In vivo 'turn on' fluorescence detection of free cysteine in zebrafish kidney and liver.
Cysteine is directly associated with a wide range of biological processes. Besides its essential role in protein synthesis, cysteine undergoes a variety of post-translational modifications which modulate several physiological processes. Dysregulated cysteine metabolism is associated with several neurodegenerative disorders. Accordingly, restoring cysteine balance has therapeutic benefits. It is therefore essential to detect the presence of endogenous free cysteine in order to understand different physiological modes of action inside the cell. Here, a carbazole-pyridoxal conjugate system (CPLC) has been developed to detect endogenous free cysteine in the liver and kidney of an adult zebrafish. In consequence, we have also determined the fluorescence intensity statistics of zebrafish kidney and liver images. CPLC interacts in a very fascinating way with two cysteine molecules through chemodosimetric and chemosensing approaches which are conclusively proved by different spectroscopic analyses (UV-vis, fluorescence, NMR) and theoretical calculations (DFT). The detection limit of CPLC towards cysteine is 0.20 μM. Moreover, this preliminary experiment has been done using HuH-7 cell line to check the permeability of CPLC, interaction with cysteine intracellularly, and assessment of the toxicity of CPLC, if any, before performing details in-vivo experiments in zebrafish model.


Fatal Chronic Active Epstein-Barr Virus Infection in a Rheumatoid Arthritis Patient Treated with Abatacept.
Chronic active Epstein-Barr virus (CAEBV) T-cell type infection, systemic form, is characterized by persistent infectious mononucleosis-like symptoms, high Epstein-Barr virus (EBV) DNA levels in the peripheral blood, organ damage, and a poor prognosis. The association between CAEBV and rheumatoid arthritis (RA) is unclear. We report a case of fatal CAEBV T-cell type infection in an RA patient undergoing treatment with cytotoxic T-lymphocyte-associated antigen 4 immunoglobulin fusion protein (abatacept, ABT). CAEBV can rapidly worsen in RA patients receiving ABT. Thus, we should try to establish an early diagnosis in patients with CAEBV infection.


Interventions to reduce aggressive care at end of life among patients with cancer: a systematic review.
Little is known about effective interventions to reduce aggressive end-of-life care in patients with cancer. We did a systematic review to assess what interventions are associated with reductions in aggressive end-of-life cancer care. We searched MEDLINE, CINAHL, Embase, Scopus, and PsychINFO for randomised control trials (RCTs), quasi-experimental, and observational studies published before Jan 19, 2018, which aimed to improve measures of aggressive end-of-life care for patients with cancer. We developed a taxonomy of interventions using the Systems Engineering Initiative for Patient Safety (SEIPS) model to summarise existing interventions that addressed aggressive care for patients with cancer. Of the 6451 studies identified by our search, five RCTs and 31 observational studies met the final inclusion criteria. Using the SEIPS framework, 16 subcategories of interventions were identified. With the exception of documentation of end-of-life discussions in the electronic medical record, no single intervention type or SEIPS domain led to consistent improvements in aggressive end-of-life care measures. The ability to discern the interventions' effectiveness was limited by inconsistent use of validated measures of aggressive care. Seven (23%) of 31 observational studies and no RCTs were at low risk of bias according to Cochrane's Risk of Bias tool. Evidence for improving aggressive end-of-life cancer care is limited by the absence of standardised measurements and poor study design. Policies and studies to address the gaps present in end-of-life care for cancer are necessary.


Case Report: Protracted Eosinophilic Meningitis due to Probable Angiostrongyliasis.
Eosinophilic meningitis is classically caused by Angiostrongylus cantonensis. Treatment usually includes supportive care and corticosteroids. Anthelminthic drugs are often avoided because of the risk of an inflammatory reaction to dying larvae. The duration of symptoms in most cases is up to a few weeks. We describe a case of eosinophilic meningitis, likely due to Angiostrongylus spp. infection, with recurrent symptoms and persistent cerebrospinal fluid eosinophilia despite corticosteroid treatment, over a period of almost 5 months. This only resolved after treatment with albendazole.


Towards cheminformatics-based estimation of drug therapeutic index: Predicting the protective index of anticonvulsants using a new quantitative structure-index relationship approach.
The overall efficacy and safety profile of a new drug is partially evaluated by the therapeutic index in clinical studies and by the protective index (PI) in preclinical studies. In-silico predictive methods may facilitate the assessment of these indicators. Although QSAR and QSTR models can be used for predicting PI, their predictive capability has not been evaluated. To test this capability, we developed QSAR and QSTR models for predicting the activity and toxicity of anticonvulsants at accuracy levels above the literature-reported threshold (LT) of good QSAR models as tested by both the internal 5-fold cross validation and external validation method. These models showed significantly compromised PI predictive capability due to the cumulative errors of the QSAR and QSTR models. Therefore, in this investigation a new quantitative structure-index relationship (QSIR) model was devised and it showed improved PI predictive capability that superseded the LT of good QSAR models. The QSAR, QSTR and QSIR models were developed using support vector regression (SVR) method with the parameters optimized by using the greedy search method. The molecular descriptors relevant to the prediction of anticonvulsant activities, toxicities and PIs were analyzed by a recursive feature elimination method. The selected molecular descriptors are primarily associated with the drug-like, pharmacological and toxicological features and those used in the published anticonvulsant QSAR and QSTR models. This study suggested that QSIR is useful for estimating the therapeutic index of drug candidates.


Determination of carboxylic SWCNTs in river water by microextraction in ionic liquid and determination by Raman spectroscopy.
The paper proposes a simple approach for the preconcentration of carboxylated single-walled carbon nanotubes and their determination in river water samples. The method is based on a microliquid-liquid extraction into an ionic liquid (bmim PF6) in the presence of a cationic surfactant (CTAC). 10 μL of the ionic liquid phase are microfiltrated by using a home-made filtration device having a small diameter. The membrane was of cellulose with a pore size of 5 μm. Finally, the carbon nanotubes retained in the membrane are directly analyzed by Raman spectroscopy, which allows their direct characterization and quantification. The limit of detection was 0.050 mg L(-1). The precision, for a 1.4 mg L(-1) concentration of carbon nanotubes, is 3.2%.


Neurological symptoms in Hypophosphatasia.
Hypophosphatasia (HPP) typically manifests with fractures, tooth loss, and muscle pain. Although mental health diagnoses and neurological symptoms have not been previously well documented in HPP, they occur commonly. The recognition of non-traditional symptoms may improve patient satisfaction, preempt costly evaluation and misdiagnosis, and lead to further treatment options. Hypophosphatasia (HPP) is an inborn error of metabolism due to deficiency of tissue non-specific alkaline phosphatase (TNSALP). It is traditionally characterized by rickets in children and osteomalacia in adults, along with fractures, tooth loss, and muscle pain. Neurological symptoms and mental health diagnoses have not been widely reported, and we therefore report their prevalence in a cohort of patients with HPP. A retrospective chart review was performed on a series of 82 HPP patients. Patient charts were reviewed to identify the possible presence and onset of 13 common neurological symptoms. Median age was 36 years (2 to 79). Seventeen had adult onset HPP (> 18 years) and 65 had pediatric onset HPP (< 18 years). Median time from symptom onset to HPP diagnosis was 8 years (0 to 67). Seventy-four percent had a family history of bone disease, while 17% had a family history of neurologic disease. Bone problems occurred in 89%, dental problems in 77%, and muscle problems in 66%. Fatigue occurred in 66%, headache in 61%, sleep disturbance in 51%, gait change in 44%, vertigo in 43%, depression in 39%, anxiety in 35%, neuropathy in 35%, and hearing loss in 33%. The extra-skeletal manifestations of HPP, specifically neurological symptoms, have not been previously well documented. However, mental health diagnoses and neurological symptoms such as headache and sleep disturbance occur commonly in patients with HPP. The recognition of non-traditional symptoms in HPP may improve patient satisfaction, preempt costly evaluation and misdiagnosis, and may lead to further treatment options.


Immune-complex deposits in "pauci-immune" glomerulonephritis: a case report and brief review of recent literature.
Anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis is considered a "pauci-immune" disease, characterized by absent or mild glomerular tuft staining for immunoglobulin and/or complement. We describe a 72-year-old man with progressive renal failure over five months who was found to have P-ANCA associated crescentic glomerulonephritis. Renal biopsy also revealed immunofluorescence staining for Immunoglobulin G and C3. Treatment comprised corticosteroids, cyclophosphamide, and plasmapheresis but unfortunately kidney function did not recover, likely due to substantial interstitial fibrosis at diagnosis. This case illustrates that serologic evaluation for ANCAs should not be discounted when immune deposits are present. Prompt diagnosis is warranted.


Evolving trends in sinus surgery: What is the impact of balloon sinus dilation?
Balloon dilation (BD) represents a minimally invasive alternative to endoscopic sinus surgery (ESS). Although BD was introduced in 2006, distinct Current Procedural Terminology (CPT) codes were not available until 2011, making prior analysis of population-based trends difficult. Our objectives were to evaluate these trends and compare any changes to the use of traditional ESS techniques. Geographic trends also were evaluated. Medicare Part B national datasets encompassing procedures from 2011 to 2015 were obtained. ESS CPT codes (frontal sinusotomy, maxillary antrostomy with/without tissue removal, sphenoidotomy) and BD codes were searched to determine temporal trends in their use. Additionally, state carriers were individually evaluated for geographic trends. National use of BD increased greater than five-fold (39,193 from 7,496 among Medicare patients), whereas the use of ESS increased by only 5.9%. This increase in BD was observed across all sites, including the sphenoid (7.0x), maxillary (5.1x), and frontal (4.7x) sinuses. In the most recent year for which data was available (2015), a significantly greater portion of sinus procedures in these sites utilized BD in the South (42.1%) compared to the Northeast (30.6%), West (29.5%), and Midwest (25.3%) regions (P < 0.0001). The performance of BD has increased markedly in recent years. Because the use of ESS codes remain stable, observed BD trends are unlikely to be due simply to greater familiarity with newer CPT coding. The reasons for the striking increase in BD popularity are speculative and beyond the scope of this analysis, but further study may be needed. NA. Laryngoscope, 128:1299-1303, 2018.


The relation of rhodopsin and scotopic retinal sensitivity in sector retinitis pigmentosa.
We used reflection retinal densitometric, psychophysical, and electroretinographic techniques to study the scotopic retinal function of a mother and her three daughters who had clinical evidence of a sectoral type of retinitis pigmentosa. Retinal regions with, and those without, ophthalmoscopic signs of degeneration were investigated. During dark adaptation, the time courses of rhodopsin regeneration and recovery of scotopic sensitivity were similar to normal as was the relation of rhodopsin to scotopic threshold. In dark-adapted eyes, threshold increases were not proportional to rhodopsin loss. The results of psychophysical tests of background adaptation and temporal summation, and analysis of the relation of electroretinographic a- to b-wave amplitudes, led to the conclusion that abnormalities of photoreceptor cell function central to the rhodopsin-bearing outer segments accounted for the increased thresholds.


The pri-let-7a-2 rs1143770C>T is associated with prognosis of surgically resected non-small cell lung cancer.
Evidence indicates that let-7 of microRNA may be a prognostic factor in lung cancer. Genetic variation in microRNA precursors could influence the processing and expression of microRNAs, which could affect the prognosis of lung cancer. We aimed to investigate the impact of single nucleotide polymorphisms (SNPs) of pri-let-7 on the prognosis of non-small cell lung cancer (NSCLC). A total of 761 patients with surgically resected NSCLC were included. Four SNPs (pri-let-7a-2 rs1143770 and rs629367, pri-let-7a-1 rs10739971, and pri-let-7f-2 rs17276588) were genotyped using sequenom mass spectrometry-based genotyping assay. Overall survival (OS) and disease-free survival (DFS) were evaluated using Kaplan-Meier method and Cox proportional hazards model. Of the 4 SNPs evaluated, the rs1143770C>T was found to be significantly associated with OS and DFS. The rs1143770 CT or TT genotype exhibited a significantly better OS and DFS compared with the rs1143770 CC genotype (adjusted hazard ratio for OS=0.67, confidence interval, 0.49-0.91, P=0.01 and adjusted hazard ratio for DFS=0.74, confidence interval, 0.58-0.95, P=0.02). This observation indicates that pri-let-7a-2 rs1143770C>T may have a prognostic impact on surgically resected NSCLC.


Prelamin A is involved in early steps of muscle differentiation.
Lamin A is a nuclear lamina constituent implicated in a number of human disorders including Emery-Dreifuss muscular dystrophy. Since increasing evidence suggests a role of the lamin A precursor in nuclear functions, we investigated the processing of prelamin A during differentiation of C2C12 mouse myoblasts. We show that both protein levels and cellular localization of prelamin A are modulated during myoblast activation. Similar changes of lamin A-binding proteins emerin and LAP2alpha were observed. Furthermore, prelamin A was found in a complex with LAP2alpha in differentiating myoblasts. Prelamin A accumulation in cycling myoblasts by expressing unprocessable mutants affected LAP2alpha and PCNA amount and increased caveolin 3 mRNA and protein levels, while accumulation of prelamin A in differentiated muscle cells following treatment with a farnesyl transferase inhibitor appeared to inhibit caveolin 3 expression. Our data provide evidence for a critical role of the lamin A precursor in the early steps of muscle cell differentiation.


Incidence, morbidity and mortality, and diagnosis of twin gestations.
Twin gestations have higher morbidity and mortality than singleton pregnancies. This is related to the teratogenic event of twinning itself, as well as to physiologic changes associated with twinning. Early diagnosis, careful monitoring, and knowledge of potential problems may help the alert obstetrician to improve outcome.


Cytochemical observations of the coiled bodies in neurons of rat sympathetic ganglia.
Coiled bodies were investigated by means of ultrastructural cytochemistry. Preferential staining methods for localization of various proteins (ribonucleoproteins, basic proteins, phosphoproteins and glycoproteins) and DNA were applied. The results of cytochemical tests revealed that coiled bodies have a proteinaceous nature. They are composed of ribonucleoproteins, probably of nucleolar origin. They also contain phosphoproteins and glycoproteins but lack cytochemically detectable DNA. Coiled bodies present ultrastructural and cytochemical characteristics similar to the fibrillar part of the nucleous and to the interchromatin granules. The origin and possible functional role of coiled bodies are briefly discussed.


Decreases in motor unit firing rate during sustained maximal-effort contractions in young and older adults.
Previous studies have suggested that older adults may be more resistant to muscular fatigue than young adults. We sought to determine whether motor unit firing rate might be a factor that determines the response to fatiguing exercise in young and older subjects. Motor unit recordings and muscular forces were obtained from the tibialis anterior (TA) muscle of 11 young and 8 older individuals. Maximal voluntary force was first measured during maximal-effort dorsiflexion contractions. Each subject then performed a series of 15 maximal isometric contractions, with each contraction lasting 30s. A 10-s rest period separated the fatiguing contractions. As a result of the fatiguing exercise, both subject groups demonstrated a significant loss in maximal force. The force decline was less in the older adults (20.4%) than in the young adults (33.8%). As expected, prior to muscle fatigue, maximal firing rates in the TA muscle were greater in the young (28.1+/-5.8 imp/s) than in the older adults (22.3+/-4.8 imp/s). The decrease in motor unit firing rate with fatigue was also greater in the young adults (34.9%), than in the older adults (22.0%). These results suggest that the greater fatigue-resistance exhibited by older individuals might be explained by the fact that the decline in motor unit firing rate during fatigue is greater in young persons than it is in older adults.


Antiparkinsonian effects of caffeine depend upon pavlovian drug conditioning processes.
Caffeine induces the antiparkinsonian response of contralateral rotation in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions following exposure to the direct-acting dopamine agonist apomorphine. This effect of caffeine has been attributed to a 'priming' effect of apomorphine which enables the supersensitive dopamine receptors to respond to caffeine and other methylxanthines. These studies, however, did not differentiate between conditioning and pharmacological variables. To resolve this issue, a Pavlovian conditioning procedure was employed in which separate groups of 6-OHDA rats were given 0.05 mg/kg (s.c.) apomorphine treatments paired or unpaired with a test environment. The animals in the paired or conditioning treatment groups subsequently exhibited contralateral rotation when tested with caffeine (10 mg/kg, i.p.), whereas animals in the unpaired or 'priming' treatment groups displayed only enhanced ipsilateral rotation. The activation of the conditioned contralateral rotation by caffeine in the paired group occurred even after the response was suppressed by extinction. This preferential activation following extinction of a previously conditioned drug response by caffeine implicates caffeine mechanisms (e.g. adenosine antagonism) in drug conditioning processes.


Update: influenza activity--United States and worldwide, May 22-September 3, 2005, and 2005-06 season vaccination recommendations.
Influenza A (H3N2) viruses circulated worldwide, and Influenza A (H1) and B viruses were reported less frequently during May 22-September 3, 2005. In North America, isolates of influenza A (H3N2), A (H1), and influenza B were identified sporadically. This report summarizes influenza activity in the United States and worldwide since the last MMWR update.


Muscle strength quantification in small animals: a new transcutaneous technique in rabbits.
The objective of this study was to develop a new, simple, and noninvasive technique to measure the force produced by dorsi-flexion of the foot in small animals. In addition, this study aimed to quantitatively describe changes in muscle and soft tissue structures using histomorphometry. The recovery of the dorsi-flexing muscles in the tibialis anterior compartment in New Zealand White rabbits was evaluated after musculoskeletal trauma by measuring isometric contractions after submaximal transcutaneous electrical stimulation of the peroneal nerve. The trauma included muscle and bone trauma that was treated with limb shortening followed by distraction osteogenesis. Muscle contractions were initiated at an amplitude of 5.1 mA for a duration of 2.56 ms at intervals of 50 ms. Based on consecutive measurements of the force on days 5, 10, 15, 20, 25, and 30 postsurgery, a positive trend in recovery of the stimulated force produced by dorsi-flexion of the foot was observed. The muscle strength at 30 days postsurgery was compared to that measured presurgery (baseline): 55% of the animals had dorsi-flexion strength that was 60% below that of the presurgery baseline muscle strength; 36% of the animals had dorsi-flexion strength that was greater than 60% of the baseline measure, indicating that there was a significant decrease in force produced by dorsi-flexion of the foot after trauma on all testing days (p < 0.01) and that a severe muscular injury was set with limited recovery. This technique provides a new option for examining muscle regeneration and rehabilitation in small animals.


Phenotypic screening of compound libraries as a platform for the identification of antibiotic adjuvants: Identification of colistin adjuvants from a natural product library.
The identification of antibiotic adjuvants, small molecules that potentiate the activity of conventional antibiotics, provides an orthogonal approach to the development of new antibiotics in the fight against drug resistant bacterial infections. Methods to identify novel adjuvants could potentially aid efforts to overcome the increasing prevalence of resistance and stave off the onset of a "post-antibiotic era." Phenotypic whole cell screens allow for the identification of hits with the necessary properties to access their biomolecular target, and may also facilitate the discovery of novel adjuvant targets. A phenotypic screening platform is outlined, in which a natural product library was explored for activity with antibiotics from several mechanistically distinct classes against clinically important bacterial species. General approaches to delineating the mechanism of action of hit compounds identified from phenotypic screens are described, followed by specific approaches to uncovering the mechanism of action of the colistin adjuvants identified from the natural product screen.


Structures of Native-like Nucleosomes: One Step Closer toward Understanding the Structure and Function of Chromatin.
Genomic DNA in eukaryotes is organized into chromatin through association with core histone proteins to form nucleosomes. To understand the structure and function of chromatin, we must determine the structures of nucleosomes containing native DNA sequences. However, to date, our knowledge of nucleosome structures is mainly based on the crystallographic studies of the nucleosomes containing non-native DNA sequences. Here, we discuss the technical issues related to the determination of the nucleosome structures and review the few structural studies on native-like nucleosomes. We show how an antibody fragment-aided single-particle cryo-EM can be a useful method to determine the structures of nucleosomes containing genomic DNA. Finally, we provide a perspective for future structural studies of some native-like nucleosomes that play critical roles in chromatin functions.


Distinct genetic profile with recurrent population-specific missense variants in Korean adult atypical hemolytic uremic syndrome.
Atypical hemolytic uremic syndrome (aHUS) is a rare thrombotic microangiopathy (TMA), characterized by micro-angiopathic hemolytic anemia, thrombocytopenia, and renal failure. In more than half of cases, genetic defects leading to overactivation of the alternative complement system have been identified. In this study, we investigated genetic defects in Korean adult patients with aHUS. Sixty-six Korean adult patients with aHUS were ascertained from the Korean TMA Registry. Genetic variants of 15 aHUS-related genes (eight core genes [CFH, CFB, CFI, CD46, C3, THBD, PLG, and DGKE] and seven candidate genes [CFP, C4BPA, and CHFR1-5]) were analyzed from exome sequencing data. Multiplex ligation-dependent probe amplification of CFH and related genes was performed to detect hybrid genes or large deletions. Thirty patients (45%) had at least one aHUS-related variant (s) in eight core genes (total 40 variant alleles). The most frequently affected gene was CFH (13/40, 32%), followed by THBD (8/40, 20%) and CD46 (7/40, 18%). The two most common variants were Asp486Tyr of THBD (N = 7) and Tyr1058His-Val1060Leu of CFH (N = 5, linked on the same allele), accounting for 30% (12/40). In seven candidate genes, 19 variants were detected. When combined, 40 patients (61%) had at least one variant in 15 core or candidate genes. No patients had anti-CFH Ab or hybrid gene/CFHR1 homozygous deletions. The genetic profile of Korean adult aHUS was unique with recurrent missense variants, demonstrating ethnicity- and age-dependent differences in the genetic background of aHUS.


Diagnostic utility and safety of intracoronary nicorandil as a hyperemic agent for the measurement of fractional flow reserve.
We investigated the diagnostic utility and safety of intracoronary bolus administration of nicorandil compared with intravenous administration of adenosine for evaluating FFR in patients with intermediate (40-70%) coronary stenosis. The FFR values obtained with nicorandil and adenosine showed linear relationship. This correlation is statistically significant with regression coefficient of 0.932 (R2 = 0.834, p < 0.001). The side effects such as bronchospasm, hypotension, and bradycardia were significantly higher after administration of adenosine compared to nicorandil (20% vs. 1.66%, p = 0.001). Intracoronary use of nicorandil seems to be promising in offering the advantages of lesser side effects, similar efficacy, and lesser cost as compared to adenosine.


Synthesis and interaction with midkine of biotinylated chondroitin sulfate tetrasaccharides.
Regiospecifically sulfated chondroitin sulfate repeating tetrasaccharides, CS-OO, GlcAβ-GalNAcβ-GlcAβ-GalNAcβ;CS-EE, GlcAβ-GalNAc(4S6S)β-GlcAβ-GalNAc(4S6S)β; and CS-AA, GlcAβ-GalNAc(4S)β-GlcAβ-GalNAc(4S)β, having biotin linked with a hydrophilic linker at the reducing terminal were synthesized effectively by a coupling of the corresponding disaccharide units and regioselective sulfation. CS-EE showed greater affinity for midkine than CS-AA and CS-OO.


Ancient hunters and their modern representatives: William Sollas's (1849-1936) Anthropology from disappointed bridge to trunkless tree and the instrumentalisation of racial conflict.
During the first decades of the 20th century, many anthropologists who had previously adhered to a linear view of human evolution, from an ape via Pithecanthropus erectus (today Homo erectus) and Neanderthal to modern humans, began to change their outlook. A shift towards a branching model of human evolution began to take hold. Among the scientific factors motivating this trend was the insight that mammalian evolution in general was best represented by a branching tree, rather than by a straight line, and that several new fossil hominids were discovered that differed significantly in their morphology but seemed to date from about the same period. The ideological and practical implications of imperialism and WWI have also been identified as formative of the new evolutionary scenarios in which racial conflict played a crucial role. The paper will illustrate this general shift in anthropological theory for one particular scientist, William Sollas (1849-1936). Sollas achieved a synthesis of human morphological and cultural evolution in what I will refer to as an imperialist model. In this theoretical framework, migration, conflict, and replacement became the main mechanisms for progress spurred by 'nature's tyrant,' natural selection.


Impact of a wastewater treatment plant on microbial community composition and function in a hyporheic zone of a eutrophic river.
The impact of the installation of a technologically advanced wastewater treatment plant (WWTP) on the benthic microbial community of a vinyl chloride (VC) impacted eutrophic river was examined two years before, and three and four years after installation of the WWTP. Reduced dissolved organic carbon and increased dissolved oxygen concentrations in surface water and reduced total organic carbon and total nitrogen content in the sediment were recorded in the post-WWTP samples. Pyrosequencing of bacterial 16S rRNA gene fragments in sediment cores showed reduced relative abundance of heterotrophs and fermenters such as Chloroflexi and Firmicutes in more oxic and nutrient poor post-WWTP sediments. Similarly, quantitative PCR analysis showed 1-3 orders of magnitude reduction in phylogenetic and functional genes of sulphate reducers, denitrifiers, ammonium oxidizers, methanogens and VC-respiring Dehalococcoides mccartyi. In contrast, members of Proteobacteria adapted to nutrient-poor conditions were enriched in post-WWTP samples. This transition in the trophic state of the hyporheic sediments reduced but did not abolish the VC respiration potential in the post-WWTP sediments as an important hyporheic sediment function. Our results highlight effective nutrient load reduction and parallel microbial ecological state restoration of a human-stressed urban river as a result of installation of a WWTP.


Fatigue and soft tissue vibration during prolonged running.
Muscle tuning paradigm proposes that the mechanical properties of soft tissues are tuned in such a way that its vibration amplitude become minimized. Therefore, the vibrations of soft tissue are heavily damped. However, it has been hypothesized that the ability of muscle tuning decreases with fatigue. This study investigated the changes in vibration characteristics of soft tissue with fatigue. Vibrations of the gastrocnemius muscle of 8 runners during a prolonged run protocol on a treadmill at constant velocity (4 ms(-1)) were measured using a tri-axial accelerometer. The vibration amplitude is calculated using the Fourier transform and a wavelet-based method was used to calculate the damping coefficient. The results showed that: (1) the vibration amplitude in longitudinal direction increased with fatigue, which may be interpreted as the decreased muscle function with fatigue. (2) The amplitude increase percent strongly depended on the vibration frequency. (3) The damping coefficient of the gastrocnemius increased with fatigue. A 1-DOF mass-spring-damper model was used in order to validate the wavelet based method and simulate the observed phenomena.


Comparison of administrative data with the Association of Coloproctology of Great Britain and Ireland (ACPGBI) colorectal cancer database.
This study compared case volume and operative mortality from surgery for colorectal cancer in England derived from Hospital Episode Statistics (HES) with the Association of Coloproctology of Great Britain and Ireland (ACPGBI) colorectal cancer database. Data extracted from HES records for 2001-2002 for patients undergoing one of seven procedures for colorectal cancer were compared with those from the ACPGBI database. The primary endpoint was a 30-day post-operative mortality. 16,346 patients from HES were compared with 7,635 from the ACPGBI database. For trusts with patients in both databases, HES reported 12% more procedures than ACPGBI (7,516 vs 6,617). Records of anterior resection revealed reasonable agreement between HES and the ACPGBI databases (difference, 2%). By trust, the overall correlation between the reported procedures was 0.660. Reported crude mortality was inconsistent between the databases, with mortality from abdominoperineal excision of rectum showing the poorest correlation (r = 0.253). Overall, agreement between reported caseload and mortality was reasonable at a national, but not hospital, level. Investigation of differences between the two databases at unit level may help to detect under reporting of cases. The combination of data from both sources could be used to develop an enhanced system for monitoring outcomes from colorectal surgery in England.


[Wearables to support self-management of older adults with chronic diseases : A qualitative study from the perspectives of patients and physicians].
The use of wearable devices (WD) is discussed as an option to support elderly chronically ill people. These technologies lack essential research regarding the improvement of self-management. This study aimes to identify perspectives, expectations and their underlying background of patients and physicians with respect to the usage of WDs to enhance self-management. In this study a total of 14 patients and physicians were surveyed using a semi-structured questionnaire design. The data were analyzed by qualitative content analysis. The participants have in general a positive attitude towards the use of WDs with respect to memory function, self-control, sense of security, documentation of vital parameters and communication about the disease, as well as suitability for everyday use; however, in many cases participants are concerned about the usage of WDs for a variety of reasons. They perceive the device as unnecessary or they lack technological self-confidence and felt controlled as well as data protection concerns. Participant responses show prerequisites which should be met for the usage of a WD requiring an individual needs assessment. The results show a potential of WDs to improve self-management. The usage of WD could have a positive effect on the course of the disease; however, personality and environmental factors should be taken into account to individually adjust and support the usage of WDs. Furthermore, the application of WDs should be integrated into a structured training program accompanied by healthcare professionals. For this purpose, funding and time-oriented framework conditions should be established.


Noninvasive acoustical detection of coronary artery disease: a comparative study of signal processing methods.
Previous studies have indicated heart sounds may contain information useful in the detection of occluded coronary arteries. During diastole, coronary blood flow is maximum, and the sounds associated with turbulent blood flow through partially occluded coronary arteries should be detectable. In order to detect such sounds, recordings of diastolic heart sound segments were analyzed by using four signal processing techniques; the Fast Fourier Transform (FFT), the Autoregressive (AR), the Autoregressive Moving Average (ARMA), and the Minimum-Norm (Eigen-vector) methods. To further enhance the diastolic heart sounds and reduce background noise, an Adaptive filter was used as a preprocessor. The power ratios of the FFT method and the poles of the AR, ARMA, and Eigen-vector methods were used to diagnose patients as diseased or normal arteries using a blind protocol without prior knowledge of the actual disease states of the patients to guard against human bias. Results showed that normal and abnormal records were correctly distinguished in 56 of 80 cases using the Fast Fourier Transform (FFT), in 63 of 80 cases using the AR, in 62 of 80 cases using the ARMA method, and in 67 of 80 cases using the Eigenvector method. Among all four methods, the Eigenvector methods showed the best diagnostic performance when compared with the FFT, AR, and ARMA methods. These results confirm that high frequency acoustic energy between 300 and 800 Hz is associated with coronary stenosis.


TREM2 and microglia exosomes: a potential highway for pathological tau.
Tau pathology appears to spread along neuronal networks via the template misfolding of tau by pathological tau conformations. The mechanisms underlying neuron-to-neuron transmission of tau are unclear and recent work demonstrates a role for microglia in the spread of tau pathology. In this Commentary, we discuss a recent study that found that loss of TREM2 expression resulted in exacerbated spread of tau pathology that depended on microglial exosomes. These important findings highlight the role of the microglial endolysosomal system and TREM2 in the spread of tau pathology.


Identifying a living great-grandson of the Lakota Sioux leader Tatanka Iyotake (Sitting Bull).
A great-grandson of the legendary Lakota Sioux leader Sitting Bull (Tatanka Iyotake), Ernie LaPointe, wished to have their familial relationship confirmed via genetic analysis, in part, to help settle concerns over Sitting Bull's final resting place. To address Ernie LaPointe's claim of family relationship, we obtained minor amounts of genomic data from a small piece of hair from Sitting Bull's scalp lock, which was repatriated in 2007. We then compared these data to genome-wide data from LaPointe and other Lakota Sioux using a new probabilistic approach and concluded that Ernie LaPointe is Sitting Bull's great-grandson. To our knowledge, this is the first published example of a familial relationship between contemporary and a historical individual that has been confirmed using such limited amounts of ancient DNA across such distant relatives. Hence, this study opens the possibility for broadening genealogical research, even when only minor amounts of ancient genetic material are accessible.


Intracoronary compared with intravenous bolus abciximab application during primary percutaneous coronary intervention in ST-segment elevation myocardial infarction: cardiac magnetic resonance substudy of the AIDA STEMI trial.
The aim of the AIDA STEMI (Abciximab i.v. Versus i.c. in ST-elevation Myocardial Infarction) cardiac magnetic resonance (CMR) substudy was to investigate potential benefits of intracoronary versus intravenous abciximab bolus administration on infarct size and reperfusion injury in ST-segment elevation myocardial infarction. The AIDA STEMI trial randomized 2,065 patients to intracoronary or intravenous abciximab and found similar rates of major adverse cardiac events at 90 days with significantly less congestive heart failure in the intracoronary abciximab group. CMR can directly visualize myocardial damage and reperfusion injury, thereby providing mechanistic and pathophysiological insights. We enrolled 795 patients in the AIDA STEMI CMR substudy. CMR was completed within 1 week after ST-segment elevation myocardial infarction. Central core laboratory-masked analyses for quantified ventricular function, volumes, infarct size, microvascular obstruction, hemorrhage, and myocardial salvage were performed. The area at risk (p = 0.97) and final infarct size (16% [interquartile range: 9% to 25%] versus 17% [interquartile range: 8% to 25%], p = 0.52) did not differ significantly between the intracoronary and the intravenous abciximab groups. Consequently, the myocardial salvage index was similar (52 [interquartile range: 35 to 69] versus 50 [interquartile range: 29 to 69], p = 0.25). There were also no differences in microvascular obstruction (p = 0.19), intramyocardial hemorrhage (p = 0.19), or ejection fraction (p = 0.95) between both treatment groups. Patients in whom major adverse cardiac events occurred had significantly larger infarcts, less myocardial salvage, and more pronounced ventricular dysfunction. This largest multicenter CMR study in ST-segment elevation myocardial infarction patients to date demonstrates no benefit of intracoronary versus intravenous abciximab administration on myocardial damage and/or reperfusion injury. Infarct size determined by CMR was significantly associated with major adverse cardiac events.


No aggression in a 4-year-old boy with an androgen-producing tumour: case report.
The androgen testosterone plays a critical role in many aspects of sexual differentiation. Also, it is thought to induce aggressive behaviours or to play a role in social dominance. In this case report a 4-year-old boy is described whose testosterone and dehydroepiandrosterone sulphate (DHEA-S) levels were raised to pubertal levels due to a testosterone producing testis tumour. This provided the unique opportunity to examine the effects of elevated levels of androgens on levels of aggression or on social dominance before the onset of puberty. The present case report does not support the hypothesis of a causal relationship between testosterone and aggression or between testosterone and social dominance in young children.


A nano-targeted co-delivery system based on gene regulation and molecular blocking strategy for synergistic enhancement of platinum chemotherapy sensitivity in ovarian cancer.
Ovarian cancer (OC) has a low five-year survival rate, mainly because of its drug resistance to chemotherapy. It is the key to reverse drug resistance to combine multiple sensitization pathways to play a synergistic role. A nano scaled targeted co-delivery system (P123-PEI-G12, PPG) modified by bifunctional peptide tLyP-1-NLS (G12) was fabricated by using Pluronic P123 conjugated with low molecular weight polyethyleneimine (PEI). This delivery system can co-delivery Olaparib (Ola) and p53 plasmids to synergistically enhance the sensitivity of OC to platinum-based chemotherapy. P53@P123-PEI-G2/Ola (Co-PPGs) can achieve efficient tumor accumulation and cellular internalization through G12-mediated targeting. Co-PPGs then break down in the tumor cells, releasing the drug. Co-PPGs significantly enhanced the sensitivity of cisplatin (DDP) in platinum-resistant ovarian cancer (PROC) and synergistically inhibited the proliferation of PROC in vitro and in vivo. The sensitizing and synergistic effects of Co-PPGs were related to the activation of p53, inhibition of poly-ADP-ribose polymerase (PARP) and p-glycoprotein (P-gp) expression. This work provides a promising strategy for the effective treatment of PROC.


Mechanical properties of hydroxyapatite-reinforced gelatin as a model system of bone.
The elastic Young's modulus of hydroxyapatite-reinforced gelatin as a mechanical model system of bone was measured as a function of the volume fraction of hydroxyapatite, phi h. Initially, the Young's modulus gradually increased with an increase in phi h and then increased rapidly in the vicinity of phi h approximately 0.2. The phi h dependence of the Young's modulus was analysed by means of the theory of composite materials. It was found that with the increase in phi h the initial uniform stress deformation mode of the sample changed to the uniform strain deformation mode. The non-linear character in phi h dependence of the Young's modulus of this system was considered to reproduce well the novel behaviour of the mechanical properties of bone as a function of the mineral fraction. The situation was considered to be similar to a percolation problem. A preliminary analysis revealed that the critical exponent about the viscosity of the system accorded with the theoretically expected value. The result may present the evidence that the discontinuous point in mechanical properties of bone would be originated from an interaction such as a percolation of mineral particles on a matrix protein.


Improved cardiac contraction imaging in live Drosophila embryos.
Drosophila melanogaster is a powerful model organism in which to address the genetics of cardiac patterning and heart development. This system allows the pairing of live imaging with the myriad available genetic and transgenic techniques to not only identify the genes that are critical for heart development, but to assess their impact on heart function in living organisms. There are several described methods to assess cardiac function in Drosophila. However, these approaches are restricted to imaging of mid- to late-instar larval and adult hearts. This technical hurdle therefore does not allow for the recording and analysis of cardiac function in embryos bearing strong mutations that do not hatch into larvae. Our technical innovation lies in transgenically labeling the cells of the Drosophila heart and using line scan-based confocal imaging to repeatedly image the walls of the heart. By plotting this line scan as a kymograph, heart contractions can be visualized and assayed, thereby allowing for quantification of physiological defects. This method can be used to obtain physiological data from known mutations that affect cardiac development yet are incapable of hatching into larvae for conventional analysis.•Use transgenic methods to label heart proper walls•Use high-speed line scanning to capture position of heart proper walls•Create X vs. time plot to visualize and quantify contractions over imaging period.


Peptide YY in gastrointestinal disorders.
The changes in PYY in several gastrointestinal disorders and their possible clinical implications are reviewed. The changes in PYY seem to be an adaptive response to alterations in the patho-physiological condition caused by the disease. This becomes evident in gastrointestinal disorders such as diabetes gastroenteropathy, inflammatory bowel diseases, celiac disease, systemic sclerosis and post-intestinal resection state. On the other hand, changes in PYY in chronic idiopathic slow transit constipation appear to be primary and could be one of the etiologic factors of the disease. PYY does not seem to be involved in colorectal carcinoma. Although gastrointestinal dysmotility in neuro-muscular diseases is evident, PYY is not affected. The changes in PYY in gastrointestinal disorders could be beneficial in clinical practice. Thus, in cases where an increase or decrease in PYY is desirable, a diet that increases or decreases PYY synthesis and release can be followed, or a receptor agonist or antagonist can be utilized.


Reliability of TMS motor evoked potentials in quadriceps of subjects with chronic hemiparesis after stroke.
Transcranial magnetic stimulation (TMS) non-invasively measures excitability of central motor pathways in humans and is used to characterize neuroplasticity after stroke. Using TMS to index lower extremity neuroplasticity after gait rehabilitation requires test-retest reliability. This study assesses the reliability of TMS-derived variables measured at bilateral quadriceps of chronic hemiparetic stroke survivors. Results support using measures of both paretic and nonparetic motor threshold, motor evoked potential (MEP) latencies; and nonparetic MEP amplitudes. Implications for longitudinal research are discussed.


[Post-traumatic growth: Some conceptual considerations].
Post-traumatic growth (PTG) is a quite new concept of positive psychology proposed in the mid-1990s which is still rather confidential in France. This article aims to propose a full description of this concept from an historical view to epidemiological data through underlying mechanisms and evaluation. A literature search identifying relevant results was performed through the Pubmed database. PTG refers to positive psychological changes experienced as a result of a traumatic life event in order to rise to a higher level of functioning. That is to say that people experiencing psychological struggle following adversity may often see positive outcomes in the aftermath of trauma. Domains of PTG include appreciation of life, relationships with others, new possibilities in life, personal strength and spiritual change. A self-report scale, the Post-Traumatic Growth Inventory (PTGI), has been developed. PTG has been demonstrated after various traumatic events such as transport accidents, natural disasters, interpersonal violence or medical problems, with a prevalence ranging from 3 to 98 % depending on the type of trauma. The concept of resilience and some evaluation bias may have been deleterious for the development of the PTG concept in the French-speaking world. There is a need to consolidate data to understand the pathway leading to PTG, noticeably to identify factors contributing to PTG that can help to promote the growth as a new therapy for trauma.


Longitudinal evaluation of myofiber microstructural changes in a preclinical ALS model using the transverse relaxivity at tracer equilibrium (TRATE): A preliminary study.
T2⁎ relaxivity contrast imaging may serve as a potential imaging biomarker for amyotrophic lateral sclerosis (ALS) by noninvasively quantifying the tissue microstructure. In this preliminary longitudinal study, we investigated the Transverse Relaxivity at Tracer Equilibrium (TRATE) in three muscle groups between SOD1-G93A (ALS model) rat and a control population at two different timepoints. The control group was time matched to the ALS group such that the second timepoint was the onset of disease. We observed a statistically significant decrease in TRATE over time in the gastrocnemius, tibialis, and digital flexor muscles in the SOD1-G93A model (p-value = 0.003, 0.008, 0.005; respectively), whereas TRATE did not change over time in the control group (p-value = 0.4777, 0.6837, 0.9682; respectively). Immunofluorescent staining revealed a decrease in minimum fiber area and cell density in the SOD1-G93A model when compared to the control group (p-value = 6.043E-10 and 2.265E-10, respectively). These microstructural changes observed from histology align with the theorized biophysical properties of TRATE. We demonstrate that TRATE can longitudinally differentiate disease associated atrophy from healthy muscle and has potential to serve as a biomarker for disease progression and ultimately therapy response in patients with ALS.


Monitoring the intracellular pH of Zygosaccharomyces bailii by green fluorescent protein.
It is generally known that intracellular pH (pH(i)) plays a vital role in cell physiology and that pH(i) homeostasis is essential for normal cellular functions. Therefore, it is desirable to know the pH(i) during cell life cycle or under various growth conditions. Different methods to measure pH(i) have been developed and among these methods, the use of pH-sensitive green fluorescent protein (GFP) as a pH(i) indicator is a promising technique. By using this approach, not only can more accurate pH(i) results be obtained but also long-term experiments on pH(i) can be performed. In this study, the wild type Zygosaccharomyces bailii, a notorious food spoilage yeast, was transformed with a plasmid encoding a pH-sensitive GFP (i.e. pHluorin), enabling the pH(i) of the yeast to be determined based on cellular fluorescent signals. After the transformation, growth and pH(i) of the yeast were investigated in four different acidic conditions at 22°C during 26days. From the experimental results, the transformation effectiveness was verified and a good correlation between yeast growth and pH(i) was noticed. Particularly, it was observed that the yeast has an ability to tolerate a significant pH(i) drop during exponential phase and a subsequent pH(i) recovery in stationary phase, which may underlie the exceptional acid resistance of the yeast. This was the first time that a GFP-based approach for pH(i) measurement was applied in Z. bailii and that the pH(i) of the yeast was monitored during such a long period (26days). It can be expected that greater understanding of the physiological properties and mechanisms behind the special acid resistance of the yeast will be obtained from further studies on this new yeast strain.


COVID-19 therapeutics: Clinical application of repurposed drugs and futuristic strategies for target-based drug discovery.
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes the complicated disease COVID-19. Clinicians are continuously facing huge problems in the treatment of patients, as COVID-19-specific drugs are not available, hence the principle of drug repurposing serves as a one-and-only hope. Globally, the repurposing of many drugs is underway; few of them are already approved by the regulatory bodies for their clinical use and most of them are in different phases of clinical trials. Here in this review, our main aim is to discuss in detail the up-to-date information on the target-based pharmacological classification of repurposed drugs, the potential mechanism of actions, and the current clinical trial status of various drugs which are under repurposing since early 2020. At last, we briefly proposed the probable pharmacological and therapeutic drug targets that may be preferred as a futuristic drug discovery approach in the development of effective medicines.


A ten-year experience with the pediatric Kock pouch.
In 1981, a five-year experience with the pediatric Kock pouch was reported. This series has now increased to 20 patients with an overall experience of 10 years. There were 12 females and eight males ranging in age from 13 to 19 years. These pouches were all elective: 18 were converted from standard ileostomies, (six with proctectomy or Hartmann procedure), and two had a total proctocolectomy. Three of these conversions were for failed Swenson, Soave, and Duhamel procedures. Sixteen children had ulcerative colitis, three Hirschsprung's disease (one with colon atresia and imperforate anus with rectovaginal fistula), and one colonic polyposis (Gardner's syndrome). None had Crohn's disease. The 100% follow-up shows that 19 of the 20 teenagers have been followed for more than 1 year. The most important conclusions from this 10-year review of 20 teenage Kock pouch patients are (1) this continues to be a difficult operation with a significant potential for complications. (2) After 15 months, there is a very small incidence of nipple valve and outflow tract problems, but the possibility of pouchitis remains between 15 months and 5 years. (3) After 5 years, the chances of any kind of a problem with the Kock pouch are minimal. These children are all well, continent, happy, and back to a virtually normal life that includes marriage and pregnancy. The pediatric Kock pouch continues to be a reasonable alternative for the appropriate teenager, when a standard ileostomy is not desired and/or a pelvic pouch is impossible. It must be done by a surgeon with the necessary interest and experience. Long-term follow-up is essential.


Curcumin amorphous solid dispersions benefit from hydroxypropyl methylcellulose E50 to perform enhanced anti-inflammatory effects.
The solubility and permeability enhancement of curcumin (Cur) is crucial for its manufacture and application in medical field. Herein, Cur amorphous solid dispersions (ASDs) with enhanced drug solubility and permeability was formulated by Eudragit EPO (EuD) and biological macromolecules of hydroxypropyl methylcellulose E50 (HPMC), and significant functions of HPMC for Cur ASDs were mainly studied. The results showed that the mean particle size of Cur decreased from more than 300 nm to less than 200 nm with the addition of HPMC in excipient aqueous solution evidenced by dynamic light scattering result, confirming that HPMC had the ability to inhibit crystallization by lowering drug-rich droplets in the initial mixing process. Innovatively for molecular dynamic modeling study, crystalline Cur molecules in EuD medium trended to aggregate while not for EuD/HPMC 1:1 and EuD/HPMC 3:1 medium. HPMC functioned as surfactant converted the arrangement of phospholipid bilayers to un-ordered, and un-ordered state of phospholipids lead to the enhancement of Cur transmembrane using HPMC as auxiliary excipient. Cur-EuD/HPMC 3:1 contributed greatly to the Cur permeability, leading to obtain superior relative oral bioavailability and anti-inflammatory effect. Cur ASDs with proper amount of HPMC can be rendered as outstanding therapeutic strategy for medical application.


Engineering a hierarchical carbon supported magnetite nanoparticles composite from metal organic framework and graphene oxide for lithium-ion storage.
Fe based metal organic framework (MOF) materials are being extensively investigated as a precursor sample for engineering carbon supported iron containing nanoparticles composites. Rational design and engineering Fe-containing MOFs with optimized structures using economic and eco-friendly methods is a challenging task. In this work, 1,3,5-benzenetricarboxylic acid (C9H6O6, trimesic acid, H3BTC) and metal Fe are employed to synthesize a MOF sample Fe-BTC in a mild hydrothermal condition. Moreover, with the addition of a small quantity of graphene oxide (GO) as dispersant, a redox coprecipitation reaction has taken place where small Fe-BTC domains well dispersed by reduced graphene oxide (RGO). The Fe-BTC/RGO intermediate sample is finally converted to the hierarchical Fe3O4@C/RGO composite, which delivers an ultrahigh specific capacity of 1262.61 mAh·g-1 at 200 mA·g-1 after 150 cycles and a superior reversible capacity of 910.65 mAh·g-1 at 1000 mA·g-1 after 300 cycles in half cells. The full cell performance for the Fe3O4@C/RGO composite have been studied. It is also revealed that the improved structural stability, high pseudocapacitive contribution and enhanced lithium-ion and electron transportation conditions jointly guarantee the outstanding lithium-ion storage performances for the Fe3O4@C/RGO composite over long-time cycling. The synthesized samples have good potential for wider application.


Alteration of pulmonary function in diabetic nephropathy.
Type 2 diabetes mellitus is increasing worldwide with an alarming rate. It is associated with the development of various chronic complications. The aim of this study was to explore the alteration of pulmonary function, and its association with renal complications in people with type 2 diabetes mellitus. This cross-sectional study was conducted on three groups; 40 diabetic subjects without nephropathy (urinary albumin<30 mg/day), 40 subjects with nephropathy (urinary albumin≥30 mg/day), and 40 healthy subjects as the control group. The subjects with nephropathy were divided into those with microalbuminuria (urinary albumin=30-300 mg/day) and those with macroalbuminuria (urinary albumin>300 mg/day) .Diabetic subjects were matched to the control group in terms of age, sex, and BMI. Pulmonary function tests were performed and the results were compared between groups. Forced vital capacity (FVC; % predicted), forced expiratory volume in 1 second (FEV1; % predicted), and peak expiratory flow (PEF; % predicted) were significantly lower in subjects with diabetic nephropathy compared to the healthy controls (P<0.05). Meanwhile, in diabetic subjects, FVC and FEV1 were lower in those with diabetic nephropathy compared to those with normal albumin excretion (P<0.05). On the other hand, FEV1/FVC was significantly higher in diabetic people with nephropathy.Furthermore, a significant difference was observed between FVC and FEV1 in diabetic people with microalbuminuria compared to those with macroalbuminuria. This study showed that the pulmonary function was impaired in people with Diabetes. The progression of diabetic nephropathy to more advanced stages was also associated with more impairment of pulmonary function.


Polymorphisms of HLA class II predispose children and adolescents with type 1 diabetes mellitus to autoimmune thyroid disease.
To determine the prevalence of autoimmune thyroid disease (AITD) in children and adolescents with type 1 diabetes mellitus (DM), and assess whether the development of AITD is correlated with specific DQ-A and DQ-B loci of the HLA class II antigens, we analyzed thyroid function using anti-thyroid antibodies and HLA-DQ-A and -DQ-B polymorphisms in 69 patients with type 1 DM, in 75 normal healthy controls, and in 21 patients with AITD but without type 1 DM. Eighteen patients (26%) in the diabetic patients had AITD. In the diabetic patients, DQA1*0301 and DQB1*0302 occurred more frequently than in controls [DQA1*0301: OR = 1.939, 95% CI = 1.210-3.109 (P = 0.008, P(c) (corrected P) < 0.05); DQB1*0302: OR = 2.558, 95% CI = 1.354-4.832 (P = 0.005, P(c), > 0.05)]. Compared with controls, non-diabetic subjects with AITD showed higher frequency of DQA1*0301 (P(c), < 0.05) and DQB1*0601 (P(c) > 0.05), but these alleles were not contributing factors in the development of AITD in diabetic patients. In diabetic patients, DQB1*0201, known as susceptible allele of type 1 DM was not a contributing factor in the development of AITD in diabetic patients. Unlike DQB1*0201, DQB1*0401 was more frequently found in diabetic patients with AITD than in controls [OR = 4.053, 95% CI = 1.607-10.221 (P = 0.0017, P(c) < 0.05)] or than in non-diabetic AITD patients [OR = 15.769, 95% CI = 1.905-130.530(P = 0.002, P(c) < 0.05)]. In non-diabetic subjects, DQB1*0401 did not provide susceptibility for AITD. Our results suggest that HLA DQB1*0401 is a predisposing genetic marker for the development of AITD in patients with type 1 DM in Korea.


Intravenous gammaglobulin treatment in HIV-1 infection.
The two main indications for the use of intravenous gammaglobulin--antibody replacement therapy and immunomodulation--are pertinent only for a few scenarios in HIV-1 infection. The role of gammaglobulin in the treatment of HIV-1 infection has changed significantly with the introduction of highly active antiretroviral therapy. Antiretroviral drugs have not only controlled the progression of disease but also had far-reaching effects on HIV-1-induced immunologic aberrations. Complete or partial immunologic reconstitution and prevention of immunologic damage have been the hallmarks of success for highly active antiretroviral therapy. This article addresses the use of gammaglobulin before and after the era of effective antiretroviral therapies.


Validation of a priori candidate Alzheimer's disease SNPs with brain amyloid-beta deposition.
The accumulation of brain amyloid β (Aβ) is one of the main pathological hallmarks of Alzheimer's disease (AD). However, the role of brain amyloid deposition in the development of AD and the genetic variants associated with this process remain unclear. In this study, we sought to identify associations between Aβ deposition and an a priori evidence based set of 1610 genetic markers, genotyped from 505 unrelated individuals (258 Aβ+ and 247 Aβ-) enrolled in the Australian Imaging, Biomarker & Lifestyle (AIBL) study. We found statistically significant associations for 6 markers located within intronic regions of 6 genes, including AC103796.1-BDNF, PPP3R1, NGFR, KL, ABCA7 & CALHM1. Although functional studies are required to elucidate the role of these genes in the accumulation of Aβ and their potential implication in AD pathophysiology, our findings are consistent with results obtained in previous GWAS efforts.


6-Hydroxydopamine lesions of the olfactory tubercle do not alter (+)-amphetamine-conditioned place preference.
Rats received bilateral infusions of 6-hydroxydopamine into the olfactory tubercle, resulting in a substantial (89%) local depletion of dopamine. This treatment did not significantly alter conditioned place preference produced by (+)-amphetamine, suggesting that the mesolimbic dopaminergic projection to olfactory tubercle does not mediate the rewarding effects of (+)-amphetamine in rats.


Experimental colonization of an expanded polytetrafluoroethylene vascular graft with Staphylococcus aureus: a quantitative and morphologic study.
We developed an animal model to reproduce hematogenous seeding of vascular grafts with Staphylococcus aureus. Expanded polytetrafluoroethylene (ePTFE) grafts were implanted in 41 dogs as thoracoabdominal aortic bypasses for six durations of implantation between 2 hours and 6 months. The inoculum containing an average of 10(8) viable bacteria/ml was then injected intravenously in 1 minute. Normal dog aortas were used as controls. They entrapped very few bacteria (0.7 +/- 1.7 colony-forming unit [CFU]/cm2). Colonization of ePTFE grafts was maximal after 2 hours of implantation (589 +/- 733 CFU/cm2). Bacterial entrapment decreased after 2 days (225 +/- 315 CFU/cm2, p less than 0.001) and 8 days (70 +/- 115 CFU/cm2, p less than 0.001) of implantation, but it was similar after 8 days, 1 month (83 +/- 90 CFU/cm2), or 6 months (93 +/- 143 CFU/cm2) of implantation. Colonization of ePTFE measured after 2 months of implantation (371 +/- 591 CFU/cm2) was significantly higher (p less than 0.001) than after 1 or 6 months of implantation. More than 500 CFU/cm2 were seen in 37% of the prosthetic fragments tested after 2 hours of exposure to blood; 99% of the fragments tested after 6 months of implantation trapped less than 500 CFU/cm2. Scanning electron microscopy showed that staphylococci were mostly seen on native fibrin deposits, particularly after 2 hours and 2 months of implantation. That persistent susceptibility of a flow surface devoid of endothelium to hematogenous bacterial colonization has to be taken into account to prevent delayed graft infections. Furthermore, it would be important to compare the ePTFE with other types of grafts whose healing phenomena are different.


New insights into the history of rice domestication.
The history of rice domestication has long been a subject of debate. Recently obtained genetic evidence provides new insights into this complex story. Genome-wide studies of variation demonstrate that the two varietal groups in Oryza sativa (indica and japonica) arose from genetically distinct gene pools within a common wild ancestor, Oryza rufipogon, suggesting multiple domestications of O. sativa. However, the evolutionary history of recently cloned domestication genes adds another layer of complexity to the domestication of rice. Although some alleles exist only within specific subpopulations, as would be expected if the domestications occurred independently, other major domestication alleles are common to all cultivated O. sativa varieties. Our current view of rice domestication supports multiple domestications coupled with limited introgression that transferred key domestication alleles between divergent rice gene pools.


Bifenthrin disrupts cytochrome c oxidase activity and reduces mitochondrial DNA copy number through oxidative damage in pool barb (Puntius sophore).
Bifenthrin (BF), a synthetic pyrethroid is used worldwide for both agricultural and non-agricultural purposes due to its high insecticidal activity and low toxicity in mammals. However, its improper usage implies a possible risk to aquatic life. The study was aimed to correlate the association of BF toxicity with mitochondrial DNA copy number variation in edible fish Punitus sophore. The 96-h LC50 of BF in P. sophore was 3.4 μg/L, fish was treated with sub-lethal doses ((⅒ and ⅕ of LC50;0.34 μg/L, 0.68 μg/L) of BF for 15 days. The activity and expression level of cytochrome c oxidase (Mt-COI) were measured to assess mitochondrial dysfunction caused by BF. Results showed BF reduced the level of Mt-COI mRNA in treated groups, hindered complex IV activity and increased ROS generation leading to oxidative damage. mtDNAcn was decreased in the muscle, brain and liver after BF treatment. Furthermore, BF induced neurotoxicity in brain and muscle cells through the inhibition of AchE activity. The treated groups showed elevated level of malondialdehyde (MDA) and an imbalance of antioxidant enzymes activity. Molecular docking and simulation analysis also predicted that BF binds to the active sites of the enzyme and restricts the fluctuation of its residues. Hence, outcome of the study suggests reduction of mtDNAcn could be a potential biomarker to assess Bifenthrin induced toxicity in aquatic ecosystem.


AP-1 is a regulatory transcription factor of inflammaging in the murine kidney and liver.
Aging is characterized by chronic low-grade inflammation in multiple tissues, also termed "inflammaging", which represents a significant risk factor for many aging-related chronic diseases. However, the mechanisms and regulatory networks underlying inflammaging across different tissues have not yet been fully elucidated. Here, we profiled the transcriptomes and epigenomes of the kidney and liver from young and aged mice and found that activation of the inflammatory response is a conserved signature in both tissues. Moreover, we revealed links between transcriptome changes and chromatin dynamics through integrative analysis and identified AP-1 and ETS family transcription factors (TFs) as potential regulators of inflammaging. Further in situ validation showed that c-JUN (a member of the AP-1 family) was mainly activated in aged renal and hepatic cells, while increased SPI1 (a member of the ETS family) was mostly induced by elevated infiltration of macrophages, indicating that these TFs have different mechanisms in inflammaging. Functional data demonstrated that genetic knockdown of Fos, a major member of the AP-1 family, significantly attenuated the inflammatory response in aged kidneys and livers. Taken together, our results revealed conserved signatures and regulatory TFs of inflammaging in the kidney and liver, providing novel targets for the development of anti-aging interventions.


Selective degeneration of chemosensitive primary sensory neurones induced by capsaicin: glial changes.
Capsaicin treatment of newborn rats results in the degeneration of primary sensory neurones involved in the mediation of chemogenic pain. In the present study glial changes following the pharmacologically-induced degeneration of unmyelinated primary afferent fibres terminating in Rexed's laminae I and II of the spinal cord were investigated. Light microscopy revealed an increase in the number of phagocytic glial cells in this area, reaching a maximum at 24 h after the administration of capsaicin; they had almost completely disappeared by 72 h. At the ultrastructural level these cells were characterized by their elongate or irregular nuclei with a pronounced heterochromatin pattern, a moderately dense cytoplasmic matrix, hour-glass shaped mitochondria and very large numbers of heterogeneous dense bodies and lipid droplets. On the basis of these observations, these cells were considered to represent reactive microglial cells engaged in the phagocytosis of degenerated neuronal debris. The possible origin and mode of elimination of these elements from the central nervous tissue is briefly discussed.


A case of cystic meningioma mimicking an astrocytoma.
In a 25-year-old woman, suddenly complaining of irritation and soon after of paretic symptoms in the right upper limb, a CT scan showed a large cystic mass in the left parietal lobe. As cerebral angiography was not helpful, a cystic astrocytoma was suspected. After total surgical removal of the cyst, the histological examination revealed, to our surprise, a syncytial meningioma. The rate cases of similar cystic meningioma reported in the literature are reviewed and the usefulness of biopsy on every suspected cerebral neoplasm is stressed.


Granulocyte-colony-stimulating factor induces increased serum levels of soluble interleukin 2 receptors preceding engraftment in autologous bone marrow transplantation.
The serum levels of soluble interleukin 2 receptors (sIL-2R) were determined in 19 patients who received high-dose chemotherapy and an autologous or syngeneic bone marrow transplant (BMT) for treatment of Hodgkin's disease (n = 18) or non-Hodgkin's lymphoma (n = 1). Twelve patients received granulocyte colony-stimulating factor (G-CSF) from day 0 or day +1 after autologous BMT until the white blood cell count had been stable for 9 d above 1 x 10(9)/l, the remaining seven patients did not receive growth factors. In all G-CSF-treated patients the sIL-2R levels increased steadily in the early post-transplant course, even in the absence of infection. This increase was statistically significant 2-4 d prior to the appearance of leucocytes in the peripheral blood (median 340 pM versus median 256 pM immediately after BMT, P < 0.025) and peaked with the appearance of first peripheral blood leucocytes (median 536 pM, P < 0.001). Cessation of G-CSF administration resulted in a decline of sIL-2R levels. In contrast, five of seven patients without G-CSF treatment did not exhibit an sIL-2R increase before or at the time of engraftment. Infection was associated with a rise of sIL-2R levels. A correlation between sIL-2R levels and total leucocyte count, lymphocyte count, or CD25+ lymphocyte count was not evident. These data suggest that after autologous BMT G-CSF induces increased sIL-2R levels, which occur independent of lymphocyte activation. This may be compatible with involvement of immature bone marrow cells in G-CSF-induced sIL-2R release.


Reconstruction of the hard palate using free iliac bone covered with a jejunal flap.
In this paper we report the reconstruction of a large defect of the hard palate by covering free iliac bone with a jejunal flap. The new palate is moist and tough but not bulky. This new method brings with it the useful concept that the jejunum might nourish the free bone through its serosa.


Improved Glottic Exposure for Robotic Microlaryngeal Surgery: A Case Series.
Robotic surgery has become the standard of care for many procedures outside of otolaryngology and now is gaining momentum within our specialty. The da Vinci (Intuitive Surgical, Sunnyvale, CA) robot has several advantages to human hands, including removal of tremor and better access to lesions because of increased degree of movement of the articulated instruments. The glottis has rarely been addressed using robotic surgery because access was previously thought to be difficult because of the limitations of currently used retractors, which include poor base of tongue and oral commissure retraction resulting in lack of exposure of the glottis in many patients and lack of space for the robotic instruments to occupy. We present a case series using the Modular Oral Retractor (MOR) system to show that the glottic larynx can be accessed by the da Vinci instrumentation. The MOR system provides better exposure of the anterior commissure and by using oral commissure retraction provides excellent space for the robotic arms to work. The MOR system potentially makes robotic microlaryngeal surgery more feasible for the otolaryngology-head and neck surgeon.


Effect of immunosuppression on damage, leukocyte infiltration, and regeneration after severe warm ischemia/reperfusion renal injury.
Post-ischemia/reperfusion (I/R) damage, accompanied by leukocyte infiltration, is unavoidable in renal transplantation, as is the need for immunosuppressive treatment. Influence of immunosuppressive treatment on post-I/R renal damage, nonalloimmune cellular infiltration, and regeneration is not well studied. Uninephrectomized inbred LEW rats were submitted to warm renal ischemia of 45 minutes/60 minutes, and received different immunosuppressive regimens: cyclosporine (CsA) 10 mg/kg/day subcutaneously in the neck daily, or mycophenolate mofetil (MMF) 20 mg/kg/day by daily oral gavage. Control animals underwent sham operation (unilateral nephrectomy) with immunosuppressive treatment or ischemia with vehicle administration. In addition the effect of MMF/mycophenolic acid (MPA) on renal tubule cell proliferation in culture was studied with bromodeoxyuridine incorporation. The post-I/R interstitial cellular infiltration/proliferation consisted mainly of mononuclear leukocytes [first monocytes/macrophages (Mo/MPhi) followed by CD4+ cells]. This mononuclear cell infiltration became apparent 24 hours after injury at the time of acute tubular necrosis, and was most prominent during the phase of regeneration. Severe I/R combined with CsA aggravated morphologic damage and dysfunction, without effect on tubular cell proliferation and tubular regeneration. Early leukocyte infiltration was qualitatively and quantitatively comparable to control animals, yet decreased moderately later in time. In contrast, MMF in combination with severe I/R did not influence initial morphologic damage and dysfunction. Although the initial leukocyte infiltration was comparable to control animals, the subsequent mononuclear cell accumulation, especially CD4 T cells decreased dramatically during MMF treatment. This was concomitant with a decrease of tubular cell proliferation and hence tubular regeneration. Increasing MPA concentrations in renal tubular cell culture caused a significant decrease in total cell number, and an almost arrest of bromodeoxyuridine incorporation, as measurement of cell proliferation. Immunosuppressive treatment with CsA or MMF affected significantly and in a different manner post-I/R renal morphologic damage, interstitial leukocyte, accumulation and regeneration.


Partial purification and characterization of an extracellular proteinase from Aeromonas hydrophila strain A4.
An extracellular metalloproteinase from Aeromonas hydrophila strain A4, isolated from milk, was purified by a factor of 300 by chromatography on DEAE-cellulose and Sephadex G-150. The enzyme had a mol. wt of 43,000 and contained 2 g atom Ca/mol. It was active over a pH range 4.8-9.5 and had optimum activity on casein at pH 7.0 with Km = 0.17 mM. It was strongly inactivated by metal chelators and the apoenzyme was fully reactivated with Ca2+, Mn2+ or Co2+. Heavy metal ions such as Ag+, Hg2+, Fe2+, Zn2+, Cd2+, Ni2+ and Cu2+ totally or partly inactivated the enzymic activity at 5 mM concentration. The enzyme was not inactivated by diisopropylfluorophosphate, soyabean trypsin inhibitor or sulphydryl group reagents. It was optimally active at 45 degrees C; above 50 degrees C activity declined rapidly, but significant activity persisted at 4 degrees C. It was heat labile in phosphate or Tris-maleate buffer but exogenous Ca2+ afforded protection.


A novel yellow pigment, furpipate, derived from lysine and furfural.
Furfural is an important intermediate compound of the Maillard reaction of pentose or ascorbic acid. We examined the browning of furfural and lysine by heating these compounds in solution and found two yellow compounds. The first, furpipate, is a novel pipecolic acid derivative and was (Z)-3-(2-furylmethylidene)-3H, 4H, 5H, 6H-pyridine-2-carboxylic acid. The second was decarboxylated-furpipate. Furpipate shows absorption maxima at 370 nm and 310 nm under acidic and alkaline conditions, respectively. This compound was the major colored compound of the heated solution containing lysine and furfural.


Light microscopic observations on cat Renshaw cells after intracellular staining with horseradish peroxidase. II. The cell bodies and dendrites.
The cell bodies and dendritic trees of five lumbosacral Renshaw cells of adult cats were studied in the light microscope (LM) after intracellular injection with horseradish peroxidase (HRP). The cell bodies were all located in the ventral part of lamina VII. The dendrites extended up to 0.7 mm from the cell body into the neighbouring parts of laminae VIII and IX as well as into more dorsal parts of lamina VII. The dendritic branching was sparse and about half the dendrites were unbranched. The mean diameter of the cell body was positively correlated to both the combined and mean diameters of the first-order dendrites. Between four and eight dendrites originated from the cell bodies. The number of dendritic end-branches, the combined dendritic length, the mean dendritic length from the cell body to the termination of the end branches, the distance from the cell body to the termination of the most remote end-branch, the dendritic surface area, and the dendritic volume all correlated positively with the diameter of the parent first-order dendrite. The dendritic tapering was somewhat more pronounced in the Renshaw cells than previously observed in alpha- and gamma-motoneurons. The present data are discussed in relation to previous morphological observations on Renshaw cells and alpha- and gamma-motoneurons.


Generalized eruptive histiocytoma in children.
Generalized eruptive histiocytoma is a papular, non-X, nonlipidic, self-healing histiocytosis affecting mainly adults. This article describes the clinical, histologic, ultrastructural, and immunologic findings in four children, aged 10 months to 4 years, who were suffering from this disease. Generalized eruptive histiocytoma of children differs from generalized eruptive histiocytoma of adults only in that the lesions are not symmetrically distributed, they do not affect the mucous membranes, and they may become xanthomatous.


Increased density of M1 receptors in the hippocampus of juvenile rats chronically deprived of NGF.
Binding studies were used to assess the changes in affinity and/or number of M1 muscarinic receptors in hippocampi from juvenile rats chronically deprived of NGF. NGF deprivation was obtained by implanting into right ventricle at postnatal day 2 (P2) hybrydoma cells secreting high levels of monoclonal antibodies against NGF (alphaD11). Parenteral myeloma cells (P3U) were used as controls. Competition experiments were used to characterise the [3H]-PNZ binding sites in membrane preparations of hippocampi from rats sacrificed at P15. [3H]-PNZ bound M1 receptors both in P3U and alphaD11 group as shown by displacing potency order of antagonists: TLZ=4-DAMP>PNZ>p-F-HHSiD>MTC. The deprivation of NGF for two weeks significantly increased the number of M1 receptors without changing the Ki values of antagonists with exception of methoctramine which showed an increase in affinity in alphaD11 group. Similar changes in binding parameters were already observed after the first week of anti-NGF treatment. In contrast, a treatment for a week with implant at postnatal day 15 failed to produce any changes in M1 binding parameters. These results provide further physiological evidence for developmentally regulated modulatory role of NGF in the cholinergic function in the hippocampus.


Transposable elements maintain genome-wide heterozygosity in inbred populations.
Elevated levels of inbreeding increase the risk of inbreeding depression and extinction, yet many inbred species are widespread, suggesting that inbreeding has little impact on evolutionary potential. Here, we explore the potential for transposable elements (TEs) to maintain genetic variation in functional genomic regions under extreme inbreeding. Capitalizing on the mixed mating system of Arabidopsis lyrata, we assess genome-wide heterozygosity and signatures of selection at single nucleotide polymorphisms near transposable elements across an inbreeding gradient. Under intense inbreeding, we find systematically elevated heterozygosity downstream of several TE superfamilies, associated with signatures of balancing selection. In addition, we demonstrate increased heterozygosity in stress-responsive genes that consistently occur downstream of TEs. We finally reveal that TE superfamilies are associated with specific signatures of selection that are reproducible across independent evolutionary lineages of A. lyrata. Together, our study provides an important hypothesis for the success of self-fertilizing species.


Fusarium species associated with banana fruit rot and their potential toxigenicity.
Banana fruits exhibiting signs of decay were collected from markets in the United States and Italy. Fungi isolated from the lesions on the banana fruits wereFusarium moniliforme, F subglutinans, andF. semitectum var.majus. When the fungal strains were cultivated on maize kernels, the cultures did not produce zearalenone (ZON), zearalenols (á-, â-ZOH), and trichothecenes [deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-AcDON), T-2 toxin (T-2), diacetoxyscirpenol (DAS)]. Fumonisins and fusarin C (FUS-C) were not detected naturally nor in bananas purchased in the U.S. and artificially infected withFusarium. Moniliformin (M) (up to 267 mg/kg) was detected in maize kernel cultures ofF. subglutinans from bananas. No mycotoxins were detected in naturally infected fruits. Although no mycotoxins were detected in the extracts from corn cultures ofF. semitectum var.majus, the extracts were toxic to brine shrimp and mice.


Formation of intracellular canaliculi in reaggregated striated duct cells of rat submandibular gland during short-term stationary culture.
Reaggregated striated duct cells of rat submandibular gland formed deep tubular invaginations of the cell membrane, i.e. intracellular canaliculi, which are not present in the original tissue, after 24 h of the stationary culture.


Hesperinusninae Papp & Krivosheina (Diptera: Hesperinidae) from Georgia: the second record of this peculiar species.
A second record of Hesperinusninae Papp & Krivosheina, 2010 is given on the basis of material collected by sweep net from the northern slope of the Saguramo range north of Tbilisi, Georgia. The habitus and male terminalia are illustrated and the systematics briefly discussed.


Admission Norton scale scores (ANSS) are associated with post-operative complications following spine fracture surgery in the elderly.
We sought to determine if low ANSS, usually associated with high pressure ulcer risk, are also associated with post-operative complications following spine fracture surgery in the elderly. This was a retrospective cross-sectional study conducted at the division of orthopedic surgery in a tertiary medical center between January 2008 and October 2010. The medical charts of consecutive elderly (≥ 65 years) patients admitted for spine fracture surgery were studied for the following measurements: ANSS, demographic data, co-morbidities, and post-operative complications. Except for pressure ulcers, post-operative complications included: acute coronary syndrome, acute renal failure, confusion, pneumonia, urinary tract infection, venous thromboembolism, and wound infection. The final cohort included 90 patients: 66 (73.3%) females and 24 (26.7%) males. Mean age for the entire cohort was 78.9 ± 0.7 years. Most patients had lumbar fractures (n=49; 54.4%) or thoracal fractures (n=26; 28.9%). Most patients underwent kyphoplasty (n=65; 72.2%). Mean ANSS was 15.9 ± 0.3, and 29 (32.2%) patients had low (<15) ANSS. Patients with low ANSS had significantly more post-operative complications relative to patients with high ANSS (1.0 ± 0.2 vs. 0.2 ± 0.1; p<0.0001). Among all post-operative complications, urinary tract infection was independently associated with ANSS (p<0.0001). Binary regression analysis showed that ANSS were independently associated with post-operative complications (p=0.001). We conclude that low ANSS are associated with post-operative complications and urinary tract infection in particular, following spine fracture surgery in the elderly. Hence, the Norton scoring system may be used for predicting and preventing post-operative complications in this population.


ZeMYB9 regulates cyanidin synthesis by activating the expression of flavonoid 3'-hydroxylase gene in Zinnia elegans.
Petal color in Zinnia elegans is characterized mainly by anthocyanin accumulation. The difference in the content of anthocyanins, especially cyanidins, affects petal coloration in Z. elegans, but the underlying regulatory mechanism remains elusive. Here, we report one R2R3-MYB transcription factor from subgroup 6, ZeMYB9, acting as a positive regulator of anthocyanin accumulation in Z. elegans. Up-regulated expression of ZeMYB9 and flavonoid 3'-hydroxylase gene (ZeF3'H) was detected in the cultivar with higher cyanidin content. ZeMYB9 could specifically activate the promoter of ZeF3'H, and over-expression of ZeMYB9 induces much greater anthocyanin accumulation and higher expression level of anthocyanin biosynthetic genes in both petunia and tobacco. And then, ZeMYB9 was demonstrated to interact with ZeGL3, a bHLH transcription factor belonging to IIIf subgroup. Promoter activity of ZeF3'H was significantly promoted by co-expressing ZeMYB9 and ZeGL3 compared with expressing ZeMYB9 alone. Moreover, transient co-expression of ZeMYB9 and ZeGL3 induced anthocyanin accumulation in tobacco leaves. Our results suggest that ZeMYB9 could enhance cyanidin synthesis and regulate petal color in Z. elegans though activating the expression of ZeF3'H, by itself or interacting with ZeGL3.


Author Correction: Increase of isoflavones in the aglycone form in soybeans by targeted crossings of cultivated breeding material.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


The Helicobacter heilmannii hofE and hofF Genes are Essential for Colonization of the Gastric Mucosa and Play a Role in IL-1β-Induced Gastric MUC13 Expression.
Helicobacter heilmannii is a zoonotic bacterium associated with gastric disease in humans. We recently showed that H. heilmannii binds to human gastric mucins and epithelial cells and highlighted a potential role for the murine Muc13 mucin in gastric Helicobacter colonization. The aims of this study were to investigate the role of the H. heilmannii hof gene locus encoding HofH/F/E/G/C/D in adhesion to the gastric mucosa and induction of increased gastric Muc13 expression. Bacterial hof gene and host gene expression experiments, Helicobacter binding assays and experimental infection studies in mice were performed. H. pylori and its ΔhofF mutant were included for comparison. Helicobacter heilmannii strains lacking HofE or HofF showed a clear decrease in binding to gastric mucins and epithelial cells as well as a lower gastric colonization level in the stomach of Balb/c mice at 4 and 9 weeks post-infection compared to the H. heilmannii wildtype strain. Interestingly, H. heilmannii ΔhofE and ΔhofF and H. pylori ΔhofF did not induce an increased expression of MUC13 in human gastric epithelial cells and of Muc13 in the stomach of mice. Finally, we demonstrated that IL-1β is induced in the stomach as a response to Helicobacter colonization which on its turn is involved in the expression of MUC13/Muc13 in the gastric epithelium. These novel results in Helicobacter research identified H. heilmannii HofE and HofF as adhesins and suggest an important role of H. heilmannii HofE and HofF and H. pylori HofF in IL-1β-induced gastric MUC13/Muc13 expression.


Effect of vertebral fractures on function, quality of life and hospitalisation the AGES-Reykjavik study.
understanding the determinants of health burden after a fracture in ageing populations is important. assess the effect of clinical vertebral and other osteoporotic fractures on function and the subsequent risk of hospitalisation. individuals from the prospective population-based cohort study Age, Gene/Environment Susceptibility (AGES)-Reykjavik study were examined between 2002 and 2006 and followed up for 5.4 years. a total of 5,764 individuals, 57.7% women, born 1907-35, mean age 77. four groups with a verified fracture status were used; vertebral fractures, other osteoporotic fractures excluding vertebral, non-osteoporotic fractures and not-fractured were compared and analysed for the effect on mobility, strength, QoL, ADL, co-morbidity and hospitalisation. worst performance on functional tests was in the vertebral fracture group for women (P < 0.0001) and the other osteoporotic fractures group for men (P < 0.05). Both vertebral and other osteoporotic fractures, showed an increased risk of hospitalisation, HR = 1.4 (95% CI: 1.3-1.7) and 1.2 (95% CI: 1.1-1.2) respectively (P < 0.0001). Individuals with vertebral fractures had 50% (P < 0.0001) longer hospitalisation than not-fractured and 33% (P < 0.002) longer than the other osteoporotic fractures group. individuals with a history of clinical vertebral fracture seem to carry the greatest health burden compared with other fracture groups, emphasising the attention which should be given to those individuals.


Human Leukocyte Antigens (HLA) Genes Association in Type 1 Diabetic Nephropathy.
Diabetic nephropathy is a common worldwide multifactorial disease where involvement of genetic factors is well etablished. The aim of this study was to investigate the HLA genes implication in the development of type 1 diabetic nephropathy. We performed a case- control study where one hundred and fifty subjects were examined. Patients were divided in two groups; with and without type 1 diabetic nephropathy. HLA typing was performed using Polymerase Chain Reaction- Sequence Specific Oligonucleotide (PCR- SSO) method. HLA association to clinical phenotype and HLA haplotype analysis was also investigated. HLA B*51 is increased in patients without type 1 diabetic nephropathy (7.14% vs. 0 %, P <0.05, OR= 0), however no other studied alleles seem to have any effect (all P>0.05). Haplotype analysis also does not reveal any significant association, however, A*02-B*18-DRB1*03-DQA1*05- DQB1*03 haplotype shows a tendency to be associated with the development of diabetic nephropathy (P = 0.05). These results suggest a protective effect of HLA B*51 allele from type 1 diabetic nephropathy. However, further studies are required in order to clarify its potential implication as a protective marker.


Single dose of 300 IU hCG in the early luteal phase in superovulated ewes: Effects on corpora lutea, progesterone profile, and embryo recovery.
This study aimed to evaluate the effects of hCG treatment during the early luteal phase on ovarian function, progesterone profile, and embryo yield in superovulated ewes. Superovulated sheep were randomly assigned to receive 300 IU hCG i.m. (GhCG, n = 24) or not (GControl, n = 25) at 96 h after the removal of the progesterone (P4) device (D13). Non-surgical embryo recovery (NSER) was performed eight days after P4 withdrawal. Ultrasound evaluations were performed on D13, D14, D16, and D17. Blood samples were collected on D14, D16, and D17. Superovulation scores were recorded based on the number of corpora lutea (CL) as follows: 1 (≤ 2), 2 (3-5), 3 (6-8), and 4 (≥ 9). NSER efficiency, superovulation response, and luteal tissue area were similar in both groups (P > 0.05). Structural luteolysis tended to be higher in GControl (P = 0.07; 47.0 %) while functional luteolysis was similar in both groups (P > 0.05; 0.0 % and 5.9 %). The recovery rate was greater (P < 0.05) in GhCG (89.8 %) compared with GControl (71.0 %), with similar overall ova/embryo numbers observed for both groups (P > 0.05). GhCG showed a higher concentration of animals with a superovulatory response score of 4 (54.5 %; P < 0.05) compared with the lowest scores. Plasma progesterone on D16 was higher (P < 0.05) in GhCG ewes (11.1 ± 1.5 vs 6.9 ± 1.5 ng/mL). In conclusion, the hCG treatment improved circulating P4 and embryo recovery rate, tended to maintain luteal functionality, and thus constitutes an additional tool for improving embryo yield in superovulated ewes.


Pleomorphic Adenoma of Upper Lip: A Rare Case Presentation.
Pleomorphic adenoma is the most common neoplasm of the salivary glands and is most commonly located in the parotid followed by the submandibular glands. The most common intraoral site includes hard and soft palate. This case report describes a rare and unusual lesion found in a 21 years old female, which was diagnosed as pleomorphic adenoma of the minor salivary glands in the upper lip. The tumor was a circumscribed and firm mass, about 3 cm in diameter, almost protruding below the nose. Complete excision was performed by intraoral route and the histo-pathologic analysis showed pleomorphic adenoma. The tumor did not recur.


An anatomical investigation on the muscles of the pelvic outlet in crab-eating monkey (Macaca irus) and Japanese monkey (Macaca fuscata) with special reference to their nerve supply.
For a fuller understanding of the nerve supply to the muscles of the pelvic outlet in man, 4 pelvic-halves of crab-eating monkeys and 6 pelvic-halves of Japanese monkeys were minutely dissected. 1) The composition of the pudendal plexus tends to be limited to 2 segments, S1 and S2. 2) If we consider the origin of the nerves, the pudendal plexus is divided into 2, the first or medial and the second or lateral parts. From the first part arise the pelvic splanchnic nerves, the nerve to the iliopubocaudalis and the nerve to the ischiocaudalis. From the second part the dorsal nerve of the penis or clitoris, the perineal nerve and the inferior rectal nerve originate. 3) A laminate arrangement exists among the 3 nerves from the first part at their origin; the pelvic splanchnic nerves are situated ventrally, and the nerve to the ischiocaudalis dorsally, with the nerve to the iliopubocaudalis in between. No obvious laminate arrangement exists among the 3 nerves from the second part. 4) The part of the iliopubocaudalis, contiguous with the rectal wall but without attaching to it, has no branches of supply from the perineal nerve and the inferior rectal nerve. 5) A detailed discussion of our findings in relation to man, is given below.


Parasite-derived microRNAs in plasma as novel promising biomarkers for the early detection of hydatid cyst infection and post-surgery follow-up.
Currently, cystic echinococcosis (CE) follow-up is a serious concern among surgeons. MicroRNAs (miRNAs) are small, endogenous, non-coding RNAs which are present in human body fluids in a highly stable form. Recently, it is observed that Echinococcus granulosus expresses a large number of miRNAs in its developmental stages. The current study aimed at evaluating the capacity of parasitic miRNAs to serve as plasma biomarkers for hydatid cysts before and after CE surgery. Hydatidosis patients were identified using radiological and histopathological examinations. Following RNA extraction and cDNA synthesis, the expression levels of parasite-derived miRNAs including egr-miR-71 and egr-let-7 were quantitatively evaluated using real-time polymerase chain reaction (RT-PCR) in 30 hydatid cyst-infected individuals before surgery and an equal number of healthy controls. Then, three- and six-month follow-ups were performed after cystectomy. To analyze parasite-derived miRNAs, the relative fold change between uninfected and infected samples was determined and normalized to hsa-miR-16-5p as the housekeeping internal control. RT-PCR demonstrated that egr-miR-71 and egr-let-7 were specifically amplified in all the plasma samples from the infected individuals with hydatid cyst; yet they were significantly down-regulated at three and six months' post-surgery (P < 0.05). The egr-miR-71 had a higher level of expression in larval stage compared with egr-let-7. The results of the current study indicated that hydatid cyst-derived miRNAs including egr-miR-71 and egr-let-7 can be detected in human plasma. Considering the changes in the expression levels of these miRNAs after three and six months, it seems that these miRNAs, especially egr-miR-71, could serve as novel promising biomarkers for the early diagnosis and monitoring of hydatidosis.


[Descriptions and microscopic identification of Argyreia acuta Lour].
To provide evidences for the identification of Argyreia acuta Lour. By descriptions and microscopic identification. The characters including stomata covered by many glandular hairs in dorsal surface of leaf of Argyreia acuta were obvious. The result provided evidences for the identification of Argyreia acuta Lour.