.
Phosphatidylinositol 3-kinase Vps34 complexes regulate intracellular membrane trafficking in endocytic sorting, cytokinesis, and autophagy. We present the 4.4 angstrom crystal structure of the 385-kilodalton endosomal complex II (PIK3C3-CII), consisting of Vps34, Vps15 (p150), Vps30/Atg6 (Beclin 1), and Vps38 (UVRAG). The subunits form a Y-shaped complex, centered on the Vps34 C2 domain. Vps34 and Vps15 intertwine in one arm, where the Vps15 kinase domain engages the Vps34 activation loop to regulate its activity. Vps30 and Vps38 form the other arm that brackets the Vps15/Vps34 heterodimer, suggesting a path for complex assembly. We used hydrogen-deuterium exchange mass spectrometry (HDX-MS) to reveal conformational changes accompanying membrane binding and identify a Vps30 loop that is critical for the ability of complex II to phosphorylate giant liposomes on which complex I is inactive.


A label-free impedance assay in endothelial cells differentiates the activation and desensitization properties of clinical S1P1 agonists.
Sphingosine-1 phosphate receptor-1 (S1P1 ) activation maintains endothelial barrier integrity, whereas S1P1 desensitization induces peripheral blood lymphopenia. The latter is exploited in the approval and/or late-stage development of receptor-desensitizing agents targeting the S1P1 receptor in multiple sclerosis, such as siponimod, ozanimod, and ponesimod. SAR247799 is a recently described G protein-biased S1P1 agonist that activates S1P1 without desensitization and thus has endothelial-protective properties in patients without reducing lymphocytes. As SAR247799 demonstrated endothelial-protective effects at sub-lymphocyte-reducing doses, the possibility exists that other S1P1 modulators could also exhibit endothelial-protective properties at lower doses. To explore this possibility, we sought to quantitatively compare the biased properties of SAR247799 with the most advanced clinical molecules targeting S1P1 . In this study, we define the β-arrestin pathway component of the impedance profile following S1P1 activation in a human umbilical vein endothelial cell line (HUVEC) and report quantitative indices of the S1P1 activation-to-desensitization ratio of various clinical molecules. In a label-free impedance assay assessing endothelial barrier integrity and disruption, the mean estimates (95% confidence interval) of the activation-to-desensitization ratios of SAR247799, ponesimod, ozanimod, and siponimod were 114 (91.1-143), 7.66 (3.41-17.2), 6.35 (3.21-12.5), and 0.170 (0.0523-0.555), respectively. Thus, we show that SAR247799 is the most G protein-biased S1P1 agonist currently characterized. This rank order of bias among the most clinically advanced S1P1 modulators provides a new perspective on the relative potential of these clinical molecules for improving endothelial function in patients in relation to their lymphocyte-reducing (desensitization) properties.


Morphine 6 glucuronide stimulates nitric oxide release in mussel neural tissues: evidence for a morphine 6 glucuronide opiate receptor subtype.
We have previously demonstrated that Mytilus edulis pedal ganglia contain opiate alkaloids, i.e., morphine and morphine 6 glucuronide (M6G), as well as mu opiate receptor subtype fragments exhibiting high sequence similarity to those found in mammals. Now we demonstrate that M6G stimulates pedal ganglia constitutive nitric oxide (NO) synthase (cNOS)-derived NO release at identical concentrations and to similar peak levels as morphine. However, the classic opiate antagonist, naloxone, only blocked the ability of morphine to stimulate cNOS-derived NO release and not that of M6G. CTOP, a mu-specific antagonist, blocked the ability of M6G to induce cNOS-derived NO release as well as that of morphine, suggesting that a novel mu opiate receptor was present and selective toward M6G. In examining a receptor displacement analysis, both opiate alkaloids displaced [3H]-dihydromorphine binding to the mu opiate receptor subtype. However, morphine exhibited a twofold higher affinity, again suggesting that a novel mu opiate receptor may be present.


Capsulorhexis: Pearls and pitfalls.
A critical step in phacoemulsification (as well as extracapsular cataract extraction) is making a window in anterior capsule wall (i.e. anterior capsulotomy). Continuous Curvilinear Capsulorhexis (CCC) has become recognized as the standard method of anterior capsulectomy. Techniques employed for CCC have undergone sustained evolution. The present review evaluates elementary principles of CCC. Management of CCC in the presence of small pupil and pseudoexfoliation syndrome is discussed. Main differences of pediatric CCC from its adult-style counterpart and finally several techniques of rescue of an extending capsulorhexis are also reviewed.


Histologic aspects of pulmonary barotrauma in critically ill patients with acute respiratory failure.
To describe histologically pulmonary barotrauma in mechanically ventilated patients with severe acute respiratory failure. Assessment of histologic pulmonary barotrauma. A 14-bed surgical intensive care unit (SICU) PATIENTS: The lungs of 30 young critically ill patients (mean age 34 +/- 10 years) were histologically examined in the immediate post-mortem period. None of them were suspected of pre-existing emphysema. Clinical events and ventilatory settings used during mechanical ventilation were compared with lung histology. Airspace enlargement, defined as the presence of either alveolar overdistension in aerated lung areas or intraparenchymal pseudocysts in nonaerated lung areas, was found in 26 of the 30 lungs examined (86%). Patients with severe airspace enlargement (2.6-40 mm internal diameter) had a significantly greater incidence of pneumothorax (8 versus 2, p < 0.05), were ventilated using higher peak airway pressures (56 +/- 18 cmH2O versus 44 +/- 10 cmH2O, p < 0.05) and tidal volumes (12 +/- 3 ml/kg versus 9 +/- 2 ml/kg, p < 0.05), were exposed significantly longer to toxic levels of oxygen (8.6 +/- 9.4 days versus 1.9 +/- 2 days at FIO2 > 0.6, p < 0.05) and lost more weight (6.3 +/- 9.2 kg versus 0.75 +/- 5.8 kg, p < 0.05) than patients with mild airspace enlargement (1-2.5 mm internal diameter). Underlying histologic lesions responsible for clinical lung barotrauma consist of pleural cysts, bronchiolar dilatation, alveolar overdistension and intraprenchymal pseudocysts. Mechanical ventilation appears to be an aggravating factor, particularly when high peak airway pressures and large tidal volumes are delivered by the ventilator.


Ovarian reserve tests in infertility practice and normal fertile women.
The decline in fecundity with the age of the woman is mainly attributed to the loss of follicles from the ovary and a decrease in oocyte quality. Evaluation of the aging status of the ovary in an individual woman has been hampered by a lack of knowledge with regard to the relative contribution of these two factors. Most if not all so called ovarian reserve tests (ORT) reflect indirectly the remaining follicle pool in the ovary. Direct a priori assessment of oocyte quality is not possible to date. In this section the predictive value of several ovarian reserve tests for the outcome of fertility treatment is listed and commented. In addition, the study of several of the ORTs in normal, fertile women is described. From the data presented dynamic testing of the ovarian function by the clomiphene citrate and GnRH agonist stimulation test, as well as static testing by the use of ultrasound based antral follicle counts seem to offer the highest clinical value. Studies performing direct comparison of these tests are needed, as well as analysis of the way these tests should direct decision making in infertility diagnosis and treatment.


Camellia euphlebia protects against corticosterone-induced apoptosis in differentiated PC12 cells by regulating the mitochondrial apoptotic pathway and PKA/CREB/BDNF signaling pathway.
Camellia euphlebia is a Chinese folk medicine, known for its multiple pharmacological properties. Our previous studies have demonstrated its antidepressant activity by several animal models of depression. The possible underlying mechanism was further explored by investigating the neuroprotective effect of Camellia euphlebia extract (CEE) on corticosterone-induced apoptosis in neuronally differentiated PC12 cells. The results of methyl-thiazolyl-tetrazolium assay, lactate dehydrogenase release assay, Hoechst 33342 staining, propidium iodide staining, AV-FITC/PI double staining and DNA fragmentation analysis consistently indicated that pretreatment of PC12 cells with CEE at 20-80 μg/mL significantly reversed 300 μmol/L corticosterone-induced apoptosis in a dose dependent manner. Furthermore, intracellular mitochondrial membrane potential, reactive oxygen species accumulation, calcium level, Bcl-2/Bax ratio, caspase activity were assessed, and the results indicated that CEE exhibited its anti-apoptotic effect through the regulation of mitochondrial apoptosis pathway. Additionally, CEE increased the cyclic adenosine monophosphate-dependent protein kinase (PKA) level, which phosphorylated cAMP response element binding protein (CREB), and finally elevated the mRNA expression of brain-derived neurotrophic factor (BDNF) gene. It is speculated that the antidepressant effect of CEE in vivo may be associated with the cytoprotection of neuron damaged by corticosterone, and the cellular mechanism involves the mitochondrial-mediated apoptosis and PKA-CREB-BDNF signaling pathway.


On the Analysis of Clustering in an Irradiated Low Alloy Reactor Pressure Vessel Steel Weld.
Radiation induced clustering affects the mechanical properties, that is the ductile to brittle transition temperature (DBTT), of reactor pressure vessel (RPV) steel of nuclear power plants. The combination of low Cu and high Ni used in some RPV welds is known to further enhance the DBTT shift during long time operation. In this study, RPV weld samples containing 0.04 at% Cu and 1.6 at% Ni were irradiated to 2.0 and 6.4×1023 n/m2 in the Halden test reactor. Atom probe tomography (APT) was applied to study clustering of Ni, Mn, Si, and Cu. As the clusters are in the nanometer-range, APT is a very suitable technique for this type of study. From APT analyses information about size distribution, number density, and composition of the clusters can be obtained. However, the quantification of these attributes is not trivial. The maximum separation method (MSM) has been used to characterize the clusters and a detailed study about the influence of the choice of MSM cluster parameters, primarily on the cluster number density, has been undertaken.


Phorbol ester, retinoic acid and diacylglycerol decrease ecto- but increase total basal-protein kinase activity of human fibroblasts.
Studies have been carried out on intact human lung fibroblasts (HLF) in situ to investigate the effect of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and the anti-tumor promoter retinoic acid (RA) on ecto-protein kinases. The ecto-kinase reaction of the HLF-cells was cAMP-independent, showed an apparent Km for ATP of 6.99 +/- 0.35 (microM) and was substantially inhibited by TPA and RA. With the notable exception of a approximately 57 kD phosphoprotein both compounds decreased the overall phosphorylation of intact cells. In contrast to RA-treatment, however, TPA caused the release of a high molecular weight (approximately 210 kD) phosphoprotein from the HLF. RA was the most potent retinoid in reducing ecto-kinase activity. The physiological modulators of protein kinase C: 1,2- and 1,3-diolein as well the synthetic 1,2-dioctanoylglycerol decreased the ecto-kinase activity to an extent similar to that of TPA. The drop in ecto-kinase activity of HLF-cells in situ caused by TPA, RA and the diacylglycerols was accompanied by an increase in total basal-(Mg++-dependent) protein kinase activity present in extracts of treated cells. The results suggest an important role of ecto-kinase in the response of intact cells to TPA and RA.


Systemic lupus erythematosus and myoclonic epileptic manifestations.
Systemic lupus erythematosus (SLE) frequently involves the central nervous system (CNS) and, in fact, epileptic manifestations may be one of the earliest symptoms of SLE. These early occurrences of epilepsy, however, can easily be misdiagnosed as indication of pure epileptic syndrome when the SLE diagnosis is still largely incomplete. We present a young girl who developed myoclonic photosensitive seizures at the onset of the illness, erroneously diagnosed as manifestation of a "pure" epileptic syndrome. Shortly after the onset of an anticonvulsant therapy (lamotrigine), there was a remarkable impairment of the general clinical condition: at that time a diagnosis of SLE was made and a specific treatment began. However, the seizures persisted and evolved toward status epilepticus which needed pentobarbitone therapy in an intensive care unit (ICU). After recovery, the girl gradually got better and during the 23 months of follow-up she received only corticosteroid therapy and did not experience seizures nor SLE relapses.


Deep-rooted perennial crops differ in capacity to stabilize C inputs in deep soil layers.
Comprehensive climate change mitigation necessitates soil carbon (C) storage in cultivated terrestrial ecosystems. Deep-rooted perennial crops may help to turn agricultural soils into efficient C sinks, especially in deeper soil layers. Here, we compared C allocation and potential stabilization to 150 cm depth from two functionally distinct deep-rooted perennials, i.e., lucerne (Medicago sativa L.) and intermediate wheatgrass (kernza; Thinopyrum intermedium), representing legume and non-legume crops, respectively. Belowground C input and stabilization was decoupled from nitrogen (N) fertilizer rate in kernza (100 and 200 kg mineral N ha-1), with no direct link between increasing mineral N fertilization, rhizodeposited C, and microbial C stabilization. Further, both crops displayed a high ability to bring C to deeper soil layers and remarkably, the N2-fixing lucerne showed greater potential to induce microbial C stabilization than the non-legume kernza. Lucerne stimulated greater microbial biomass and abundance of N cycling genes in rhizosphere soil, likely linked to greater amino acid rhizodeposition, hence underlining the importance of coupled C and N for microbial C stabilization efficiency. Inclusion of legumes in perennial cropping systems is not only key for improved productivity at low fertilizer N inputs, but also appears critical for enhancing soil C stabilization, in particular in N limited deep subsoils.


Network-based diffusion analysis reveals cultural transmission of lobtail feeding in humpback whales.
We used network-based diffusion analysis to reveal the cultural spread of a naturally occurring foraging innovation, lobtail feeding, through a population of humpback whales (Megaptera novaeangliae) over a period of 27 years. Support for models with a social transmission component was 6 to 23 orders of magnitude greater than for models without. The spatial and temporal distribution of sand lance, a prey species, was also important in predicting the rate of acquisition. Our results, coupled with existing knowledge about song traditions, show that this species can maintain multiple independently evolving traditions in its populations. These insights strengthen the case that cetaceans represent a peak in the evolution of nonhuman culture, independent of the primate lineage.


Radioimmunoassay of plasma 18-hydroxy-11-deoxycorticosterone and its response to ACTH.
A radioimmunoassay for the measurement of 18-OH-DOC in plasma was developed using an antiserum raised against the gamma-lactone derivative. The steroids with the greatest degree of cross reaction were 18-OH-corticosterone-gamma-lactone and aldosterone-gamma-lactone which showed cross-reactivities of 1.96% and 0.47% respectively. These and other interfering steroids were eliminated by chromatography of the extracts on columns of Sephadex LH-20. The lowest limit of detection of 18-OH-DOC in 1 ml of plasma corresponded to 33 pmol-1. The intra-assay precision was 9.7, 4.8 and 2.6% at 102.0, 316.1 and 1144.0 pmol 1(-1) respectively and the interassay precision was 15.3 and 5.4% at 71.3 and 404.7 pmol 1(-1) respectively. The amount of 18-OH-DOC measured (y) which showed a high degree of correlation (r = 0.999) with the amount added (x) to plasma in the range 240--1920 pmol 1(-1) could be predicted from the linear least squares equation y = 1.006x + 31.3. The concentration of 18-OH-DOC in ten normal subjects was 172.1 +/- 39.1 pmol 1(-1) at 09.00 h, 100.9 +/- 16.9 pmol 1(-1) at 12.00 h and 95.8 +/- 33.3 pmol 1(-1) at 16.30 h. Plasma 18-OH-DOC and cortisol levels were measured after various intravenous doses of ACTH in three patient with esential hypertension. Lower doses of ACTH caused similar percentage increases in both hormones but higher doses caused considerably greater increases in 18-OH-DOC. These results confirm the ACTH dependancy of 18-OH-DOC secretion.


[Acute prostatitis].
A urinary infection in a febrile man is classiquely defined as a prostatitis. Investigation exams look for complicating factors or post voiding residual which should be drained. Antibiotic treatment should begin with a fluroquinolone or cephalosporin gr 3 for 3 to 6 weeks.


Histones trigger sterile inflammation by activating the NLRP3 inflammasome.
Sterile cell death mediated inflammation is linked to several pathological disorders and involves danger recognition of intracellular molecules released by necrotic cells that activate different groups of innate pattern recognition receptors. Toll-like receptors directly interact with their extrinsic or intrinsic agonists and induce multiple proinflammatory mediators. In contrast, the NLRP3 inflammasome is rather thought to represent a downstream element integrating various indirect stimuli into proteolytic cleavage of interleukin (IL)-1β and IL-18. Here, we report that histones released from necrotic cells induce IL-1β secretion in an NLRP3-ASC-caspase-1-dependent manner. Genetic deletion of NLRP3 in mice significantly attenuated histone-induced IL-1β production and neutrophil recruitment. Furthermore, necrotic cells induced neutrophil recruitment, which was significantly reduced by histone-neutralizing antibodies or depleting extracellular histones via enzymatic degradation. These results identify cytosolic uptake of necrotic cell-derived histones as a triggering mechanism of sterile inflammation, which involves NLRP3 inflammasome activation and IL-1β secretion via oxidative stress.


Superior results of return to sport after double-bundle versus single-bundle anterior cruciate ligament reconstruction in young active patients.
To compare return to sport and clinical results in young active patients who underwent anatomic single-bundle (SB) versus double-bundle (DB) anterior cruciate ligament reconstruction (ACLR). Young active patients undergoing SB or DB ACLR from 2017 to 2019 at our institution were retrospectively reviewed. The primary outcome measures were the rate and time to return to sports, with secondary measures including the Lachman test, pivot shift test, Lysholm scores, International Knee Documentation Committee (IKDC) scores and graft rupture. The study included a total of 90 patients (DB group, 42; SB group, 48), with a mean follow-up of 27.1 ± 6.1 months. Young active patients who underwent DB ACLR had a higher rate of return to pivoting sports than those who underwent SB ACLR (HR = 2.4; 95% confidence interval [CI]: 1.4, 4.1; p = 0.013). The DB group returned to pivoting sports at a mean ± SD of 11.0 ± 2.9 months compared with 12.7 ± 2.7 months in the SB group (p = 0.01). There was one traumatic failure in the SB group and one contralateral ACL rupture in the DB group. There was no significant difference in the rate and time to return to running, Lachman test, pivot-shift test, Lysholm or IKDC scores in either group. Both anatomical SB and DB techniques achieved satisfactory clinical outcomes. DB techniques led to superior performance of return to pivoting sports but nonsignificant differences in time and rate of return to running, passive stability measurement, subjective knee function outcome and graft rupture rate in both groups at the 2-year follow-up. The DB ACLR should be considered a viable option to treat young patients with high activity demands. III.


Aquaporin 5 expression is frequent in prostate cancer and shows a dichotomous correlation with tumor phenotype and PSA recurrence.
Aquaporin 5 (AQP5) is an androgen-regulated member of a family of small hydrophobic integral transmembrane water channel proteins regulating cellular water homeostasis and growth signaling. To evaluate its clinical impact and relationship with key genomic alterations in prostate cancer, AQP5 expression was analyzed by immunohistochemistry on a tissue microarray containing 12427 prostate cancers. The analysis revealed weak to moderate immunostaining in normal prostate epithelium. In prostate cancers AQP5 staining levels were more variable and also included completely negative and highly overexpressing cases. Negative, weak, moderate, and strong AQP5 staining was found in 25.0%, 32.5%, 32.5%, and 10.0% of 10239 interpretable tumors. Comparison of AQP5 expression levels with tumor characteristics showed a dichotomous pattern with both high and low staining levels being linked to unfavorable tumor phenotype. AQP5 was negative in 28%, 23%, 24%, and 35% of tumors with Gleason score ≤3 + 3, 3 + 4, 4 + 3 and ≥4 + 4, while the rate of strongly positive cases continuously increased from 7.0% over 10.0% and 12.0% to 13.0% in cancers with Gleason score ≤3 + 3, 3 + 4, 4 + 3 and ≥4 + 4. AQP5 expression was also related to ERG positivity and phosphatase and tensin homolog (PTEN) deletion (P < .0001 each). Strong AQP5 positivity was seen in 15.5% of ERG-positive and 5.8% of ERG-negative cancers (P < .0001) as well as in 14.7% of cancers with PTEN deletion and 9.4% of cancers without PTEN deletion. Remarkably, both negativity and strong positivity of AQP5 were linked to unfavorable disease outcome. This was however only seen in subgroups defined by TMPRSS2-ERG fusion and/or PTEN deletion. In summary, AQP5 can be both overexpressed and lost in subgroups of prostate cancers. Both alterations are linked to unfavorable outcome in molecularly defined cancer subgroups. It is hypothesized that this dichotomous role of AQP5 is due to two highly different mechanisms as to how the protein can influence cancer cells, that is, hydraulic motility regulation and Ras/MAPK pathway activation.


Enhanced oxygen reduction upon Ag-Fe-doped polyacrylonitrile@UiO-66-NH2 nanofibers to improve power-generation performance of microbial fuel cells.
Microbial fuel cells (MFCs) have great potential as a new energy technology that utilizes microorganisms to produce electrical energy by decomposing organic matter. A cathode catalyst is key to achieving an accelerated cathodic oxygen reduction reaction (ORR) in MFCs. We prepared a Zr-based metal organic-framework-derived silver-iron co-doped bimetallic material based on electrospun nanofibers by promoting the in situ growth of UiO-66-NH2 on polyacrylonitrile (PAN) nanofibers and named it as CNFs-Ag/Fe-m:n doped catalyst (m:n were 0, 1:1, 1:2, 1:3, and 2:1, respectively). Experimental results combined with density functional theory (DFT) calculations reveal that a moderate amount of Fe doped in CNFs-Ag-1:1 reduces the Gibbs free energy in the last step of the ORR. This indicates that Fe doping improves the performance of the catalytic ORR, and MFCs equipped with CNFs-Ag/Fe-1:1 exhibit a maximum power density of 737. 45 mW m-2, significantly higher than that obtained for MFCs using commercial Pt/C (457.99 mW m-2).


Confinement during Covid-19 outbreak modifies athletes' self-based goals.
Because achievement goals are context-specific, the study first investigated the evolution of two achievement goals of 697 regular athletes, namely self-approach goals (improving oneself) and self-avoidance goals (avoiding regression), before and during the confinement situation and the physical exercise restrictions due to the Covid-19 outbreak. Secondly, we sought to examine the potential predicting role of self-approach and self-avoidance goals on athletes' intention to exercise during confinement, while self-avoidance goals were usually not related to this outcome in a more traditional context. Using a retrospective correlational design, the results of repeated measures ANOVA highlighted that self-approach goals scores decreased while self-avoidance goals scores increased and became the athletes' goals with the highest score during confinement. The results of hierarchical regression analyses showed that self-approach and self-avoidance goals were both found as positive predictors of intention to exercise during confinement. This study reinforces the assumptions that (a) a specific achievement setting encourages the adoption of different achievement goals (which was identified here with regular athletes in an unusual context of confinement), (b) self-avoidance goals are not always maladaptive, and (c) shifting among multiple goals according to the requirements of the situation may be beneficial.


[The potentiation of betazol stimulated gastric acidity by prednisolone in dogs (author's transl)].
In a total of 46 dogs divided into 5 groups the acute effect of a high dose of prednisolone (40 mg/kg i.v.) on betazol stimulated gastric seccretion (5mg/kh s.c.) was investigated. There was no effect of prednisolone alone. The combination of betazol and prednisolone showed a significant potentiation of betazol stimulation. This effect was not seen after truncal vagotomy before stimulation. The mechanism is either cholinergic or an interaction in the metabolism of histamine.


Quadriceps weakness in knee osteoarthritis: the effect on pain and disability.
(1) To determine the importance of quadriceps strength, structural change, and psychological status in terms of knee pain in the community. (2) To determine the relative importance of quadriceps function, structural change, and psychological status with respect to disability in subjects with knee pain. 300 men and women with pain and 300 controls without pain (aged 40-79) were seen. Isometric quadriceps strength (MVC) was measured and muscle activation was assessed by twitch superimposition. Disability (Western Ontario McMaster Osteoarthritis Index (WOMAC)) and anxiety and depression were assessed (Hospital Anxiety and Depression Index (HAD)). Radiographs were obtained of the tibiofemoral and patellofemoral joints and total score for osteophyte, narrowing, and sclerosis calculated for each knee. Subjects with knee pain had lower voluntary quadriceps strength than those without pain (p < 0.005). Quadriceps activation was also lower (p < 0.005), but did not fully explain the reduction in strength. When analysed by multiple logistic regression: quadriceps strength (odds ratio 18.8, CI 4.8, 74.1 for MVC < or = 10 kgF); depression (odds ratio 2.4, CI 1.0, 5.5 for HAD score > or = 8); and radiographic change (odds ratio 4.1, CI 1.9, 8.6 for radiographic score > or = 4) were independently associated with pain. In those with knee pain, disability was independently associated with quadriceps strength (odds ratio 8.2, CI 1.5, 44.4 for MVC < or = 10 kgF) and depression (odds ratio 6.2, CI 2.1, 18.0 for HAD score > or = 8); but not with radiographic score. Quadriceps strength is strongly associated with knee pain and disability in the community, even when activation and psychological factors are taken into account. This has important therapeutic implications.


Fractal texture analysis of the healing process after bone loss.
Radiological assessment of treatment effectiveness of guided bone regeneration (GBR) method in postresectal and postcystal bone loss cases, observed for one year. Group of 25 patients (17 females and 8 males) who underwent root resection with cystectomy were evaluated. The following combination therapy of intraosseous deficits was used, consisting of bone augmentation with xenogenic material together with covering regenerative membranes and tight wound closure. The bone regeneration process was estimated, comparing the images taken on the day of the surgery and 12 months later, by means of Kodak RVG 6100 digital radiography set. The interpretation of the radiovisiographic image depends on the evaluation ability of the eye looking at it, which leaves a large margin of uncertainty. So, several texture analysis techniques were developed and used sequentially on the radiographic image. For each method, the results were the mean from the 25 images. These methods compute the fractal dimension (D), each one having its own theoretic basis. We used five techniques for calculating fractal dimension: power spectral density method, triangular prism surface area method, blanket method, intensity difference scaling method and variogram analysis. Our study showed a decrease of fractal dimension during the healing process after bone loss. We also found evidence that various methods of calculating fractal dimension give different results. During the healing process after bone loss, the surfaces of radiographic images became smooth. The result obtained show that our findings may be of great importance for diagnostic purpose.


MXene as a novel cartridge for N-glycan enrichment.
In this study, we applied MXene as column cartridge for N-glycan enrichment from human samples with a focus on the analysis of sialic acid linkages using a derivatisation protocol followed by glycan analysis via Matrix Assisted Laser Desorption Ionisation-Time Of Flight Mass Spectrometry (MALDI-TOF-MS). The MXene-based cartridge enriches a higher number of glycans (i.e., sialylated and bisecting N-glycans) when compared to the commercial HILIC columns. We demonstrate the strong potential of MXene as a stationary phase in MS glycomic analysis.


Salvage procedure for failed Bowers' hemiresection interposition technique in the distal radioulnar joint.
Three patients who continued to have distal radioulnar joint pain following Bowers' hemiresection interposition technique were treated by converting the resection arthroplasty into a Sauvé-Kapandji procedure. The resected 10 mm segment from the distal ulnar metaphysis was used as an interposition bone graft in the arthrodesis site, placed between the sigmoid notch of the radius and distal end of the ulna. After a minimum follow-up of 3 years, all three patients were satisfied with the procedure, were pain-free, and the preoperative range of wrist and forearm motion had increased. All three returned to their previous working activities.


Internal light source for deep photodynamic therapy.
Photodynamic therapy (PDT) for deep-seated lesion is seriously hindered by the limited depth of visible light penetration. Most recently, researchers have designed a genetically-encoded NanoLuc-miniSOG with internal light source for self-excitation, which is highly beneficial for deep PDT.


Novel HCV NS5B polymerase inhibitors derived from 4-(1',1'-dioxo-1',4'-dihydro-1'lambda(6)-benzo[1',2',4']thiadiazin-3'-yl)-5-hydroxy-2H-pyridazin-3-ones. Part 3: Further optimization of the 2-, 6-, and 7'-substituents and initial pharmacokinetic assessments.
5-Hydroxy-3(2H)-pyridazinone derivatives were investigated as inhibitors of genotype 1 HCV NS5B polymerase. Lead optimization led to the discovery of compound 3a, which displayed potent inhibitory activities in biochemical and replicon assays [IC(50) (1b)<10nM; IC(50) (1a)=22 nM; EC(50) (1b)=5nM], good stability toward human liver microsomes (HLM t(1/2)>60 min), and high ratios of liver to plasma concentrations 12h after a single oral administration to rats.


Effect of metal tolerant plant growth promoting Bradyrhizobium sp. (vigna) on growth, symbiosis, seed yield and metal uptake by greengram plants.
The nickel and zinc tolerant plant growth promoting Bradyrhizobium sp. (vigna) RM8 was isolated from nodules of greengram, grown in metal contaminated Indian soils. The plant growth promoting (PGP) potentials of strain RM8 was assessed both in the presence and absence of nickel and zinc under in vitro conditions. Strain RM8 tolerated a high level of nickel (300 microg ml(-1)) and zinc (1400 microg ml(-1)) on yeast extract mannitol agar medium. Bradyrhizobium sp. (vigna) strain RM8 produced 13.3 microg ml(-1) of indole acetic acid in Luria Bertani broth at 100 microg ml(-1) of tryptophan which increased to 13.6 microg ml(-1) at 50 microg Ni ml(-1) and 13.5 microg ml(-1) at 300 microg Zn ml(-1). Strain RM8 was positive for siderophore, HCN and ammonia both in the absence and presence of nickel and zinc. The PGP activity of this strain was further evaluated with increasing concentrations of nickel and zinc using greengram as a test crop. The bioinoculant enhanced the nodule numbers by 82%, leghaemoglobin by 120%, seed yield by 34%, grain protein by 13%, root N by 41% and shoot N by 37% at 290 mg Ni kg(-1) soil. At 4890 mg Zn kg(-1) soil, the bioinoculant increased the nodule numbers by 50%, leghaemoglobin by 100%, seed yield by 36%, grain protein by 13%, root N by 47% and shoot N by 42%. The bioinoculant strain RM8 reduced the uptake of nickel and zinc by plant organs compared to plants grown in the absence of bioinoculant. This study suggested that the bioinoculant due to its intrinsic abilities of growth promotion and attenuation of the toxic effects of nickel and zinc could be exploited for remediation of metal from nickel and zinc contaminated sites.


Hormones, glutathione status and protein S-thiolation.
The formation of mixed disulfides between proteins and glutathione has been discussed as a potentially interesting metabolic signal. The S-thiolation of proteins with glutathione has been observed in several systems in vitro. We have correlated the increase in glutathione disulfide (GSSG) with the amount of protein mixed disulfides. The methodological aspects are briefly presented; normal values for protSSG are about 20-30 nmol per g wet weight of liver. Several processes have been related to changes in the thiol redox state. The stimulation of flux through the pentose phosphate pathway during the metabolism of t-butyl hydroperoxide is presented, and the increase in cellular activity of glucose-6-phosphate dehydrogenase is correlated with the increase in the level of protSSG. Hormonal stimulation of GSH efflux from the liver by vasopressin or by alpha-adrenergic agonists such as phenylephrine or epinephrine is presented and discussed in relation to physiological states of peripheral (non hepatic) GSH utilization. Preliminary work relates the release of GSH to the perturbations in thiol redox state in inflammation and in exercise.


Portable Raman leaf-clip sensor for rapid detection of plant stress.
Precision agriculture requires new technologies for rapid diagnosis of plant stresses, such as nutrient deficiency and drought, before the onset of visible symptoms and subsequent yield loss. Here, we demonstrate a portable Raman probe that clips around a leaf for rapid, in vivo spectral analysis of plant metabolites including carotenoids and nitrates. We use the leaf-clip Raman sensor for early diagnosis of nitrogen deficiency of the model plant Arabidopsis thaliana as well as two important vegetable crops, Pak Choi (Brassica rapa chinensis) and Choy Sum (Brassica rapa var. parachinensis). In vivo measurements using the portable leaf-clip Raman sensor under full-light growth conditions were consistent with those obtained with a benchtop Raman spectrometer measurements on leaf-sections under laboratory conditions. The portable leaf-clip Raman sensor offers farmers and plant scientists a new precision agriculture tool for early diagnosis and real-time monitoring of plant stresses in field conditions.


Effect of nicotinic acid supplementation in vivo on oxygen radical-induced genetic damage in human lymphocytes.
The ability of nicotinic acid to protect human lymphocytes in vivo against oxygen radical-induced DNA strand breakage was tested. NAD+ concentrations rose progressively in lymphocytes to nearly 5 times baseline levels in human volunteers ingesting nicotinic acid (100 mg/day) for 8 weeks. Strand breaks decreased proportionately to NAD+ concentrations over this time period in lymphocytes exposed to oxygen radicals. After 8 weeks of supplementation with nicotinic acid, radical-treated lymphocytes incubated for 24 h evidenced significantly less DNA damage compared to controls.


Investigations into the seasonal presence of Mycoplasma species in fattening lambs.
The presence of infection with Mycoplasma species in association with lung consolidation, environmental temperature and relative humidity was investigated in 410 clinically healthy fattening lambs from five different feedlots in Extremadura (southwestern Spain). Isolates of Mycoplasma species were obtained (n= 117), including Mycoplasma ovipneumoniae (n = 18) and Mycoplasma arginini (n = 99). Two seasonal periods were identified. The first period, which included February, March, September, October, and November, had an average temperature of 17.5 ± 4.7 °C and a relative humidity of 61.3 ± 15.8%. The second seasonal period, which included the months from April to August, had an average temperature of 22.9 ± 5.5 °C and a relative humidity of 48.4 ± 10.7%. Most Mycoplasma species were isolated from the second seasonal period, indicating that higher temperatures and lower relative humidity favour the presence of Mycoplasma species. M. arginini was also associated with lung consolidation.


CEACAM6 promotes cholangiocarcinoma migration and invasion by inducing epithelial-mesenchymal transition through inhibition of the SRC/PI3K/AKT signaling pathway.
The immunoglobulin superfamily member carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) is overexpressed in a wide variety of human cancer types, and is associated with tumor invasion and migration. The aim of the present study was to determine the role of CEACAM6 in cholangiocarcinoma (CCA) invasion and migration in vitro. The results showed that CEACAM6 was highly expressed in CCA tissues, and that the expression level of CEACAM6 was negatively associated with the degree of differentiation of CCA. Silencing CEACAM6 inhibited cell viability, invasion and migration but promoted cell apoptosis in a human CCA cell line (RBE). In addition, CEACAM6 knockdown decreased the expression of an antiapoptotic protein (Bcl-2), an interstitial cell marker (N-cadherin), extracellular matrix proteins (MMP-2 and MMP-9), a transcription factor helix protein (Twist-related protein 1), an intermediate tumor cell scaffold marker (vimentin), a protein involved in tumor nutrient vascular formation (VEGFA) and a tumorigenesis factor (intercellular cell adhesion molecule-1), but increased the expression of pro-apoptotic proteins (Bax, and cleaved caspases-3, -8 and -9) and an epithelial cell marker protein (E-cadherin). Furthermore, CEACAM6-small interfering RNA reduced the expression of the SRC/PI3K/AKT signaling transduction pathway. Taken together, these results suggested that CEACAM6 may be an epithelial-mesenchymal transition biomarker and a potential therapeutic target in human CCA.


Stereochemistry in functionalized macrocycle complexes: control of hydroxyl substituent orientation.
Use of a hydroxyl-functionalized open chain tetramine in a template reaction based on its Cu(II) complex leads, after reduction, to a new tetraaza macrocycle with both amino and hydroxyl substituents. The macrocycle is formed predominantly as its trans (anti) isomer, though the cis form is detectable and both have been structurally characterized in the form of their metal complexes. Although both the Cu(II) and the Co(III) complexes of the tetramine precursor ligand have the hydroxyl group in an axial position of a chair six-membered chelate ring, the trans macrocycle forms Co(III) complexes with this substituent in both equatorial and axial positions.