A cohort cost analysis of lumbar laminectomy--current trends in surgeon and hospital fees distribution.
Spine-related health-care expenditures accounted for $86 billion dollars in 2005, a 65% increase from 1997. However, when adjusting for inflation, surgeons have seen decreased reimbursement rates over the last decade. To assess contribution of surgeon fees to overall procedure cost, we reviewed the charges and reimbursements for a noninstrumented lumbar laminectomy and compared the amounts reimbursed to the hospital and to the surgeon at a major academic institution. Retrospective review of costs associated with lumbar laminectomies. Seventy-seven patients undergoing lumbar laminectomy for spinal stenosis throughout an 18-month period at a single academic medical center were included in this study. Cost and number of laminectomy levels. The reimbursement schedule of six academic spine surgeons was collected over 18 months for performed noninstrumented lumbar laminectomy procedures. Bills and collections by the hospital and surgeon professional fees were comparatively analyzed and substratified by number of laminectomy levels and patient insurance status. Unpaired two-sample Student t test was used for analysis of significant differences. During an 18-month period, patients underwent a lumbar laminectomy involving on average three levels and stayed in the hospital on average 3.5 days. Complications were uncommon (13%). Average professional fee billing for the surgeon was $6,889±$2,882, and collection was $1,848±$1,433 (28% overall, 30% for private insurance, and 23% for Medicare/Medicaid insurance). Average hospital billing for the inpatient hospital stay minus professional fees from the surgeon was $14,766±$7,729, and average collection on such bills was $13,391±$7,256 (92% overall, 91% for private insurance, and 85% for Medicare/Medicaid insurance). Based on this analysis, the proportion of overall costs allocated to professional fees for a noninstrumented lumbar laminectomy is small, whereas those allocated to hospital costs are far greater. These findings suggest that the current focus on decreasing physician reimbursement as the principal cost saving strategy will lead to minimal reimbursement for surgeons without a substantial drop in the overall cost of procedures performed.


Integration of Microbial Transformation Mechanism of Polyphosphate Accumulation and Sulfur Cycle in Subtropical Marine Mangrove Ecosystems with Spartina alterniflora Invasion.
Excessive phosphorus can lead to eutrophication in marine and coastal ecosystems. Sulfur metabolism-associated microorganisms stimulate biological phosphorous removal. However, the integrating co-biotransformation mechanism of phosphorus and sulfur in subtropical marine mangrove ecosystems with Spartina alterniflora invasion is poorly understood. In this study, an ecological model of the coupling biotransformation of sulfur and phosphorus is constructed using metagenomic analysis and quantitative polymerase chain reaction strategies. Phylogenetic analysis profiling, a distinctive microbiome with high frequencies of Gammaproteobacteria and Deltaproteobacteria, appears to be an adaptive characteristic of microbial structures in subtropical mangrove ecosystems. Functional analysis reveals that the levels of sulfate reduction, sulfur oxidation, and poly-phosphate (Poly-P) aggregation decrease with increasing depth. However, at depths of 25-50 cm in the mangrove ecosystems with S. alterniflora invasion, the abundance of sulfate reduction genes, sulfur oxidation genes, and polyphosphate kinase (ppk) significantly increased. A strong positive correlation was found among ppk, sulfate reduction, sulfur oxidation, and sulfur metabolizing microorganisms, and the content of sulfide was significantly and positively correlated with the abundance of ppk. Further microbial identification suggested that Desulfobacterales, Anaerolineales, and Chromatiales potentially drove the coupling biotransformation of phosphorus and sulfur cycling. In particular, Desulfobacterales exhibited dominance in the microbial community structure. Our findings provided insights into the simultaneous co-biotransformation of phosphorus and sulfur bioconversions in subtropical marine mangrove ecosystems with S. alterniflora invasion.


Trends in malaria morbidity following the introduction of artesunate plus amodiaquine combination in M'lomp village dispensary, south-western Senegal.
In Thailand, South Africa and Zanzibar, a decrease in malaria morbidity was observed following the introduction of artemisinin-based combination therapy (ACT). In Senegal, therapeutic trials supervised the in vivo efficacy of artesunate plus amodiaquine from 1999 to 2005 at the M'lomp village dispensary. The trends in malaria morbidity in this village were evaluated from 2000 to 2002. Each year, between July and December inclusive, fevers treated with antimalarials and slide-proven, uncomplicated malaria cases were collected from dispensary health records. Data were also collected in 1998, just prior to ACT introduction. Pearson's chi square tests and Student tests were used to compare two percentages or two means respectively (alpha = 0.05). Between 1998 and 2002, the total number of fevers treated with antimalarials and their repetitiveness progressively decreased: From 2824 to 945 fevers and from 17.6% to 9.7% (RR1998-2002 = 0.55; [0.44-0.69]; p < 0.0001) respectively. Considering uncomplicated malaria cases only, a decrease was observed in their total number between 2001 and 2002, from 953 to 570 cases. The incidence rate and repetitiveness also decreased. The incidence rate fell from 46.1% in 2001 to 37.5% in 2002 (p < 0.0001) and the repetitiveness decreased from 13.0% in 2000 to 6.6% in 2002 (RR2000-2002 = 0.51; [0.35-0.72]; p = 0.0001). The percentage of uncomplicated malaria cases treated with ACT increased, from 18.9% in 2000 to 64.0% in 2002, making it tempting to conclude an impact on malaria morbidity. Nonetheless, the decline in incidence rate of uncomplicated malaria was slight and a lower recorded rainfall was reported in 2002 which could also explain this decline. The context in which ACT is introduced affects the impact on malaria morbidity. In M'lomp, in contrast to studies in Thailand, South Africa and Zanzibar, ACT coverage of malaria cases was low and no vector control measure was deployed. Moreover, the malaria transmission level is higher. In sub-Saharan countries, in order to optimize the impact on malaria morbidity, ACT deployment must be supported, on the one hand, by a strengthening of public health system to ensure a high ACT coverage and, on the other hand, by others measures, such vector control measures.


Dermal permeation data and models for the prioritization and screening-level exposure assessment of organic chemicals.
High-throughput screening (HTS) models are being developed and applied to prioritize chemicals for more comprehensive exposure and risk assessment. Dermal pathways are possible exposure routes to humans for thousands of chemicals found in personal care products and the indoor environment. HTS exposure models rely on skin permeability coefficient (KP; cm/h) models for exposure predictions. An initial database of approximately 1000 entries for empirically-based KP data was compiled from the literature and a subset of 480 data points for 245 organic chemicals derived from testing with human skin only and using only water as a vehicle was selected. The selected dataset includes chemicals with log octanol-water partition coefficients (KOW) ranging from -6.8 to 7.6 (median=1.8; 95% of the data range from -2.5 to 4.6) and molecular weight (MW) ranging from 18 to 765g/mol (median=180); only 3% >500g/mol. Approximately 53% of the chemicals in the database have functional groups which are ionizable in the pH range of 6 to 7.4, with 31% being appreciably ionized. The compiled log KP values ranged from -5.8 to 0.1cm/h (median=-2.6). The selected subset of the KP data was then used to evaluate eight representative KP models that can be readily applied for HTS assessments, i.e., parameterized with KOW and MW. The analysis indicates that a version of the SKINPERM model performs the best against the selected dataset. Comparisons of representative KP models against model input parameter property ranges (sensitivity analysis) and against chemical datasets requiring human health assessment were conducted to identify regions of chemical properties that should be tested to address uncertainty in KP models and HTS exposure assessments.


Social cognition in the we-mode.
According to many philosophers and scientists, human sociality is explained by the unique capacity to share the mental states of others. Shared intentionality has been widely debated in the past two decades in ways that also enlighten the current 'interactive turn' in social cognition. In this article, we examine the function and significance for interacting agents of sharing minds in an irreducibly collective mode called the 'we-mode'. This first-person plural perspective captures the viewpoint of individuals engaged in social interactions and thus expands each individual's potential for social understanding and action. This proposal shows that a non-reductionist, interaction-based approach can be developed that nevertheless resists recent suggestions concerning the constitutive role of interaction for social cognition.


Formation of benzo[a]pyrene-DNA adducts by microsomal enzymes: comparison of maternal and fetal liver, fetal hematopoietic cells and placenta.
The formation of benzo[a]pyrene (BP)-DNA adducts was studied in vitro in the presence of microsomes prepared from the isolated labyrinth zone of the rat placenta, the hematopoietic erythroblast cells of the fetal liver, the fetal liver, as well as the maternal liver. Pregnant rats received beta-naphthoflavone (beta NF; 15 mg/kg, i.p.) on day 17 gestation. One day later, placentae, fetal and maternal livers were obtained and hematopoietic erythroblast cells were separated from hepatocytes in the fetal livers. The respective microsomal fractions were incubated in the presence of calf thymus DNA, NADPH-regenerating system and [3H]BP (300 microCi) at 37 degrees C for 30 min. Following beta NF pretreatment, the levels of covalent binding (pmol/mg DNA/mg microsomal protein) for maternal liver, fetal liver, placenta and erythroblast cells were: 28.4, 2.4, 0.31 and 3.9, respectively, with the hematopoietic erythroblast cells being the most active among fetal tissue preparations. The extent of transplacental induction compared to control was greatest in the hematopoietic cells (18-fold) followed by fetal liver (16-fold) and labyrinth zone (5-fold). Further experiments characterized the BP-DNA adducts formed by induced microsomes. DNA was isolated, purified and digested sequentially with DNase I, snake venom phosphodiesterase type II and alkaline phosphatase type III. The deoxynucleoside-BP adducts were purified on a Sephadex LH-20 column and then separated on HPLC and the adducts were quantitated radiometrically. Seven distinct adducts were separated on HPLC and named A-G in order of elution. Adduct B was prominent in all preparations (22-55% total radioactivity). The adduct profile and retention time for peak B is similar to that reported for the adduct formed by microsomal activation of 9-hydroxy BP. Peak D constituted a major fraction (19%) in maternal liver profiles in comparison with the three fetal tissue preparations (8%). In subsequent experiments, peak D was shown to be derived from reaction of (+/-)7 beta,8 alpha-dihydroxy-9 alpha,10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) with DNA. Peak C was unique to erythroblast cell and labyrinth profiles, while peak G was specific for maternal liver and fetal liver profiles. These results demonstrate that fetal liver and its hematopoietic cells are significant sites of BP bioactivation which may contribute to the fetal toxicity of polyaromatic hydrocarbons.


Progression of rearrangements at T cell receptor beta and gamma gene loci during athymic differentiation of bone marrow cells in vitro.
A previously described in vitro system that supports T cell differentiation from bone marrow (BM) precursors was analyzed for T cell receptor gene rearrangement and expression. Cultured populations from days (d.) 0, 3, 6, and 12-13 were fused with BW5147. Only hybridomas from d.6 and d.12-13 bore BM-derived rearrangements. The rearrangement complexity was higher on d.12 than d.6 in that patterns consistent with D beta 1-J beta 1 and D beta 2-germ-line configurations decreased while V-D-J beta 2 and V gamma 2-J gamma 1 joining became dominant. Northern blots of d.13 BM cultures revealed gamma, alpha, and beta (1.0 and 1.3 kb) transcripts. Parallels between patterns in BM cultures and thymus ontogeny were recognized.


A comparative analysis of growth kinetics, image analysis, and biofuel potential of different algal strains.
Due to the global population growth and economic development, energy demand has increased worldwide. Countries take steps to improve their alternative and renewable energy sources. Algae is one of the alternative energy sources and can be used to produce renewable biofuel. In this study, nondestructive, practical, and rapid image processing techniques were applied to determine the algal growth kinetics and biomass potential of four algal strains, including C. minutum, Chlorella sorokiniana, C. vulgaris, and S. obliquus. Laboratory experiments were conducted to determine different aspects of biomass and chlorophyll production of those algal strains. Suitable non-linear growth models, including Logistic, modified Logistic, Gompertz, and modified Gompertz models, were employed to determine the growth pattern of algae. Moreover, the methane potential of harvested biomass was calculated. The algal strains were incubated for 18 days, and the growth kinetics were determined. After the incubation, the biomass was harvested and assessed for its chemical oxygen demand content and biomethane potential. Among the tested strains, C. sorokiniana was the best in biomass productivity (111.97 ± 0.9 mg L-1d-1). The calculated vegetation indices, namely; colorimetric difference, color index vegetation, vegetative, excess green, excess green minus excess red, combination, and brown index values showed a significant correlation with biomass and chlorophyll content. Among the tested growth models, the modified Gompertz shows the best growth pattern. Further, the estimated theoretical CH4 yield was highest for C. minutum (0.98 mL g-1) compared to other tested strains. The present findings suggest that image analysis can be used as an alternative method to study the growth kinetics and biomass production potential of different algae during cultivation in wastewater.


Drosophila Activin signaling promotes muscle growth through InR/TORC1-dependent and -independent processes.
The Myostatin/Activin branch of the TGF-β superfamily acts as a negative regulator of vertebrate skeletal muscle size, in part, through downregulation of insulin/insulin-like growth factor 1 (IGF-1) signaling. Surprisingly, recent studies in Drosophila indicate that motoneuron-derived Activin signaling acts as a positive regulator of muscle size. Here we demonstrate that Drosophila Activin signaling promotes the growth of muscle cells along all three axes: width, thickness and length. Activin signaling positively regulates the insulin receptor (InR)/TORC1 pathway and the level of Myosin heavy chain (Mhc), an essential sarcomeric protein, via increased Pdk1 and Akt1 expression. Enhancing InR/TORC1 signaling in the muscle of Activin pathway mutants restores Mhc levels close to those of the wild type, but only increases muscle width. In contrast, hyperactivation of the Activin pathway in muscles increases overall larval body and muscle fiber length, even when Mhc levels are lowered by suppression of TORC1. Together, these results indicate that the Drosophila Activin pathway regulates larval muscle geometry and body size via promoting InR/TORC1-dependent Mhc production and the differential assembly of sarcomeric components into either pre-existing or new sarcomeric units depending on the balance of InR/TORC1 and Activin signals.


Long-term Effect of Lifestyle Interventions on the Cardiovascular and All-Cause Mortality of Subjects With Prediabetes and Type 2 Diabetes: A Systematic Review and Meta-analysis.
Lifestyle interventions improve the metabolic control of individuals with hyperglycemia. We aimed to determine the effect of lifestyle interventions on cardiovascular and all-cause mortality in this population. Searches were made through MEDLINE, Cochrane CENTRAL, Embase, and Web of Science (no date/language restriction, until 15 May 2022). We included randomized clinical trials (RCTs) of subjects with prediabetes and type 2 diabetes, comparing intensive lifestyle interventions with usual care, with a minimum of 2 years of active intervention. Data from the 11 RCTs selected were extracted in duplicate. A frequentist and arm-based meta-analysis was performed with random-effects models to estimate relative risk (RR) for mortality, and heterogeneity was assessed through I2 metrics. A generalized linear mixed model (GLMM) was used to confirm the findings. Lifestyle interventions were not superior to usual care in reducing cardiovascular (RR 0.99; 95% CI 0.79-1.23) or all-cause (RR 0.93; 95% CI 0.85-1.03) mortality. Subgroup, sensitivity, and meta-regression analyses showed no influence of type of intervention, mean follow-up, age, glycemic status, geographical location, risk of bias, or weight change. All of these results were confirmed with the GLMM. Most studies had a low risk of bias according to the RoB 2.0 tool and the certainty of evidence was moderate for both outcomes. Most studies had a low risk of bias according to the RoB 2.0 tool, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach resulted in moderate certainty of evidence for both outcomes. Differences in lifestyle programs and in usual care between the studies should be considered in the interpretation of our results. Intensive lifestyle interventions implemented so far did not show superiority to usual care in reducing cardiovascular or all-cause mortality for subjects with prediabetes and type 2 diabetes.


Isolation of Yersinia enterocolitica and Y. frederiksenii from forest soil, Federal Republic of Germany.
This is the first report of Yersinia frederiksenii from soil in Europe and of Yersinia enterocolitica sensu stricto from soil in the Federal Republic of Germany. These organisms were isolated from deciduous forest soil, but were not found in grassland soils.


Erratum to: Mechanistic attributes of S100A7 (psoriasin) in resistance of anoikis resulting tumor progression in squamous cell carcinoma of the oral cavity.
[This corrects the article DOI: 10.1186/s12935-015-0226-9.].


Can tourism development enhance livelihood capitals of rural households? Evidence from Huangshan National Park adjacent communities, China.
Measuring the change of the livelihood capitals of rural households in park-adjacent communities under the background of tourism development is an important predictor to identify the sustainable development status of national parks. This paper constructs measurement indicators of the livelihood capitals of rural household in communities surrounding national parks and takes Huangshan National Park, located in eastern China, as an example to calculate characteristics of spatiotemporal changes in the livelihood capitals of rural households, analyze the effect of tourism development on livelihood capitals in adjacent communities in 2006 and 2015. The findings indicate that the annual growth of the total livelihood capital has comparatively strong rigidity. However, there are some differences in temporal changes between different types of livelihood capitals. The distribution of zones of medium and high livelihood capital is mainly distributed in the communities adjacent to the national park research, education and recreation area (RERA). In addition, the total livelihood capital takes the RERA as the centre and decays over distance, which demonstrates that tourism development is an effective way to enhance the livelihood capitals. On the other hand, there is a spatial attenuation effect of tourism development on the enhancement of the livelihood capitals.


Lowering extracellular pH evokes inositol polyphosphate formation and calcium mobilization.
Changing extracellular pH (pHo) from 7.4 to 6.1 increased [3H]inositol bis- and trisphosphates approximately 10- and 5-fold, respectively, in 15 s in human fibroblasts. [3H]Inositol phosphate increased less rapidly than the polyphosphates. Bradykinin similarly increased [3H]inositol phosphates. Shifting pHo from 7.4 to 6.0 evoked a large spike in cytosolic free Ca2+ [( Ca2+]i) which was primarily caused by the release of stored Ca2+. Changing pHo from 7.4 to 6.0 decreased cytoplasmic pH to approximately 7.0. Moderate decreases in intracellular pH had no effect on [Ca2+]i or 45Ca2+ efflux. Decreasing pHo strikingly increased 45Ca2+ efflux and decreased total cell Ca2+ similarly to bradykinin. Changing pHo from 7.4 to approximately 6.4 produced half-maximal effects on [Ca2+]i, 45Ca2+ efflux, and total Ca2+. Cycling pHo between 7.4 and 6.0 produced repetitive decreases and increases in total Ca2+. Bradykinin released the Ca2+ which was reaccumulated after an acid pulse indicating that Ca2+ had returned to the hormone-sensitive pool. Decreasing pHo also released stored Ca2+ from coronary endothelial, neuroblastoma, and umbilical artery muscle cells, but not from rat aortic smooth muscle or human epidermoid carcinoma (A431) cells. We suggest that lowering pHo stimulates a phosphoinositidase-coupled receptor by protonating a functional group with a pKa near 6.5.


Urine drug testing in the context of opioid analgesic prescribing for chronic pain: a content analysis of U.S. state laws in 2022.
In response to the opioid crisis, U.S. states have passed laws requiring urine drug testing (UDT) when opioid analgesics are prescribed for chronic pain. We sought to identify state law UDT requirements. We searched NexisUni legal database using terms related to UDT, chronic pain, and opioids. We included laws effective during spring 2022 that required UDT when opioids were prescribed for chronic pain. We performed deductive content analysis, coding laws for mandated UDT frequency, type of clinician and type of payer to whom the law applied, and circumstances under which UDT was mandated. We found 32 laws across 13 states that met our inclusion criteria. UDT requirements varied substantially by state, including with regard to the type of clinician to whom the law applied, the mandated frequency of UDT (eg, at initiation/assessment, at least annually, more than once per year), and the circumstances in which UDT was mandated (eg, patient had substance use disorder; dosage/day threshold). Relatively few states have UDT mandates associated with prescribing opioids as chronic pain treatment. When developing policy indicators for empirical studies, researchers evaluating how UDT policy affects health outcomes must consider the complexity and lack of uniformity of UDT requirements. In addition, even if states mandate UDT, it is unclear whether clinicians understand the best way to use the test results.


Closure of trocar wounds in laparoscopic operations. The threading technique.
A method of fascial closure utilizing a hypodermic needle as a conduit for threading the suture through the fascia is described. This technique is designed to make use of vertical space rather than horizontal space, which is lacking in the small trocar wounds. The technique is easy to master and teach and has resulted in secure closures in over 150 wounds.


Bioprosthetic valve thrombosis and degeneration following transcatheter aortic valve implantation (TAVI).
Bioprosthetic valve thrombosis (BPVT) is a recognised complication of prosthetic aortic valves and can be found in up to 13% of patients after transcatheter implantation. The mechanism of BPVT is not well known, abnormal flow conditions in the new and native sinuses and lack of functional endothelialisation are suspected causes. BPVT may result in valve dysfunction, possibly related to degeneration, and recurrence of patient symptoms, or remain subclinical. BPVT is best diagnosed at multiphase gated computed tomography (CT) angiography as the presence of reduced leaflet motion (RELM) and hypoattenuating aortic leaflet thickening (HALT). Although CT is used to exclude BPVT in symptomatic patients and those with increased valve gradients, the value of screening and prophylactic anticoagulation is debatable.


State-dependency in brain stimulation studies of perception and cognition.
We address the importance of understanding initial states of neuronal populations and of state-dependent responses in cognitive neuroscience experiments with special emphasis on brain stimulation studies of perception and cognition. The approach we present is based on evidence that behavioural and perceptual effects of transcranial magnetic stimulation (TMS) are determined by initial neural activation state; by systematically manipulating neural activation states before application of TMS, one can selectively target specific, even spatially overlapping neural populations within the affected region. This approach is potentially of great benefit to cognitive neuroscience and remediation programmes as it combines high spatial and functional resolution with the ability to assess causality.


A kidney transplant recipient with renal cell carcinoma derived from a native kidney.
A case of renal cell adenocarcinoma which originated from a left native kidney following kidney transplantation, with widespread metastases, including multiple bone and liver metastases, is presented herein. An extensive clinical investigation, including bone marrow biopsy, liver biopsy, abdominal computerized tomography, excretory urography and examination of the gastrointestinal tract failed to determine the site of the primary lesion in this patient. Examination at autopsy revealed a small adenocarcinoma of the left native kidney with lobulated nodular capsular invasion and metastases to the bone and liver.


Bowel bypass arthritis dermatitis syndrome: a histological and electron microscopical study.
A case of dermal vasculitis with arthralgia after intestinal bypass surgery is reported. A 36-year-old woman developed arthralgia and skin rash, 1 year after an ileo-jejunal bypass operation was performed for overweight (130 kg). Skin biopsy showed leucocytoclastic vasculitis in the dermis. E.M. study showed clumps of platelets around small dermis blood vessels, and polymorphous perivascular infiltration. The symptoms subsided after tetracycline treatment.


Recent developments in (15)N NMR relaxation studies that probe protein backbone dynamics.
Nuclear Magnetic Resonance (NMR) relaxation is a powerful technique that provides information about internal dynamics associated with configurational energetics in proteins, as well as site-specific information involved in conformational equilibria. In particular, (15)N relaxation is a useful probe to characterize overall and internal backbone dynamics of proteins because the relaxation mainly reflects reorientational motion of the N-H bond vector. Over the past 20 years, experiments and protocols for analysis of (15)N R (1), R 2, and the heteronuclear (15)N-{(1)H} NOE data have been well established. The development of these methods has kept pace with the increase in the available static-magnetic field strength, providing dynamic parameters optimized from data fitting at multiple field strengths. Using these methodological advances, correlation times for global tumbling and order parameters and correlation times for internal motions of many proteins have been determined. More recently, transverse relaxation dispersion experiments have extended the range of NMR relaxation studies to the milli- to microsecond time scale, and have provided quantitative information about functional conformational exchange in proteins. Here, we present an overview of recent advances in (15)N relaxation experiments to characterize protein backbone dynamics.


Celebrating 100 years of Drosophila research.
The seventeenth EMBO Conference on the Molecular and Developmental Biology of Drosophila took place in Kolymbari, Crete, between 20 and 26 June 2010. The conference covered a broad range of topics and much progress was made by combining two or more fields of study. Such combinations included quantitative approaches to cell and developmental biology, dissecting interrelations of physiology and development and integrated genomic analysis.


Diagnostic impact of monitoring transcranial motor-evoked potentials to prevent ischemic complications during endovascular treatment for intracranial aneurysms.
The present study aimed to determine the incidence of intraprocedural motor-evoked potential (MEP) changes and to correlate them with intraprocedural ischemic complications and postprocedural neurological deficits in patients after endovascular intracranial aneurysm treatment. This study analyzed data from 164 consecutive patients who underwent endovascular coil embolization to treat intracranial aneurysms under transcranial MEP monitoring. We analyzed associations between significant changes in MEP defined as > 50% decrease in amplitude, and intraprocedural complications as well as postoperative neurological deficits. Factors associated with postprocedural neurological deficits were also assessed. The treated aneurysms were predominantly located in the anterior circulation (71%). Fourteen (9%) were located at perforators or branches that supplied the pyramidal tract. Intraprocedural complications developed in eight (5%) patients, and four of eight (50%) patients occurred postprocedural neurological deficits. Significant intraprocedural MEP changes occurred during seven of eight endovascular procedures associated with intraprocedural complications and salvage procedures were performed immediately. Among these changes, four transient MEP changes, recovered within 10 min, were not associated with postprocedural neurological deficits, whereas three permanent MEP changes were associated with postprocedural neurological deficits and mRS ≥ 1 at discharge. Aneurysms located at perforators/branches supplying the pyramidal tract, and permanent intraprocedural MEP changes were associated with postprocedural neurological deficits. We conclude that intraprocedural transcranial MEP monitoring can reliably identify ischemic changes and can initiate prompt salvage procedures during endovascular aneurysm treatment.


1-Methyl-4-phenylpyridine (MPP+) is toxic to mesencephalic dopamine neurons in culture.
1-Methyl-4-phenylpyridine (MPP+) is the product of oxidative metabolism by monoamine oxidase of the Parkinson-inducing agent 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). MPP+ was tested for neurotoxicity on the dopaminergic neurons of embryonic rat midbrain in culture. Compared with MPTP, MPP+ was a more potent neurotoxin for the cultured dopamine (DA) neurons as determined by decrease in [3H]DA uptake by the cultures and decrease in endogenous levels of DA and homovanillic acid. Catecholamine histofluorescence demonstrated the loss of fluorescing fibers after exposure to MPP+. The reduced analogue of MPTP, namely 1-methyl-4-phenylpiperidine, had no significant neurotoxic action on the dopaminergic neurons in culture.


Cytokines in brain ischemia--the role of TNF alpha.
1. The role of cytokines and other inflammatory mediators in the progression of ischemic brain injury is a new and exciting era of research. Evidence in support for a role for TNF alpha in this respect is emerging as evidence on de novo upregulation of TNF alpha following ischemia is now well established. 2. TNF alpha administered directly to the brain parenchyma elicits local microvascular injury in the form of pericapillary edema and leukocyte adhesion to cerebral capillaries. 3. TNF alpha administered into the cerebroventricular space prior to ischemia augment the extent of tissue damage and neurological deficits. 4. Specific and potent inhibitors of TNF alpha synthesis or TNF alpha receptors must be developed and tried to prove firmly a role for TNF alpha in ischemic brain injury.


Weak measurement of the Goos-Hänchen shift.
It is well known from quantum mechanics that weak measurements offer a means of amplifying and detecting very small phenomena. We present here the experimental observation of the Goos-Hänchen shift via a weak measurement approach.


Lateralisation of intranasal trigeminal chemosensory event-related potentials.
To determine whether or not chemosensory event-related brain potentials (CSERP) elicited by nociceptive unilateral intranasal (CO2) trigeminal stimulation are lateralized and, if they are, whether this hemispheric lateralization is related to the side of the stimulated nostril. Nine healthy right-handed subjects participated to the study. CSERPs were recorded after left or right monorhinal CO2 stimulation. Latency and baseline-to-peak amplitude of each CSERP component were compared across stimulation conditions (left and right nostril), scalp locations (lower-frontal, frontal, mid-temporal, central, posterior-temporal, parietal) and hemispheres (left or right), using a three-factor analysis of variance (ANOVA) for repeated measures. Intranasal trigeminal CO2 stimulation elicited a large N400-P550 complex. This complex was preceded by an earlier N300 component. Whatever the stimulated nostril, N300, N400 and P550 amplitudes were significantly higher on the right as compared to the left hemisphere, at lower-frontal recording sites. The side of chemosensory stimulation (left or right nostril) did not significantly affect CSERP components. This study showed that in healthy right-handed volunteers with normal olfactory ability, intranasal chemosensory trigeminal stimulation may elicit a series of event-related brain potentials, which all display a significant right-hemisphere predominance, irrespective of the stimulated nostril. The observed lateralization was maximal at lower-frontal recording sites.


Construction and in vitro characterization of a chimeric simian and human immunodeficiency virus with the RANTES gene.
Chimeric simian-human immunodeficiency virus (SHIV) containing the env gene of HIV-1 infects macaque monkeys and provides basic information that is useful for the development of HIV-1 vaccines. Regulated-on-activation-normal-T-cell-expressed-and-secreted (RANTES), a CC-chemokine, enhances antigen-specific T helper type-1 responses against HIV-1. With the final goal of testing the adjuvant effects of RANTES in SHIV-macaque models, we constructed a SHIV having the RANTES gene (SHIV-RANTES) and characterized its properties in vitro. SHIV-RANTES replicated both in human and monkey T cell lines. Along with SHIV-RANTES replication, RANTES was detected in the supernatant of human and monkey cell cultures, at maximal levels of 98.5 and 4.1 ng/ml, respectively. A flow cytometric analysis showed that the expressed RANTES down-modulated CC-chemokine receptor 5 (CCR5) on PM1 cells, which was restored by adding anti-RANTES antibody. UV-irradiated culture supernatants from the SHIV-RANTES-infected cells suppressed replication of CCR5-tropic HIV-1 BaL in PM-1 cells. Differentiating real-time RT-PCR showed that pre-infection of SHIV-RANTES in C8166 cells expressing CCR5 suppressed the replication of HIV-1 BaL. Biological activity of the expressed RANTES and the inserted RANTES gene in SHIV-RANTES remained stable after 10 passages. These results suggest that SHIV-RANTES is worth testing in macaque models.


Cotton CENTRORADIALIS/TERMINAL FLOWER 1/SELF-PRUNING genes functionally diverged to differentially impact plant architecture.
Genes of the CENTRORADIALIS/TERMINAL FLOWER 1/SELF-PRUNING (CETS) family influence meristem identity by controlling the balance between indeterminate and determinate growth, thereby profoundly impacting plant architecture. Artificial selection during cotton (Gossypium hirsutum) domestication converted photoperiodic trees to the day-neutral shrubs widely cultivated today. To understand the regulation of cotton architecture and exploit these principles to enhance crop productivity, we characterized the CETS gene family from tetraploid cotton. We demonstrate that genes of the TERMINAL FLOWER 1 (TFL1)-like clade show different roles in regulating growth patterns. Cotton has five TFL1-like genes: SELF-PRUNING (GhSP) is a single gene whereas there are two TFL1-like and BROTHER OF FT (BFT)-like genes, and these duplications are specific to the cotton lineage. All genes of the cotton TFL1-like clade delay flowering when ectopically expressed in transgenic Arabidopsis, with the strongest phenotypes failing to produce functional flowers. GhSP, GhTFL1-L2, and GhBFT-L2 rescue the early flowering Attfl1-14 mutant phenotype, and the encoded polypeptides interact with a cotton FD protein. Heterologous promoter::GUS fusions illustrate differences in the regulation of these genes, suggesting that genes of the GhTFL1-like clade may not act redundantly. Characterizations of the GhCETS family provide strategies for nuanced control of plant growth.


Middle cerebral artery intraplaque hemorrhage: prevalence and clinical relevance.
Little is known about the composition of middle cerebral artery (MCA) plaques and how they relate to clinical status. Using high-resolution magnetic resonance imaging (HR-MRI), we aimed to examine the occurrence of high signal on T1-weighted fat-suppressed images (HST1) of MCA plaques, which are highly suggestive of fresh or recent intraplaque hemorrhage. We retrospectively analyzed the HR-MRI and clinical data of 107 adult patients with high-grade (>70%) MCA stenosis. On HR-MRI, HST1 within an MCA plaque was defined as an area with an intensity >150% of the signal of adjacent muscles. The relationship between HST1 and clinical presentations was analyzed. A total of 109 stenotic MCAs (46 symptomatic and 63 asymptomatic) on 981 image slices were analyzed. HST1 was revealed on HR-MRI in 11 vessels (10.1%, 9 symptomatic and 2 asymptomatic). The occurrence rate of HST1 between symptomatic and asymptomatic MCAs was significantly different (19.6% vs 3.2%, p = 0.01). HST1 within MCA plaque on HR-MRI is associated with ipsilateral stroke. Our results provide new insight into the vascular biology of MCA atherosclerosis.


Heme-regulated inhibitor: an overlooked eIF2α kinase in cancer investigations.
Heme-regulated inhibitor (HRI) kinase is a serine-threonine kinase, controlling the initiation of protein synthesis via phosphorylating α subunit of eIF2 on serine 51 residue, mainly in response to heme deprivation in erythroid cells. However, recent studies showed that HRI is also activated by several diverse signals, causing dysregulations in intracellular homeostatic mechanisms in non-erythroid cells. For instance, it was reported that the decrease in protein synthesis upon the 26S proteasomal inhibition by MG132 or bortezomib is mediated by increased eIF2α phosphorylation in an HRI-dependent manner in mouse embryonic fibroblast cells. The increase in eIF2α phosphorylation level through the activation of HRI upon 26S proteasomal inhibition is believed to protect cells against the buildup of misfolded and ubiquitinated proteins, having the potential to trigger the apoptotic response. In contrast, prolonged and sustained HRI-mediated eIF2α phosphorylation can induce cell death, which may involve ATF4 and CHOP expression. Altogether, these studies suggest that HRI-mediated eIF2α phosphorylation may be cytoprotective or cytotoxic depending on the cells, type, and duration of pharmacological agents used. It is thus hypothesized that both HRI activators, inducing eIF2α phosphorylation or HRI inhibitors causing disturbances in eIF2α phosphorylation, may be effective as novel strategies in cancer treatment if the balance in eIF2α phosphorylation is shifted in favor of autophagic or apoptotic response in cancer cells. It is here aimed to review the role of HRI in various biological mechanisms as well as the therapeutic potentials of recently developed HRI activators and inhibitors, targeting eIF2α phosphorylation in cancer cells.


Chemical deglycosylation can induce methylation, succinimide formation, and isomerization.
Interpretation of deglycosylation studies relies heavily on the absence of modifications to the polypeptide chain. We have found that by using a common chemical deglycosylation technique, one can effect at least three changes in a peptide's structure: methylation, isomerization, and ring formation. It was determined that the conditions of chemical deglycosylation introduce a +14 Da shift in the masses of our model peptides, RKDVY, RKEVY, and horseradish peroxidase. This shift is localized to acidic functional groups and is interpreted as methylation of the free carboxylates in our models. An additional shift in mass of -18 Da is found in the model peptide RKDVY consistent with the loss of water associated with succinimide ring formation in this peptide. Chemical treatment induced isomerization of aspartyl residues to isoaspartyl residues in another model peptide, tetragastrin. These results indicate that one should use caution when interpreting the results of chemical deglycosylation experiments.


Simultaneous continuous recording of accommodation and pupil size using the modified Shin-Nippon SRW-5000 autorefractor.
The internal optics of the recent models of the Shin-Nippon SRW-5000 autorefractor (also marketed as the Grand Seiko WV-500) have been modified by the manufacturer so that the infrared measurement ring has been replaced by pairs of horizontal and vertical infrared bars, on either side of fixation. The binocular, open field-of-view, allowing the accommodative state to be objectively monitored while a natural environment is viewed, has made the SRW-5000 a valuable tool in further understanding the nature of the oculomotor response. It is shown that the root-mean-square of model eye measures was least (0.017 +/- 0.002 D) when the separation of the horizontal measurement bars were averaged twice. The separation of the horizontal bars changes by 3.59 pixels/dioptre (r2 = 0.99), allowing continuous on-line analysis of the refractive state at up to 60 Hz temporal resolution to an accuracy of <0.001 D, with pupils >3 mm. The pupil edge is not obscured in the diagonal axis by the measurement bars, unlike the ring of the original optics, so in the newer model pupil size can be measured simultaneously at the same rate with a resolution of <0.001 mm. The measurements of accommodation and pupil size are relatively unaffected by eccentricity of viewing up to +/-10 degrees from the visual axis and instrument focusing inaccuracies over a range of 10 mm towards the eye and 5 mm away from the eye. The resolution and temporal properties of the analysis are therefore ideal for the simultaneous measurement of dynamic accommodation and pupil responses.


Enhanced cellular uptake of protoporphyrine IX/linolenic acid-conjugated spherical nanohybrids for photodynamic therapy.
Protoporphyrin IX (PpIX) has wide applications in photodynamic diagnosis and photodynamic therapy (PDT) in many human diseases. However, poor water solubility and cancer cell localization limit its direct application for PDT. We improved the water-solubility and cellular internalization of PpIX to enhance PDT efficacy by developing biocompatible PpIX/linolenic acid-conjugated polyhedral oligomeric silsesquioxane (PPLA) nanohybrids. The resulting PPLA nanohybrids exhibited a quasi-spherical shape with a size of <200nm. (1)H NMR analysis confirmed the synthesis of PPLA. The singlet oxygen formation of PPLA nanohybrids on laser irradiation was detected by photoluminescence emission. Fluorescence-activated cell sorting (FACS) analysis displayed higher cellular internalization of PPLA compared with free PpIX. In addition, PPLA nanohybrids exhibited significantly reduced dark-toxicity and a high phototoxicity mostly because of apoptotic cell death against human gastric cancer cells. These results imply that the PPLA nanohybrid system may be applicable in PDT.


Mutations in ANKLE2, a ZIKA Virus Target, Disrupt an Asymmetric Cell Division Pathway in Drosophila Neuroblasts to Cause Microcephaly.
The apical Par complex, which contains atypical protein kinase C (aPKC), Bazooka (Par-3), and Par-6, is required for establishing polarity during asymmetric division of neuroblasts in Drosophila, and its activity depends on L(2)gl. We show that loss of Ankle2, a protein associated with microcephaly in humans and known to interact with Zika protein NS4A, reduces brain volume in flies and impacts the function of the Par complex. Reducing Ankle2 levels disrupts endoplasmic reticulum (ER) and nuclear envelope morphology, releasing the kinase Ballchen-VRK1 into the cytosol. These defects are associated with reduced phosphorylation of aPKC, disruption of Par-complex localization, and spindle alignment defects. Importantly, removal of one copy of ballchen or l(2)gl suppresses Ankle2 mutant phenotypes and restores viability and brain size. Human mutational studies implicate the above-mentioned genes in microcephaly and motor neuron disease. We suggest that NS4A, ANKLE2, VRK1, and LLGL1 define a pathway impinging on asymmetric determinants of neural stem cell division.


Genome-wide scan in Hispanics highlights candidate loci for brain white matter hyperintensities.
To investigate genetic variants influencing white matter hyperintensities (WMHs) in the understudied Hispanic population. Using 6.8 million single nucleotide polymorphisms (SNPs), we conducted a genome-wide association study (GWAS) to identify SNPs associated with WMH volume (WMHV) in 922 Hispanics who underwent brain MRI as a cross-section of 2 community-based cohorts in the Northern Manhattan Study and the Washington Heights-Inwood Columbia Aging Project. Multiple linear modeling with PLINK was performed to examine the additive genetic effects on ln(WMHV) after controlling for age, sex, total intracranial volume, and principal components of ancestry. Gene-based tests of association were performed using VEGAS. Replication was performed in independent samples of Europeans, African Americans, and Asians. From the SNP analysis, a total of 17 independent SNPs in 7 genes had suggestive evidence of association with WMHV in Hispanics (p < 1 × 10-5) and 5 genes from the gene-based analysis with p < 1 × 10-3. One SNP (rs9957475 in GATA6) and 1 gene (UBE2C) demonstrated evidence of association (p < 0.05) in the African American sample. Four SNPs with p < 1 × 10-5 were shown to affect binding of SPI1 using RegulomeDB. This GWAS of 2 community-based Hispanic cohorts revealed several novel WMH-associated genetic variants. Further replication is needed in independent Hispanic samples to validate these suggestive associations, and fine mapping is needed to pinpoint causal variants.


MRI scanning in patients implanted with a round window or stapes coupled floating mass transducer of the Vibrant Soundbridge.
Conclusion MRI examinations in patients with an alternatively coupled VSB can lead to unpleasant side-effects. However, the residual hearing was not impaired, whereas the hearing performance with the VSB was decreased in one patient which could be fixed by a surgical revision. Different experiences for the VSB 503 can be expected. Objective To investigate the in vivo effects of MRI scanning on the Vibrant Soundbridge system (VSB) with an alternatively coupled Floating Mass Transducer (FMT). Method Sixty-five VSB (502) implantees were included in this study. Of them, 42 questionnaires could be evaluated with the patients' statements about their medical, otological, and general condition before, during, and after an MRI scan which was indicated for different medical reasons, despite the previous implantation of an alternatively coupled Vibrant Soundbridge System. Results In four patients (9.5%), five MRI examinations were performed. These were done for different indications (e.g. knee and shoulder joint diagnostics). During the scanning, noise and subjectively perceived distortion of the implant were described. A deterioration of the hearing gain with the VSB in place was found in one patient. A decrease of the hearing threshold was not observed.


Bulleyaconitine A depresses neuropathic pain and potentiation at C-fiber synapses in spinal dorsal horn induced by paclitaxel in rats.
Paclitaxel, a widely used chemotherapeutic agent, often induces painful peripheral neuropathy and at present no effective drug is available for treatment of the serious side effect. Here, we tested if intragastrical application of bulleyaconitine A (BLA), which has been approved for clinical treatment of chronic pain in China since 1985, could relieve the paclitaxel-induced neuropathic pain. A single dose of BLA attenuated the mechanical allodynia, thermal hyperalgesia induced by paclitaxel dose-dependently. Repetitive administration of the drug (0.4 and 0.8 mg/kg, t.i.d. for 7 d) during or after paclitaxel treatment produced a long-lasting inhibitory effect on thermal hyperalgesia, but not on mechanical allodynia. In consistency with the behavioral results, in vivo electrophysiological experiments revealed that spinal synaptic transmission mediated by C-fiber but not A fiber was potentiated, and the magnitude of long-term potentiation (LTP) at C-fiber synapses induced by the same high frequency stimulation was ~50% higher in paclitaxel-treated rats, compared to the naïve rats. Spinal or intravenous application of BLA depressed the spinal LTP, dose-dependently. Furthermore, patch clamp recordings in spinal cord slices revealed that the frequency but not amplitude of both spontaneous excitatory postsynaptic current (sEPSCs) and miniature excitatory postsynaptic currents (mEPSCs) in lamina II neurons was increased in paclitaxel-treated rats, and the superfusion of BLA reduced the frequency of sEPSCs and mEPSCs in paclitaxel-treated rats but not in naïve ones. Taken together, we provide novel evidence that BLA attenuates paclitaxel-induced neuropathic pain and that depression of spinal LTP at C-fiber synapses via inhibiting presynaptic transmitter release may contribute to the effect.


Transcatheter mitral repair according to the cause of mitral regurgitation: real-life data from the Spanish MitraClip registry.
Transcatheter mitral valve repair (TMVR) with MitraClip is a therapeutic option for high surgical risk patients with severe mitral regurgitation (MR). The main objective of this study was to analyze differences in outcomes in patients with severe MR according to the cause of MR. Observational, multicenter, and prospective study with consecutive patient inclusion. The primary endpoint was the combination of all-cause mortality and new readmissions due to heart failure after 1 year. We compared clinical and procedural characteristics and the event rate for each MR group. We performed a multivariate analysis to identify predictive variables for the primary endpoint. A total of 558 patients were included: 364 (65.2%) with functional etiology, 111 (19.9%) degenerative and 83 (14.9%) mixed. The mean age was 72.8±11.1 years and 70.3% of the sample were men. There were 95 (17%) events in the overall sample. No significant differences were found in the 3 groups in the number of primary outcome events: 11 (11.3%) in degenerative MR, 71 (21.3%) in functional MR, and 13 (18.1%) in mixed MR (P=.101). Independent predictors were functional class (P=.029), previous surgical revascularization (P=.031), EuroSCORE II (P=.003), diabetes mellitus (P=.037), and left ventricular ejection fraction (P=.015). This study confirms the safety and efficacy of TMVR with MitraClip irrespective of MR etiology in real-life data and shows the main factors related to prognosis during the first year of follow up.


[Obstetric data in a population with postural changes during labor and delivery].
The aim of this study was to describe the potential impact of an active birth on classical obstetrical outcomes, as labor duration, cesarean section rate, couples and team satisfactions. This observational study was prospective, monocentric and took place between May 2007 and February 2009 at the maternity ward of the University Hospital of Caen, France. An "active birth" was defined as an active latent-phase (having a change in position and/or a bath and/or a walk) followed by at least three changes in position during the active phase. The suggested positions were: lateral or dorsal decubitus, ROSA, on all fours, seated, standing and crouch. A position must have lasted at least 20 minutes to be considered. Out of the 1906 women included, 828 had an active birth (43.4%). Due to our definition of an "active birth", a "non-active birth" was significantly associated with a quicker labor. An "active birth" was associated with a decreased rate of cesarean section (OR=0.71; IC95%=[0.51-0.99]). The parturients satisfaction median was 9 on a scale of 0 to 10, the spouses'one was 10. Midwives were more satisfied when it was an "active birth". Significant associations with active births were highlighted, which would require to be validated by a randomised study. This practise plenty satisfied couples and midwives. In fact, no litterature exists to date. A consensus about the definition of an active birth is still necessary in order to lead to guidelines.


A new thiophene and two new monoterpenoids from Xanthium sibiricum.
Three new compounds (1-3), together with six known compounds (4-9), were isolated from the fruits of Xanthium sibiricum. The structures and the absolute configurations of sibiricumthionol (1), (+)-(5Z)-6-methyl-2-ethenyl-5-hepten-1,2,7-triol [(+)-2], ( - )-(5Z)-6-methyl-2-ethenyl-5-hepten-1,2,7-triol [( - )-2], (2E,4E,1'S, 2'R, 4'S, 6'R)-dihydrophaseic acid (3), (+)-xanthienopyran [(+)-4] and ( - )-xanthienopyran [( - )-4] were established by extensive spectroscopic analyses, X-ray crystallographic analysis, ECCD analysis and ECD calculations. Caffeic acid (7) and caffeic acid ethyl ester (8) weekly inhibited α-glucosidase enzymatic activity by 44.5% and 40.2%, respectively, at 40 μM. Protocatechuic acid (9) selectively exhibited cytotoxicity against HepG2 cell lines, with an IC50 value of 2.92 μM.


Reproductive cycle and in vitro maturation of canine oocyte: A meta-analysis approach.
Different outcomes of canine in vitro oocyte maturation depend on the phases of the donor's estrus cycle. This study aimed to examine this topic using a meta-analysis approach. From 1765 identified records in three major scientific databases, 145 were selected after the screening, 27 were evaluated for eligibility, and, finally, by removing 3 studies with high heterogeneity, 11 studies were used for the meta-analysis. The anestrus (ANE) phase was the reference for evaluating the luteal (LUT) and follicular (FOL) phases. The effect size data were selected as dichotomous types, and publication bias and heterogeneity were used for the quality assessments. The results showed a higher risk ratio (RR) of meiosis resumption in oocytes from the germinal vesicle stage in the LUT and FOL phases (∼30% more than ANE oocytes). The RR of being oocytes at the germinal vesicle breakdown (GVBD) stage was similar in all three phases. When compared to ANE, the RR of oocytes reaching the metaphase I (MI) stage from GVBD were higher in the FOL and LUT phases (30% and 14%, respectively). Moreover, the rate of oocytes reaching metaphase II (MII) was higher in the FOL and LUT phases (85% and 30%, respectively) than in the ANE phase. Being at an active phase (FOL or LUT phases) increased the rates of transition from the GVBD to MI stages (18%) and the MI to MII stages (48%) as compared with the ANE phase. It was assumed that oocytes in the LUT phase can reach GVBD and MI, whereas oocytes in the FOL phase are more capable of reaching MII than oocytes in anestrus.


[Effect of occupational therapy on the psychosocial status of patients with myocardial infarction at the second stage of rehabilitation].
Occupational therapy was added to the rehabilitation program at the second stage of rehabilitation in 42 myocardial infarction patients. Its psychosocial effect was assessed by psychological tests in comparison to a control group of patients, unexposed to occupational therapy.


Id1 suppresses anti-tumour immune responses and promotes tumour progression by impairing myeloid cell maturation.
A central mechanism of tumour progression and metastasis involves the generation of an immunosuppressive 'macroenvironment' mediated in part through tumour-secreted factors. Here we demonstrate that upregulation of the Inhibitor of Differentiation 1 (Id1), in response to tumour-derived factors, such as TGFβ, is responsible for the switch from dendritic cell (DC) differentiation to myeloid-derived suppressor cell expansion during tumour progression. Genetic inactivation of Id1 largely corrects the myeloid imbalance, whereas Id1 overexpression in the absence of tumour-derived factors re-creates it. Id1 overexpression leads to systemic immunosuppression by downregulation of key molecules involved in DC differentiation and suppression of CD8 T-cell proliferation, thus promoting primary tumour growth and metastatic progression. Furthermore, advanced melanoma patients have increased plasma TGFβ levels and express higher levels of ID1 in myeloid peripheral blood cells. This study reveals a critical role for Id1 in suppressing the anti-tumour immune response during tumour progression and metastasis.


Using Fluorescence Imaging to Track Drug Delivery and Guide Treatment Planning In Vivo.
Imaging has become an indispensable tool in both clinical medicine and preclinical sciences. It enables doctors to locate sites of cancer/disease, track drug delivery, and guide operative planning, thus enhancing the treatment efficacy. Recently, we developed a multimodal theranostic lipid nanoparticles, named HPPS(NIR)-chol-siRNA with its built-in near-infrared (NIR) fluorescent probe core as a useful surrogate for tracking small interfering RNA (siRNA) delivery. By using the image co-registration of computed tomography (CT) and fluorescence molecular tomography (FMT), we achieved noninvasive assessment and treatment planning of siRNA delivery into the orthotopic tumor, thus enabling efficacious RNA interference (RNAi) therapy. In this chapter, we introduce this method to illustrate the use of CT-FMT co-registration for tracking drug delivery and guiding treatment planning in vivo.


Comparative study of PSMA expression in the prostate of mouse, dog, monkey, and human.
Intraprostatic PSMA targeted prodrugs/protoxins are under development in our laboratory. Future toxicologic studies of these therapies require identification of animal models that express PSMA within the prostate. PSMA enzymatic activity and protein expression was determined. PSMA expression in the prostates of mouse, dog, and monkey were compared to humans by real-time PCR analysis. No substrate hydrolysis was observed in dog or monkey prostate homogenates. Monkey prostate was negative for PSMA protein expression. No significant PSMA mRNA levels were detected by real time PCR in mouse, dog, or monkey prostate tissue compared to PSMA negative tissues. PSMA is not expressed in any significant amount in the prostates of mouse, beagle dog, or macaque monkeys in this study but is expressed in high levels by human prostate. These non-human species, therefore, are not suitable toxicologic models to assess prostate damage from PSMA-activated intraprostatic prodrug/protoxin therapies.


The effect of hyperthermia on aqueous humor dynamics in rabbits.
Hyperthermia increased intraocular pressure (Po) by approximately 5 mm Hg in rabbit eyes. This increase was not associated with changes in plasma osmolarity, blood lactate, or pH. Episcleral venous pressure (Pv) decreased from a baseline of 11 +/- 1 mm Hg(mean +/- SEM) to 8 +/- 1 mm Hg after one hour of hyperthermia. Outflow facility (c) as measured by tonography remained unchanged. Aqueous humor flow [c(Po - Pv)] as estimated by tonography increased by about 126%. The elevation of intraocular pressure was not prevented by aspirin pretreatment nor altered by unilateral optic nerve transection.


Accuracy of Estimated Continuous Cardiac Output Monitoring (esCCO) Using Pulse Wave Transit Time (PWTT) Compared to Arterial Pressure-based CO (APCO) Measurement during Major Surgeries.
Pulse wave transit time is a novel method of estimating continuous cardiac output (esCCO). Since there are not many studies evaluating esCCO, we compared it with arterial pressure based cardiac output (APCO) method (FloTrac). In this prospective single-center observational study, we included 50 adult patients planned to undergo supramajor oncosurgeries, where major blood loss and extensive fluid shifts were expected. Cardiac output (CO) measurements were obtained by both methods at five distinct time points, giving us 250 paired readings of stroke volume index (SVI) and cardiac index (CI). We analyzed these readings using Pearson's correlation coefficient and Bland-Altman plots, along with other appropriate statistical tests. There was significant correlation between CI and SVI measured by the esCCO and APCO. Bland-Altman plot analysis for CI showed a bias of -0.44 L/minute/m2, precision of 0.74, and the limits of agreement of -1.89 and +1.01, while the percentage error was 46.29%. Bland-Altman analysis for SVI showed a bias -5.07 mL with a precision of 9.36, and the limits of agreement to be -23.4 to +13.28. The percentage error was 46.56%. This study demonstrated that esCCO tended to underestimate the CI to a large degree, particularly while estimating the cardiac output in the lower range. We found that the limits of agreement between two methods were wide, which are not likely to be clinically acceptable. Further studies with larger number of data points, obtained in a similar subset of patients, for cardiac output measurement in the perioperative period will certainly help determine if pulse wave transit time (PWTT) is here to stay (CTRI No.: CTRI/2019/08/020543). Joshi M, Rathod R, Bhosale SJ, Kulkarni AP. Accuracy of Estimated Continuous Cardiac Output Monitoring (esCCO) Using Pulse Wave Transit Time (PWTT) Compared to Arterial Pressure-based CO (APCO) Measurement during Major Surgeries. Indian J Crit Care Med 2022;26(4):496-500.


Intraocular pressure and tear production changes in pregnant women at term pregnancy and immediate post-partum: A pilot study.
To study the intraocular pressure (IOP) and tear production changes in uncomplicated pregnant women at term pregnancy and immediate postpartum. The patients admitted in the Department of Obstetrics and Gynaecology for delivery were included in the study. A total of 106 participants who were at term uncomplicated pregnancy were selected according to the inclusion and exclusion criteria. They were subjected to type 1 Schirmer's testing and intraocular pressure measurement by Perkin's tonometer before and after delivery. There was no significant pre- and postdelivery IOP difference between the different age groups (<30 and ≥30 years), mode of delivery, and parity. There was a statistically significant (P < 0.001) increase in mean tear production (Schirmer's test) after delivery, irrespective of age group, mode of delivery, and gravida status. However, no significant intergroup difference was observed. There was no significant change in IOP before and after delivery in uncomplicated pregnancies. However, a statistically significant increase in tear production was observed in the immediate postpartum period.


Association between ethylene oxide exposure and prevalence of COPD: Evidence from NHANES 2013-2016.
Environmental exposures are major risk factors for chronic obstructive pulmonary disease (COPD). Ethylene oxide (EO) is a ubiquitous organic compound and adversely affects human health. However, it remains unknown whether EO exposure increases the risk of COPD. This study aimed to explore the association between EO exposure and the prevalence of COPD. In this cross-sectional study, 2243 participants were analyzed from the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2016. Participants were classified into four groups according to quartiles of log10-transformed hemoglobin adducts of EO (HbEO) levels. HbEO levels were measured using the modified Edman reaction and high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). Logistic regression, restricted cubic spline regression model, and subgroup analysis were used to assess whether EO exposure was associated with the risk of COPD. A multivariate linear regression model was used to investigate the correlation between HbEO levels and inflammatory factors. A mediating analysis was conducted to estimate whether inflammatory factors were involved in the effects of HbEO on the prevalence of COPD. Participants with COPD had higher HbEO levels than those without COPD. Log10-transformed HbEO levels were associated with an increased risk of COPD after adjusting for all covariates. [Q4 vs. Q1 in model II: OR = 2.15, 95 % CI: 1.20-3.85, P = 0.010, P for trend = 0.009]. Moreover, a nonlinear J-shaped relationship was observed between HbEO levels and the risk of COPD. Furthermore, HbEO levels were positively correlated with inflammatory cells. In addition, white blood cells and neutrophils mediated the relationship between HbEO and the prevalence of COPD with mediated proportions of 10.37 % and 7.55 %, respectively. These findings indicate that EO exposure has a J-shaped association with the risk of COPD. Inflammation is a key mediator involved in the effects of EO exposure on COPD.


Rapid painless diagnosis of viral respiratory infection.
The concordance of nasal compared with nasopharyngeal swabs was assessed for the diagnosis of respiratory viral infections, and the degree of discomfort associated with each procedure was compared. The use of nasal swabs was shown to be as accurate but significantly less painful than nasopharyngeal swabs for virus diagnosis.


Predicting clinical scores in Huntington's disease: a lightweight speech test.
Using brief samples of speech recordings, we aimed at predicting, through machine learning, the clinical performance in Huntington's Disease (HD), an inherited Neurodegenerative disease (NDD). We collected and analyzed 126 samples of audio recordings of both forward and backward counting from 103 Huntington's disease gene carriers [87 manifest and 16 premanifest; mean age 50.6 (SD 11.2), range (27-88) years] from three multicenter prospective studies in France and Belgium (MIG-HD (ClinicalTrials.gov NCT00190450); BIO-HD (ClinicalTrials.gov NCT00190450) and Repair-HD (ClinicalTrials.gov NCT00190450). We pre-registered all of our methods before running any analyses, in order to avoid inflated results. We automatically extracted 60 speech features from blindly annotated samples. We used machine learning models to combine multiple speech features in order to make predictions at individual levels of the clinical markers. We trained machine learning models on 86% of the samples, the remaining 14% constituted the independent test set. We combined speech features with demographics variables (age, sex, CAG repeats, and burden score) to predict cognitive, motor, and functional scores of the Unified Huntington's disease rating scale. We provided correlation between speech variables and striatal volumes. Speech features combined with demographics allowed the prediction of the individual cognitive, motor, and functional scores with a relative error from 12.7 to 20.0% which is better than predictions using demographics and genetic information. Both mean and standard deviation of pause durations during backward recitation and clinical scores correlated with striatal atrophy (Spearman 0.6 and 0.5-0.6, respectively). Brief and examiner-free speech recording and analysis may become in the future an efficient method for remote evaluation of the individual condition in HD and likely in other NDD.


Effects of water depth on choice of spatially separated prey by Notonecta glauca L.
In laboratory experiments, the predator, Notonecta glauca L., was exposed to varying densities of surfacedwelling culicine mosquito larvae and the bottom-inhabiting isopod, Asellus aquaticus L., in either shallow or deep water at 20° C. At this temperature N. glauca spends most of the time at the water's surface, so, by changing water depth the accessibility of Asellus to the predator was manipulated relative to a consistent Culex presence.All N. glauca spent more time submerged in shallow (75 mm) than in deep (275 mm) water but submergence times were independent of exposure to different prey combinations. Mature females made more descents and remained submerged longer than males.All N. glauca captured more Asellus in shallow than in deep water but males and newly-moulted females captured Culex predominantly, in all treatments, regardless of water depth or prey availability. Mature females captured mostly Asellus in shallow water and Culex in deep water. When presented with small rather than large Asellus, mature females spent an equivalent amount of time submerged as in the large Asellus treatments and ate the same number of Asellus but more Culex.By foraging on Culex larvae, male and newly moulted female N. glauca maximise their rate of energy intake. In contrast, mature females may actively select Asellus to optimise something other than energy (e.g. specific nutrients). Alternatively their predation on Asellus may be simply a consequence of a high encounter rate with this prey type, reflecting habitat use determined by factors that do not concern prey capture directly.


24-hour urine creatinine excretion in pregnancy.
A total of 489 consecutive 24-hour urine collection from 162 patients were analyzed for creatinine excretion. The 24-hour creatinine excretion increased with the urine volume. Creatinine excretions in 24-hour urine collections were not statistically different between in- and out-patients. The results indicate that the mean urine creatinine per 24 hours is 1.08 g for 24-hour urine volumes between 500 and 1500 ml. For urine volumes greater than 1500 ml it is 1.22 g. For 24-hour urine volumes less than 500 ml, the mean creatinine is 0.63 g.


The biliary elimination of sulfamerazin in rat and man--a comparison.
Sulfamerazin (S) was given to rats (380 mumol kg-1 body wt, i.v.) and to man (95 mumol kg-1, orally). Bile was collected from the common bile duct in both rats and man (T-tube drain) for 21 and 28 hours, respectively. The calculated amount of S eliminated by bile was seven-times higher in the rat (8.4% of the given dose) than in man. This is the consequence of the higher concentration ratio bile to blood in the rat (0.95) compared with man (0.31) as well as of the differences in bile flow rate of 0.046 and 0.0082 ml min-1 kg-1 in rat and man, respectively.


FGF1-FGFR1 axis promotes tongue squamous cell carcinoma (TSCC) metastasis through epithelial-mesenchymal transition (EMT).
Increasing evidences suggest a close association between tumor metastasis and the inflammatory factors secreted by tumor microenvironment. It has been reported that epithelial mesenchymal-transition (EMT) plays a significant role during multiple types of tumor metastasis and progression induced by inflammatory factor from tumor microenvironment. Previous researches implied that fibroblast growth factor 1 (FGF1) can promote tumor progression and cause poor prognosis in several types of malignant tumors via interacting with its receptor fibroblast growth factor receptor 1 (FGFR1). However, the effects of FGF1-FGFR1 on tongue squamous cell carcinoma (TSCC) are not yet completely understood. In the present study, we evaluated the effects and function of FGF1-FGFR1 axis on TSCC metastasis. In addition, we investigated whether the EMT pathway is involved in these effects, thus modulating the TSCC progression. The expression of FGFR1 was measured both in tongue cancer cell lines and tissues by qRT-PCR and western blot. We found that FGFR1 was up-regulated in TSCC tissues compared to non-neoplastic tongue tissues. Additionally, overexpression of FGFR1 is positively associated with poor differentiation and metastasis potential. Furthermore, the function of FGF1-FGFR1 was examined in TSCC cell line. The results implied that FGF1 can obviously promote Cal27 cells migration and invasion abilities through FGFR1, while the motile and invasive capabilities can be severely attenuated when knockdown the expression of FGFR1 by specific siRNAs. Further investigation results show that FGF1-FGFR1 axis promotes TSCC metastasis by modulating EMT pathway. However, this effect can be inhibited by blocking the FGF1-FGFR1 axis using FGFR1 specific siRNAs. In conclusion, our findings of the present study provide the evidences that FGF1-FGFR1 axis promotes the TSCC metastasis through the EMT pathway.


Prospects for a virus non-structural protein as a subunit vaccine.
The design of contemporary vaccines to date has been dependent upon our understanding of the process of stimulation of protective immunity by virion proteins. However, studies with the flaviviruses have demonstrated that protective immunity can be elicited by a non-structural protein, NS1. Surprisingly, immunity to infection is stimulated in the absence of neutralizing antibodies. The information concerning NS1-induced immunity is described and is discussed with relevance to the role of the protein in immunity and vaccine development, against flavivirus diseases. The possibility exists that the phenomenon of non-structural protein induced immunity is applicable to the prophylaxis of other virus diseases.


Resurgence of West Nile neurologic disease in the United States in 2012: what happened? What needs to be done?
The resurgence in cases of neurologic disease caused by West Nile virus (WNV) in the United States in 2012 came as a surprise to the general public and to many non-arbovirus researchers. Following the introduction of WNV into the US in 1999, the number of human infections rose dramatically, peaking in 2002-03. However, cases declined from 2008-11, and it was unclear if the virus would continue to have a low-level endemic transmission pattern with occasional outbreaks, like the related flavivirus, Saint Louis encephalitis virus, or a more active pattern with annual outbreaks, including occasional years with large epidemics, like Japanese encephalitis virus. The large epidemic in 2012 suggests that the United States can expect periodic outbreaks of West Nile fever and neurologic disease in the coming years. In this paper, we consider the causes of the upsurge in WNV infections during the past year and their implications for future research and disease control measures.


Cardiac effects of magnesium with special reference to anaesthesia: a review.
The role of magnesium in myocardial metabolism and the effects of magnesium deficiency on myocardial contraction and the electrocardiogram have been described. The causes of a magnesium deficiency have been discussed in some detail. Finally, the inter-relationship between magnesium and the mitochondrial enzyme systems concerned with oxidative phosphorylation is stressed. The early detection of magnesium deficiency by routine methods is imperative for the prevention of abnormal cardiac metabolism and the maintenance of the functional and structural integrity of cardiac muscle during anaesthesia.


Does the Use of Intraoperative Pressure Sensors for Knee Balancing in Total Knee Arthroplasty Improve Clinical Outcomes? A Comparative Study With a Minimum Two-Year Follow-Up.
It is undetermined whether using sensors for knee balancing in total knee arthroplasty (TKA) improves patient outcomes. The purpose of this study was to compare clinical outcomes of sensor balance (SB) with manual balance (MB) TKA with a minimum two-year follow-up. A consecutive series of 207 MB TKAs was compared with 222 SB TKAs between April 2014 and April 2017. A single surgeon performed all surgeries, using the same prosthesis. The primary end point was the aggregated mean change in four subscales of the Knee injury and Osteoarthritis Outcome Score (KOOS4) between preoperative and two-year time points. Secondary outcomes included mean differences between groups in all five KOOS subscales, proportions of knee balancing procedures, and rates of reoperations including revisions and manipulations for stiffness. The mean changes in the KOOS4 aggregated means for MB TKA (42.4; standard deviation, 29.1) and SB TKA (41.5; standard deviation, 25.0) were not significantly different (mean difference, 0.9; 95% confidence interval: -2.6 to 4.4, P = .62). There were significantly more balancing procedures in the SB group (55.9% versus 16.9%; P < .01). There were no significant differences in the number of reoperations (1.4% SB versus 1.4% MB; P = .71) or manipulations for stiffness (3.7% SB versus 4.4% MB; P = .69). The use of sensors in TKA to achieve knee balance did not result in improved clinical outcomes, despite significantly increasing the number of surgical interventions required to achieve a balanced knee. Sensors did not alter the rates of revision surgery or requirements for manipulation. It remains to be determined whether precise soft-tissue balancing improves prosthetic survivorship and joint biomechanics.


Comprehensive lipid analysis of green Arabica coffee beans by LC-HRMS/MS.
Lipids play an important role in coffee bean development, coffee brew and in the effects of coffee on human health. They account for around 17% of the dry bean weight and encompass different classes and subclasses, mostly triacylglycerols (TAG) and a minor quantity of phospholipids (PL) and βN-alkanoyl-5-hydroxytryptamides (C-5HT). To comprehensive profile these different lipids, it is important to evaluate extraction methods that provide high lipid coverage and to analyze the lipids in high-resolution techniques. In this work, liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS/MS) was employed to comprehensive profile lipids from green Arabica coffee beans and to evaluate the extraction efficiency and lipid coverage of three methods: Bligh-Dyer (BD), Folch (FO), and Matyash (MA). The MA method yielded the greatest number of annotated compounds (131 lipids) compared to the other methods. In the positive electrospray ionization (ESI) mode, the main difference among extraction methods was observed for TAG and diacylglycerols, whereas for the negative ESI it was observed differences for phosphatidylinositol (PI), lysophosphatidylinositol and phosphatidic acid (p < 0.05). The analysis of coffees from different maturation stages and/or post-harvest processes were also performed using the MA method. Immature beans were discriminated from mature and overripe beans by its lower levels of C-5HT, PI, phosphatidylcholine, lysophosphatidylcholine, phosphatidylethanolamine, and lysophosphatidylethanolamine. These results can help to better understand the coffee lipid composition and its association with coffee quality.


Influence of growth conditions on production of capsular and extracellular polysaccharides by Rhizobium leguminosarum.
The influence of growth rate and medium composition on exopolymer production by Rhizobium leguminosarum was studied. When grown in medium containing 10 g/l mannitol and 1 g/l glutamic acid, Rhizobium leguminosarum biovar trifolii TA-1 synthesized up to 2.0 g/l of extracellular polysaccharide (EPS), and up to 1.6 g/l of capsular polysaccharide (CPS). Under non-growing cell conditions in medium without glutamic acid, CPS synthesis by strain TA-1 could proceed to 2.1 g/l, while EPS-production remained relatively low (0.8 g/l). Maximal CPS-yield was 2.9 g CPS/l medium in a medium containing 20 g/l mannitol and 2 g/l glutamic acid. The EPS-deficient strain R. leguminosarum RBL5515, exo4::Tn5 was able to produce CPS to similar levels as strain TA-1, but CPS-recovery was easier because of the low viscosity of the medium and growth of the cells in pellets. With strain TA-1 in nitrogen-limited continuous cultures with a constant biomass of 500 mg cell protein/l, EPS was the most abundant polysaccharide present at every dilution rate D (between 0.12 and 0.02 h-1). The production rates were 50-100 mg/g protein/h for EPS and 15-20 mg/g protein/h for CPS. Only low amounts of cyclic beta-(1,2)-glucans were excreted (10-30 mg/l) over the entire range of growth rates.


Review on advances in nanoscale microscopy in cement research.
With the rapid advancement of nanotechnology, manipulation and characterization of materials in nano scale have become an obvious part of construction related technology. This review will focus on some of the nanoscopy techniques that are most frequently used in current research of cement based nanostructured materials. In particular scanning electron microscopy, transmission electron microscopy, atomic force microscopy, scanning tunneling microscopy, tomography, scanning transmission X-ray microscopy and laser scanning confocal microscopy are addressed. A number of case studies related to microscopic characterization of nano materials utilizing the aforementioned techniques from the published literature are discussed. While these approaches are beginning to yield promising insight, continued progress will definitely provide a potential sustainable solution for the design, development and promotion towards nanoscale engineering of cementitious materials.


Knowledge and attitude to dental implant placement amongst a group of Nigerian dentist.
The perceptions and experiences of dentists from different specialties on the use of dental implant and its applications can be instrumental in its use exhaustively. To determine the opinions and experiences of a population of Nigerian dentists towards dental implant. Data for the study were collated using a self-administered questionnaire. The questionnaire assessed the familiarity of the participants with various implant systems, their designs, sizes and loading as well as the provision of replacement for missing teeth. The estimated functional life of an implant was reported to be less than 5 years by 2.5% of the respondents; 5 to 10 years by 11.3% of the respondents; 10 to 20 years by 26.3% and more than 20 years by 28.7% of the respondents while 31.3% had no idea about the estimated functional life of an implant. Exposure and experience with dental implants were low as only 30.0% of the respondents had attended any dental implant course/training with 95.0% of the respondents expressing the opinion that they did not have enough training in dental implantology. The exposure and experience with dental implants was low among the respondents.


[Genetic disorders of surfactant].
Lung diseases associated with surfactant metabolism disorders represent a significant but heterogeneous group of rare disorders. Intra-alveolar accumulation of protein related to surfactant dysfunction leads to cough, hypoxemia and radiological diffuse infiltration. Inherited deficiency of pulmonary surfactant protein B (SP-B) was initially described in term newborns who develop severe respiratory failure at birth. More recently, mutations in surfactant protein C (SP-C) or in proteins required for surfactant synthesis such as ATP-binding cassette, sub-family A, member 3 (ABCA3) or NK2 homeobox 1 (NKX2-1) were identified in newborns with respiratory distress but also in children with diffuse infiltrative pneumonia. The aim of this review is to describe the clinical presentation of these diseases but also the diagnostic tools and the treatments options available.


REM sleep without atonia and vestibular-evoked myogenic potentials: clinical brainstem dysfunction in early-stage Parkinson's disease and isolated REM sleep behavior disorder.
To determine whether the onset of rapid eye movement (REM) sleep behavior disorder (RBD) is associated with changes in brainstem neuronal pathway dysfunction as reflected by vestibular-evoked myogenic potentials (VEMPs) and to evaluate associations between VEMPs and REM sleep without atonia (RSWA) in patients with early-stage Parkinson's disease (PD) and isolated RBD (iRBD). Eighty-two early-stage PD patients, 40 iRBD patients, and 41 healthy control individuals underwent one-night video-polysomnography (vPSG) and VEMPs examination. We compared cervical (cVEMP), ocular (oVEMP), and masseter (mVEMP) VEMP parameters among PD with RBD (PD + RBD), PD without RBD (PD-RBD), iRBD, and control groups and analyzed correlations between VEMPs and RSWA in PD and iRBD groups. The PD + RBD group showed delays in bilateral cVEMP (Lp13, Ln23, Rn23: all p < 0.05) and oVEMP (Ln10, Rn10, Rp15: all p < 0.05) peak latencies compared with the PD-RBD group. Total cVEMP scores were higher in the PD + RBD group than in the iRBD group (p = 0.033). In PD patients, phasic RSWA was correlated with total cVEMP scores (p = 0.003), and tonic RSWA was correlated with left oVEMP scores (p = 0.013). Brainstem neurophysiology as evidenced by altered VEMPs in patients with PD and iRBD could reflect disease evolvement. Moreover, VEMPs alterations may vary depending on the presence of RBD in PD patients. The associations between altered RSWA and VEMP parameters highlight the meaningfulness of detecting brainstem dysfunction in early-stage PD.


Functional homology between yeast piD261/Bud32 and human PRPK: both phosphorylate p53 and PRPK partially complements piD261/Bud32 deficiency.
Yeast piD261/Bud32 belongs to the piD261 family of atypical protein kinases structurally conserved, from Archaea to human. The disruption of its gene is causative of severely defective growth. Its human homologue, PRPK, interacts with and phosphorylates the oncosuppressor p53 protein, which is lacking in yeast. Here we show that on one hand piD261/Bud32 interacts with and phosphorylates human p53 in vitro, on the other hand PRPK can partially complement the phenotype of yeast lacking the gene encoding piD261/Bud32. These data indicate that, despite considerable structural divergence, members of the piD261 family from distantly related organisms display a remarkable functional conservation.


Interferon production and tumor cell killing by human lymphocytes stimulated in mixed-lymphocyte culture.
The in vitro synthesis of interferon (IFN) by human lymphocytes stimulated in mixed-lymphocyte culture (MLC) was examined. The production of IFN in MLC was restricted to T lymphocytes and maximum levels of IFN were detected in supernatants from cells incubated for 5 to 7 days. The IFN produced was identified as IFN-gamma by antibody neutralization. To identify the T cell responsible for IFN production, purified T lymphocytes were separated into subpopulations after incubation in 5 mM theophylline. Theophylline-resistant (T-res) T cells retain the ability to form sheep erythrocyte (SRBC) rosettes and are depleted in IgG Fc receptor-positive T cells (T gamma cells). Theophylline-sensitive (T-sens) T cells fail to form rosettes after theophylline treatment and are enriched in T gamma cells. In addition, analyses using monoclonal antibodies showed that T-sens cells were enriched in OKM1-, HNK-1-, and 7.2-positive cells and T-res cells contained increased numbers of 9.6- and OKT4-positive cells. Following MLC stimulation, equivalent levels of IFN-gamma were produced by T-res and T-sens cells and both subpopulations maintained natural killer (NK)-like cytotoxicity against K562 target cells. Addition of partially purified IFN-gamma to unstimulated T-res and T-sens cells resulted in the maintenance of NK-like cytotoxicity in a manner analogous to that observed after MLC. Additional experiments indicated that peripheral blood lymphocytes depleted of 9.6- or OKM1-positive cells by complement-mediated lysis were devoid of cytotoxicity against K562 cells. Furthermore, MLC stimulation of 9.6- or OKM1-depleted cells failed to restore cytotoxic activity. In summary, these experiments demonstrate that the maintenance of NK-like cytotoxicity by MLC-stimulated T cells is associated with the synthesis of IFN-gamma, that MLC stimulated T-res and T-sens T-cell subsets produce equivalent amounts of IFN, and that 9.6- or OKM1-positive cells are required for the maintenance of NK-like cytotoxicity in MLC.


Longitudinal changes in lung function following initiation of lumacaftor/ivacaftor combination.
The combination of lumacaftor and ivacaftor (LUM/IVA) is a recently approved CFTR modulator treatment for homozygous F508del CF patients. Our study aimed at evaluating the change in the rate of lung function decline after one-year treatment with LUM/IVA. The study evaluated patients homozygous for F508del, 12 to 23 years old. All had been treated for one year with LUM/IVA. The collected data included the percent predicted values of FEV1 (ppFEV1) and FVC (ppFVC), and the FEV1/FVC ratio (FEV1/FVC), that corresponded to 12, 24, and 36 months prior to, and 12 months after the initiation of LUM/IVA; also, the 3 highest values of the ppFEV1 (and the corresponding ppFVC, and FEV1/FVC) for the periods 0-12 months, 12-24 months, and 24-36 months prior to as well as the 12-month period after the initiation of LUM/IVA. The baseline lung function was estimated before the commencement of the drug. Data were analyzed longitudinally with generalized estimating equations models and continuous linear splines. A single knot was used that corresponded to the time point of LUM/IVA initiation. Fifty-two patients were analyzed. The multivariate longitudinal analysis of spirometric indices with linear splines demonstrated a significant change in the slopes of ppFEV1 and ppFVC decline, reflecting a significant improvement after the initiation of LUM/IVA treatment. In this real-world study, lung function improved over a relatively short time period of only one year, after the commencement of LUM/IVA.


Surgical treatment algorithms for post-burn contractures.
Burn contractures produce restrictions in motion and unacceptable aesthetic results, frequently with persistent wounds. Proper planning and tissue selection are essential to minimize donor site morbidity optimizing outcomes. The principle of burn reconstructive surgery requires that the defects after release should be replaced with donor tissues which have matching texture and color as well as enough pliability. Autologous skin grafting or flap surgeries meet these criteria to replace scar tissues and resurface the subsequent to post-released scar defects. Despite the benefits, the use of flaps is often limited in burn patients for many reasons. If a surgeon intends to release completely and reconstruct in one-stage operation, a large defect may result in large donor site morbidity, necessitating flap surgery including free flap surgery. A lot of different methods and procedures are available for resurfacing the defects, and these are reviewed. In this article, algorithms for the release of burn contractures and reconstructive methods are presented. These treatment algorithms should aid in achieving significant improvement in both joint motions and aesthetic deformities.


Prion protein dynamics before aggregation.
Prion diseases, like Alzheimer's disease and Parkinson disease, are rapidly progressive neurodegenerative disorders caused by misfolding followed by aggregation and accumulation of protein deposits in neuronal cells. Here we measure intramolecular polypeptide backbone reconfiguration as a way to understand the molecular basis of prion aggregation. Our hypothesis is that when reconfiguration is either much faster or much slower than bimolecular diffusion, biomolecular association is not stable, but as the reconfiguration rate becomes similar to the rate of biomolecular diffusion, the association is more stable and subsequent aggregation is faster. Using the technique of Trp-Cys contact quenching, we investigate the effects of various conditions on reconfiguration dynamics of the Syrian hamster and rabbit prion proteins. This protein exhibits behavior in all three reconfiguration regimes. We conclude that the hamster prion is prone to aggregation at pH 4.4 because its reconfiguration rate is slow enough to expose hydrophobic residues on the same time scale that bimolecular association occurs, whereas the rabbit sequence avoids aggregation by reconfiguring 10 times faster than the hamster sequence.


Current concepts and challenges in the radiologic assessment of brain tumors in children: part 2.
Assessing tumor response is a large part of everyday clinical work in neuroradiology. However in the setting of tumor treatment, distinguishing tumor progression from treatment-related changes is difficult on conventional MRI sequences. This is made even more challenging in children where mainstay advanced imaging techniques that are often used to decipher progression versus treatment-related changes have technical limitations. In this review, we highlight the challenges in pediatric neuro-oncologic tumor assessment with discussion of pseudophenomenon including pseudoresponse and pseudoprogression. Additionally, we discuss the advanced imaging techniques often employed in neuroradiology to distinguish between pseudophenomenon and true progressive disease.


Varenicline and neuronal nicotinic acetylcholine receptors: a new approach to the treatment of co-occurring alcohol and nicotine addiction?
Alcohol and nicotine dependence are serious public health problems worldwide. They are associated with substantial morbidity and mortality, as well as adverse social effects and increased healthcare costs. Although efficacious treatments are available for these disorders, additional therapeutic options are required to ensure greater treatment utilization. In this paper, we describe the empirical basis on which varenicline, a nicotinic partial agonist approved for smoking cessation, may also have utility in the treatment of alcohol addiction. We sought to identify papers examining nicotine dependence, alcohol dependence, smoking, alcohol, and varenicline for possible inclusion in the present review. We identified over 600 papers through Pubmed/Medline, PsychINFO, and Google Scholar. We found 12 papers taking into consideration the following criteria: original language English, varenicline effect on alcohol consumption. Animal studies have shown that varenicline reduces alcohol consumption. Two recent studies showed that varenicline also reduces alcohol consumption in humans. Both nicotine and alcohol interact with α4β2 and α3β4 nicotinic acetylcholine (ACh) receptors located in the ventral tegmental area of the brain, inducing dopamine (DA) release at the nucleus accumbens. Varenicline binds to nicotinic ACh receptors, where it has partial agonist effects, producing a moderate and constant level of DA release both in the mesolimbic pathway and in the prefrontal cortex. Through these effects, varenicline may reduce alcohol craving, seeking, and consumption, in addition to promoting smoking cessation. Additional studies are needed to confirm the efficacy of varenicline in the treatment of alcohol dependence.


Effects of migrating Gasterophilus intestinalis larvae (Diptera: Gasterophilidae) on the mouth of the horse.
Lesions were formed in the mouth of the horse by first- and second-stage Gasterophilus intestinalis larvae. The lesions resulted as larvae burrowed through the top millimeter of the tongue and then became embedded in the interdental gingiva. Appearance of the lesion was dependent on the degree of larval burrowing activity and healing that had taken place. Active tunneling production occurred at the posterior end of the lesion. Extensive change in configuration and color was apparent along the longer lesions with active larvae. Virtually all tissue in the path of the larvae was removed while forming a tunnel. Tissue destroyed included tops of the lamina propria mucosae evaginations and the deeper portions of the lamina epithelialis mucosae. Histopathologic findings showed that the tissue removed included the nerve and blood supply of the proprial evaginations. Hemorrhage and exocytosis into the tunnels included erythrocytes mixed with some macrophages, lymphocytes and scant numbers of eosinophils. Air shafts excavated in the tongue by larvae enabled bacteria to enter into the tunnels. Bacteria became adhered to larvae and initiated microabscesses. Microabscesses were composed of clotted erythrocytes, bacteria, disintegrating epithelial cells, and large numbers of neutrophils. Cells surrounding the tunnel exhibited pyknosis, epithelial hydropic degeneration and became separated from each other. Healing of tongue lesions occurred as epithelial cell growth below raised the tunnel upward and affected tissue desquamated. Interdental gingiva invaded by larvae were hyperemic and denuded of epithelia. Recession and ulceration of the gingiva produced periodontal pockets. Extensive invasion by larvae led to compound periodontal pockets. Larval mouth hooks were embedded in the submucosa of the pockets and tore at engorged capillaries. The cephalic portion of embedded larvae became surrounded by a cellular exudate containing erythrocytes and mononuclear cells. Attachment of second-stage larvae at the root of the tongue did not produce observable damage.


In vitro Effect of 810 nm and 940 nm Diode Laser Irradiation on Proliferation of Human Gingival Fibroblasts and Expression of Procollagen Gene.
Factors promoting fibroblast proliferation and collagen synthesis can subsequently enhance wound healing. This study aimed to assess the effect of 810 and 940 nm diode laser on fibroblast proliferation and procollagen gene expression. In this study, human gingival fibroblasts were cultured in Dulbecco's modified Eagle's medium and underwent 810 and 940 nm diode laser irradiation once, twice, thrice and four times at 1, 3, 5 and 7 days after culture. The methyl thiazolyl tetrazolium assay was performed to assess the proliferation while the real-time polymerase chain reaction was performed to assess the expression of procollagen gene at the mRNA level. We applied two-way ANOVA and Tukey's test for analysis. Wavelength had no significant effect on the proliferation of gingival fibroblasts, but increasing the number of irradiation sessions of both wavelengths increased the proliferation of human gingival fibroblasts. Significant differences were noted in the number of human gingival fibroblasts between groups irradiated 1 and 4 and also 2 and 4 times. Procollagen gene was well expressed in all groups but its expression was significantly higher in 940 nm laser group after four irradiation cycles. Four times radiation of 940 nm laser seems to be more effective than all others.