Similar patterns of neural activity predict memory function during encoding and retrieval.
Neural networks that span the medial temporal lobe (MTL), prefrontal cortex, and posterior cortical regions are essential to episodic memory function in humans. Encoding and retrieval are supported by the engagement of both distinct neural pathways across the cortex and common structures within the medial temporal lobes. However, the degree to which memory performance can be determined by neural processing that is common to encoding and retrieval remains to be determined. To identify neural signatures of successful memory function, we administered a delayed free-recall task to 187 neurosurgical patients implanted with subdural or intraparenchymal depth electrodes. We developed multivariate classifiers to identify patterns of spectral power across the brain that independently predicted successful episodic encoding and retrieval. During encoding and retrieval, patterns of increased high frequency activity in prefrontal, MTL, and inferior parietal cortices, accompanied by widespread decreases in low frequency power across the brain predicted successful memory function. Using a cross-decoding approach, we demonstrate the ability to predict memory function across distinct phases of the free-recall task. Furthermore, we demonstrate that classifiers that combine information from both encoding and retrieval states can outperform task-independent models. These findings suggest that the engagement of a core memory network during either encoding or retrieval shapes the ability to remember the past, despite distinct neural interactions that facilitate encoding and retrieval.


[Rehabilitation in multiple sclerosis: complexity, continuity and efficacy].
Multiple sclerosis (MS) today is a wide-spread disease of young adults of 22-25 years of age, which influences their everyday life, affecting movement, behavior and family life. After 2-5 years of untreated MS the patients become complete invalids. The organization of the process of rehabilitation for these patients includes the activity to restore MS patients' ability to work, serve themselves, continue education. Taking into consideration the increasing support from the state of different organizations of disabled patients, a new infrastructure of the system of rehabilitation of these disabled patients, new approaches to their organizations, law and information support should be introduced. Rehabilitation process in MS has five main directions--psychosocial, sociomedical, family, professional and legal.


Controlled Organization of Inorganic Materials Using Biological Molecules for Activating Therapeutic Functionalities.
Precise control over the assembly of biocompatible three-dimensional (3D) nanostructures would allow for programmed interactions within the cellular environment. Nucleic acids can be used as programmable crosslinkers to direct the assembly of quantum dots (QDs) and tuned to demonstrate different interparticle binding strategies. Morphologies of self-assembled QDs are evaluated via gel electrophoresis, transmission electron microscopy, small-angle X-ray scattering, and dissipative particle dynamics simulations, with all results being in good agreement. The controlled assembly of 3D QD organizations is demonstrated in cells via the colocalized emission of multiple assembled QDs, and their immunorecognition is assessed via enzyme-linked immunosorbent assays. RNA interference inducers are also embedded into the interparticle binding strategy to be released in human cells only upon QD assembly, which is demonstrated by specific gene silencing. The programmability and intracellular activity of QD assemblies offer a strategy for nucleic acids to imbue the structure and therapeutic function into the formation of complex networks of nanostructures, while the photoluminescent properties of the material allow for optical tracking in cells in vitro.


Crosstalk between BMP and Notch Induces Sox2 in Cerebral Endothelial Cells.
Bone morphogenetic protein (BMP) and Notch signaling are critical for endothelial cell (EC) differentiation in vascular development. Recent studies have shown that excess BMP activity induces Notch signaling in cerebral ECs resulting in arteriovenous malformation (AVMs). However, it is unclear how the crosstalk between BMP and Notch signaling affects cerebral EC differentiation at the gene regulatory level. Here, we report that BMP6 activates the activin receptor-like kinase (ALK) 3, a BMP type 1 receptor, to induce Notch1 receptor and Jagged1 and Jagged2 ligands. We show that increased expression of the Notch components alters the transcriptional regulatory complex in the SRY-Box 2 (Sox2) promoter region so as to induce its expression in cerebral ECs. Together, our results identify Sox2 as a direct target of BMP and Notch signaling and provide information on how altered BMP and Notch signaling affects the endothelial transcriptional landscape.


Nitric oxide-dependent and nitric oxide-independent transcriptional responses to high shear stress in endothelial cells.
Shear stress modulates gene expression in endothelial cells (ECs) partly through nitric oxide (NO), acting via enhanced cGMP formation by guanylyl cyclase (GC). We addressed non-cGMP-mediated transcriptional responses to shear stress in human umbilical ECs subjected to high-laminar shear stress (25 dyn/cm2; 150 minutes). RNA was isolated, reverse-transcribed, Cy3/5-labeled, and hybridized to 19 K human microarrays. High shear (n=6), high shear with 100 micromol/L L-NAME (n=3), and high shear with 10 micromol/L ODQ (GC inhibitor) in the perfusate (n=3) was compared with samples not subjected to flow. Among genes responding to high shear were HMOX1 (up) and PPARG (down). A high percentage of gene expression modulation by shear was absent during concomitant L-NAME or ODQ. Several transcriptional modulators were found (up: SOX5, SOX25, ZNF151, HOXD10; down: SOX11); a number of genes were regulated by shear and by shear with ODQ, but not regulated during L-NAME, indicating a nitric oxide synthase (NOS)-dependent, guanylyl cyclase (GC)-independent pathway. Several genes only responded to shear stress during L-NAME, others only responded to shear during ODQ. Upstream binding site analysis indicated shear stress and NO-dependent regulation of transcription via SOX5 and SOX9. Although NO importantly modulated the effect of shear stress on EC transcription, HMOX1 was consistently induced by shear stress, but not dependent on NOS or GC. Using bio-informatics software and databases, a promoter analysis identified SOX5 and SOX9 as potential, novel, shear-sensitive, and NO-dependent transcriptional regulators. The role of HMOX1 as a potential backup for NOS and the downstream role of SOXes should be explored.


A quantitative genetic analysis of schizotypal personality traits.
Previous twin studies investigating the heritability of schizotypy have often had limited power and have failed to measure the disorganization/social anxiety component. Seven hundred and thirty-three female twin pairs, drawn from the Institute of Psychiatry Volunteer Twin Register, completed the Oxford-Liverpool Inventory of Feelings and Experiences and the Peters et al. Delusions Inventory. Structural equation modelling was carried out on scores for MZ and DZ twin pairs. The best fitting models for all scales comprised additive genetic and unique environmental effects. Heritability was estimated at approximately 50% for most scales, although it was lower at 37% for the PDI scale. Multivariate structural equation model fitting revealed a best-fitting model in which additive genetic and unique environmental influences act through a single common pathway for Cognitive Disorganization, Unusual Experiences and the PDI, and through a separate common pathway for Cognitive Disorganization and Introvertive Anhedonia. The various components of schizotypy are moderately heritable. Multivariate model fitting indicates that at least two latent factor structures are required to account for the covariation between the various components of schizotypy. The positive and negative components of schizotypy are relatively genetically independent, although each in turn may be related to Cognitive Disorganization.


Advances in Diagnostic Approaches for Viral Etiologies of Diarrhea: From the Lab to the Field.
The applications of correct diagnostic approaches play a decisive role in timely containment of infectious diseases spread and mitigation of public health risks. Nevertheless, there is a need to update the diagnostics regularly to capture the new, emergent, and highly divergent viruses. Acute gastroenteritis of viral origin has been identified as a significant cause of mortality across the globe, with the more serious consequences seen at the extremes of age groups (young and elderly) and immune-compromised individuals. Therefore, significant advancements and efforts have been put in the development of enteric virus diagnostics to meet the WHO ASSURED criteria as a benchmark over the years. The Enzyme-Linked Immunosorbent (ELISA) and Polymerase Chain Reaction (PCR) are the basic assays that provided the platform for development of several efficient diagnostics such as real-time RT-PCR, loop-mediated isothermal amplification (LAMP), polymerase spiral reaction (PSR), biosensors, microarrays and next generation sequencing. Herein, we describe and discuss the applications of these advanced technologies in context to enteric virus detection by delineating their features, advantages and limitations.


The image of the round atelectasis in the transverse plane: a CT study.
Computerized tomography (CT) was performed on 6 patients presenting a round atelectasis of the lung. It showed that the image of the round atelectasis in the transverse plane is specific and has analogous characteristics to the image produced in conventional tomography. CT scanning showed that more lung segments were involved in the collapse than was suggested by conventional tomography. The restrictive nature of the round atelectasis was evident on the CT scan.


The Impact of Mandatory Food-Marketing Regulations on Purchase and Exposure: A Narrative Review.
(1) Background: Several governments have enforced a series of actions to improve the local food environment and reduce obesity-related diseases in the population by implementing statutory regulations to reduce or ban the marketing of products that are considered unhealthy based on nutrient profile systems or them being high in fat, sugar, and salt (HFSS); (2) Objective: This narrative review is aiming to provide a comprehensive exploration of the available evidence on the impact of identified mandatory regulations restricting food marketing, including advertisements and packages on the exposure and purchase of HFSS food products, to help justify the need for these regulations; (3) Methods: Articles were retrieved by searching electronic databases, including EBSCO Education, PubMed, Scopus, Web of Science, and Google Scholar from 2012 up to December 2022; (4) Results: A total of 12 articles were included in this review. Almost all mandatory food-marketing regulations have evidence in favor of reducing HFSS food purchases and exposure; (5) Conclusions: Protecting children and adolescents from food and beverage marketing through mandatory regulations is a crucial step toward tackling global childhood and adolescent obesity and securing a healthier environment for future generations.


Body saccades of Drosophila consist of stereotyped banked turns.
The flight pattern of many fly species consists of straight flight segments interspersed with rapid turns called body saccades, a strategy that is thought to minimize motion blur. We analyzed the body saccades of fruit flies (Drosophila hydei), using high-speed 3D videography to track body and wing kinematics and a dynamically scaled robot to study the production of aerodynamic forces and moments. Although the size, degree and speed of the saccades vary, the dynamics of the maneuver are remarkably stereotypic. In executing a body saccade, flies perform a quick roll and counter-roll, combined with a slower unidirectional rotation around their yaw axis. Flies regulate the size of the turn by adjusting the magnitude of torque that they produce about these control axes, while maintaining the orientation of the rotational axes in the body frame constant. In this way, body saccades are different from escape responses in the same species, in which the roll and pitch component of banking is varied to adjust turn angle. Our analysis of the wing kinematics and aerodynamics showed that flies control aerodynamic torques during the saccade primarily by adjusting the timing and amount of span-wise wing rotation.


ProteomicsDB: toward a FAIR open-source resource for life-science research.
ProteomicsDB (https://www.ProteomicsDB.org) is a multi-omics and multi-organism resource for life science research. In this update, we present our efforts to continuously develop and expand ProteomicsDB. The major focus over the last two years was improving the findability, accessibility, interoperability and reusability (FAIR) of the data as well as its implementation. For this purpose, we release a new application programming interface (API) that provides systematic access to essentially all data in ProteomicsDB. Second, we release a new open-source user interface (UI) and show the advantages the scientific community gains from such software. With the new interface, two new visualizations of protein primary, secondary and tertiary structure as well an updated spectrum viewer were added. Furthermore, we integrated ProteomicsDB with our deep-neural-network Prosit that can predict the fragmentation characteristics and retention time of peptides. The result is an automatic processing pipeline that can be used to reevaluate database search engine results stored in ProteomicsDB. In addition, we extended the data content with experiments investigating different human biology as well as a newly supported organism.


Chronic back pain and associated work and non-work variables among farmworkers from Starr County, Texas.
This study estimated the prevalence of chronic back pain among migrant farmworker family members and identified associated work and non-work variables. Migrant farmworkers (n = 390 from 267 families) from Starr County, Texas were interviewed in their home once a year for 2 years. The original survey included items measuring demographics, smoking, sleep, farm work, and chronic back pain. For this cross-sectional analysis, multi-level logistic regression was used to identify associated work and other variables associated with chronic back pain while accounting for intraclass correlations due to repeated measures and multiple family members. The prevalence of chronic back pain during the last migration season ranged from 9.5% among the youngest children to 33.3% among mothers. Variables significantly associated with chronic back pain were age (odds ratio [OR], 1.03, per year increase), depressive symptoms while migrating (OR, 8.72), fewer than 8 hours of sleep at home in Starr County (OR, 2.26), fairly bad/very bad quality of sleep while migrating (OR, 3.25), sorting crops at work (OR, 0.18), and working tree crops (OR, 11.72). The role of work exposures, depressive symptoms, and sleep in chronic back pain among farmworkers warrants further examination. Refinements in outcome and exposure assessments are also needed given the lack of a standardized case definition and the variety of tasks and crops involved in farm work in the United States.


What we know and what we think we know: Revealing misconceptions about coastal management for sandy beaches along the U.S. Atlantic Seaboard.
Management of coastal areas is necessary to maintain and protect existing permanent structures. Coastal erosion management falls into soft and hard shoreline stabilization options with the United States tending to favor hard. However, post-Hurricane Sandy 2012, soft dune and beach replenishment have become more favorable in the U.S. with support being necessarily contingent upon an understanding of the pros, cons, and concepts surrounding each management strategy. Misconceptions could thus lead to a halt in progress and poor decisions with implications for community safety. We sought to gain a better understanding of current knowledge surrounding best practices in coastal management communities. Our assumption was that misconceptions in one coastal area, New Jersey, are likely echoed in other coastal areas in the U.S. and internationally. We employed a two-phase research design with an exploratory phase using semi-structured interview guidelines to collect data from a quota sample of 53 local residents and then tested the distribution of knowledge about coastal management facts by asking a convenience sample of 300 residents a structured set of 15 questions. Study participants identify differences in how beaches are managed and how protected they conversely consider an area to be. Dunes are generally preferred over hard engineering and replenishment. However, many key concepts regarding how dunes function naturally, with regards to the role of vegetation and fencing, are poorly understood suggesting a need for greater education surrounding these topics. Participants support continued tax investment in coastal areas to avoid retreat but recognize a tragedy of the commons in such actions for future generations. Learning who knows what, may contribute to more fruitful dialogues among stakeholders to pave the way for the adoption of suitable and sustainable management practices for better protected shorelines.


Single cell analysis of clonal architecture in acute myeloid leukaemia.
We used single cell Q-PCR on a micro-fluidic platform (Fluidigm) to analyse clonal, genetic architecture and phylogeny in acute myeloid leukaemia (AML) using selected mutations. Ten cases of NPM1c mutant AML were screened for 111 mutations that are recurrent in AML and cancer. Clonal architectures were relatively simple with one to six sub-clones and were branching in some, but not all, patients. NPM1 mutations were secondary or sub-clonal to other driver mutations (DNM3TA, TET2, WT1 and IDH2) in all cases. In three of the ten cases, single cell analysis of enriched CD34+/CD33- cells revealed a putative pre-leukaemic sub-clone, undetectable in the bulk CD33+ population that had one or more driver mutations but lacked NPM1c. Cells from all cases were transplanted into NSG mice and in most (8/10), more than one sub-clone (#2-5 sub-clones) transplanted. However, the dominant regenerating sub-clone in 9/10 cases was NPM1+ and this sub-clone was either dominant or minor in the diagnostic sample from which it was derived. This study provides further evidence, at the single cell level, for genetic variegation in sub-clones and stem cells in acute leukaemia and demonstrates both a preferential order of mutation accrual and parallel evolution of sub-clones.


Cannabis, tobacco smoking, and lung function: a cross-sectional observational study in a general practice population.
Health concerns around cannabis use have focused on the potential relationship with psychosis but the effect of cannabis smoking on respiratory health has received less attention. To investigate the association between tobacco-only smoking compared with tobacco plus cannabis smoking and adverse outcomes in respiratory health and lung function. The design was cross-sectional with two groups recruited: cigarette smokers with tobacco pack-years; cannabis smokers with cannabis joint-years. Recruitment occurred in a general practice in Scotland with 12 500 patients. Exposures measured were tobacco smoking (pack-years) and cannabis smoking (joint-years). Cannabis type (resin, herbal, or both) was recorded by self-report. Respiratory symptoms were recorded using NHANES and MRC questionnaires. Lung function was measured by spirometry (FEV1/FVC ratio). Participants consisted of 500 individuals (242 males). Mean age of tobacco-only smokers was 45 years; median tobacco exposure was 25 pack-years. Mean age of cannabis and tobacco smokers was 37 years; median tobacco exposure was 19 pack-years, rising to 22.5 when tobacco smoked with cannabis. Although tobacco and cannabis use were associated with increased reporting of respiratory symptoms, this was higher among those who also smoked cannabis. Both tobacco and cannabis users had evidence of impaired lung function but, in fully adjusted analyses, each additional joint-year of cannabis use was associated with a 0.3% (95% confidence interval = 0.0 to 0.5) increase in prevalence of chronic obstructive pulmonary disease. In adults who predominantly smoked resin cannabis mixed with tobacco, additional adverse effects were observed on respiratory health relating to cannabis use.


Defect induced ferromagnetism in MgO and its exceptional enhancement upon thermal annealing: a case of transformation of various defect states.
MgO particles of few micron size are synthesized through a sol-gel method at different annealing temperatures such as 600 °C (MgO-600), 800 °C (MgO-800) and 1000 °C (MgO-1000). EDX and ICP-AES studies confirmed a near total purity of the sample with respect to paramagnetic metal ion impurities. Magnetic measurements showed a low temperature weak ferromagnetic ordering with a TC (Curie temperature) around 65 K (±5 K). Unexpectedly, the saturation magnetization (Ms) was found to be increased with increasing annealing temperature during synthesis. It was observed that with J = 1 or 3/2 or S = 1 or 3/2, the experimental points are fitted well with the Brillouin function of weak ferromagnetic ordering. A positron annihilation lifetime measurement study indicated the presence of a divacancy (2VMg + 2VO) cluster in the case of the low temperature annealed compound, which underwent dissociations into isolated monovacancies of Mg and O at higher annealing temperatures. An EPR study showed that both singly charged Mg vacancies and oxygen vacancies are responsible for ferromagnetic ordering. It also showed that at lower annealing temperatures the contribution from was very low while at higher annealing temperatures, it increased significantly. A PL study showed that most of the F+ centers were present in their dimer form, i.e. as centers. DFT calculation implied that this dimer form has a higher magnetic moment than the monomer. After a careful consideration of all these observations, which have been reported for the first time, this thermally tunable unusual magnetism phenomenon was attributed to a transformation mechanism of one kind of cluster vacancy to another.


Impact of the adequacy of energy intake on intensive care unit mortality in patients receiving enteral nutrition.
To investigate the relationship between adequacy of energy intake and intensive care unit mortality in patients receiving exclusive enteral nutrition therapy. Observational and prospective study conducted during 2008 and 2009. Patients above 18 years with exclusive enteral nutrition therapy for at least 72 hours were included. The adequacy of energy intake was estimated by the administered/prescribed ratio. Non-conditional logistic regression was used to assess the relationship between predictive variables (adequacy of energy intake, APACHE II, gender, age, and intensive care unit length of stay) and intensive care unit mortality. Sixty-three patients (mean 58 years, 27% mortality) were included, 47.6% of whom received more than 90% of the energy prescribed (mean adequacy 88.2%). Mean energy balance was -190 kcal/day. Significant associations between death in the intensive care unit and the variables age and intensive care unit length of stay were observed, after removing the variables adequacy of energy intake, APACHE II, gender and age during the modeling process. In our study, adequacy of energy intake did not affect intensive care unit mortality. Carefully followed enteral nutrition protocols, resulting in an administered/prescribed ratio above 70%, are apparently not sufficient to impact the mortality rates in the intensive care unit. Therefore, it may not be necessary to achieve 100% of the targeted energy, considering the high frequency of enteral feeding interruptions due to gastrointestinal intolerance and fasting for tests and procedures. Additional research is needed to identify the optimal energy intake for improved outcomes and reduced costs.


Alleviating the Neglected Tropical Diseases: Recent Developments in Diagnostics and Detection.
Neglected tropical diseases (NTDs) are communicable diseases caused by a group of bacteria, viruses, protozoa and helminths prevalent in more than 145 countries that affect the world's poverty stricken populations. WHO enlists 18 NTDs amongst people living in endemic areas having inaccessibility to preventive measures. Steps to reduce the global disease burden of the NTDs need attention at multi-factorial levels. Control programmes, mass drug administrations, transmission checks, eradication surveillances and diagnoses are some of them. The foremost in this list is confirmatory diagnosis. A comprehensive summary of the innovative, high-impact, multiplexed, low-cost diagnostic tools developed in the last decade that helped to meet the needs of users can depict a holistic approach to further evaluate potential technologies and reagents currently in research. Major Advancements: A literature survey based on developing nano-biotechnological platforms to meet the diagnostic challenges in NTDs towards development of a useful point-of-care (POC) unit is reported. However, in order to pave the way for complete eradication more sensitive tools are required that are user-friendly and applicable for use in endemic and low-resource settings. There are various novel research progresses/advancements made for qualitative and quantitative measurement of infectious load in some diseases like dengue, Chagas disease and leishmaniasis; though further improvements on the specificity and sensitivity front are still awaited. Strategies to combat the problem of antimicrobial drug resistance in diagnosis of NTDs have also been put forward by various research groups and organizations. Moreover, the state-of-the-art "omics" approaches like metabolomics and metagenomics have also started to contribute constructively towards diagnosis and prevention of the NTDs. A concrete solution towards a single specimen based common biomarker detection platform for NTDs is lacking. Identifying robust biomarkers and implementing them on simple diagnostic tools to ease the process of pathogen detection can help us understand the obstacles in current diagnostic measures of the NTDs.


Noninvasive imaging findings of idiopathic renal arteriovenous fistula.
Renal arteriovenous fistula (AVF) is an uncommon clinical entity, which can be congenital, acquired, or idiopathic. Diagnosis is aided by radiological studies, with digital subtraction angiography as a gold standard. However, Doppler ultrasound with color Doppler interrogation and computed tomography (CT) angiography are alternative imaging techniques that are noninvasive and can be used for patients to whom no intervention is planned. In this report, we present a case of idiopathic renal AVF diagnosed by Doppler ultrasound and CT angiography. Grayscale ultrasound showed a cyst-like lesion which was confirmed to be a focal aneurysmatic dilatation with heterogeneous fill-in and turbulent blood flow on color Doppler and spectral analysis. CT angiography demonstrated multiple aneurysmatic dilatations of the segmental branch and early opacification of right renal vein on the arterial phase, consistent with renal AVF.


Identification of the major prostaglandin glycerol ester hydrolase in human cancer cells.
Prostaglandin glycerol esters (PG-Gs) are produced as a result of the oxygenation of the endocannabinoid, 2-arachidonoylglycerol, by cyclooxygenase 2. Understanding the role that PG-Gs play in a biological setting has been difficult because of their sensitivity to enzymatic hydrolysis. By comparing PG-G hydrolysis across human cancer cell lines to serine hydrolase activities determined by activity-based protein profiling, we identified lysophospholipase A2 (LYPLA2) as a major enzyme responsible for PG-G hydrolysis. The principal role played by LYPLA2 in PGE2-G hydrolysis was confirmed by siRNA knockdown. Purified recombinant LYPLA2 hydrolyzed PG-Gs in the following order of activity: PGE2-G > PGF2α-G > PGD2-G; LYPLA2 hydrolyzed 1- but not 2-arachidonoylglycerol or arachidonoylethanolamide. Chemical inhibition of LYPLA2 in the mouse macrophage-like cell line, RAW264.7, elicited an increase in PG-G production. Our data indicate that LYPLA2 serves as a major PG-G hydrolase in human cells. Perturbation of this enzyme should enable selective modulation of PG-Gs without alterations in endocannabinoids, thereby providing a means to decipher the unique functions of PG-Gs in biology and disease.


Biological and Cultural Causes of Seasonality of Deaths in Historical Populations From Poland.
Seasonal fluctuations in mortality and their causes in the nineteenth century Polish rural populations: wealthy, agriculturally and economically advanced populations from Wielkopolska, and poor populations from Silesia and Galicia (southern Poland) were described. Data-sources included parish death registers from the Roman Catholic parish of Dziekanowice in the region of Wielkopolska, Prussian statistical yearbooks for the Pozna Province as well as information from previous publications regarding Silesia and Galicia. The 19th century patterns were compared with those in present-day Poland. The occurrence of seasonality of deaths was assessed with: the Chi-squared test, the Kolmogorov-Smirnov test, and the Autoregressive Integrated Moving Average Models (ARIMA). In all populations there was a winter maximum of the number of deaths, while the minimum occurred in early summer. In the poor populations of Silesia and Galicia another statistically significant increase in the incidence of deaths was observed in the early spring. In the rich and modern villages of Wielkopolska there was no spring increase in the number of deaths, however, in all populations of Wielkopolska, irrespective of a particular pattern, a secondary mortality peak occurred in the late summer and autumn. Statistical tests used in this study did not show any clear differences in the distribution of the seasonality of deaths between the populations of Wielkopolska on the one hand, and the populations from Galicia and Silesia, on the other hand. The statistical significance of differences was, however, evident between populations representing the two distinguished by secondary peaks death seasonality patterns. Seasonal death increase split the populations under study into two groups according to the criterion of wealth.


Occupational survey of the educational outputs of the first established program of cardiac technology speciality in the Kingdom of Saudi Arabia (2013-2022): A cross-sectional study.
The demand for qualified cardiac technology (CT) graduates is increasing in Saudi Arabia. This study aimed to provide the first descriptive occupational survey of the educational outputs of the first established CT speciality program in the Kingdom of Saudi Arabia over the past 10 years. This was a cross-sectional, survey-based study. An online self-administered survey was distributed to all alumni who graduated from the CT program between 2013 and 2022 at the Imam Abdulrahman bin Faisal University (IAU) in the Eastern Province of Saudi Arabia. Of the 238 graduates, 164 completed the survey (72.2%). All the respondents (100%) were women, 56% were aged 25-30 years, 58.5% were married, the majority (95.7%) held a bachelor's degree, and (93.3%) lived in the eastern region. Of the respondents, 33.7% specialised in cardiac catheterisation and 66.3% in echocardiography. Of those, 66.4% were employed, which was similar between both subspecialties and predominantly in the Eastern region (83.9%). A total of 57.9% of participants attributed the reason for unemployment to limited opportunities in the Eastern province (vs. 15.8% across the country). A total of 76.6% of the respondents reported that most job opportunities were in the Central region (Riyadh). The main barriers and limitations to unemployment reported by the alumni were the need for childcare assistance, further training, and poor job search/interview skills. Of the respondents, 42% expressed a desire to change their career path because of limited job opportunities (10.7%) followed by a change in career interest post-graduation (7.9%). The employment rate of IAU CT alumni was high (66.4%) and predominantly based in the Eastern region of Saudi Arabia, and 42% expressed a desire to change their career path due to limited regional job opportunities. The findings from this study will help inform the future of speciality across the kingdom and shape the potential for expansion.


Longitudinal Changes of Cytokines and Appetite in Older Hospitalized Patients.
There are few data on the longitudinal association of cytokine and appetite among older hospitalized patients. We aimed to investigate the impact of the changes of inflammatory cytokines on appetite in older hospitalized patients. A total of 191 patients (mean age 81.3 ± 6.6 years, 64% women) participated in this prospective longitudinal observational study. Appetite was evaluated using the Edmonton Symptom Assessment System on admission and after seven days. Serum cytokines such as IL-1β, IL-6, IL-8, IL-10, IL-12p70, IL-17, IL-18, IL-23 and IL-33, IFN-α2, IFN-γ, TNF-α and MCP-1 were measured both times. No significant differences in the mean serum levels of all the cytokines could be detected overtime in relation to appetite changes, except for IL-18. Appetite significantly deteriorated overtime in patients with increasing IL-18 levels and improved in those without significant changes in IL-18 levels. In a stepwise regression analysis, changes of IL-18 levels were the major independent predictor for the changes of patients' appetite and explained 4% of the variance, whereas other cytokines and variables, such as age, sex, infection and disease, did not show any impact on appetite changes. We conclude that IL-18 seems to exert a significant impact on appetite in acutely ill older hospitalized patients and should, therefore, be considered as a potential target in the diagnosis, prevention and treatment of malnutrition.


Annular tears and disk herniation: prevalence and contrast enhancement on MR images in the absence of low back pain or sciatica.
To evaluate the prevalence and radiologic findings of annular tear (especially of contrast material enhancement), bulging disk, and disk herniation on T2-weighted and gadolinium-enhanced T1-weighted magnetic resonance (MR) images in people without low back pain (LBP) or sciatica. Thirty-six volunteers without LBP and/or sciatica (18 with no symptoms in their lifetime and 18 who were pain free for at least 6 months) were examined with sagittal and axial T2-weighted fast spin-echo (SE) and sagittal gadolinium-enhanced T1-weighted fast SE imaging. The prevalence and MR findings of bulging disk, focal protrusion, extrusion, and nonenhancing or enhancing annular tears were assessed. The prevalence of bulging disk and focal disk protrusion was 81% (29 volunteers) and 33% (12 volunteers), respectively. There were no extrusions. Twenty-eight annular tears were found in 20 patients (56%); 27 tears (96%) also showed contrast enhancement. Annular tears and focal disk protrusions on MR images, with or without contrast enhancement, are frequently found in an asymptomatic population. Extruded disk herniation, displacement of nerve root, and interruption of annuloligamentous complex are unusual findings in an asymptomatic population and can be more closely related to patients with LBP or sciatica.


Genetic and epigenetic risk factors for diabetic kidney disease.
Diabetes is increasing at daunting rates worldwide, and approximately 40% of affected individuals will develop kidney complications. Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease, and there are significant healthcare costs providing appropriate renal replacement therapies to affected individuals. For several decades, investigators have sought to discover inherited risk factors and biomarkers for DKD. In recent years, advances in high-throughput laboratory techniques and computational analyses, coupled with the establishment of multicenter consortia, have helped to identify genetic loci that are replicated across multiple populations. Several genome-wide association studies (GWAS) have been conducted for DKD with further meta-analysis of GWAS and comprehensive "single gene" meta-analyses now published. Despite these efforts, much of the inherited predisposition to DKD remains unexplained. Meta-analyses and integrated-omics pathway studies are being used to help elucidate underlying genetic risks. Epigenetic phenomena are increasingly recognized as important drivers of disease risk, and several epigenome-wide association studies have now been completed. This review describes key findings and ongoing genetic and epigenetic initiatives for DKD.


Acute and late outcomes of unprotected left main stenting in comparison with surgical revascularization.
The purpose of this study was to compare the early and late results of percutaneous and surgical revascularization of left main coronary artery stenosis. Unprotected left main coronary artery (ULMCA) stenting is being investigated as an alternative to bypass surgery. We randomly assigned 105 patients with ULMCA stenosis to percutaneous coronary intervention (PCI; 52 patients) or coronary artery bypass grafting (CABG; 53 patients). The primary end point was the change in left ventricular ejection fraction (LVEF) 12 months after the intervention. Secondary end points included 30-day major adverse events (MAE), major adverse cardiac and cerebrovascular events (MACCE), length of hospitalization, target vessel failure (TVF), angina severity and exercise tolerance after 1 year, and total and MACCE-free survival. A significant increase in LVEF at the 12-month follow-up was noted only in the PCI group (3.3 +/- 6.7% after PCI vs. 0.5 +/- 0.8% after CABG; p = 0.047). Patients performed equally well on stress tests, and angina status improved similarly in the 2 groups. PCI was associated with a lower 30-day risk of MAE (p < 0.006) and MACCE (p = 0.03) and shorter hospitalizations (p = 0.0007). Total and MACCE-free 1-year survival was comparable. Left main TVF was similar in the 2 groups. During the 28.0 +/- 9.9-month follow-up, there were 3 deaths in the PCI group and 7 deaths in the CABG group (p = 0.08). Patients with ULMCA disease treated with PCI had favorable early outcomes in comparison with the CABG group. At 1 year, LVEF had improved significantly only in the PCI group. After more than 2 years, MACCE-free survival was similar in both groups with a trend toward improved survival after PCI.


Loss of UCP2 attenuates mitochondrial dysfunction without altering ROS production and uncoupling activity.
Although mitochondrial dysfunction is often accompanied by excessive reactive oxygen species (ROS) production, we previously showed that an increase in random somatic mtDNA mutations does not result in increased oxidative stress. Normal levels of ROS and oxidative stress could also be a result of an active compensatory mechanism such as a mild increase in proton leak. Uncoupling protein 2 (UCP2) was proposed to play such a role in many physiological situations. However, we show that upregulation of UCP2 in mtDNA mutator mice is not associated with altered proton leak kinetics or ROS production, challenging the current view on the role of UCP2 in energy metabolism. Instead, our results argue that high UCP2 levels allow better utilization of fatty acid oxidation resulting in a beneficial effect on mitochondrial function in heart, postponing systemic lactic acidosis and resulting in longer lifespan in these mice. This study proposes a novel mechanism for an adaptive response to mitochondrial cardiomyopathy that links changes in metabolism to amelioration of respiratory chain deficiency and longer lifespan.


Tyrosinase inhibitors from terrestrial and marine resources.
Tyrosinase is a multifunctional copper-containing enzyme widely distributed in plants and animals, which catalyzes both the hydroxylation of tyrosine into o-diphenols and the oxidation of o-diphenols into o-quinones. Tyrosinase is known to be a key enzyme for melanin biosynthesis in plants and animals. Tyrosinase inhibitors, therefore, can be clinically useful for the treatment of some dermatological disorders associated with melanin hyperpigmentation. They also find uses in cosmetics for whitening and depigmentation after sunburn. This review describes 236 compounds obtained from terrestrial and marine plants, animals, microorganisms and macrofungi which have been shown to inhibit tyrosinase. The mechanism of action of tyrosinase, together with the mode of action of inhibitors is described. The relative activities of the different compounds are recorded. The literature on plant-origin inhibitors is extensive, and their chemistry and biological activity have been intensively reviewed. This review will therefore be deliberately cover new classes of inhibitors from terrestrial and marine plants, animals, microorganisms and macrofungi, as well as the traditional classes. The present paper summarizes and discusses the scientific results on the discovery of natural tyrosinase inhibitors.


Pain and pessimism: dairy calves exhibit negative judgement bias following hot-iron disbudding.
Pain is defined as an unpleasant sensory and emotional experience associated with actual or potential tissue damage, but emotional states are difficult to directly assess in animals. Researchers have assessed pain using behavioural and physiological measures, but these approaches are limited to understanding the arousal rather than valence of the emotional experience. Cognitive bias tasks show that depressed humans judge ambiguous events negatively and this technique has been applied to assess emotional states in animals. However, limited research has examined how pain states affect cognitive processes in animals. Here we present the first evidence of cognitive bias in response to pain in any non-human species. In two experiments, dairy calves (n = 17) were trained to respond differentially to red and white video screens and then tested with unreinforced ambiguous colours in two or three test sessions before and two sessions after the routine practice of hot-iron disbudding. After disbudding calves were more likely to judge ambiguous colours as negative. This 'pessimistic' bias indicates that post-operative pain following hot-iron disbudding results in a negative change in emotional state.


Machine Learning-Based Gait Mode Prediction for Hybrid Knee Prosthesis Control.
Recently, hybrid prosthetic knees, which can combine the advantages of passive and active prosthetic knees, have been proposed for individuals with a transfemoral amputation. Users could potentially take advantage of the passive knee mechanics during walking and the active power generation during stair ascent. One challenge in controlling the hybrid knees is accurate gait mode prediction for seamless transitions between passive and active modes. However, data imbalance between passive and active modes may impact the performance of a classifier. In this study, we used a dataset collected from nine individuals with a unilateral transfemoral amputation as they ambulated over level ground, inclines, and stairs. We evaluated several machine learning-based classifiers on the prediction of passive (level-ground walking, incline walking, descending stairs, and donning and doffing the prosthesis) and active mode (ascending stairs). In addition, we developed a generative adversarial network (GAN) to create synthetic data for improving classification performance. The results indicated that linear discriminant analysis and random forest might be the best classifiers regarding sensitivity to the active mode and overall accuracy, respectively. Further, we demonstrated that using the GAN-based synthetic data for training improves the sensitivity of classifiers.


Sliding-strip microfluidic device enables ELISA on paper.
This article describes a 3D microfluidic paper-based analytical device that can be used to conduct an enzyme-linked immunosorbent assay (ELISA). The device comprises two parts: a sliding strip (which contains the active sensing area) and a structure surrounding the sliding strip (which holds stored reagents-buffers, antibodies, and enzymatic substrate-and distributes fluid). Running an ELISA involves adding sample (e.g. blood) and water, moving the sliding strip at scheduled times, and analyzing the resulting color in the sensing area visually or using a flatbed scanner. We demonstrate that this device can be used to detect C-reactive protein (CRP)-a biomarker for neonatal sepsis, pelvic inflammatory disease, and inflammatory bowel diseases-at a concentration range of 1-100ng/mL in 1000-fold diluted blood (1-100µg/mL in undiluted blood). The accuracy of the device (as characterized by the area under the receiver operator characteristics curve) is 89% and 83% for cut-offs of 10ng/mL (for neonatal sepsis and pelvic inflammatory disease) and 30ng/mL (for inflammatory bowel diseases) CRP in 1000-fold diluted blood respectively. In resource-limited settings, the device can be used as a part of a kit (containing the device, a fixed-volume capillary, a pre-filled tube, a syringe, and a dropper); this kit would cost ~ $0.50 when produced in large scale (>100,000 devices/week). This kit has the technical characteristics to be employed as a pre-screening tool, when combined with other data such as patient history and clinical signs.


The Societal Cost of Dementia in Singapore: Results from the WiSE Study.
There is currently limited evidence on the economic burden that dementia exerts on multi-ethnic Asian populations. The present study aimed to estimate the economic cost of dementia in Singapore. We used data from the Well-being of the Singapore Elderly study, a nationally representative survey of the older Singapore Resident population aged 60 years and above. Generalized linear modeling was used to estimate factors associated with costs. The total cost of dementia in 2013 was estimated at S$532 million (95% CI, S$361 million to S$701 million) while the annual cost per person was estimated at S$10,245 per year (95% CI, S$6,954 to S$12,495). Apart from dementia, higher total societal cost were also significantly associated with older age, Indian ethnicity, and those who were diagnosed with heart problems, stroke, diabetes or depression, whereas being divorced/separated, lower education, and those who were diagnosed with hypertension were significantly associated with lower total societal cost. The study provides a rich body of information on healthcare utilization and cost of dementia, which is essential for future planning of services for the elderly population.


Association of milk protein genes with fertilization rate and early embryonic development in Holstein dairy cattle.
Concomitant with intensive selection for increased milk yield, reproductive performance of dairy cows has declined in the last decades, in part due to an unfavourable genetic relationship between these traits. Given that the six main milk protein genes (i.e. whey proteins and caseins) are directly involved in milk production and hence have been a target of the strong selection aimed at improving milk yield in dairy cattle, we hypothesized that these genes could show selection footprints associated with fertility traits. In this study, we used an in-vitro fertilization (IVF) system to test genetic association between 66 single nucleotide polymorphisms (SNPs) in the four caseins (αS1-casein, αS2-casein, β-casein and κ-casein) and the two whey protein genes (α-lactalbumin and β-lactoglobulin) with fertilization rate and early embryonic development in the Holstein breed. A total of 6893 in-vitro fertilizations were performed and a total of 4661 IVF embryos were produced using oocytes from 399 ovaries and semen samples from 12 bulls. Associations between SNPs and fertility traits were analysed using a mixed linear model with genotype as fixed effect and ovary and bull as random effects. A multiple testing correction approach was used to account for the correlation between SNPs due to linkage disequilibrium. After correction, polymorphisms in the LALBA and LGB genes showed significant associations with fertilization success and blastocyst rate. No significant associations were detected between SNPs located in the casein region and IVF fertility traits. Although the molecular mechanisms underlying the association between whey protein genes and fertility have not yet been characterized, this study provides the first evidence of association between these genes and fertility traits. Furthermore, these results could shed light on the antagonistic relationship that exists between milk yield and fertility in dairy cattle.


Antidepressants and cognitive-behavioral therapy for symptom syndromes.
Somatic symptoms are common in primary care and clinicians often prescribe antidepressants as adjunctive therapy. There are many possible reasons why this may work, including treating comorbid depression or anxiety, inhibition of ascending pain pathways, inhibition of prefrontal cortical areas that are responsible for "attention" to noxious stimuli, and the direct effects of the medications on the syndrome. There are good theoretical reasons why antidepressants with balanced norepinephrine and serotonin effects may be more effective than those that act predominantly on one pathway, though head-to-head comparisons are lacking. For the 11 painful syndromes review in this article, cognitive-behavioral therapy is most consistently demonstrated to be effective, with various antidepressants having more or less randomized controlled data supporting or refuting effectiveness. This article reviews the randomized controlled trial data for the use of antidepressant and cognitive-behavior therapy for 11 somatic syndromes: irritable bowel syndrome, chronic back pain, headache, fibromyalgia, chronic fatigue syndrome, tinnitus, menopausal symptoms, chronic facial pain, noncardiac chest pain, interstitial cystitis, and chronic pelvic pain. For some syndromes, the data for or against treatment effectiveness is relatively robust, for many, however, the data, one way or the other is scanty.


Exploring the gap in healthcare for injured and uninsured research participants in the United States.
In the United States 46 million people are uninsured and it is from within this population that many 'normal, healthy' research participants are selected. Research institutions and sponsors are not required to compensate or provide free treatment to participants when they incur research-related harm, and most studies do not stipulate the provision of free medical care to treat research-related adverse events. The consequence for uninsured participants is that they must assume these medical costs unless they successfully sue the study sponsor or research institution. This article discusses the matter of healthy volunteers becoming 'the sick' as a result of research participation, and proposes guidance for the informed consent process in order to optimize awareness about injury potential and injury compensation. Guidance regarding health screening for these volunteers is also presented.


Etoposide with/without G-CSF with busulfan and cyclophosphamide as conditioning for bone marrow transplantation. The BMT Team.
To increase the efficacy of bone marrow transplantation (BMT), we have tried to add etoposide (VP-16) to busulfan/cyclophosphamide (BU/CY). Twelve patients received 16 mg/kg of BU and 120 mg/kg of CY with 15-30 mg/kg of VP-16. Another two patients received 5 micrograms/kg of G-CSF with 30 mg/kg of VP-16. Patients tolerated escalating doses of VP-16 without any significant hepatotoxicity. Their maximal level of bilirubin was 37.6 micromol/L (2.2 mg/dl), and there was no significant skin toxicity or mucositis. By contrast, two patients who received G-CSF with 30 mg/kg of VP-16 developed hyperbilirubinemia and veno-occlusive disease, which terminated this phase I study. VP-16 can be safely combined with BU/CY < or = 30 mg/kg in three divided doses, and its effect on survival should be evaluated. G-CSF added to this regimen, however, should be used with great caution.


Transvenous embolization along with intraprocedural image fusion technique for complex intracranial dural arteriovenous fistula.
This study aimed to investigate the efficacy and safety of an intraprocedural image fusion technique using flat-panel detector computed tomography-based rotational angiography (FDCT-RA) and image fusion (IF) for the transvenous approach in treating intracranial dural arteriovenous fistulas (dAVFs). A retrospective review was conducted on patients who underwent transvenous embolization for dural AVFs. The patients were classified into two groups according to the treatment technique used: the FDCT-RA and IF technique group and the conventional technique group. The primary outcomes assessed were the angiographic and clinical outcomes, complications, fluoroscopy time, and radiation exposure. Univariate analyses were performed to compare the two treatment modalities. Eighty-six patients with intracranial dAVFs were treated with transvenous embolization (TVE), of which 37 patients underwent transvenous approach with flat-panel detector computed tomography-based rotational angiography (FDCT-RA) and image fusion (IF) technique used. The FDCT-RA and IF group showed difference in the location of dAVFs, occlusion state of the sinus, and access routes in comparison to the conventional treatment group. The FDCT-RA and IF technique was predominantly used for dAVFs involving the anterior condylar confluence and cavernous sinus with ipsilateral inferior petrosal sinus (IPS) occlusion. Patients treated with this technique demonstrated a higher rate of complete occlusion (91.9%, n = 34) compared to those treated with the conventional technique (79.6%, n = 39), but this difference was not statistically significant (p = 0.136). Although the implementation of this technique during the treatment procedure showed a tendency to decrease both fluoroscopy duration and radiation dose, the observed results did not reach statistical significance (p = 0.315, p = 0.130). The intraprocedural image fusion technique using FDCT-RA for transvenous treatment of intracranial dAVFs could provide help in treatment of dAVFs of certain locations or access routes. It might provide aid in microcatheter navigation, without increasing the radiation exposure and fluoroscopy time.


Radial probe endobronchial ultrasound for the diagnosis of peripheral lung cancer: systematic review and meta-analysis.
Improved diagnostic sensitivity of bronchsocopy for the investigation of peripheral pulmonary lesions (PPLs) with the use of radial probe endobroncial ultrasound (EBUS) has been reported, although diagnostic performance varies considerably. A systematic review of published literature evaluating radial probe EBUS accuracy was performed to determine point sensitivity and specificity, and to construct a summary receiver-operating characteristic curve. Sub-group analysis and linear regression was used to identify possible sources of study heterogeneity. 16 studies with 1,420 patients fulfilled inclusion criteria. Significant inter-study variation in EBUS method was noted. EBUS had point specificity of 1.00 (95% CI 0.99-1.00) and point sensitivity of 0.73 (95% CI 0.70-0.76) for the detection of lung cancer, with a positive likelihood ratio of 26.84 (12.60-57.20) and a negative likelihood ratio of 0.28 (0.23-0.36). Significant inter-study heterogeneity for sensitivity was observed, with prevalence of malignancy, lesion size and reference standard used being possible sources. EBUS is a safe and relatively accurate tool in the investigation of PPLs. Diagnostic sensitivity of EBUS may be influenced by the prevalence of malignancy in the patient cohort being examined and lesion size. Further methodologically rigorous studies on well-defined patient populations are required to evaluate the generalisability of our results.


Rheumatologists' Views and Experiences in Managing Rheumatoid Arthritis in Elderly Patients: A Qualitative Study.
In this qualitative study we analyzed the (1) influence of age, comorbidity, and frailty on management goals in elderly patients with RA; (2) experiences of rheumatologists regarding the use of the Disease Activity Score at 28 joints (DAS28) to monitor disease activity; and (3) differences in management strategies in elderly patients with RA compared to their younger counterparts. Rheumatologists were purposively sampled for a semistructured interview. Two readers independently read and coded the interview transcripts. Important concepts were taxonomically categorized and combined in overarching themes by using NVivo 11 software. Seventeen rheumatologists (mean age 44.8 yrs, SD 7.7 yrs; 29% male) from 9 medical centers were interviewed. Preserving an acceptable level of functioning was the most important management goal in patients ≥ 80 years and in patients with high levels of comorbidity and frailty. The DAS28 score less frequently steered the management strategy, because rheumatologists commented that comorbidity and an age-related erythrocyte sedimentation rate elevation might distort the DAS28 score. Instead, management of elderly patients highly depended on comorbidity, frailty, and their subsequent effects such as cognitive and physical decline, dependency, and polypharmacy. Presence of 1 or more of these factors frequently resulted in a less future-oriented management approach with less emphasis on the maximal prevention of joint erosions. The treat-to-target model is not automatically adopted in the elderly patient population. Future evidence-based RA management recommendations for elderly patients with RA are needed and should account for factors such as comorbidity and frailty.


Sound Vibration-Triggered Epigenetic Modulation Induces Plant Root Immunity Against Ralstonia solanacearum.
Sound vibration (SV) is one of the several environmental stimuli that induce physiological changes in plants including changes in plant immunity. Immune activation is a complicated process involving epigenetic modifications, however, SV-induced epigenetic modifications remain unexplored. Here, we performed an integrative analysis comprising chromatin immunoprecipitation (ChIP) and microRNA sequencing (miRNA-seq) to understand the role of SV-mediated epigenetic modifications in immune activation in Arabidopsis thaliana against the root pathogen Ralstonia solanacearum. Plants exposed to SV (10 kHz) showed abundant H3K27me3 modification in the promoter regions of aliphatic glucosinolate biosynthesis and cytokinin signaling genes, leading to transcriptional changes that promote immunity. Additionally, 10 kHz SV down-regulated miR397b expression, thus activating three target LACCASE transcripts that mediate cell wall reinforcement via lignin accumulation. Taken together, SV triggers epigenetic modification of genes involved in secondary metabolite biosynthesis, defense hormone signaling, and pre-formed defense in A. thaliana, leading to the activation of plant immunity against R. solanacearum.


Head-eye movement control tests in patients with chronic neck pain; inter-observer reliability and discriminative validity.
Head-eye movement control deficit is an identified problem in patients with chronic neck pain, particularly in cases of whiplash associated disorders (WAD). To date, there is no evidence concerning the reliability and validity of visually assessed active head-eye movement control tests. Therefore, the objectives of the present cross-sectional study were, a) to develop a test battery; and b) to investigate inter-observer reliability and discriminative validity in patients with chronic neck pain compared to healthy controls. The study was conducted at two physiotherapy clinics in Switzerland. Ethics Committee approval was obtained. Ten active head-eye coordination tests, on 23 patients with chronic neck pain and associated symptoms and 19 healthy controls, were videotaped. The tests included eye movements in the neutral head position and 45° relative neck rotation, gaze stability and sequential head-eye movements. All tests were performed in the sitting and standing positions. Two blinded physiotherapists independently rated the randomized videos. Performance was rated as "negative", "moderately positive" or "clearly positive". Weighted kappa (wK) and 95% confidence intervals (CI) were calculated to investigate inter-observer reliability. Good reliability was defined as wK >0.5 with a lower boundary of 95% CI >0.2. Odds ratios (to define cut-off points) and the distribution of the classificator, numbers of positive tests, were calculated. Three out of ten tests showed "excellent" (wK 0.82 to 0.86), five out of ten tests showed "substantial" (wK 0.69 to 0.79) and two out of ten tests showed "moderate" (wK 0.54 to 0.59) reliability. Results were comparable in the sitting and standing positions. On average, three out of five tests were rated positive in patients and one out of five tests was rated positive in healthy controls. An odds ratio of 13.3 to 18.6 was obtained using ≥2/5 tests as a cut-off point. Visual assessment by physiotherapists of head-eye movement control tests is reliable. The test battery is able to discriminate between patients with chronic neck pain and healthy controls. There were no differences in performance between the sitting and standing positions. The test battery can therefore be reduced to five tests. Further research is needed to identify the test-retest stability and responsiveness.


Chimaerism detection in bovine twins, triplets and quadruplets using sex chromosome-linked markers.
The phenomenon of chimaerism occurs in the majority of cattle twin pregnancies. The objectives of this study were to develop a powerful diagnostic test for chimaerism in bovine male and female co-twins using X and Y chromosome-linked markers and to determine the extent of chimaerism in twins, triplets and quadruplets. We developed a multiplex PCR set of three polymorphic markers on chromosome X (DIK2865, DIK2283, AGLA257), where the presence of >1 and >2 alleles per marker is sufficient to prove chimaerism in males and females, respectively. In addition, a specific segment on chromosome Y (BOV97M) is included in the set to indicate chimaerism in females. Visualization of chimaeric alleles was best for DNA extracted from blood, fair for DNA from vaginal smears and failed for DNA extracted from hair. The power of chimaerism identification using this set of markers for DNA extracted from blood was calculated as 99% in males and virtually 100% in females. All females and males in heterosexual twins, triplets and quadruplets displayed evidence of a chimaeric allele in at least one and maximum of three of three X chromosome markers analysed. In addition, all females showed the presence of the BOV97M segment and were validated as chimaeric by the standard clinical diagnosis of impaired vaginal length. Quantitative PCR analysis of BOV97M copies in all twins vs. their sires showed a mean ratio of 45-68% in females and 39-49% in males, indicating a substantial symmetrical exchange of cells among all co-twins. The proposed analysis of X and Y chromosome-linked markers is advantageous to previous methods based on Y chromosome sequences only, because it detects chimaerism in both male and female co-twins.


Measurement of antibody affinity for cell surface antigens using an enzyme-linked immunosorbent assay.
We present a fast, simple, and accurate method to determine the affinity constants of antibodies that bind to cell surface antigens. This procedure utilizes intact cells and native, unmodified antibody in a conventional enzyme-linked immunosorbent assay. Target cells are incubated with serial dilutions of antibody and allowed to reach equilibrium. Cells are then pelleted by centrifugation, and aliquots of unbound antibody in the supernatant are added to a microtiter plate precoated with capture antibody and measured in a conventional enzyme-linked immunosorbent assay (ELISA). We measured the affinity constant of murine monoclonal antibody CLB-1H-gran2, which binds to K562 cells (a human erythroleukemia line), and compared the ELISA-based results to those obtained by flow cytometric determination of antibody affinity. The affinity constants obtained by the two methods are in good agreement. The affinity constant is calculated utilizing only the concentrations of bound and free antibody, so that the actual antigen concentration (or number of antigenic sites per cell) need not be known. However, the number of antibody molecules bound per cell can be estimated from the results.


Carbon monoxide generated by heme oxygenase 1 suppresses endothelial cell apoptosis.
Heme oxygenase 1 (HO-1) inhibits apoptosis by regulating cellular prooxidant iron. We now show that there is an additional mechanism by which HO-1 inhibits apoptosis, namely by generating the gaseous molecule carbon monoxide (CO). Overexpression of HO-1, or induction of HO-1 expression by heme, protects endothelial cells (ECs) from apoptosis. When HO-1 enzymatic activity is blocked by tin protoporphyrin (SnPPIX) or the action of CO is inhibited by hemoglobin (Hb), HO-1 no longer prevents EC apoptosis while these reagents do not affect the antiapoptotic action of bcl-2. Exposure of ECs to exogenous CO, under inhibition of HO-1 activity by SnPPIX, substitutes HO-1 in preventing EC apoptosis. The mechanism of action of HO-1/CO is dependent on the activation of the p38 mitogen-activated protein kinase (MAPK) signaling transduction pathway. Expression of HO-1 or exposure of ECs to exogenous CO enhanced p38 MAPK activation by TNF-alpha. Specific inhibition of p38 MAPK activation by the pyridinyl imidazol SB203580 or through overexpression of a p38 MAPK dominant negative mutant abrogated the antiapoptotic effect of HO-1. Taken together, these data demonstrate that the antiapoptotic effect of HO-1 in ECs is mediated by CO and more specifically via the activation of p38 MAPK by CO.


Statistical analysis of tongue images for feature extraction and diagnostics.
In this paper, an in-depth analysis on the statistical distribution characteristics of human tongue color that aims to propose a mathematically described tongue color space for diagnostic feature extraction is presented. Three characteristics of tongue color space, i.e., tongue color gamut that defines the range of colors, color centers of 12 tongue color categories, and color distribution of typical image features in the tongue color gamut, are elaborately investigated in this paper. Based on a large database, which contains over 9000 tongue images collected by a specially designed noncontact colorimetric imaging system using a digital camera, the tongue color gamut is established in the CIE chromaticity diagram by an innovatively proposed color gamut boundary descriptor using one-class SVM algorithm. Thereafter, centers of 12 tongue color categories are defined accordingly. Furthermore, color distributions of several typical tongue features, such as red points and petechial points, are obtained to build a relationship between the tongue color space and color distributions of various tongue features. With the obtained tongue color space, a new color feature extraction method is proposed for diagnostic classification purposes, with experimental results validating its effectiveness.


Immunological evaluation of meningococcal group C polysaccharide-tetanus toxoid conjugate in mice.
Neisseria meningitidis group C polysaccharide-tetanus toxoid conjugate was prepared to obtain the polysaccharide component in a thymus-dependent form and to preserve the immunogenic properties of the tetanus toxoid component. Biochemical and immunochemical analyses of this conjugate revealed that (i) it was composed of equal amounts of polysaccharide and protein; (ii) the antigenic activity of the polysaccharide component was greatly reduced; (iii) it contained about 10% free polysaccharide; (iv) the composition was not homogeneous; and (v) only 5% of the tetanus toxoid component was present at the surface of the conjugate molecules. In this study, the influence of these characteristics on the antibody response to both components in mice was investigated. The dose-response relationship, the persistence of antibodies, a possible antigenic competition, and the specificities of the antibodies induced were also studied. Our data suggest that the conjugate behaves as a pronounced thymus-dependent antigen, that the tetanus toxoid component is more immunogenic at lower dosages (0.8 and 20 ng) than equivalent doses of tetanus vaccine, that the presence of free polysaccharide does not influence the induction of antibodies to polysaccharide by the conjugate, and that no antibodies to new structures in the conjugate are induced. These characteristics favor the application of this conjugate as a vaccine for human use.


Regulation of Toll signaling and inflammation by β-arrestin and the SUMO protease Ulp1.
The Toll signaling pathway has a highly conserved function in innate immunity and is regulated by multiple factors that fine tune its activity. One such factor is β-arrestin Kurtz (Krz), which we previously implicated in the inhibition of developmental Toll signaling in the Drosophila melanogaster embryo. Another level of controlling Toll activity and immune system homeostasis is by protein sumoylation. In this study, we have uncovered a link between these two modes of regulation and show that Krz affects sumoylation via a conserved protein interaction with a SUMO protease, Ulp1. Loss of function of krz or Ulp1 in Drosophila larvae results in a similar inflammatory phenotype, which is manifested as increased lamellocyte production; melanotic mass formation; nuclear accumulation of Toll pathway transcriptional effectors, Dorsal and Dif; and expression of immunity genes, such as Drosomycin. Moreover, mutations in krz and Ulp1 show dosage-sensitive synergistic genetic interactions, suggesting that these two proteins are involved in the same pathway. Using Dorsal sumoylation as a readout, we found that altering Krz levels can affect the efficiency of SUMO deconjugation mediated by Ulp1. Our results demonstrate that β-arrestin controls Toll signaling and systemic inflammation at the level of sumoylation.


The effect of spatial orientation on detecting motion trajectories in noise.
A series of experiments investigated the extent to which the spatial orientation of a signal line affects discrimination of its trajectory from the random trajectories of background noise lines. The orientation of the signal line was either parallel (iso-) or orthogonal (ortho-) to its motion direction and it was identical in all respects to the noise (orientation, length and speed) except for its motion direction, rendering the signal line indistinguishable from the noise on a frame-to-frame basis. We found that discrimination of ortho-trajectories was generally better than iso-trajectories. Discrimination of ortho-trajectories was largely immune to the effects of spatial jitter in the trajectory, and to variations in step size and line-length. Discrimination of iso-trajectories was reliable provided that step-size was not too short and did not exceed line length, and that the trajectory was straight. The new result that trajectory discrimination in moving line elements is modulated by line orientation suggests that ortho- and iso-trajectory discrimination rely upon two distinct mechanisms: iso-motion discrimination involves a 'motion-streak' process that combines motion information with information about orientation parallel to the motion trajectory, while ortho-motion discrimination involves extended trajectory facilitation in a network of receptive fields with orthogonal orientation tuning.


Mortality from systemic lupus erythematosus in England and Wales, 1974-1983.
Mortality rates from systemic lupus erythematosus (SLE) in England and Wales were estimated from Office of Population Censuses and Surveys data from 1974 to 1983, by age and sex. Age-specific average annual mortality rates showed unimodal distributions for both sexes with maximal death rates in the 65-74-year age groups. The overall age-adjusted mortality rate for females was about four times that in males, 3.94 versus 1.02 per million person-years, respectively. Examination of individual age-specific rates showed an early sharp rise in females producing female-to-male ratios which exceeded 10 in the 25-34-year age group. Age-adjusted annual mortality rates in females significantly declined during the 10-year interval studied from 4.47 to 2.99 per million person-years (p = 0.0083). These patterns of mortality from SLE observed in England and Wales are comparable to those reported among Caucasians in the United States during a similar time period.


Digital processing for improvement of ultrasonic abdominal images.
Digital processing that increases resolution by spatial deconvolution and histogram-based amplitude mapping has been used to improve ultrasonic abdominal image quality. The processing was applied to pulse-echo ultrasound data obtained from clinical imaging instrumentation modified to permit digital recording of signals in either RF or video forms for subsequent off-line analysis. Spatial deconvolution was accomplished both along the axis and across the width of the ultrasonic beam. Axial deconvolution was carried out on RF data with a point spread function derived from the echo of a wire target. Lateral deconvolution was performed on the video envelope placed in a matrix by an inverse filter with parameters that adjust themselves to the spatial frequency content of the image being processed. Resultant image amplitudes were mapped into a hyperbolic distribution to increase image contrast for improved demonstration of low amplitudes. The combination of processing produced resolution improvements to show boundaries more sharply and contrast changes to demonstrate more detail in the images.


Disease-specific survival for limited-stage small-cell lung cancer affected by statistical method of assessment.
In general, prognosis and impact of prognostic/predictive factors are assessed with Kaplan-Meier plots and/or the Cox proportional hazard model. There might be substantive differences from the results using these models for the same patients, if different statistical methods were used, for example, Boag log-normal (cure-rate model), or log-normal survival analysis. Cohort of 244 limited-stage small-cell lung cancer patients, were accrued between 1981 and 1998, and followed to the end of 2005. The endpoint was death with or from lung cancer, for disease-specific survival (DSS). DSS at 1-, 3- and 5-years, with 95% confidence limits, are reported for all patients using the Boag, Kaplan-Meier, Cox, and log-normal survival analysis methods. Factors with significant effects on DSS were identified with step-wise forward multivariate Cox and log-normal survival analyses. Then, DSS was ascertained for patients with specific characteristics defined by these factors. The median follow-up of those alive was 9.5 years. The lack of events after 1966 days precluded comparison after 5 years. DSS assessed by the four methods in the full cohort differed by 0-2% at 1 year, 0-12% at 3 years, and 0-1% at 5 years. Log-normal survival analysis indicated DSS of 38% at 3 years, 10-12% higher than with other methods; univariate 95% confidence limits were non-overlapping. Surgical resection, hemoglobin level, lymph node involvement, and superior vena cava (SVC) obstruction significantly impacted DSS. DSS assessed by the Cox and log-normal survival analysis methods for four clinical risk groups differed by 1-6% at 1 year, 15-26% at 3 years, and 0-12% at 5 years; multivariate 95% confidence limits were overlapping in all instances. Surgical resection, hemoglobin level, lymph node involvement, and superior vena cava (SVC) obstruction all significantly impacted DSS. Apparent DSS for patients was influenced by the statistical methods of assessment. This would be clinically relevant in the development or improvement of clinical management strategies.


Health halo or genuine product development: Are better-for-you alcohol products actually healthier?
Alcoholic products marketed as better-for-you is an emerging trend in Australia that has received limited research attention to date. This study aimed to examine the nutrient profiles of alcoholic products marketed as better-for-you that are available in the Australian market. We extracted the details of alcoholic product announcements published on the Drinks Trade website in 2019 and 2020 containing at least one keyword used to promote better-for-you products. The alcohol, energy, carbohydrate and sugar content of each product was recorded and assessed against existing classifications for alcohol strength and sugar and carbohydrate content. We identified 144 products promoted as better-for-you. The majority of products (85%, n = 122) were classified as full-strength, and the median alcohol content across each alcohol product category was classified as full-strength. Most of the energy content came from alcohol, with 62% of products deriving at least 75% of their energy content from alcohol. Alcoholic products marketed as better-for-you appear to rely on an illusion of healthfulness, without addressing the ingredient of most concern to health, the alcohol content. SO WHAT?: Controls on alcohol marketing should be expanded to limit the use of health and nutrient claims. Mandatory labelling of alcoholic products with nutrition information would support consumers to be better informed about the contents of alcoholic products.


Dispersing away from bad genotypes: the evolution of Fitness-Associated Dispersal (FAD) in homogeneous environments.
Dispersal is a major factor in ecological and evolutionary dynamics. Although empirical evidence shows that the tendency to disperse varies among individuals in many organisms, the evolution of dispersal patterns is not fully understood. Previous theoretical studies have shown that condition-dependent dispersal may evolve as a means to move to a different environment when environments are heterogeneous in space or in time. However, dispersal is also a means to genetically diversify offspring, a genetic advantage that might be particularly important when the individual fitness is low. We suggest that plasticity in dispersal, in which fit individuals are less likely to disperse (Fitness-Associated Dispersal, or FAD), can evolve due to its evolutionary advantages even when the environment is homogeneous and stable, kin competition is weak, and the cost of dispersal is high. Using stochastic simulations we show that throughout the parameter range, selection favors FAD over uniform dispersal (in which all individuals disperse with equal probability). FAD also has significant long-term effects on the mean fitness and genotypic variance of the population. We show that FAD evolves under a very wide parameter range, regardless of its effects on the population mean fitness. We predict that individuals of low quality will have an increased tendency for dispersal, even when the environment is homogeneous, there is no direct competition with neighbors, and dispersal carries significant costs.


Resurgent sodium current and action potential formation in dissociated cerebellar Purkinje neurons.
Voltage-dependent sodium channels were studied in dissociated cerebellar Purkinje neurons from rats. In whole-cell recordings, a tetrodotoxin (TTX)-sensitive inward current was elicited when the membrane was repolarized to voltages between -60 and -20 mV after depolarizations to +30 mV long enough to produce maximal inactivation. At -40 mV, this "resurgent" current peaked in 8 msec and decayed with a time constant of 30 msec. With 50 mM sodium as a charge carrier, the resurgent current was on average approximately 120 pA. CA3 pyramidal neurons had no such current. The current may reflect recovery of inactivated channels through open states, because in Purkinje neurons (but not CA3 neurons) there was partial recovery from inactivation at -40 mV, coinciding with the rise of resurgent current. In single-channel recordings, individual channels gave openings corresponding to resurgent and conventional transient current. Action potentials were recorded from dissociated neurons under current clamp to investigate the role of the resurgent current in action potential formation. Purkinje neurons fired spontaneously at approximately 30 Hz. Hyperpolarization to -85 mV prevented spontaneous firing, and brief depolarization then induced all-or-none firing of conglomerate action potentials comprising three to four spikes. When conglomerate action potentials were used as command voltages in voltage-clamp experiments, TTX-sensitive sodium current was elicited between spikes. The falling phase of an action potential is similar to voltage patterns that activate resurgent sodium current, and thus, resurgent sodium current likely contributes to the formation of conglomerate action potentials in Purkinje neurons.


Antonio Grossich- on the centenary of his introduction of iodine tincture painting in the preoperative infection control.
The article presents the life and achievements of Doctor Antonio Grossich, the head of the Department of surgery and gynecology of the Civic hospital in Rijeka. He wrote several literary works, but deserves to be remembered for his clinical and experimental work on antiseptic and aseptic procedure. He introduced the method of painting the operative field with 10% iodine tincture at first in traumas, then in general surgery. The method, for its rapidity, efficacy and not expensive had soon a worldwide success. He also participated actively in the political life of Rijeka before and after the World War I.


In vivo PET imaging of cardiac presynaptic sympathoneuronal mechanisms in the rat.
The sympathetic nervous system of the heart plays a key role in the pathophysiology of various cardiac diseases. Small-animal models are valuable for obtaining further insight into mechanisms of cardiac disease and therapy. To determine the translational potential of cardiac neuronal imaging from rodents to humans, we characterized the rat sympathetic nervous system using 3 radiotracers that reflect different subcellular mechanisms: (11)C-meta-hydroxyephedrine (HED), a tracer of neuronal transport showing stable uptake and no washout in healthy humans; (11)C-phenylephrine (PHEN), a tracer of vesicular leakage and intraneuronal metabolic degradation with initial uptake and subsequent washout in humans; and (11)C-epinephrine (EPI), a tracer of vesicular storage with stable uptake and no washout in humans. We used a small-animal PET system to study healthy male Wistar rats at baseline, after desipramine (DMI) pretreatment (DMI block), and with DMI injection 15 min after tracer delivery (DMI chase). The rats were kept under general isoflurane anesthesia while dynamic emission scans of the heart were recorded for 60 min after radiotracer injection. A myocardial retention index was determined by normalizing uptake at 40 min to the integral under the arterial input curve. Washout rates were determined by monoexponential fitting of myocardial time-activity curves. At baseline, HED showed high myocardial uptake and sustained retention, EPI showed moderate uptake and significant biphasic washout, and PHEN showed moderate uptake and monoexponential washout. The average (+/- SD) left ventricular retention index for HED, PHEN, and EPI was 7.38% +/- 0.82%/min, 3.43% +/- 0.45%/min, and 4.24% +/- 0.59%/min, respectively; the washout rate for HED, PHEN, and EPI was 0.13% +/- 0.23%/min, 1.13% +/- 0.35%/min, and 0.50% +/- 0.24%/min, respectively. The DMI chase resulted in increased washout only for HED. DMI block decreased myocardial uptake of all tracers by less than 90%. Kinetic profiles of HED in the rat myocardium were similar to those of HED in humans, suggesting comparable neuronal transport density. Unlike in humans, however, significant washout of EPI and faster washout of PHEN were encountered, consistent with high intraneuronal metabolic activity, high catecholamine turnover, and reduced vesicular storage. This evidence of increased neuronal activity in rodents has implications for translational studies of cardiac neuronal biology in humans.


Mechanism for reactivation of N-cyclopropylbenzylamine-inactivated monoamine oxidase by amines.
The effect of 18 different amines, two mercaptans, and two alcohols on the reactivation of N-cyclopropylbenzylamine- (N-CBA-) inactivated bovine liver monoamine oxidase (MAO) is described. All of the compounds that reactivate the enzyme produce a time-dependent pseudo-first-order return of enzyme activity and exhibit saturation kinetics. There is no direct correlation between the ability of a compound to serve as a substrate for native MAO and its ability to reactivate N-CBA-inactivated MAO. Amines containing an aromatic moiety, in general, are better reactivators than the aliphatic amines. The amine must be primary or secondary in order for reactivation to occur. The distance between the aromatic portion and the amino group is critical to the reactivation properties of the compound. The mercaptans and alcohols do not reactivate N-CBA-inactivated MAO, nor do they interfere with the reactivation reaction by benzylamine. Three mechanisms for the reactivation reaction are considered. One involves initial Schiff base formation with the active site adduct produced by N-CBA inactivation of MAO followed by base-catalyzed beta-elimination to the imine of acrolein. The second mechanism is the same as the first except no prior Schiff base formation is invoked. The third mechanism is an SN2 displacement by the amine of the active site amino acid residue attached to the adduct. Experiments are carried out to exclude the SN2 mechanism. The results of the reactivation experiments favor the Shiff base mechanism.


Transcriptional and post-transcriptional processes regulate expression of RNA encoding the small subunit of ribulose-1,5-biphosphate carboxylase differently in petunia and in soybean.
The effects of white light, far-red light and darkness on the in vitro transcription and RNA levels of the small subunit of ribulose-1,5-bisphosphate carboxylase (rbcS) were investigated in petunia and in soybean. In petunia plants treated with 48 hours of darkness the in vitro transcription rate of two of the rbcS subfamilies of petunia, rbcS A and rbcS C, declined 32- and 8-fold respectively, whereas treatment of dark-adapted plants with light caused the in vitro transcription rate of these subfamilies to return to their light-grown levels. Relative RNA levels of rbcS A and rbcS C declined in parallel with in vitro transcription rate changes upon treatment of petunia plants with darkness. However, while relative RNA levels of rbcS C changed in parallel with in vitro transcription rate under all conditions of far-red light and white light tested, there were differences between the changes in rbcS A in vitro transcription rate and RNA levels which were consistent with post-transcriptional regulation of rbcS A RNA. In addition we observed that nuclei isolated from the leaves of plants which were exposed to darkness for periods of 72 hours or longer were transcriptionally inactive. Similar experiments on the in vitro transcription and relative levels of the rbcS RNA in soybean seedlings have lead to the hypothesis that rbcS RNA is less stable in light than in darkness. In contrast, small decreases in rbcS in vitro transcription rate in mature soybean plants treated with darkness were accompanied by large decreases in rbcS RNA, suggesting that rbcS RNA was degraded more rapidly in darkness than in light in these plants. We have shown that differences in the modulation of rbcS RNA levels by post-transcriptional mechanisms exist between plants which belong to different orders, and between different developmental states of the same plant species.


Modern approaches to blood pressure measurement.
Blood pressure (BP) is usually measured by conventional sphygmomanometry. Although apparently simple, this procedure is fraught with many potential sources of error. This review focuses on two alternative techniques of BP measurement: ambulatory monitoring and self measurement. BP values obtained by ambulatory monitoring or self measurement are characterised by high reproducibility, are not subject to digit preference or observer bias, and minimise the transient rise of the blood pressure in response to the surroundings of the clinic or the presence of the observer, the so called white coat effect. For ambulatory monitoring, the upper limits of systolic/diastolic normotension in adults include 130/80 mm Hg for the 24 hour BP and 135/85 and 120/70 mm Hg for the daytime BP and night time BP, respectively. For the the self measured BP these thresholds include 135/85 mm Hg. Automated BP measurement is most useful to identify patients with white coat hypertension. Whether or not white coat hypertension predisposes to sustained hypertension remains debated. However, outcome is better correlated with the ambulatory BP than with the conventional BP. In patients with white coat hypertension, antihypertensive drugs lower the BP in the clinic, but not the ambulatory BP, and also do not improve prognosis. Ambulatory BP monitoring is also better than conventional BP measurement in assessing the effects of treatment. Ambulatory BP monitoring is necessary to diagnose nocturnal hypertension and is especially indicated in patients with borderline hypertension, elderly patients, pregnant women, patients with treatment resistant hypertension, and also in patients with symptoms suggestive of hypotension. The newer techniques of BP measurement are now well established in clinical research, for diagnosis in clinical practice, and will increasingly make their appearance in occupational and environmental medicine.


Delayed graft function in kidney transplantation.
Delayed graft function (DGF) has several long-term graft implications in the field of kidney transplantation and remains a challenge. The incidence of DGF is on the rise because of an increasing use of marginal kidneys in an era of organ shortage. Risk factors for DGF are numerous and stem from multiple sources in the transplant chain starting from the donor to its final allocation in the recipient. There is no FDA-approved therapy for DGF, and several therapies are being studied to mitigate ischemic injury and prolong graft survival. Published data from studies suggest that ischemia-reperfusion injury (IRI) and immune responses to transplants are the leading cause of DGF, which in turn is associated with an increased incidence in acute renal rejection. Several novel methods are being developed and are undergoing further clinical validation to prove as an effective therapy against DGF. Recent studies have proposed several different mechanisms to mitigate ischemic injury to prevent acute renal injury, both of which are representative of DGF. New therapies must be effectively reviewed to ensure advancement of DGF prevention. A number of immunotherapies targeted towards inhibition of complement activation in addition to other novel therapies might prove promising towards mitigating DGF.


Low levels of antigenic variability in fluconazole-susceptible and -resistant Candida albicans isolates from human immunodeficiency virus-infected patients with oropharyngeal candidiasis.
Three serial isolates of Candida albicans were obtained by direct swab or by oral saline rinses from each of five human immunodeficiency virus-infected patients with recurrent oropharyngeal candidiasis. Genotyping techniques confirmed the presence of a persistent strain in multiple episodes from the same patient, which was different from the strains isolated from other patients. Fluconazole susceptibility was determined by both an agar dilution method and the National Committee for Clinical Laboratory Standards macrobroth procedure. In four of these patients the strains developed fluconazole resistance, and in one patient the strain remained susceptible. The different isolates were propagated as yeast cells on a synthetic medium, and their cell wall proteinaceous components were extracted by treatment with beta-mercaptoethanol. Protein and mannoprotein components present in the extracts were analyzed by electrophoresis, immunoblotting, and lectin-blotting techniques. The analysis showed a similar composition, with only minor qualitative and quantitative differences in the polypeptidic and antigenic patterns associated with the cell wall extracts from serial isolates from the same patient, as well as those from different strains isolated from different patients. Use of monospecific antibodies generated against two immunodominant antigens during candidiasis (enolase and the 58-kDa fibrinogen-binding mannoprotein) demonstrated their expression in all isolates tested. Overall, the antigenic makeup of C. albicans strains remained constant during the course of infection and was not affected by development of fluconazole resistance. In contrast to previous reports, the low degree of antigenic variability observed in this study may be due to the fact that the isolates were obtained from a highly homogeneous population of patients and to the uniformity in techniques used for the isolation, storage, and culture of the different strains, as well as extraction methodologies.


Culling experiments demonstrate size-class specific biomass increases with mortality.
Size-selective mortality inevitably leads to a decrease in population density and exerts a direct negative effect on targeted size classes. But density and population size structure are also shaped by food-dependent processes, such as individual growth, maturation, and reproduction. Mortality relaxes competition and thereby alters the dynamic interplay among these processes. As shown by the recently developed size-structured theory, which can account for food-dependent individual performance, this altered interplay can lead to overcompensatory responses in size class-specific biomass, with increasing mortality. We experimentally tested this theory by subjecting laboratory fish populations to a range of size-selective mortality rates. Overall, the results were in agreement with theoretical predictions. Biomass of the juvenile size class increased above control levels at intermediate adult mortality rates and thereafter declined at high mortality rates. Juvenile biomass also increased when juveniles themselves were subjected to intermediate mortality rates. Biomass in other size classes decreased with mortality. Such biomass overcompensation can have wide-ranging implications for communities and food webs, including a high sensitivity of top predators to irreversible catastrophic collapses, the establishment of alternative stable community states, and the promotion of coexistence and biodiversity.


Plant mitochondrial F0F1 ATP synthase. Identification of the individual subunits and properties of the purified spinach leaf mitochondrial ATP synthase.
Spinach leaf mitochondrial F0F1 ATPase has been purified and is shown to consist of twelve polypeptides. Five of the polypeptides constitute the F1 part of the enzyme. The remaining polypeptides, with molecular masses of 28 kDa, 23 kDa, 18.5 kDa, 15 kDa, 10.5 kDa, 9.5 kDa and 8.5 kDa, belong to the F0 part of the enzyme. This is the first report concerning identification of the subunits of the plant mitochondrial F0. The identification of the components is achieved on the basis of the N-terminal amino acid sequence analysis and Western blot technique using monospecific antibodies against proteins characterized in other sources. The 28-kDa protein crossreacts with antibodies against the subunit of bovine heart ATPase with N-terminal Pro-Val-Pro- which corresponds to subunit F0b of Escherichia coli F0F1. Sequence analysis of the N-terminal 32 amino acids of the 23-kDa protein reveals that this protein is similar to mammalian oligomycin-sensitivity-conferring protein and corresponds to the F1 delta subunit of the chloroplast and E. coli ATPases. The 18.5-kDa protein crossreacts with antibodies against subunit 6 of the beef heart F0 and its N-terminal sequence of 14 amino acids shows a high degree of sequence similarity to the conserved regions at N-terminus of the ATPase subunits 6 from different sources. ATPase subunit 6 corresponds to subunit F0a of the E. coli enzyme. The 15-kDa protein and the 10.5-kDa protein crossreact with antibodies against F6 and the endogenous ATPase inhibitor protein of beef heart F0F1-ATPase, respectively. The 9.5-kDa protein is an N,N'-dicyclohexylcarbodiimide-binding protein corresponding to subunit F0c of the E. coli enzyme. The 8.5-kDa protein is of unknown identity. The isolated spinach mitochondrial F0F1 ATPase catalyzes oligomycin-sensitive ATPase activity of 3.5 mumol.mg-1.min-1. The enzyme catalyzes also hydrolysis of GTP (7.5 mumol.mg-1.min-1) and ITP (4.4 mumol.mg-1.min-1). Hydrolysis of ATP was stimulated fivefold in the presence of amphiphilic detergents, however the hydrolysis of other nucleotides could not be stimulated by these agents. These results show that the plant mitochondrial F0F1 ATPase complex differs in composition from the other mitochondrial, chloroplast and bacterial ATPases. The enzyme is, however, more closely related to the yeast mitochondrial ATPase and to the animal mitochondrial ATPase than to the chloroplast enzyme. The plant mitochondrial enzyme, however, exhibits catalytic properties which are characteristic for the chloroplast enzyme.