The importance of fungi and mycology for addressing major global challenges*.
In the new bioeconomy, fungi play a very important role in addressing major global challenges, being instrumental for improved resource efficiency, making renewable substitutes for products from fossil resources, upgrading waste streams to valuable food and feed ingredients, counteracting life-style diseases and antibiotic resistance through strengthening the gut biota, making crop plants more robust to survive climate change conditions, and functioning as host organisms for production of new biological drugs. This range of new uses of fungi all stand on the shoulders of the efforts of mycologists over generations: the scientific discipline mycology has built comprehensive understanding within fungal biodiversity, classification, evolution, genetics, physiology, ecology, pathogenesis, and nutrition. Applied mycology could not make progress without this platform. To unfold the full potentials of what fungi can do for both environment and man we need to strengthen the field of mycology on a global scale. The current mission statement gives an overview of where we are, what needs to be done, what obstacles to overcome, and which potentials are within reach. It further provides a vision for how mycology can be strengthened: The time is right to make the world aware of the immense importance of fungi and mycology for sustainable global development, where land, water and biological materials are used in a more efficient and more sustainable manner. This is an opportunity for profiling mycology by narrating the role played by fungi in the bioeconomy. Greater awareness and appreciation of the role of fungi can be used to build support for mycology around the world. Support will attract more talent to our field of study, empower mycologists around the world to generate more funds for necessary basic research, and strengthen the global mycology network. The use of fungi for unlocking the full potentials of the bioeconomy relies on such progress. The fungal kingdom can be an inspiration for even more.


Dual-isotope subtraction SPECT-CT in parathyroid localization.
The aim of this study was to investigate the accuracy of locating parathyroid adenomas using dual-Isotope subtraction single-photon emission computed tomography-computed tomography (SPECT-CT) in comparison with clinical follow-up and pathology findings from surgery. A retrospective cohort study of dual-isotope subtraction SPECT-CT was carried out on 224 consecutive patients who were diagnosed with primary hyperparathyroidism. All the patients were injected with 20 MBq of iodine-123-iodide, followed 20 min later by 900 MBq of technetium-99m-sestamibi. Planar neck and chest views and SPECT-CT images were acquired 15 min after administration, followed by an additional planar image set at 2 h to view washout; all images were dual energy. In all, 115 out of 224 of the patients imaged underwent parathyroid surgery. The imaging results were compared with pathology findings when available and, in those who did not undergo surgery, and in some complex cases, with clinical measures after a 2-year clinical follow-up period. Out of the 224 patients, 135 patients had complete pathology and/or clinical follow-up data and were included in the analysis. The sensitivity of the subtraction SPECT-CT findings was measured to be 95%, with a specificity of 89% for the detection and localization of parathyroid adenomas. The positive predictive value was found to be 97% and the negative predictive value was found to be 83%. The accuracy of the technique was 94% in detecting parathyroid adenoma and 92% in accurate localization. Dual-isotope subtraction SPECT-CT imaging has a very high sensitivity and specificity in detecting and locating a parathyroid adenoma, showing that it is a very reliable preoperative imaging technique in primary hyperparathyroidism.


The chemistry of the vitamin B3 metabolome.
The functional cofactors derived from vitamin B3 are nicotinamide adenine dinucleotide (NAD+), its phosphorylated form, nicotinamide adenine dinucleotide phosphate (NADP+) and their reduced forms (NAD(P)H). These cofactors, together referred as the NAD(P)(H) pool, are intimately implicated in all essential bioenergetics, anabolic and catabolic pathways in all forms of life. This pool also contributes to post-translational protein modifications and second messenger generation. Since NAD+ seats at the cross-road between cell metabolism and cell signaling, manipulation of NAD+ bioavailability through vitamin B3 supplementation has become a valuable nutritional and therapeutic avenue. Yet, much remains unexplored regarding vitamin B3 metabolism. The present review highlights the chemical diversity of the vitamin B3-derived anabolites and catabolites of NAD+ and offers a chemical perspective on the approaches adopted to identify, modulate and measure the contribution of various precursors to the NAD(P)(H) pool.


[Free amino acids in human blood during the initial period of exposure to antiorthostatic hypokinesia].
The concentration of 17 free amino acids in plasma of 6 test subjects, aged 20, who were for 7 days exposed to head-down tilt and remained on a controlled diet, was measured. The study revealed an increase in the concentration of most amino acids by the end of day 3 and all amino acids by the end of day 7. This indicates that the diet used is a good source of the required amino acids and that there are processes which facilitate an increase of amino acids during the first days of exposure. The concentration of most amino acids returned to the baseline level on the 7th recovery day.


Mollugin Has an Anti-Cancer Therapeutic Effect by Inhibiting TNF-α-Induced NF-κB Activation.
The NF-κB signaling pathway plays a pivotal role in regulating the immune response and inflammation. However, it has been shown that NF-κB also has a major role in oncogenesis. Therefore, NF-κB inhibitors have been considered as potential drugs against cancer. Herein, we searched for NF-κB inhibitors from natural sources and identified mollugin from the roots of Rubia cordifolia L. as an inhibitor of NF-κB activation. We found that mollugin significantly inhibited the expression of an NF-κB reporter gene induced by tumor necrosis factor (TNF)-α in a dose-dependent manner. Moreover, mollugin inhibited TNF-α-induced phosphorylation and nuclear translocation of p65, phosphorylation and degradation of inhibitor of κB (IκBα), and IκB kinase (IKK) phosphorylation. Furthermore, we discovered that pretreatment of cells with mollugin prevented the TNF-α-induced expression of NF-κB target genes, such as genes related to proliferation (COX-2, Cyclin D1 and c-Myc), anti-apoptosis (Bcl-2, cIAP-1 and survivin), invasion (MMP-9 and ICAM-1), and angiogenesis (VEGF). We also demonstrated that mollugin potentiated TNF-α-induced apoptosis and inhibited proliferation of HeLa cells. We further demonstrated in vivo that mollugin suppressed the growth of tumor xenografts derived from HeLa cells. Taken together, mollugin may be a valuable candidate for cancer treatment by targeting NF-κB.


Synthesis and pharmacological evaluation of new pyrazolidine-3, 5-diones as AT(1) angiotensin II receptor antagonists.
On the basis of the structure of the non-peptide receptor antagonist irbesartan, a new series of AT(1) ligands was designed. In these compounds the central imidazolone nucleus of irbesartan was replaced by a pyrazolidine-3,5-dione structure. The key intermediate N-alkylpyrazolidine-3,5-diones were synthesized according to a new and general method. The most active compounds possess a spirocyclopentane ring at position 4, a linear butyl chain at position 1, and the [2'-(5-tetrazolyl)biphenyl-4-yl]methyl or [2'-(benzoylaminosulfonyl)biphenyl-4-yl]methyl group at position 2. Affinity toward the AT(1) and AT(2) receptors was assessed by the ability of the compounds to competitively displace [(3)H]AII from its specific binding sites. The most active compounds, 28 and 48, displayed high affinity for the AT(1) receptor, good selectivity AT(1) versus AT(2), and potent in vitro antagonist activity.


Predicting the distribution of synaptic strengths and cell firing correlations in a self-organizing, sequence prediction model.
This article investigates the synaptic weight distribution of a self-supervised, sparse, and randomly connected recurrent network inspired by hippocampal region CA3. This network solves nontrivial sequence prediction problems by creating, on a neuron-by-neuron basis, special patterns of cell firing called local context units. These specialized patterns of cell firing--possibly an analog of hippocampal place cells--allow accurate prediction of the statistical distribution of synaptic weights, and this distribution is not at all gaussian. Aside from the majority of synapses that are, at least functionally, lost due to synaptic depression, the distribution is approximately uniform. Unexpectedly, this result is relatively independent of the input environment, and the uniform distribution of synaptic weights can be approximately parameterized based solely on the average activity level. Next, the results are generalized to other cell firing types (frequency codes and stochastic firing) and place cell-like firing distributions. Finally, we note that our predictions concerning the synaptic strength distribution can be extended to the distribution of correlated cell firings. Recent published neurophysiological results are consistent with this extension.


DNA sequencing and genotyping in miniaturized electrophoresis systems.
Advances in microchannel electrophoretic separation systems for DNA analyses have had important impacts on biological and biomedical sciences, as exemplified by the successes of the Human Genome Project (HGP). As we enter a new era in genomic science, further technological innovations promise to provide other far-reaching benefits, many of which will require continual increases in sequencing and genotyping efficiency and throughput, as well as major decreases in the cost per analysis. Since the high-resolution size- and/or conformation-based electrophoretic separation of DNA is the most critical step in many genetic analyses, continual advances in the development of materials and methods for microchannel electrophoretic separations will be needed to meet the massive demand for high-quality, low-cost genomic data. In particular, the development (and commercialization) of miniaturized genotyping platforms is needed to support and enable the future breakthroughs of biomedical science. In this review, we briefly discuss the major sequencing and genotyping techniques in which high-throughput and high-resolution electrophoretic separations of DNA play a significant role. We review recent advances in the development of technology for capillary electrophoresis (CE), including capillary array electrophoresis (CAE) systems. Most of these CE/CAE innovations are equally applicable to implementation on microfabricated electrophoresis chips. Major effort is devoted to discussing various key elements needed for the development of integrated and practical microfluidic sequencing and genotyping platforms, including chip substrate selection, microchannel design and fabrication, microchannel surface modification, sample preparation, analyte detection, DNA sieving matrices, and device integration. Finally, we identify some of the remaining challenges, and some of the possible routes to further advances in high-throughput DNA sequencing and genotyping technologies.


Analysis of Sinus Balloon Catheter Dilation Providers Based on Medicare Provider Utilization and Payment Data.
The use of balloon catheter dilation (BCD) to treat chronic rhinosinusitis has increased dramatically since its conception, necessitating further characterization of BCD providers and trends in its usage. Medicare data on BCD providers have made it possible to study recent demographic patterns. There has also been an increase in mid-level providers' scope of otolaryngologic practice that is not well defined. To better understand BCD adoption by studying volume of BCD procedures as well as training, geography, and practice socioeconomic characteristics of BCD providers for Medicare beneficiaries. We reviewed Medicare Provider Utilization and Payment Data Public Use Files for 2014 and 2015 for providers with claims for BCD of the sinuses. We extracted provider zip code, state, gender, and number of services per BCD code. We obtained median household income by zip code and geographic region based on US Census Bureau data. Providers were classified using an Internet search to determine practice setting and type of specialty training/certification. In 2014 and 2015, 428 providers performed 42 494 BCDs billed to Medicare beneficiaries. Among BCD providers, 5.1% were female, 98.1% had Doctor of Medicine/Doctor of Osteopathic Medicine credentials, and 1.9% had nurse practitioner/physician assistant credentials. Over the 2-year period, the median number of BCDs was 63 for physicians and 37 for mid-level providers. Fellowship-trained rhinologists performed a median of 38 BCDs over 2 years. The most common subspecialty certification/training was in facial plastics and reconstructive surgery. The majority of providers (63.8%) performed 1 to 99 BCDs over the 2 years. In the South, there were 21.9 BCD procedures performed per 100 000 people compared to 7.3 in the Northeast, 9.3 in the Midwest, and 8.5 in the West. There is a large range in total BCD procedures performed by individual providers, and this varies by certain provider characteristics. Mid-level providers have emerged as a significant population performing BCD.


Advantages and Limitations of Direct PCR Amplification of Bacterial 16S-rDNA from Resected Heart Tissue or Swabs Followed by Direct Sequencing for Diagnosing Infective Endocarditis: A Retrospective Analysis in the Routine Clinical Setting.
Infective endocarditis (IE) is a life-threatening disease that is associated with high morbidity and mortality. Its long-term prognosis strongly depends on a timely and optimized antibiotic treatment. Therefore, identification of the causative pathogen is crucial and currently based on blood cultures followed by characterization and susceptibility testing of the isolate. However, antibiotic treatment starting prior to blood sampling or IE caused by fastidious or intracellular microorganisms may cause negative culture results. Here we investigate the additional diagnostic value of broad-range PCR in combination with direct sequencing on resected heart tissue or swabs in patients with tissue or swab culture-negative IE in a routine clinical setting. Sensitivity, specificity, and positive and negative predictive values of broad-range PCR from diagnostic material in our patients were 33.3%, 76.9%, 90.9%, and 14.3%, respectively. We identified a total of 20 patients (21.5%) with tissue or culture-negative IE who profited by the additional application of broad-range PCR. We conclude that broad-range PCR on resected heart tissue or swabs is an important complementary diagnostic approach. It should be seen as an indispensable new tool for both the therapeutic and diagnostic management of culture-negative IE and we thus propose its possible inclusion in Duke's diagnostic classification scheme.


Ranked Levels of Influence model: selecting influence techniques to minimize IT resistance.
Implementation of electronic health records (EHR), particularly computerized physician/provider order entry systems (CPOE), is often met with resistance. Influence presented at the right time, in the right manner, may minimize resistance or at least limit the risk of complete system failure. Combining established theories on power, influence tactics, and resistance, we developed the Ranked Levels of Influence model. Applying it to documented examples of EHR/CPOE failures at Cedars-Sinai and Kaiser Permanente in Hawaii, we evaluated the influence applied, the resistance encountered, and the resulting risk to the system implementation. Using the Ranked Levels of Influence model as a guideline, we demonstrate that these system failures were associated with the use of hard influence tactics that resulted in higher levels of resistance. We suggest that when influence tactics remain at the soft tactics level, the level of resistance stabilizes or de-escalates and the system can be saved.


3D imaging of colorectal cancer organoids identifies responses to Tankyrase inhibitors.
Aberrant activation of the Wnt signalling pathway is required for tumour initiation and survival in the majority of colorectal cancers. The development of inhibitors of Wnt signalling has been the focus of multiple drug discovery programs targeting colorectal cancer and other malignancies associated with aberrant pathway activation. However, progression of new clinical entities targeting the Wnt pathway has been slow. One challenge lies with the limited predictive power of 2D cancer cell lines because they fail to fully recapitulate intratumoural phenotypic heterogeneity. In particular, the relationship between 2D cancer cell biology and cancer stem cell function is poorly understood. By contrast, 3D tumour organoids provide a platform in which complex cell-cell interactions can be studied. However, complex 3D models provide a challenging platform for the quantitative analysis of drug responses of therapies that have differential effects on tumour cell subpopulations. Here, we generated tumour organoids from colorectal cancer patients and tested their responses to inhibitors of Tankyrase (TNKSi) which are known to modulate Wnt signalling. Using compounds with 3 orders of magnitude difference in cellular mechanistic potency together with image-based assays, we demonstrate that morphometric analyses can capture subtle alterations in organoid responses to Wnt inhibitors that are consistent with activity against a cancer stem cell subpopulation. Overall our study highlights the value of phenotypic readouts as a quantitative method to asses drug-induced effects in a relevant preclinical model.


Suspected congenital hyperinsulinism in a Shiba Inu dog.
A 3-month-old male intact Shiba Inu dog was evaluated for a seizure disorder initially deemed idiopathic in origin. Seizure frequency remained unchanged despite therapeutic serum phenobarbital concentration and use of levetiracetam. The dog was documented to be markedly hypoglycemic during a seizure episode on reevaluation at 6 months of age. Serum insulin concentrations during hypoglycemia were 41 U/μL (reference range, 10-29 U/μL). The dog was transitioned to 4 times per day feeding, diazoxide was started at 3.5 mg/kg PO q8h, and antiepileptic drugs were discontinued. No clinically relevant abnormalities were identified on bicavitary arterial and venous phase contrast computed tomographic imaging. The dog remained seizure-free and clinically normal at 3 years of age while receiving 5.5 mg/kg diazoxide PO q12h and twice daily feeding. Seizures later occurred approximately twice per year and after exertion, with or without vomiting of a diazoxide dose. Blood glucose curves and interstitial glucose monitoring were used to titrate diazoxide dose and dosing interval. Congenital hyperinsulinism is well recognized in people but has not been reported in veterinary medicine.


[Clinical evaluation of antibiotic therapy of NAG-infection].
It is not concluded yet whether it is expedient to use antibiotic therapy with respect to patients and vibrio-carries with NAG-infection. Observation of a group of patients with acute gastro-intestinal infections caused by NAG-vibrio and carriers of NAG-vibrioes showed that the rate of vibrio isolation after a course of antibiotic therapy (tetracycline, levomycetin) significantly decreased as compared to that in the group of the patients subjected only to symptomatic therapy. The data of the study provided recommendation of antibacterial therapy with respect to patients with NAG-infection especially in cases with accompanying infections or invasions. As for "asymptomic" carriers antibiotic therapy is required only with respect to persons with repeated vibrio isolation.


Identification and characterization of CHO host-cell proteins in monoclonal antibody bioprocessing.
Host-cell proteins (HCPs) are the foremost class of process-related impurities to be controlled and removed in downstream processing steps in monoclonal antibody (mAb) manufacturing. However, some HCPs may evade clearance in multiple purification steps and reach the final drug product, potentially threatening drug stability and patient safety. This study extends prior work on HCP characterization and persistence in mAb process streams by using mass spectrometry (MS)-based methods to track HCPs through downstream processing steps for seven mAbs that were generated by five different cell lines. The results show considerable variability in HCP identities in the processing steps but extensive commonality in the identities and quantities of the most abundant HCPs in the harvests for different processes. Analysis of HCP abundance in the harvests shows a likely relationship between abundance and the reproducibility of quantification measurements and suggests that some groups of HCPs may hinder the characterization. Quantitative monitoring of HCPs persisting through purification steps coupled with the findings from the harvest analysis suggest that multiple factors, including HCP abundance and mAb-HCP interactions, can contribute to the persistence of individual HCPs and the identification of groups of common, persistent HCPs in mAb manufacturing.


Traditional Chinese medicine (phytotherapy): Health Technology Assessment report - selected aspects.
A summary of main aspects from a Health Technology Assessment report on Traditional Chinese Medicine (TCM) in Switzerland concerning effectiveness and safety is given. Literature search was performed through 13 databases, by scanning reference lists of articles and by contacting experts. Assessed were quality of documentation, internal and external validity. Effectiveness: 43 articles concerning 'gastrointestinal tract and liver' were assessed. The studies covering 7,436 patients were undertaken in China (35), Japan (3), USA (2) and Australia (3); 33/43 being controlled studies. 34/40 show significantly better results in the TCM-treated group. A comparison of studies on results of treatment based on a diagnosis according to TCM criteria and studies on results of treatment according to Western diagnosis shows that treatment based on TCM diagnosis improves the result. The comparison of treatment by individual medication and standard medication showed a trend in favor of individual medication. TCM training and practice for physicians in Switzerland are officially regulated. Side effects occur, but no severe effects have been registered up to now in Switzerland. TCM medicinals are imported; admission regulations are being installed. Problems due to production abroad, Internet trade, self-medication or admixtures are possible. The evaluation of the literature search provides evidence for a basic clinical effectiveness of TCM therapy. Severe side effects were not observed in Switzerland. Regulations for trading and use of medicinals prevent treatment risks. Further clinical studies in a Western context are required.


Retinal sensitivity to flicker modulation: reduced by early age-related maculopathy.
To evaluate retinal, cone-mediated flicker sensitivity (CFS) in age-related maculopathy (ARM) by quantifying response gain and threshold of the focal electroretinogram (FERG) to flicker modulation. Nineteen patients with ARM (visual acuity > or =20/30) and 11 age-matched control subjects were examined. Twelve patients had less than 20 soft drusen in the macular region and no hyper-/hypopigmentation (early lesion), whereas seven had more than 20 soft drusen and/or focal hyper-/hypopigmentation (advanced lesion). Macular (18 degree ) FERGs were elicited by a sinusoidally flickering (41 Hz) uniform field (on a light-adapting background) whose modulation depth was varied between 16.5% and 94%. Amplitude and phase of the response's fundamental harmonic were measured. In both control subjects and patients with ARM, log FERG amplitude increased with log stimulus modulation depth with a straight line (power law) relation. However, the slope (or gain) of the function was, on average, steeper in control subjects than in patients with either early or advanced lesions. Mean FERG threshold, estimated from the value of the log modulation depth that yielded a criterion response, did not differ between control subjects and patients with early lesions but was increased (0.35 log units) compared with control subjects in those with advanced lesions. In both patient groups, but not in control subjects, mean FERG phase tended to delay with decreasing stimulus modulation depth. Retinal CFS losses can be detected in ARM by evaluating the FERG as a function of flicker modulation depth. Reduced response gain and phase delays, with normal thresholds, are associated with early lesions. Increased response thresholds, in addition to gain and phase abnormalities, may reflect more advanced lesions. Evaluating CFS by FERG may directly document different stages of macular dysfunction in ARM.


Generation of enriched populations of cultured photoreceptor cells.
This laboratory has recently described a monolayer culture system that allows the survival and differentiation of chick embryo retinal neurons and photoreceptors in the absence of contamination by connective tissue, endothelial, glial, or pigmented epithelial cells. The authors report here that the photoreceptor cells can be further purified by exploiting the selective toxicity of kainic acid (KA) and beta-bungarotoxin (BBT), which are known to destroy many retinal neurons without affecting photoreceptors. When added to retinal cultures, both KA and BBT caused developmental stage- and concentration-dependent degeneration without affecting the number or qualitative properties of photoreceptors. Some retinal neurons were already sensitive to KA after only 2 days in vitro, and their number increased as the cultures matured. The maximum effect of KA (a loss of 60% of the neurons) was obtained with an 8-24 hr treatment with 2 mM KA after 6 days in vitro. Neuronal sensitivity to BBT showed a developmental pattern similar to KA. However, maximum neuronal losses produced by BBT were higher (70% of the neurons) and occurred at lower concentrations (1-2 nM). Combined treatments with KA and BBT did not show additive effects or potentiation between toxins. KA- or BBT-induced neuronal degeneration was accompanied by a greater than 90% loss of neuronal markers such as choline acetyltransferase activity or high-affinity GABA uptake. Transmission electron microscopy showed the integrity of photoreceptor cells in KA- and BBT-treated cultures. These results show that both KA and BBT are useful tools for the generation of enriched photoreceptor populations in vitro.


Beyond the skin: disease parameters in pemphigus.
Pemphigus represents a group of rare autoimmune bullous diseases that affect the skin and mucous membranes. This group has a chronic course leading to high morbidity and mortality. Because of the painful chronic-recurring blisters and/or erosions on skin and mucosa, pemphigus can impair quality of life (QOL). Therapeutic modalities, anxiety and depression can also have an additional negative impact in the QOL of the pemphigus patients. Since the nature and course of the pathology and the fact that pemphigus worsens the quality of life of affected patients, scoring systems to objectively evaluate the clinical activity of the disease and to correlate that with the QOL are needed. Nowadays the most used global scales to assess the clinical activity of pemphigus are the Autoimmune Bullous Skin Disorder Intensity Score (ABSIS), the Pemphigus Disease Area Index (PDAI) and the Pemphigus Visual Activity Scale (PVAS). To evaluate the patient's generic QOL the most used score is the Dermatology Life Quality Index (DLQI), but all the sponsered clinical trials in pemphigus are using ABQOL this rather than DLQI.


Longer Screws Decrease the Risk of Radiographic Pseudarthrosis Following Elective Anterior Cervical Discectomy and Fusion.
Retrospective cohort study. In patients undergoing elective anterior cervical discectomy and fusion (ACDF), we sought to determine the impact of screw length on: (1) radiographic pseudarthrosis, (2) pseudarthrosis requiring reoperation, and (3) patient-reported outcome measures (PROMs). A single-institution, retrospective cohort study was undertaken from 2010-21. The primary independent variables were: screw length (mm), screw length divided by the anterior-posterior vertebral body diameter (VB%), and the presence of any screw with VB% < 75% vs all screws with VB% ≥ 75%. Multivariable logistic regression controlled for age, BMI, gender, smoking, American Society of Anesthesiology grade, number of levels fused, and whether a corpectomy was performed. Of 406 patients undergoing ACDF, levels fused were: 1-level (39.4%), 2-level (42.9%), 3-level (16.7%), and 4-level (1.0%). Mean screw length was 14.3 ± 2.3 mm, and mean VB% was 74.4 ± 11.2. A total of 293 (72.1%) had at least one screw with VB% < 75%, 113 (27.8%) had all screws with VB% ≥ 75%, and 141 (34.7%) patients had radiographic pseudarthrosis at 1-year. Patients who had any screw with VB% < 75% had a higher rate of radiographic pseudarthrosis compared to those had all screws with VB% ≥ 75% (39.6% vs 22.1%, P < .001). Multivariable logistic regression revealed that a higher VB% (OR = .97, 95%CI = .95-.99, P = .035) and having all screws with VB% ≥ 75% (OR = .51, 95%CI = .27-.95, P = .037) significantly decreased the odds of pseudarthrosis at 1-year, with no difference in reoperation or PROMs (all P > .05). Longer screws taking up ≥75% of the vertebral body protected against radiographic pseudarthrosis at 1-year. Maximizing screw length in ACDF is an easily modifiable factor directly under the surgeon's control that may mitigate the risk of pseudarthrosis.


Intra-operative hydroxyethyl starch is not associated with post-craniotomy hemorrhage.
Intraoperative intravascular volume expansion with hydroxyethyl starch-based colloids is thought to be associated with an increased risk of post-craniotomy hemorrhage. Evidence for this association is limited. Associations between resuscitation with hydroxyethyl starch and risk of repeat craniotomy for hematoma evacuation were examined. Using a retrospective cohort of neurosurgical patients at Duke University Medical Center between March 2005 and March 2012, patient characteristics were compared between those who developed post-craniotomy hemorrhage and those who did not. A total of 4,109 craniotomy procedures were analyzed with 61 patients having repeat craniotomy for post-operative hemorrhage (1.5%). The rate of reoperation in the group receiving 6% High Molecular Weight Hydroxyethyl Starch (Hextend(®)) was 2.6 vs. 1.3% for patients that did not receive hetastarch (P = 0.13). The reoperation rate for those receiving 6% hydroxyethyl Starch 130/0.4 (Voluven(®)) was 1.4 vs. 1.6% in patients not receiving Voluven (P = 0.85). In this retrospective cohort, intra-operative hydroxyethyl starch was not associated with an increased risk of post-craniotomy hemorrhage.


The role of growth factors in neuronal development and plasticity.
The role of growth factors in the development of the nervous system, as well as in injury-induced plasticity, is of great interest. A neuronal growth factor is any substance that influences the growth of neurons, but two general classes of factors exist: diffusible substances and substrate-bound factors. Growth factors may affect neuronal survival as well as the extent and rate of neurite outgrowth in vitro. Although progress is slowly being made in the identification and characterization of putative growth factors, nerve growth factor (NGF) is the only identified molecule that clearly influences neuronal growth in vivo. Furthermore, although there are many examples of neuronal plasticity following injury, the role of growth factors in such rearrangements remains to be established. However, one model of collateral sprouting of axons from the peripheral nervous system (PNS) into the central nervous system (CNS) appears to involve the action of a growth factor with properties similar to NGF. The identification of specific molecules that affect neuronal growth should lead to an understanding of the etiology of degenerative neurological diseases such as Alzheimer's disease and, hopefully, to rational therapeutic approaches.


Learning Climate Perceptions as a Determinant of Employability: An Empirical Study Among European ICT Professionals.
This study investigated the role of age in the relationship between perceptions of learning climate and self- and supervisor-rated employability among European Information and Communication Technology (ICT) professionals. The psychological climate for learning was operationalized by three indicators, namely the perceptions that employees have of the learning value of their job, supervisor support for learning, and the organizational support for learning. As hypothesized, a Structural Equation Model demonstrated that the relationship between age and perceptions of learning climate was negative. The model also showed a strong positive relationship between learning climate and self-reported and supervisor-rated employability. Furthermore, learning climate perceptions appeared important for employability irrespective of life or career stage. An explorative bootstrapping-based test suggested that older workers with managerial responsibilities profit less from psychological learning climate for self-reported and supervisor-rated employability than older workers at non-managerial levels. These findings have important implications for human resource practices that aim to increase lifelong employability.


[Maternal and child health in the Fourth World. Initial results of a socio-epidemiological survey].
This paper presents the results of a qualitative survey of young mothers in deprived conditions, which was conducted as a part of a broader socio-epidemiological research on health inequalities amongst mother and child. This survey reveals that this group is not solely distinguished in terms of socio-economic categories. Cultural dimensions play also an important role in explaining their health related behaviour. The survey was aimed at determining the logic and principles of coping with health and sickness. The specific attitudes and behaviour of the survey group was described through fourteen dimensions (definition and perception of health, prevention, relations with professionals, networks used...). The results show that any approach of the health problems of this group has to take its specific health culture into account and that this approach is inevitable in any effort to promote health and reduce social inequalities for the so-called "Fourth World".


Health-related quality of life and working conditions among nursing providers.
To evaluate working conditions associated with health-related quality of life (HRQL) among nursing providers. Cross-sectional study conducted in a university hospital in the city of São Paulo, Southeastern Brazil, during 2004-2005. The study sample comprised 696 registered nurses, nurse technicians and nurse assistants, predominantly females (87.8%), who worked day and/or night shifts. Data on sociodemographic information, working and living conditions, lifestyles, and health symptoms were collected using self-administered questionnaires. The following questionnaires were also used: Job Stress Scale, Effort-Reward Imbalance (ERI) and Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). Ordinal logistic regression analysis using proportional odds model was performed to evaluate each dimension of the SF-36. Around 22% of the sample was found to be have high strain and 8% showed an effort-reward imbalance at work. The dimensions with the lowest mean scores in the SF-36 were vitality, bodily pain and mental health. High-strain job, effort-reward imbalance (ERI>1.01), and being a registered nurse were independently associated with low scores on the role emotional dimension. Those dimensions associated to mental health were the ones most affected by psychosocial factors at work. Effort-reward imbalance was more associated with health than high-strain (high demand and low control). The study results suggest that the joint analysis of psychosocial factors at work such as effort-reward imbalance and demand-control can provide more insight to the discussion of professional roles, working conditions and HRQL of nursing providers.


[A challenge to Peronism's social justice: hydatidosis in the province of Buenos Aires, 1946-1952].
This analysis of the sanitary policies enforced in the province of Buenos Aires by Domingo Alfredo Mercante--Juan Domingo Perón's right-hand man--focuses on one of his most fascinating efforts: the eradication of hydatidosis. In exploring an issue largely forgotten by historiography, the article describes how the Mercante administration (1946-52) used statistical, socioeconomic, and symbolic legitimization to place hydatidosis on the State agenda. The administration's strategies are also pinpointed: the passing of regulatory laws against this endemic disease; the creation of specific state anti-hydatidosis institutions; the creation of space for information and for interdisciplinary, interministerial, and even supranational education aimed at achieving greater knowledge of the disease and at the exchange of experiences; and, lastly, the definition of initiatives focused on relief, treatment, and prevention in animals and people.


Enhanced anticancer potency using an acid-responsive ZnO-incorporated liposomal drug-delivery system.
The development of stimuli-responsive nanocarriers is becoming important in chemotherapy. Liposomes, with an appropriate triggering mechanism, can efficiently deliver their encapsulated cargo in a controlled manner. We explored the use of acid-sensitive zinc oxide nanoparticles (ZNPs) as modulators of the responsive properties of liposomes. Nanocomplexes formed by the incorporation of ZNPs in liposomes (ZNP-liposomes) were designed to demonstrate the pH-responsive release of a drug (daunorubicin) without premature drug leakage and with the maintenance of the relevant therapeutic concentrations. The nanocomplexes were spherical in shape with a narrow size distribution and showed a high drug-encapsulating efficiency. Under acidic conditions, the ZNP-liposome nanocomplexes released the loaded drug more rapidly than bare liposomes. Using flow cytometry, confocal microscopy and an MTT assay, we demonstrated that these nanocomplexes were readily taken up by cancer cells, resulting in significantly enhanced cytotoxicity. On exposure to the acidic conditions inside cancer cells, the ZNPs rapidly decomposed, releasing the entrapped drug molecules from the ZNP-liposome nanocomplexes, producing widespread cytotoxic effects. The incorporated ZNPs were multimodal in that they not only resulted in a pH-responsive drug-delivery system, but they also had a synergistic chemo-photodynamic anticancer action. This design provides a significant step towards the development of multimodal liposome structures.


Customer service: the key to remaining competitive in managed care.
The health care industry is undergoing a rapid transformation to meet the ever-increasing needs and demands of its patient population. Employers and managed care organizations are demanding better service and higher quality care, while providers are trying to tackle reimbursement cutbacks, streamlining of services, and serving a diverse population. Providers have begun to realize that to overcome these obstacles and meet the needs of their health plans and consumers, they must focus on the demands of their customers. Health care organizations have found they can meet the demands of both the consumer and the managed care industry through initiating and maintaining a customer service program. This essay explains the importance of customer service and its link to success in the managed care environment.


Comparing Machine Learning Algorithms for Predicting Acute Kidney Injury.
Prior studies have used vital signs and laboratory measurements with conventional modeling techniques to predict acute kidney injury (AKI). The purpose of this study was to use the trend in vital signs and laboratory measurements with machine learning algorithms for predicting AKI in ICU patients. The eICU Collaborative Research Database was queried for five consecutive days of laboratory measurements per patient. Patients with AKI were identified and trends in vital signs and laboratory values were determined by calculating the slope of the least-squares-fit linear equation using three days for each value. Different machine learning classifiers (gradient boosted trees [GBT], logistic regression, and deep learning) were trained to predict AKI using the laboratory values, vital signs, and slopes. There were 151,098 ICU stays identified and the rate of AKI was 5.6 per cent. The best performing algorithm was GBT with an AUC of 0.834 ± 0.006 and an F-measure of 42.96 per cent ± 1.26 per cent. Logistic regression performed with an AUC of 0.827 ± 0.004 and an F-measure of 28.29 per cent ± 1.01 per cent. Deep learning performed with an AUC of 0.817 ± 0.005 and an F-measure of 42.89 per cent ± 0.91 per cent. The most important variable for GBT was the slope of the minimum creatinine (30.32%). This study identifies the best performing machine learning algorithms for predicting AKI using trends in laboratory values in ICU patients. Early identification of these patients using readily available data indicates that incorporating machine learning predictive models into electronic medical record systems is an inevitable requisite for improving patient outcomes.


Occupational contact dermatitis to nickel: experience of the British dermatologists (EPIDERM) and occupational physicians (OPRA) surveillance schemes.
To examine, from occupational surveillance reporting data, whether scheme reporters considered nickel exposure to play a role in occupational contact dermatitis (OCD) in the UK. Data on occupational skin disease in the UK are collected by two occupational disease surveillance schemes, EPIDERM and OPRA. Cases of OCD believed to have relevant nickel exposure reported to EPIDERM or OPRA from February 1993 to January 1999 were studied. An estimate of 1190 cases of occupational contact dermatitis thought to have relevant nickel exposure (12% of total estimated OCD) was derived from reports by dermatologists, an average of 198 per year. The highest incidence rates were seen in hairdressers (23.9/100 000 workers/year), bar staff (4.7), chefs and cooks (4.4), retail cash and checkout operators (2.8), and catering assistants (2.5). From May 1994 to January 1999, 158 cases of nickel associated dermatitis (1.9% of total OCD cases) were estimated; the most frequently reported occupations were electronic assemblers, nurses, sales assistants, and general assemblers. From July 1997 to January 1999, 547 positive patch tests to nickel were reported; in 195 cases (36%), nickel was felt to be a relevant occupational allergen (for example, coin handling). In hairdressers, nurses, cooks, and beauticians, nickel was usually considered, if relevant at all, to be only one of several causes of dermatitis. Up to 12% of total estimated cases of OCD were thought to be due in part to nickel. Results suggest that nickel hypersensitivity is one of several contributors to OCD in subjects with multiple occupational exposures. Coin handling may be a source of OCD to nickel.


Why young Dutch in-line skaters do (not) use protection equipment.
In-line skate injuries are highly preventable by the use of protective gear. We investigated how young Dutch skaters protect themselves and what factors predict the use of protective gear in order to develop campaigns to increase their safety behaviour. A survey was conducted to study protection behaviour of 872 Dutch skaters and factors influencing the use of protective gear. Written questionnaires were used, measuring behaviour and social psychological determinants towards the use of protective behaviour. Protective gear was not often used: 36% used wrist guards, 28% used kneepads, 14% used elbow pads and 5% used helmets. The use of protective gear was influenced by social influences, self-efficacy expectations and intention (R2=54%). The present study shows that young Dutch skaters should improve their safety behaviour in order to prevent skate injuries. Furthermore, the study provides clear recommendations for developing prevention programmes.


Use of water extraction variability to screen for sunflower genotypes well adapted to soil water limitation.
In conditions of water deficit, plant yield depends mostly on the ability of the plant to explore soil profile and its water uptake capacity per unit volume of soil. In this study, the value of soil water extraction properties for use in sunflower breeding was evaluated. Five experiments were carried out in pots, in greenhouses, from 2005 to 2009, in Montpellier, France. Elite sunflower cultivars and experimental hybrids obtained from a factorial cross between five female and five male inbred lines were grown. The soil water extraction performance of the plants was characterised by the soil water content at minimal stomatal conductance (SWCgs=0) and the index of water extraction (IEgen), which was calculated as the relative value of SWCgs=0 to the performance of the cultivar NKMelody. Heritability (H2) was estimated for the experimental hybrids. Phenotypic variability of the SWCgs=0 was observed with a significant effect of the environment and the genotype. The latest released cultivars were observed as the best performing one in water extraction with an IEgen under 0.85. This trait was found to be suitable for use in comparisons of the soil water extraction performances of different genotypes. The high H2 value for SWCgs=0 (0.77 and 0.81) and the significant correlation (r2=0.70, P<0.001) between the values obtained for the experimental hybrids and the mean values of the general combining ability (GCA) for the parental lines showed that this trait is heritable and could be used in plant breeding programs. Phenotyping methods and the usefulness of this trait in crop modelling are discussed.


Changes in In Vitro Susceptibility Patterns of Aspergillus to Triazoles and Correlation With Aspergillosis Outcome in a Tertiary Care Cancer Center, 1999-2015.
Azole-resistant aspergillosis in high-risk patients with hematological malignancy or hematopoietic stem cell transplantation (HSCT) is a cause of concern. We examined changes over time in triazole minimum inhibitory concentrations (MICs) of 290 sequential Aspergillus isolates recovered from respiratory sources during 1999-2002 (before introduction of the Aspergillus-potent triazoles voriconazole and posaconazole) and 2003-2015 at MD Anderson Cancer Center. We also tested for polymorphisms in ergosterol biosynthetic genes (cyp51A, erg3C, erg1) in the 37 Aspergillus fumigatus isolates isolated from both periods that had non-wild-type (WT) MICs. For the 107 patients with hematologic cancer and/or HSCT with invasive pulmonary aspergillosis, we correlated in vitro susceptibility with 42-day mortality. Non-WT MICs were found in 37 (13%) isolates and was only low level (MIC <8 mg/L) in all isolates. Higher-triazole MICs were more frequent in the second period and were Aspergillus-species specific, and only encountered in A. fumigatus. No polymorphisms in cyp51A, erg3C, erg1 genes were identified. There was no correlation between in vitro MICs with 42-day mortality in patients with invasive pulmonary aspergillosis, irrespective of antifungal treatment. Asian race (odds ratio [OR], 20.9; 95% confidence interval [CI], 2.5-173.5; P = .005) and azole exposure in the prior 3 months (OR, 9.6; 95% CI, 1.9-48.5; P = .006) were associated with azole resistance. Non-WT azole MICs in Aspergillus are increasing and this is associated with prior azole exposure in patients with hematologic cancer or HSCT. However, no correlation of MIC with outcome of aspergillosis was found in our patient cohort.


[Results of surgical treatment of gastric cancer].
Of 6260 patients operated on for gastric cancer in Donetskiy regional antitumoral centre from 1968 till 1996 palliative interventions were accomplished in 2927. Distal gastric resection was done in 1435 (54.7%) patients. Since 1974 yr. the muff-like anastomosis is applied, which promotes the prophylaxis of insufficiency of oesophago-intestinal and gastro-intestinal anastomoses, reflux-oesophagitis and reflux-gastritis occurrence. Late follow-up result of treatment was studied up in 226 patients: 30% survived 5-10 years and 7%--more than 10 years. The prognosis of patient's life depends trustworthy on the degree of the gastric lymph node system involvement.


Intersection of Stress, Social Disadvantage, and Life Course Processes: Reframing Trauma and Mental Health.
This paper describes the intersection of converging lines of research on the social structural, psychosocial, and physiological factors involved in the production of stress and implications for the field of mental health. Of particular interest are the stress sensitization consequences stemming from exposure to adversity over the life course. Contemporary stress sensitization theory provides important clinical utility in articulating mechanisms through which these multiple levels exert influence on mental health. Stress sensitization models (a) extend understanding of neurobiological and functional contexts within which extreme stressors operate and (b) make clear how these can influence psychologically traumatic outcomes. The value of interventions that are sensitive to current contexts as well as life course profiles of cumulative stress are illustrated through recent treatment innovations.


Supplemental vitamin D enhances the recovery in peak isometric force shortly after intense exercise.
Serum 25-hydroxyvitamin D (25(OH)D) concentrations associate with skeletal muscle weakness (i.e., deficit in skeletal muscle strength) after muscular injury or damage. Although supplemental vitamin D increases serum 25(OH)D concentrations, it is unknown if supplemental vitamin D enhances strength recovery after a damaging event. Reportedly healthy and modestly active (30 minute of continuous physical activity at least 3 time/week) adult males were randomly assigned to a placebo (n = 13, age, 31(5) y; BMI, 26.9(4.2) kg/m2; serum 25(OH)D, 31.0(8.2) ng/mL) or vitamin D (cholecalciferol, 4000 IU; n = 15; age, 30(6) y; BMI, 27.6(6.0) kg/m2; serum 25(OH)D, 30.5(9.4) ng/mL) supplement. Supplements were taken daily for 35-d. After 28-d of supplementation, one randomly selected leg performed an exercise protocol (10 sets of 10 repetitive eccentric-concentric jumps on a custom horizontal plyo-press at 75% of body mass with a 20 second rest between sets) intended to induce muscle damage. During the exercise protocol, subjects were allowed to perform presses if they were unable to complete two successive jumps. Circulating chemistries (25(OH)D and alanine (ALT) and aspartate (AST) aminotransferases), single-leg peak isometric force, and muscle soreness were measured before supplementation. Circulating chemistries, single-leg peak isometric force, and muscle soreness were also measured before (immediately) and after (immediately, 1-h [blood draw only], 24-h, 48-h, 72-h, and 168-h) the damaging event. Supplemental vitamin D increased serum 25(OH)D concentrations (P < 0.05; ≈70%) and enhanced the recovery in peak isometric force after the damaging event (P < 0.05; ≈8% at 24-h). Supplemental vitamin D attenuated (P < 0.05) the immediate and delayed (48-h, 72-h, or 168-h) increase in circulating biomarkers representative of muscle damage (ALT or AST) without ameliorating muscle soreness (P > 0.05). We conclude that supplemental vitamin D may serve as an attractive complementary approach to enhance the recovery of skeletal muscle strength following intense exercise in reportedly active adults with a sufficient vitamin D status prior to supplementation.


Is observation dead in follicular lymphoma? Still appropriate.
Given the incurable yet indolent nature of follicular lymphoma (FL) and the lack of a survival benefit seen with the early treatment of patients with a low tumor burden, watchful waiting has been the predominant strategy for treating asymptomatic patients with newly diagnosed FL for more than 2 decades. The success and tolerability of rituximab for the treatment of this disease, however, has led to challenges for this treatment paradigm and the consideration of early upfront treatment with rituximab monotherapy, with or without rituximab maintenance. These strategies have resulted in improvements in quality of life with a low incidence of toxicity and have led some to practice changes. However, based on uncertainty about how early treatment affects response to second treatment, the differential cost of treatment, and the lack of a survival benefit, observation remains an appropriate and viable strategy for select patients.


Investigation of the effects of cognitive tasks on balance performance in young adults.
Individuals routinely perform cognitive tasks concurrent to balance functions. The attention is one of the most important cognitive functions and it has effects on vestibular system. This study aims to investigate the connection between balance and cognitive tasks under different conditions. Visual attention tasks (VAT) and auditory attention tasks (AAT) were given to 30 healthy adults (40.42 ± 11.22 years) during functional balance tasks. Sensory Organization Test (SOT) and Adaptation Test (ADT) were used for the evaluation of postural stability and adaptation. The sounds were presented from the computer speakers in AATs, and VATs were presented in the virtual reality (VR) environment. The first SOT condition had a statistically significant difference between all dual VAT (DT-VAT) and single task (ST) (p < 0.001), but there was no statistically significant difference between ST and DT-AAT (p = 1.00). In the fourth SOT condition, there was a statistically significant difference between all DT-VATs versus ST and DT-VA (p < 0.001); there was no statistically significant difference between ST and DT-AA scores (p = 0.80). While there was a significant difference between DT-VA and ST and DT-AA (p < 0.001), no statistically significant difference was observed between ST and DT-AA in the ADT (p = 0.321). Balance performance gets worse with VAT in a VR environment. VR technology can be used to effectively evaluate balance and cognitive performance. The use of experimental environments in standard postural evaluations increases the efficiency of the postural stability tests.


Mechanisms of Graft Rejection and Immune Regulation after Lung Transplant.
Outcomes after lung transplant lag behind those of other solid-organ transplants. A better understanding of the pathways that contribute to rejection and tolerance after lung transplant will be required to develop new therapeutic strategies that take into account the unique immunological features of lungs. Mechanistic immunological investigations in an orthotopic transplant model in the mouse have shed new light on immune responses after lung transplant. Here, we highlight that interactions between immune cells within pulmonary grafts shape their fate. These observations set lungs apart from other organs and help provide the conceptual framework for the development of lung-specific immunosuppression.


Codeine Addiction and Internet Forum Use and Support: Qualitative Netnographic Study.
The use of codeine as an analgesic is well-recognized, but there are increasing concerns that for some individuals continued use may lead to misuse, dependence, and fatalities. Research suggests that those affected may represent a hard-to-reach group who do not engage with formal treatment services. This study sought to explore the experiences of people with self-reported addiction to codeine and, specifically, how a social media forum is used to communicate with others about this issue. Using a qualitative netnographic methodology, the social media forum Mumsnet was used, with permission, and searches were undertaken in 2016 of any posts that related to codeine and addiction. A total of 95 relevant posts were identified; a purposive sample of 25 posts was selected to undertake subsequent six-stage thematic analysis and development of emerging themes. These 25 posts were posted between 2003 and 2016 and comprised 757 individual posts. Individuals created posts to actively request help in relation to usually their own, but occasionally their partner's or relative's, problems relating to codeine use and self-reported "addiction." Varying levels of detail were provided in narratives of problematic codeine use. There were both positive and negative descriptions of side effects emerging, problems experiencing withdrawal, and failed attempts to discontinue codeine use. Mainly positive and supportive responses to posts were identified from those with either self-reported health profession experience or lay respondents, who often drew on their own experiences of similar problems. Treatment advice emerged in two main ways, either as signposting to formal health services or to informal approaches and often anecdotal advice about how to taper or use cold turkey techniques. Some posts were more critical of the original poster, and arguments and challenges to advice were not uncommon. Shame and stigma were often associated with users' posts and, while there was a desire to receive support and treatment advice in this forum, users often wanted to keep their codeine use hidden in other aspects of their lives. Distinctly different views emerged as to whether responsibility lay with prescribers or patients. Some users expressed anger toward doctors and their prescribing practices. This study provides a unique insight into how a public internet forum is used by individuals to confirm and seek support about problematic codeine use and of the ways others respond. The pseudonymous use of internet forums for such information and variation in treatment options suggested by often lay respondents suggest that increased formal support and awareness about codeine addiction are needed. There may be opportunities for providing further support directly on such online forums. Improvements in prescribing codeine and in the over-the-counter supply of codeine are required to prevent problematic use from occurring.


Efficient self-assembly of DNA-functionalized fluorophores and gold nanoparticles with DNA functionalized silicon surfaces: the effect of oligomer spacers.
Although strategies for the immobilization of DNA oligonucleotides onto surfaces for bioanalytical and top-down bio-inspired nanobiofabrication approaches are well developed, the effect of introducing spacer molecules between the surface and the DNA oligonucleotide for the hybridization of nanoparticle-DNA conjugates has not been previously assessed in a quantitative manner. The hybridization efficiency of DNA oligonucleotides end-labelled with gold nanoparticles (1.4 or 10 nm diameter) with DNA sequences conjugated to silicon surfaces via hexaethylene glycol phosphate diester oligomer spacers (0, 1, 2, 6 oligomers) was found to be independent of spacer length. To quantify both the density of DNA strands attached to the surfaces and hybridization with the surface-attached DNA, new methodologies have been developed. Firstly, a simple approach based on fluorescence has been developed for determination of the immobilization density of DNA oligonucleotides. Secondly, an approach using mass spectrometry has been created to establish (i) the mean number of DNA oligonucleotides attached to the gold nanoparticles and (ii) the hybridization density of nanoparticle-oligonucleotide conjugates with the silicon surface-attached complementary sequence. These methods and results will be useful for application with nanosensors, the self-assembly of nanoelectronic devices and the attachment of nanoparticles to biomolecules for single-molecule biophysical studies.


[Study of cooperative transitions in DNA using phase diagrams].
The study of the triple equilibria (A, B, Coil) and (A, B, Z) makes it possible to obtain interconnection between thermodynamic parameters of different co-operative transitions in DNA. Melting of DNA of poly[d(A--T)] was performed in a broad interval of trifluoroethanol (TFE) concentrations including those of the B to A transition range. A branch, which characterizes the helix-coil equilibrium, has a universal shape for different DNAs and the polynucleotide: melting temperature is minimum near 30% TFE and increases sharply within the region of the A form stability (greater than 65% TFE). The B-A equilibrium depends on temperature only slightly. The slope angles of the branches in the vicinity of the triple point (A, B, Coil) allow to estimate the co-operativity length of the B-A transition: it proves to be of the order of 20 base pairs for DNA and the polynucleotides. Due to the finite transition widths a peculiar situation, not studied up to now, is realized in our cases, at which three different conformations may be present in one polymeric molecule. This results in some new effects, predicted by a theory, such as stabilization by the B/A junctions of the helical state and the increase in width of the melting curves within the B-A transition interval. It thus appears that the phase diagram method may become a very informative approach to the studies of DNA metamorphosis in solution.


[Calciuretic renal function in patients with essential hypertension].
Under the conditions of standard and customary calcium use, patients suffering from essential hypertension (EH) do not manifest any changes in calciuresis either at the expense of the glomerular or tubular mechanisms. After intravenous hypercalcemic injections EH patients demonstrate well-defined disorders in calciuretic renal function, caused by inadequate suppression of tubular reabsorption of calcium by parathyroid hormone (PTH). The hormonal-renal correlations in EH patients differ from those in normals. More pronounced alterations in the concentration of radioimmune PTH and calcitonin under acute hypercalcemia are not associated with an adequate increment of fractional excretion of calcium whereas the calciuretic effect of exogenous calcium-regulating hormones (CRH) realized at the tubular level is less remarkable. Therefore EH patients manifest changes not only in CRH secretion but also in the sensitivity to them of the renal tubules. White changing parathyroid regulation of calcium metabolism prolonged administration of calcium to EH patients enhances body capabilities of resisting acute alterations in calcemia because of normalization of calciuretic renal function, especially tubular calcium transport. In addition, it lowers arterial pressure and enables reduction of the dose of calcium antagonists used in the treatment of EH.


Severe lung disease in children with cystic fibrosis missed in newborn screening.
Cystic fibrosis (CF) is now routinely diagnosed through newborn screening (NBS), but the tests employed in the USA have been evolving for two decades as missed cases become recognized and lab methods improve in association with more knowledge about CF genetics. New Jersey was among the first states to implement CF NBS in 2001 when it introduced the original two-tiered method that combined measurements of immunoreactive trypsinogen (IRT) with detection of the principal pathogenic variant (F508del) in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. With continuation of the IRT/DNA (F508del) algorithm for two decades and identification of screening false negative children, we decided to examine the condition of some missed cases with special attention to their respiratory status. To strengthen the arguments for quality improvement in New Jersey's CF NBS program, we reviewed and evaluated false negative cases to determine the potential extent of preventable patient suffering as a consequence of delayed diagnoses. Five children with CF who had false negative screening results were studied in detail. In each case there was a different cause of the negative screening results. They all had clinically significant/severe lung disease, ranging from chronic cough with CF pathogens on respiratory culture at a young age to respiratory failure. This case series highlights the consequences of false negative screening results, which served as the impetus to upgrade New Jersey's CF NBS algorithm. Implemented changes include lowering the IRT cutoff to 70 ng/mL and expanding to a 139 variant CFTR panel. In 2023, a floating IRT cutoff is anticipated to be implemented.


[The quality control of a photoprotector bag against ultraviolet light].
The action of light on parenteral nutritional solutions may affect the stability of many of their ingredients. The aim of this study is to perform quality controls on a commercial photoprotective bag by quantifying the degradation of riboflavin in isotonic saline solution during forty-eight hours. Thirty solutions were prepared using 5 mg of riboflavin in 500 ml of saline solution. These were divided into three batches; one not protected from the light, one in a black bag and the third in a commercial bag. Samples were taken at 0 and 48 hours, and were analyzed by spectrophotometry. Solutions were prepared using 1.75 mg of riboflavin in 500 ml of saline solution. The same method was followed, and the samples were analyzed by fluorometry. The results were analyzed using the Student t test. The black bag was seen to be superior to the other two as a protector against ultraviolet light. There were no significant differences between the commercial bag and the non-protective bag.


Dementia: a three-pronged strategy for primary care.
A common mistake is prematurely reassuring the patient and family that "nothing is wrong" if history and physical--with or without a brief mental status exam--is reasonably normal. Caregivers should be informed that although a cure for dementia is seldom found, there often are targets for medical intervention that could lead to improved mental and physical function for the patient.


Hysteroscopic Removal of Retained Products of Conception Implanted Over a Focal Area of Adenomyosis: A Case Report.
To describe a technique for hysteroscopic removal of retained products of conception (RPOC) implanted over an area of adenomyosis. A case report (Canadian Task Force classification III). RPOC is an unfortunate complication that may occur after the resolution of a normal pregnancy; it is more common after early pregnancy termination or spontaneous miscarriage [1]. Immediate consequences of RPOC include persistent vaginal bleeding, abdominal pain, pelvic infection, fever, and dilated cervix. Moreover, known long-term complications include the formation of intrauterine adhesions (IUAs) with the potential creation of Asherman syndrome resulting in adverse reproductive outcomes caused by subfertility, chronic pelvic pain, menstrual disturbances, and severe pregnancy complications such as abnormal placentation including the placenta accreta spectrum [2,3]. A recently published American Association of Gynecologic Laparoscopists practice report on IUAs suggests that the surgical approach used to treat intrauterine pathology could have an impact with greater risk for IUA formation when blind versus procedures under direct visualization are performed [4]. A 35-year-old patient who presented with persistent bleeding for over 5 weeks. The patient has a long history of dysmenorrhea and heavy menstrual bleeding. Magnetic resonance imaging revealed the presence of adenomyosis. She had an unfortunate spontaneous abortion at 8 weeks of gestation. On physical examination, she was found to have a dilated uterine cervix with persistent vaginal bleeding; there were no signs of infection. Pelvic ultrasound revealed an intrauterine hyperechogenic vascularized area of 2 × 2, 8 × 2 cm implanted over a focal area of adenomyosis, which is consistent with the presence of RPOC. With the aim of minimizing possible acute complications such as bleeding, infection, and uterine perforation, a hysteroscopic approach was taken to avoid performing a blind dilation and curettage. A secondary benefit of a hysteroscopic approach is a lower incidence of long-term complications such as IUAs and the consequent Asherman syndrome. We describe a hysteroscopic technique in which the use of electrosurgery is limited to minimize thermal damage of the endometrium, highlighting important tips and tricks of the procedure. Hysteroscopic removal of RPOC is a feasible and safe management option of this complication of pregnancy. We strongly suggest avoiding performing blind procedures such as dilation and curettage and favor the adoption of this modality that allows the removal of retained products of conception under direct visualization.


Functional Analyses of a Small Secreted Cysteine-Rich Protein ThSCSP_14 in Tilletia horrida.
Tilletia horrida is a biotrophic basidiomycete fungus that causes rice kernel smut, one of the most significant diseases in hybrid rice-growing areas worldwide. Little is known about the pathogenic mechanisms and functions of effectors in T. horrida. Here, we performed functional studies of the effectors in T. horrida and found that, of six putative effectors tested, only ThSCSP_14 caused the cell death phenotype in epidermal cells of Nicotiana benthamiana leaves. ThSCSP_14 was upregulated early on during the infection process, and the encoded protein was secreted. The predicted signal peptide (SP) of ThSCSP_14 was required for its ability to induce the necrosis phenotype. Furthermore, the ability of ThSCSP_14 to trigger cell death in N. benthamiana depended on suppressing the G2 allele of Skp1 (SGT1), required for Mla12 resistance (RAR1), heat-shock protein 90 (HSP90), and somatic embryogenesis receptor-like kinase (SERK3). It is important to note that ThSCSP_14 induced a plant defense response in N. benthamiana leaves. Hence, these results demonstrate that ThSCSP_14 is a possible effector that plays an essential role in T. horrida-host interactions.


Nasal Pressure Derived Airflow Limitation and Ventilation Measurements are Resilient to Reduced Signal Quality.
Obstructive sleep apnea is a disorder characterized by partial or complete airway obstructions during sleep. Our previously published algorithms use the minimally invasive nasal pressure signal routinely collected during diagnostic polysomnography (PSG) to segment breaths and estimate airflow limitation (using flow:drive) and minute ventilation for each breath. The first aim of this study was to investigate the effect of airflow signal quality on these algorithms, which can be influenced by oronasal breathing and signal-to-noise ratio (SNR). It was hypothesized that these algorithms would make inaccurate estimates when the expiratory portion of breaths is attenuated to simulate oronasal breathing, and pink noise is added to the airflow signal to reduce SNR. At maximum SNR and 0% expiratory amplitude, the average error was 2.7% for flow:drive, -0.5% eupnea for ventilation, and 19.7 milliseconds for breath duration (n = 257,131 breaths). At 20 dB and 0% expiratory amplitude, the average error was -15.1% for flow:drive, 0.1% eupnea for ventilation, and 28.4 milliseconds for breath duration (n = 247,160 breaths). Unexpectedly, simulated oronasal breathing had a negligible effect on flow:drive, ventilation, and breath segmentation algorithms across all SNRs. Airflow SNR ≥ 20 dB had a negligible effect on ventilation and breath segmentation, whereas airflow SNR ≥ 30 dB had a negligible effect on flow:drive. The second aim of this study was to explore the possibility of correcting these algorithms to compensate for airflow signal asymmetry and low SNR. An offset based on estimated SNR applied to individual breath flow:drive estimates reduced the average error to ≤ 1.3% across all SNRs at patient and breath levels, thereby facilitating for flow:drive to be more accurately estimated from PSGs with low airflow SNR.Clinical Relevance- This study demonstrates that our airflow limitation, ventilation, and breath segmentation algorithms are robust to reduced airflow signal quality.


The effects of exposure to titanium dioxide nanoparticles during lactation period on learning and memory of rat offspring.
Nanoscale titanium dioxide (TiO2), which is massively produced and widely used in living environment, seems to have a potential risk on human health. The central nervous system (CNS) is the potential susceptible target of nanoparticles, but the studies on this aspect are limited so far. The aim of this study was to evaluate the effects of exposure to TiO2 nanoparticles during lactation period on learning and memory of offspring. Lactating Wistar rats were exposed to TiO2 nanoparticles (100 mg/kg; gavage) for 21 days. The Morris water maze and passive avoidance tests showed that the exposure to TiO2 nanoparticles could significantly impair the memory and learning in the offspring. Therefore, the application of TiO2 nanoparticles and the effects of their exposure, especially during developmental period on human brain should be cautious.


[Age-related changes in the activity of free-radical processes in rat tissues and blood serum].
Activity of Cu,Zn-superoxide dismutase (SOD) in old rats' brain was found to be decreased by 46.8% as compared to young animals. The brain concentration of Schiff bases (SB) was decreased by 13.6% in old rats, whereas concentration of diene conjugates (DC), protein peroxidation (PP), and total antioxidative activity (TAA) was the same in old as well as in young rats. The liver level of the DC and TAA was also the same. The serum level of the PP, SB, and DC was increased whereas the activity of the SOD and TAA was decreased in old rats. The findings suggest occurrence of considerable age-related changes in free radical processes as well as the organ specifics of these changes in rats.


Gingival transcriptomic patterns of macrophage polarization during initiation, progression, and resolution of periodontitis.
Phenotypic and functional heterogeneity of macrophages is clearly a critical component of their effective functions in innate and adaptive immunity. This investigation hypothesized that altered profiles of gene expression in gingival tissues in health, disease, and resolution would reflect changes in macrophage phenotypes occurring in these tissues. The study used a nonhuman primate model to evaluate gene expression profiles as footprints of macrophage variation using a longitudinal experimental model of ligature-induced periodontitis in animals from 3 to 23 years of age to identify aging effects on the gingival environment. Significant differences were observed in distribution of expressed gene levels for M0, M1, and M2 macrophages in healthy tissues with the younger animals showing the least expression. M0 gene expression increased with disease in all but the aged group, while M1 was increased in adult and young animals, and M2 in all age groups, as early as disease initiation (within 0.5 months). Numerous histocompatibility genes were increased with disease, except in the aged samples. An array of cytokines/chemokines representing both M1 and M2 cells were increased with disease showing substantial increases with disease initiation (e.g. IL1A, CXCL8, CCL19, CCL2, CCL18), although the aged tissues showed a more limited magnitude of change across these macrophage genes. The analytics of macrophage genes at sites of gingival health, disease, and resolution demonstrated distinct profiles of host response interactions that may help model the disease mechanisms occurring with the formation of a periodontal lesion.


Exercise and Physical Therapy Interventions for Children with Ataxia: A Systematic Review.
The effectiveness of exercise and physical therapy for children with ataxia is poorly understood. The aim of this systematic review was to critically evaluate the range, scope and methodological quality of studies investigating the effectiveness of exercise and physical therapy interventions for children with ataxia. The following databases were searched: AMED, CENTRAL, CDSR, CINAHL, ClinicalTrials.gov, EMBASE, Ovid MEDLINE, PEDro and Web of Science. No limits were placed on language, type of study or year of publication. Two reviewers independently determined whether the studies met the inclusion criteria, extracted all relevant outcomes, and conducted methodological quality assessments. A total of 1988 studies were identified, and 124 full texts were screened. Twenty studies were included in the review. A total of 40 children (aged 5-18 years) with ataxia as a primary impairment participated in the included studies. Data were able to be extracted from eleven studies with a total of 21 children (aged 5-18 years), with a range of cerebellar pathology. The studies reported promising results but were of low methodological quality (no RCTs), used small sample sizes and were heterogeneous in terms of interventions, participants and outcomes. No firm conclusions can be made about the effectiveness of exercise and physical therapy for children with ataxia. There is a need for further high-quality child-centred research.


Chromatin Signature Identifies Monoallelic Gene Expression Across Mammalian Cell Types.
Monoallelic expression of autosomal genes (MAE) is a widespread epigenetic phenomenon which is poorly understood, due in part to current limitations of genome-wide approaches for assessing it. Recently, we reported that a specific histone modification signature is strongly associated with MAE and demonstrated that it can serve as a proxy of MAE in human lymphoblastoid cells. Here, we use murine cells to establish that this chromatin signature is conserved between mouse and human and is associated with MAE in multiple cell types. Our analyses reveal extensive conservation in the identity of MAE genes between the two species. By analyzing MAE chromatin signature in a large number of cell and tissue types, we show that it remains consistent during terminal cell differentiation and is predominant among cell-type specific genes, suggesting a link between MAE and specification of cell identity.


A prospective feasibility trial exploring novel biomarkers for neurotoxicity after isolated limb perfusion.
Isolated limb perfusion (ILP) is a regional cancer treatment in which high-dose chemotherapy is administered in an isolated extremity. The main side effect is regional toxicity, which occasionally leads to nerve damage. Measuring neuroaxonal biomarkers, might be a method predicting such complications. Therefore, the primary aim of the study is to investigate if neuronal biomarkers are measurable and alters in an isolated extremity during ILP. Secondly, if postoperative regional toxicity, alterations in sensitivity, and/or muscle strength are correlated to the biomarker levels. Eighteen scheduled ILP-patients were included in the study. Glial fibrillary acidic protein (GFAP), neurofilament light (NfL), and tau concentrations were measured in plasma sampled preoperatively, at the start and end of the ILP, on days 3 and 30, using ultrasensitive Single molecule array (Simoa) technology. The patients were assessed by a physiotherapist pre- and postoperatively. At ILP end, significantly higher NfL and tau levels were measured in the extremity than in the corresponding systemic circulation (NfL; 17 vs 6 ng/L, p < .01, tau; 1.8 vs 0.6 ng/L, p < .01), and the extremity levels were significantly increased at ILP end (NfL; 66 ± 37%, p < .001, tau; 75 ± 45%, p = .001). On days 3 and 30, significantly increased NfL and GFAP levels were measured systemically (NfL day 3: 69 ± 30%, p < .001; day 30: 76 ± 26%, p < .001; GFAP day 3: 33 ± 22%, p < .002; day 30: 33 ± 23%, p ≤ .004). Finally, no significant correlations were found between regional toxicity or between postoperative muscle or sensitivity decrease and biomarker release. During ILP, NfL and tau levels increased significantly. No obvious correlations were observed between biomarker release and regional toxicity or decreased muscle strength or sensitivity, although large-scale studies are warranted.


Metadegradomics: toward in vivo quantitative degradomics of proteolytic post-translational modifications of the cancer proteome.
Post-translational modifications enable extra layers of control of the proteome, and perhaps the most important is proteolysis, a major irreversible modification affecting every protein. The intersection of the protease web with a proteome sculpts that proteome, dynamically modifying its state and function. Protease expression is distorted in cancer, so perturbing signaling pathways and the secretome of the tumor and reactive stromal cells. Indeed many cancer biomarkers are stable proteolytic fragments. It is crucial to determine which proteases contribute to the pathology versus their roles in homeostasis and in mitigating cancer. Thus the full substrate repertoire of a protease, termed the substrate degradome, must be deciphered to define protease function and to identify drug targets. Degradomics has been used to identify many substrates of matrix metalloproteinases that are important proteases in cancer. Here we review recent degradomics technologies that allow for the broadly applicable identification and quantification of proteases (the protease degradome) and their activity state, substrates, and interactors. Quantitative proteomics using stable isotope labeling, such as ICAT, isobaric tags for relative and absolute quantification (iTRAQ), and stable isotope labeling by amino acids in cell culture (SILAC), can reveal protease substrates by taking advantage of the natural compartmentalization of membrane proteins that are shed into the extracellular space. Identifying the actual cleavage sites in a complex proteome relies on positional proteomics and utilizes selection strategies to enrich for protease-generated neo-N termini of proteins. In so doing, important functional information is generated. Finally protease substrates and interactors can be identified by interactomics based on affinity purification of protease complexes using exosite scanning and inactive catalytic domain capture strategies followed by mass spectrometry analysis. At the global level, the N terminome analysis of whole communities of proteases in tissues and organs in vivo provides a full scale understanding of the protease web and the web-sculpted proteome, so defining metadegradomics.


Stability Prediction for Mutations in the Cytosolic Domains of Cystic Fibrosis Transmembrane Conductance Regulator.
Cystic Fibrosis (CF) is caused by mutations to the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) chloride channel. CFTR is composed of two membrane spanning domains, two cytosolic nucleotide-binding domains (NBD1 and NBD2) and a largely unstructured R-domain. Multiple CF-causing mutations reside in the NBDs and some are known to compromise the stability of these domains. The ability to predict the effect of mutations on the stability of the cytosolic domains of CFTR and to shed light on the mechanisms by which they exert their effect is therefore important in CF research. With this in mind, we have predicted the effect on domain stability of 59 mutations in NBD1 and NBD2 using 15 different algorithms and evaluated their performances via comparison to experimental data using several metrics including the correct classification rate (CCR), and the squared Pearson correlation (R2) and Spearman's correlation (ρ) calculated between the experimental ΔTm values and the computationally predicted ΔΔG values. Overall, the best results were obtained with FoldX and Rosetta. For NBD1 (35 mutations), FoldX provided R2 and ρ values of 0.64 and -0.71, respectively, with an 86% correct classification rate (CCR). For NBD2 (24 mutations), FoldX R2, ρ, and CCR were 0.51, -0.73, and 75%, respectively. Application of the Rosetta high-resolution protocol (Rosetta_hrp) to NBD1 yielded R2, ρ, and CCR of 0.64, -0.75, and 69%, respectively, and for NBD2 yielded R2, ρ, and CCR of 0.29, -0.27, and 50%, respectively. The corresponding numbers for the Rosetta's low-resolution protocol (Rosetta_lrp) were R2 = 0.47, ρ = -0.69, and CCR = 69% for NBD1 and R2 = 0.27, ρ = -0.24, and CCR = 63% for NBD2. For NBD1, both algorithms suggest that destabilizing mutations suffer from destabilizing vdW clashes, whereas stabilizing mutations benefit from favorable H-bond interactions. Two triple consensus approaches based on FoldX, Rosetta_lpr, and Rosetta_hpr were attempted using either "majority-voting" or "all-voting". The all-voting consensus outperformed the individual predictors, albeit on a smaller data set. In summary, our results suggest that the effect of mutations on the stability of CFTR's NBDs could be largely predicted. Since NBDs are common to all ABC transporters, these results may find use in predicting the effect and mechanism of the action of multiple disease-causing mutations in other proteins.


Dual-Isotope SPECT/CT Imaging of the Tuberculosis Subunit Vaccine H56/CAF01: Induction of Strong Systemic and Mucosal IgA and T-Cell Responses in Mice Upon Subcutaneous Prime and Intrapulmonary Boost Immunization.
Pulmonary tuberculosis (TB), which is caused by Mycobacterium tuberculosis (Mtb), remains a global pandemic, despite the widespread use of the parenteral live attenuated Bacillus Calmette-Guérin (BCG) vaccine during the past decades. Mucosal administration of next generation TB vaccines has great potential, but developing a safe and efficacious mucosal vaccine is challenging. Hence, understanding the in vivo biodistribution and pharmacokinetics of mucosal vaccines is essential for shaping the desired immune response and for optimal spatiotemporal targeting of the appropriate effector cells in the lungs. A subunit vaccine consisting of the fusion antigen H56 (Ag85B-ESAT-6-Rv2660) and the liposome-based cationic adjuvant formulation (CAF01) confers efficient protection in preclinical animal models. In this study, we devise a novel immunization strategy for the H56/CAF01 vaccine, which comply with the intrapulmonary (i.pulmon.) route of immunization. We also describe a novel dual-isotope (111In/67Ga) radiolabeling approach, which enables simultaneous non-invasive and longitudinal SPECT/CT imaging and quantification of H56 and CAF01 upon parenteral prime and/or i.pulmon. boost immunization. Our results demonstrate that the vaccine is distributed evenly in the lungs, and there are pronounced differences in the pharmacokinetics of H56 and CAF01. We provide convincing evidence that the H56/CAF01 vaccine is not only well-tolerated when administered to the respiratory tract, but it also induces strong lung mucosal and systemic IgA and polyfunctional Th1 and Th17 responses after parenteral prime and i.pulmon. boost immunization. The study furthermore evaluate the application of SPECT/CT imaging for the investigation of vaccine biodistribution after parenteral and i.pulmon. immunization of mice.


Neuromodulation Enables Temperature Robustness and Coupling Between Fast and Slow Oscillator Circuits.
Acute temperature changes can disrupt neuronal activity and coordination with severe consequences for animal behavior and survival. Nonetheless, two rhythmic neuronal circuits in the crustacean stomatogastric ganglion (STG) and their coordination are maintained across a broad temperature range. However, it remains unclear how this temperature robustness is achieved. Here, we dissociate temperature effects on the rhythm generating circuits from those on upstream ganglia. We demonstrate that heat-activated factors extrinsic to the rhythm generators are essential to the slow gastric mill rhythm's temperature robustness and contribute to the temperature response of the fast pyloric rhythm. The gastric mill rhythm crashed when its rhythm generator in the STG was heated. It was restored when upstream ganglia were heated and temperature-matched to the STG. This also increased the activity of the peptidergic modulatory projection neuron (MCN1), which innervates the gastric mill circuit. Correspondingly, MCN1's neuropeptide transmitter stabilized the rhythm and maintained it over a broad temperature range. Extrinsic neuromodulation is thus essential for the oscillatory circuits in the STG and enables neural circuits to maintain function in temperature-compromised conditions. In contrast, integer coupling between pyloric and gastric mill rhythms was independent of whether extrinsic inputs and STG pattern generators were temperature-matched or not, demonstrating that the temperature robustness of the coupling is enabled by properties intrinsic to the rhythm generators. However, at near-crash temperature, integer coupling was maintained only in some animals while it was absent in others. This was true despite regular rhythmic activity in all animals, supporting that degenerate circuit properties result in idiosyncratic responses to environmental challenges.


Effects of corn particle size and source on performance of lactating cows fed direct-cut grass-legume forage.
We conducted two experiments to evaluate the effects of corn supplementation, source of corn, and corn particle size on performance and nutrient utilization of lactating dairy cows. In experiment 1, treatments were 1) direct-cut grass-legume forage without supplement, 2) direct-cut forage plus 10 kg DM of ground dry shelled corn-based concentrate, and 3) direct-cut forage plus 10 kg DM of coarsely ground high moisture ear corn-based concentrate. In experiment 2, treatments were 1) direct-cut grass-legume forage plus 10 kg DM of ground dry shelled corn-based concentrate, 2) direct-cut forage plus 10 kg DM of coarsely ground high moisture ear corn-based concentrate, and 3) direct-cut forage plus 10 kg of DM finely ground high moisture ear corn-based concentrate. Both experiments were designed as 3 x 3 Latin squares replicated three times. In experiment 1, yields of milk and milk protein increased with concentrate supplementation, but were not affected by source of corn. Solids-corrected milk yield tended to increase with grain supplementation. Dry matter intake increased with concentrate supplementation, but was not affected by source of corn or corn particle size. Corn supplements decreased ruminal pH and acetate to propionate ratio and increased ruminal propionate concentration. Grain supplements reduced ruminal ammonia concentration, increased concentration of urine allantoin, and increased the urinary allantoin to creatinine ratio. In the second study, fine grinding of high moisture corn reduced fecal starch plus free glucose levels and tended to increase its apparent digestibility. In both experiments, starch plus free glucose intake was higher on the diets with dry corn, but its utilization was not affected by source of corn.


Role of neutrophils in experimental septicemia and septic arthritis induced by Staphylococcus aureus.
We have previously described a murine model of hematogenously induced Staphylococcus aureus sepsis and arthritis. In this model, large numbers of granulocytes can be observed both in the circulation and locally in the inflamed synovium within 24 h after bacterial inoculation. To assess the role of neutrophils in this severe infection, mice were given granulocyte-depleting monoclonal antibody RB6-8C5 before being inoculated with S. aureus. All the control mice survived their intravenous injection with 3 x 10(7) CFU of S. aureus, whereas all the mice given RB6-8C5 antibody died of sepsis within 2 to 3 days. Even when the inoculum size was reduced sixfold (i.e., 6 x 10(6) CFU/mouse), 50% of the RB6-8C5-treated animals died within 6 days. The RB6-8C5-treated mice had a significantly higher burden of bacteria in their blood and kidneys 24 and 48 h after bacterial inoculation. In addition, when a suboptimal dose of bacteria was administered, the neutrophil-depleted animals displayed a higher frequency of arthritis than did the controls. The granulocyte-depleted animals exhibited increased levels of the proinflammatory cytokines tumor necrosis factor alpha, interleukin-6, and gamma interferon, reflecting the severity of their disease. This is the first direct demonstration of neutrophils playing a crucial protective role in the early phase of S. aureus infection.


Rosmarinic acid from Perillae Herba produces an antidepressant-like effect in mice through cell proliferation in the hippocampus.
Rosmarinic acid (RA) is one of major polyphenolic ingredients of Perillae Herba (a leaf of Perilla frutescens), and has an antidepressant-like property in animal models of depression. However, the mechanism(s) underlying this activity are unknown. Recent studies have reported that regulation of hippocampal neurogenesis is associated with the pathogenesis of depression. To elucidate the mode of action of RA-induced antidepressant-like activity, proliferative effect of RA on newborn cells in the dentate gyrus of mouse hippocampus was investigated using immunohistochemical analysis with bromodeoxyuridine (BrdU), a marker of proliferating cells. RA treatment for 7 or 14 d significantly increased in the number of BrdU-positive cells in inverse correlation with significant reductions in immobility in a forced swimming test, an animal model of depression, in a dose-dependent manner. However, locomotor activities were not affected. These results suggest that RA produces an antidepressant-like effect at least in part via the proliferation of newborn cells in the dentate gyrus of the hippocampus.


Hepatic resection for hepatolithiasis.
To analyze the results of hepatic resection for hepatolithiasis. A retrospective study of case records of patients with hepatolithiasis undergoing hepatic resection. These patients had been followed up for 3 to 38 months. They were referred to Queen Mary Hospital, a tertiary referral center in Hong Kong. Of 172 patients with hepatolithiasis seen between January 1984 and December 1981, 63 patients underwent hepatic resection because the affected liver segments were destroyed by repeated infection (n = 51), multiple cholangitic liver abscesses were found in the affected liver segments (n = 9), or concomitant intrahepatic cholangiocarcinoma was diagnosed (n = 3). Left lateral segmentectomy was performed in 42 patients, left hepatic lobectomy in 15 patients, right hepatic lobectomy in one patient, and segmentectomy in five patients. Postoperative morbidity and mortality analysis. Contrary to hepatic resection in a normal liver, dissection to isolate inflow and outflow vasculature was difficult in 52% of cases owing to severe inflammatory fibrosis at the liver hilum, at the umbilical fissure, or at the junction of hepatic vein with inferior vena cava. The operative morbidity rate was 32% and the mortality rate was 2%. The majority of complications were wound infection, subphrenic abscesses, or biliary fistulas, which could be due to the presence of infected bile (85%) and liver abscesses (25%) in this disease. Statistical analysis of the preoperative hematological and biochemical variables and the amount of intraoperative blood loss could not identify any factor with significance in correlating with the development of postoperative complications. Stones recurred in 16% after a median follow-up of 47 months. Hepatic resection is a satisfactory treatment for hepatolithiasis. The postoperative septic complication rate is high and is an intrinsic problem related to liver resection in a septic condition.


Glycine decarboxylase in Rhodopseudomonas spheroides and in rat liver mitochondria.
1. Glycine decarboxylase and glycine-bicarbonate exchange activities were detected in extracts of Rhodopseudomonas spheroides and in rat liver mitochondria and their properties were studied. 2. The glycine decarboxylase activity from both sources is stimulated when glyoxylate is added to the assay system. 3. Several proteins participate in these reactions and a heat-stable low-molecular-weight protein was purified from both sources. 4. These enzyme activities increase markedly when R. spheroides is grown in the presence of glycine, glyoxylate, glycollate, oxalate or serine. 5. All the enzymes required to catalyse the conversion of glycine into acetyl-CoA via serine and pyruvate were detected in extracts of R. spheroides; of these glycine decarboxylase has the lowest activity. 6. The increase in the activity of glycine decarboxylase on illumination of R. spheroides in a medium containing glycine, and the greater increase when ATP is also present in the medium, probably accounts for the increased incorporation of the methylene carbon atom of glycine into fatty acids found previously under these conditions (Gajdos, Gajdos-Török, Gorchein, Neuberger & Tait, 1968). 7. The results are compared with those obtained by other workers on the glycine decarboxylase and glycine-bicarbonate exchange activities in other systems.