Physiological evidence for subpopulations of cortically projecting basal forebrain neurons in the anesthetized rat.
Sixty-three cortically projecting basal forebrain neurons were identified in chloral hydrate anesthetized rats by antidromic activation from the cerebral cortex. Two subpopulations were noted: type I neurons exhibited two antidromic action potentials of constant latency and identical waveform in response to double pulse cortical stimulation. In contrast, type II neurons exhibited two antidromic action potentials of constant latency but differing waveforms in response to the double pulse paradigm. The phenomenon exhibited by type II cortically projecting basal forebrain neurons is interpreted as evidence for loss of the somatodendritic portion of the antidromic action potential with high frequency stimulation. The median latency to antidromic activation of type II neurons (13.5 ms) was significantly longer than that of type I neurons (3.9 ms). Spontaneous firing rates varied over a wide range (0-49 Hz), and there was no significant difference between the rates of type I and type II neurons. These data underscore the physiological heterogeneity of this presumptive cholinergic cortical afferent system. Anatomical studies have shown that most, but possibly not all cortically projecting basal forebrain neurons are cholinergic. The relative proportions of type I (87%) and type II (13%) neurons encountered in this study suggest that type I neurons might be cholinergic and type II neurons non-cholinergic. If substantiated, this hypothesis would permit cholinergic and non-cholinergic cortically projecting basal forebrain neurons to be distinguished using a simple test of antidromicity.


One-step transversal palatal distraction and maxillary repositioning: technical considerations, advantages, and long-term stability.
Transversal maxillary hypoplasia in adolescence is a frequently seen pathology, which can be treated with a combination of surgery and orthodontic treatment to widen the maxilla in skeletally matured patients.We evaluated the advantages of a new surgical technique: Le Fort I distraction osteogenesis using a bone-borne device. Because relapse is one of the main problems in surgical maxillary expansion, long-term stability of this new technique was evaluated. Data from 4 adult patients with maxillary restriction, class III malocclusion, or maxillary malposition were collected preoperatively, 4 months after distraction, and 5 years after distraction. Measurements were recorded on dental models to detect palatal expansion at dental level; cephalograms by lateral and posteroanterior plane were analyzed to detect maxillary movements. Maxillary measurements were substantially stable 5 years after distractions. Only minor dental movements occurred at the dental analysis after 5 years related to a lack of orthodontic contention without any compromise of the dental result (no crossbite relapse and class I stability). Le Fort I with down-fracture for expansion and repositioning by bone-borne distractor device can [corrected] be used to simultaneously widen, advance, and vertically reposition the maxilla without causing healing problems, particularly using a rigid distraction device. Long-term stability can be achieved; however, further studies with a larger number of patients will be necessary for better evaluation.


Congenital megaureter.
Megaureter is the descriptive term applied to the large, wide, dilated and often tortuous ureter, which is usually congenital. Megaureter may result from a number of causes and an accurate diagnostic classification, such as refluxing, obstructed or non-refluxing, non-obstructed, is essential for appropriate management. The 52 consecutive patients with the various forms of megaureter presented typify the various causes of the entity. Surgical intervention virtually is universal and factors bearing upon recoverability and prognosis have been analyzed.


Is Teaching Simple Surgical Skills Using an Operant Learning Program More Effective Than Teaching by Demonstration?
A surgical procedure is a complex behavior that can be constructed from foundation or component behaviors. Both the component and the composite behaviors built from them are much more likely to recur if it they are reinforced (operant learning). Behaviors in humans have been successfully reinforced using the acoustic stimulus from a mechanical clicker, where the clicker serves as a conditioned reinforcer that communicates in a way that is language- and judgment-free; however, to our knowledge, the use of operant-learning principles has not been formally evaluated for acquisition of surgical skills. Two surgical tasks were taught and compared using two teaching strategies: (1) an operant learning methodology using a conditioned, acoustic reinforcer (a clicker) for positive reinforcement; and (2) a more classical approach using demonstration alone. Our goal was to determine whether a group that is taught a surgical skill using an operant learning procedure would more precisely perform that skill than a group that is taught by demonstration alone. Two specific behaviors, "tying the locking, sliding knot" and "making a low-angle drill hole," were taught to the 2014 Postgraduate Year (PGY)-1 class and first- and second-year medical students, using an operant learning procedure incorporating precise scripts along with acoustic feedback. The control groups, composed of PGY-1 and -2 nonorthopaedic surgical residents and first- and second-year medical students, were taught using demonstration alone. The precision and speed of each behavior was recorded for each individual by a single experienced surgeon, skilled in operant learning. The groups were then compared. The operant learning group achieved better precision tying the locking, sliding knot than did the control group. Twelve of the 12 test group learners tied the knot and precisely performed all six component steps, whereas only four of the 12 control group learners tied the knot and correctly performed all six component steps (the test group median was 10 [range, 10-10], the control group median was 0 [range, 0-10], p = 0.004). However, the median "time to tie the first knot" for the test group was longer than for the control group (test group median 271 seconds [range, 184-626 seconds], control group median 163 seconds [range 93-900 seconds], p = 0.017), whereas the "time to tie 10 of the locking, sliding knots" was the same for both groups (test group mean 95 seconds ± SD = 15 [range, 67-120 seconds], control group mean 95 seconds ± SD = 28 [range, 62-139 seconds], p = 0.996). For the low-angle drill hole test, the test group more consistently achieved the ideal six-step behavior for precisely drilling the low-angle hole compared with the control group (p = 0.006 for the median number of technique success comparison with an odds ratio [at the 95% confidence interval] of 82.3 [29.1-232.8]). The mean time to drill 10 low-angle holes was not different between the test group (mean 193 seconds ± SD = 26 [range, 153-222 seconds]) and the control group (mean 146 seconds ± SD = 63 [range, 114-294 seconds]) (p = 0.084). Operant learning occurs as the behavior is constructed and is highly reinforced with the result measured, not in the time saved, but in the ultimate outcome of an accurately built complex behavior. Level II, therapeutic study.


Admission characteristics of trauma patients in whom delirium develops.
The purpose of this study was to describe the admission characteristics of trauma victims that are predictive of the development of delirium during hospitalization. In this case-control study, data (demographics, injury type, medical histories, admission laboratory values, medications, and outcomes) were obtained from the records of 120 patients in whom delirium developed and 145 in whom it did not after admission for traumatic injury. Odds ratios were employed to identify significant predictors used in a stepwise logistic regression analysis. Admission characteristics, retained after stepwise logistic regression, that were independently predictive of delirium were age more than 45 years, positive admission blood alcohol, and an elevated mean corpuscular volume. Those in whom delirium developed had longer hospital and intensive care unit lengths of stay than in whom it did not. Older patients and alcoholics are at increased risk for delirum. Therapies directed at prevention have the potential to improve care and decrease lengths of stay.


Involvement of calmodulin in the regulation of adenylate cyclase activity in guinea-pig enterocytes.
The involvement of calmodulin as an activator of adenylate cyclase activity was examined in isolated guinea-pig enterocytes and in a membrane preparation. In enterocytes, which responded to prostaglandin E1, vasoactive intestinal peptide and cholera toxin with a significant increase in the rate of cAMP formation trifluoperazine, a calmodulin antagonist, completely inhibited cAMP formation. In a membrane preparation adenylate cyclase activity was stimulated 10-20-fold by the GTP analog, guanosine 5'-[beta-imido]5'-triphosphate (Gpp[NH]p). Prostaglandin E1 and vasoactive intestinal peptide enhanced cAMP formation in this system by 2-3- and 1.2-1.6-fold. respectively. Addition of 200 nM calmodulin to membranes, in which endogenous calmodulin was decreased from 1.4 microgram/mg protein to 0.5 microgram/mg protein by washing with buffer containing EGTA and EDTA, resulted in a 3-4-fold increase of adenylate cyclase activity. The absolute increment in adenylate cyclase activity caused by calmodulin (10-15 pmol cAMP/min per mg protein) was approximately the same in the absence or presence of Gpp[NH]p. The apparent Ka for Gpp[NH]p (6 . 10-7 M) was not significantly changed by the addition of calmodulin. Although endogenous calcium (approx. 10 microM) in the enzyme assay was adequate to affect stimulation by calmodulin, a maximal effect was observed at a calcium concentration of 100 microM. These findings indicate that a calmodulin-sensitive form of adenylate cyclase is present in guinea-pig enterocytes, and that stimulation of cAMP formation in the intestinal mucosa may involve a calmodulin-mediated mechanism.


A simple structural feature is a major determinant of the identity of a transfer RNA.
Analysis of a series of mutants of an Escherichia coli alanine transfer RNA shows that substitution of a single G-U base pair in the acceptor helix eliminates aminoacylation with alanine in vivo and in vitro. Introduction of that base pair into the analogous position of a cysteine and a phenylalanine transfer RNA confers upon each the ability to be aminoacylated with alanine. Thus, as little as a single base pair can direct an amino acid to a specific transfer RNA.


A novel method for viral display of ER membrane proteins on budded baculovirus.
The baculovirus expression system has been used to express large quantities of various proteins, including membrane receptors. Here, we reveal a novel property of this expression system to be that certain membrane proteins can be displayed on the budded virus itself. We introduced the genes encoding sterol regulatory element-binding protein-2 (SREBP-2) or SREBP cleavage-activating protein (SCAP), important integral membrane proteins of the endoplasmic reticulum (ER) and/or the Golgi apparatus related to cellular cholesterol regulation, into a baculovirus vector. When insect cells were infected with SREBP-2 or SCAP recombinant viruses, it was found that these ER membrane proteins appeared on the budded baculovirus in addition to the host cell membrane fraction. Compared to proteins expressed on the cell membrane, membrane proteins displayed on virus exhibited both less aggregation and less degradation upon immunoblotting. Using this viral displayed SCAP as the screening antigen, we then generated a new monoclonal antibody specific against SCAP, which was useful for immunological localization studies. This system, which takes advantage of the viral display of membrane proteins, should prove to be a powerful additional tool for postgenomic protein analysis.


Anxiety disorders and healthcare utilization: A systematic review.
Anxiety disorders and related traits have become increasingly relevant to the study of physical health and health behaviors over the years. One important health behavior is healthcare utilization, and both over- and under-use have important implications within both personal and public health domains. Anxiety disorders are associated with reassurance-seeking, avoidance behaviors, and other characteristics and traits that may impact patterns of healthcare utilization. The current paper reviews the literature on the known associations between anxiety disorders and healthcare utilization, including studies (N = 70) that examined the association of healthcare utilization with generalized anxiety disorder, social anxiety disorder, panic disorder and agoraphobia, dental and blood-injection-injury phobias, and illness anxiety disorder/health anxiety. Overall, the majority of the studies reviewed indicate that anxiety disorders and health anxiety are associated with increased healthcare utilization across multiple care settings. In addition, there is preliminary but limited evidence that, in some cases, anxiety can be associated with delayed, irregular, or inconsistent use of healthcare services. More work is needed to fine-tune our understanding of the impact of anxiety disorders in healthcare settings.


Cognitive dysfunctions induced by a cholinergic blockade and Aβ 25-35 peptide are attenuated by salvianolic acid B.
Alzheimer's disease (AD) is a neurodegenerative disorder associated with progressive cognitive and memory loss and neuronal cell death. Current therapeutic strategies for AD are very limited; thus, traditional herbal medicines or their active constituents receive much attention. The aim of this study was to investigate the cognitive enhancing effects of salvianolic acid B (SalB) isolated from Salvia miltiorrhiza and its ameliorating effects on various drug-induced amnesic models using the passive avoidance, Y-maze, and Morris water maze tasks. Drug-induced amnesia was induced by administering scopolamine, diazepam, muscimol, or amyloid-β (Aβ)(25-35) peptide. SalB (10 mg/kg, p.o.) was found to significantly reverse the cognitive impairments induced by scopolamine (1 mg/kg, i.p.) or Aβ(25-35) (10 nmol/5 μl, i.c.v.) injection. This ameliorating effect of SalB was antagonized by the GABA(A) receptor agonists, muscimol or diazepam, respectively. In addition, SalB alone was capable of improving cognitive performances. Furthermore, SalB (100 μM) was found to inhibit GABA-induced outward Cl(-) currents in single hippocampal CA1 neuron. These results suggest that the observed ameliorations of cholinergic dysfunction- or Aβ(25-35)-induced memory impairment by SalB were mediated, in part, via the GABAergic neurotransmitter system after a single administration.


Quality of pharmacokinetic research in oncology.
The usefulness of pharmacokinetically guided individualisation of drug therapy will depend, among other things, on the quality of the analytical and pharmacokinetic methods used. We surveyed the quality of analytical and pharmacokinetics methodology and reporting in a literature search of the oncology literature from 1987 to 1992, using the Medline database. Thirty articles that examined relationships between normal tissue toxicity and area under the plasma concentration-time curve (AUC) formed the study sample. Analytical procedures were adequately described in 77% of the articles, but details of validation of the assay were seriously deficient in the great majority of articles. Methods for calculation of AUC were also deficient in over half of the articles. The findings suggest that greater attention needs to be paid to the quality of pharmacokinetic investigation in oncology, otherwise progress in the use of pharmacokinetically guided individualisation of dosage may be hindered.


Acute thrombocytopenia during cesarean section.
We report a case of a healthy 29-year-old parturient with a normal pre-operative platelet count who received combined spinal-epidural anesthesia for cesarean section, and who suffered the sudden intra-operative onset of severe thrombocytopenia (platelet count 3 × 109/L). This event was likely due to cefoxitin administered for the prophylaxis of surgical infection.


Allelotype of non-small cell lung carcinoma--comparison between loss of heterozygosity in squamous cell carcinoma and adenocarcinoma.
We examined loss of heterozygosity (LOH) on all autosomal chromosomes in 53 non-small cell lung carcinomas. Frequent LOH was observed on the long arms of chromosomes 1 (37%), 2 (31%), 5 (30%), 8 (31%), and 13 (32%), and the short arms of chromosomes 3 (54%) and 17 (62%). LOH on chromosomes 3p and 17p was observed in all informative cases of squamous cell carcinoma, but was significantly less frequent in adenocarcinomas (P = 0.003 and 0.001, respectively). Similarly, LOH on chromosome 13q was observed frequently in squamous cell carcinomas (5 of 9 informative cases, or 56%), but in only 5 of 26, or 19%, of adenocarcinomas. In contrast, LOH on chromosome 2q was observed only in adenocarcinomas. In addition, this chromosomal arm was lost more frequently in poorly differentiated, compared to well differentiated adenocarcinomas. Furthermore, a correlation between fractional allelic loss and pathohistological grade was identified. These results implicate the presence of several tumor suppressor genes associated with development and/or progression of non-small cell lung carcinomas.


The effects of the delayed type immune response upon the host.
A consistent accumulation of experimental evidence, most of it published long ago, clearly shows that a constant consequence of the immune response elicited by the Koch bacillus is that the individual becomes susceptible to be injured or killed by the tuberculous antigen, which is totally innocuous to the virgin subject. This fact led Rich to conclude that throughout the natural history of tuberculosis, as soon as the immune reaction is activated, the tuberculo-protein poured out by the germ mass will exert its detrimental capabilities manifested as the constitutional symptoms of the disease. The pathogenicity of the specific antigen in the tuberculous-type immune reaction may be extrapolated to other states that elicit the same response, including cancer and tissue transplantation. Unexplained phenomena such as the general symptoms of many neoplasias, as well as the systemic manifestations of graft rejection, may then be attributed to the shedding of antigen from the foreign cell mass into the sensitized host.


Dietary fat and hormonal effects on erythrocyte membrane fluidity and lipid composition in adult women.
Erythrocyte ghost membrane fluidity and phospholipid linoleate were significantly increased when higher levels of polyunsaturated fats were fed to healthy, free living, premenopausal women. Fluidity was assessed by diphenylhexatriene (DPH) fluorescence polarization measurements with hypotonically lysed red blood cells from 31 female subjects fed one of two sets of diets, which were formulated from typical US foods to contain polyunsaturate to saturate ratios (P/S) of 1.0 or 0.3. Both groups of women were fed diets with 40% of energy as fat for four menstrual cycles followed by low-fat diets having 20% of energy as fat for the next four menstrual cycles. Blood was sampled during the fourth cycle of each dietary period at times estimated to correspond to maximum secretions of estrogen and progesterone to assess interactive hormonal and dietary effects on membrane composition and fluidity. Red blood cell membranes were most fluid following higher levels of linoleate intake, either by higher (40%) total fat or higher P/S levels. Membrane fluidity was directly related to the phospholipid oleate and linoleate contents and inversely related to the molar cholesterol/phospholipid ratio. Hormonal status effects on the membranes were not extensive. Membrane fluidity in cells from women fed P/S = 0.3 diets was higher at 40% than at 20% fat during the luteal phase of the fourth cycle. In contrast, women fed the P/S = 1.0 diets had more fluid red cells at 40% fat during the follicular phase of the cycle. Regression analysis showed a direct linear correlation between membrane fluidity and red cell membrane insulin binding demonstrating a relation between receptor binding and cell membrane fluidity in the human female.


L-arginine and lisinopril supplementation protects against sodium fluoride-induced nephrotoxicity and hypertension by suppressing mineralocorticoid receptor and angiotensin-converting enzyme 3 activity.
Sodium fluoride (NaF) is one of the neglected environmental toxicants that has continued to silently cause toxicity to both humans and animals. NaF is universally present in water, soil, and atmosphere. The persistent and alarming rate of increase in cardiovascular and renal diseases caused by chemicals such as NaF in mammalian tissues has led to the use of various drugs for the treatment of these diseases. The present study aimed at evaluating the renoprotective and antihypertensive effects of L-arginine against NaF-induced nephrotoxicity. Thirty male Wistar rats (150-180 g) were used in this study. The rats were randomly divided into five groups of six rats each as follows: Control, NaF (300 ppm), NaF + L-arginine (100 mg/kg), NaF + L-arginine (200 mg/kg), and NaF + lisinopril (10 mg/kg). Histopathological examination and immunohistochemistry of renal angiotensin-converting enzyme (ACE) and mineralocorticoid receptor (MCR) were performed. Markers of renal damage, oxidative stress, antioxidant defense system, and blood pressure parameters were determined. L-arginine and lisinopril significantly (P < 0.05) ameliorated the hypertensive effects of NaF. The systolic, diastolic, and mean arterial blood pressure of the treated groups were significantly (P < 0.05) reduced compared with the hypertensive group. This finding was concurrent with significantly increased serum bioavailability of nitric oxide in the hypertensive rats treated with L-arginine and lisinopril. Also, there was a significant reduction in the level of blood urea nitrogen and creatinine of hypertensive rats treated with L-arginine and lisinopril. There was a significant (P < 0.05) reduction in markers of oxidative stress such as malondialdehyde and protein carbonyl and concurrent increase in the levels of antioxidant enzymes in the kidney of hypertensive rats treated with L-arginine and lisinopril. The results of this study suggest that L-arginine and lisinopril normalized blood pressure, reduced oxidative stress, and the expression of renal ACE and mineralocorticoid receptor, and improved nitric oxide production. Thus, L-arginine holds promise as a potential therapy against hypertension and renal damage.


Inhibition of lymphocyte IL2-receptor expression by factor VIII concentrate: a possible cause of immunosuppression in haemophiliacs.
Factor VIII concentrate inhibits T-cell function in vitro and in vivo. The mechanisms underlying the phenomenon were investigated. Factor VIII concentrate has a direct effect on lymphocytes, uninfluenced by haemophilic monocyte dysfunction, since it inhibited lymphocyte transformation with phorbol myristate acetate, a reaction unaffected by monocyte depletion. Inhibition of lymphocyte transformation by factor VIII concentrate is not corrected by the addition of exogenous IL2, suggesting that it does not inhibit lymphocyte function by suppression of IL2 secretion alone. Factor VIII concentrate causes profound inhibition of IL2-receptor expression (CD25); with an 89% reduction in CD25-positive CD4 cells and a 50% reduction in CD25-antigen molecules per cell. CD8 lymphocytes are similarly affected. Smaller reductions in CD71 and HLA-DR expression are also observed. Down modulation of CD25-antigen may explain the reduced IL2 secretion observed by others, and may be an important cause of immunodeficiency in HIV-seronegative haemophiliacs.


Association between interatrial septum adiposity and atrial fibrillation: transesophageal echocardiography imaging and autopsy study.
Recent clinical evidence has suggested that interatrial septal (IAS) adiposity contributes to atrial fibrillation (AF). The present study aimed to confirm the usefulness of transesophageal echocardiography (TEE) to estimate IAS adiposity in patients with AF. The histological IAS analysis based on autopsy samples sought to clarify characteristics that underlie the contribution of IAS adiposity to AF. The imaging study analyzed the TEE results in patients with AF (n = 184) in comparison with transthoracic echocardiography (TTE) and computed tomography (CT) results. The autopsy study histologically analyzed IAS in subjects with (n = 5) and without (n = 5) history of AF. In the imaging study, the ratio of interatrial septum adipose tissue (IAS-AT) volume per epicardial adipose tissue (EpAT) volume was greater in patients with persistent AF compared (PerAF) to those with paroxysmal AF (PAF). Multivariable analysis revealed that both TEE-assessed IAS thickness and TTE-assessed left atrial dimension were predicted by CT-assessed IAS-AT volume. In the autopsy study, the histologically-assessed IAS section thickness was greater in the AF group than that in the non-AF group and was positively correlated with the IAS-AT area percentage. In addition, the size of adipocytes in IAS-AT was smaller, compared to EpAT and subcutaneous adipose tissue (SAT). IAS-AT infiltrated into the IAS myocardium, as if adipose tissue split the myocardium (designated as myocardial splitting by IAS-AT). The number of island-like myocardium pieces as a result of myocardial splitting by IAS-AT was greater in the AF group than in the non-AF group and was positively correlated with the IAS-AT area percentage. The present imaging study confirmed the usefulness of TEE to estimate IAS adiposity in patients with AF without radiation exposure. The autopsy study suggested that the myocardial splitting by IAS-AT may contribute to atrial cardiomyopathy leading to AF.


Food energy values of artificial feeds for man.
The gross and metabolizable energy values of artificial enteral and parenteral feeds have been calculated from detailed composition data for amino acid, fatty acid, saccharide and other oxidizable substrates and compared with similar values calculated for conventional foods. The background to the derivation and application of calorie conversion factors is briefly reviewed. There is evidence of widespread inappropriate application of calorie conversion factors for carbohydrates and amino acid mixtures. Appropriate digestibility or availability factors for the oxidizable fractions of artificial feeds is discussed for normal adult man and the intrinsic difficulty of obtaining availability values for subjects with varying types of malabsorption or urinary and tissue losses is emphasized. The nitrogen:protein conversion ratio and the availability of energy at a biochemical level (i.e. net ATP yield per calorie) is also considered. Finally, a more uniform and appropriate approach to calculating energy values for artificial feeds for the purposes of labelling, product description and estimating energy intake of patients is called for.


Connecting the spots: Understanding cheetah reproduction to improve assisted breeding and population management.
The North American cheetah (Acinonyx jubatus) population serves as both an insurance population for their rapidly decreasing wild cohorts as well as a research population to understand the unique biology of this species. This review focus on the complexity of the female cheetah reproductive system and the recent advances that have been made towards understanding basic biology and reproductive function, and application of assisted breeding technologies to enhance reproduction and maintain genetic diversity of this species in human care. Cheetah females are non-seasonal breeders that exhibit lengthy periods of anestrus that are not associated with age, environment, or reproductive potential. It is possible to collect good quality oocytes, that support fertilisation and successful early embryonic development, regardless of female age (from 2 to 12 yr old). However, the prevalence of uterine pathologies increases with age and prevents middle to advanced age females from establishing pregnancy. Pregnancy can be diagnosed in non-sedated cheetah females via ultrasonography (first month), steroid hormone analysis (second/third month) or radiography (third month). Fecal biomarkers, such as Immunoglobulin J, show great promise for diagnosing pregnancy at an early stage as well as other physiological states. Several decades of basic research have led to efficient management of natural breeding and recent successes in assisted reproduction.


Conductive and antibacterial films by loading reduced graphene oxide/silver nanoparticles on cellulose nanofiber films.
The development of sustainable high-performance materials based on nanocellulose has received great attention in recent years. Herein, nanocellulose based composite films with highly electro-conductive and antibacterial properties have been developed by loading reduced graphene oxide (rGO)/silver nanoparticles (AgNPs) on cellulose nanofiber films via vacuum filtration process. The reduction effect of gallic acid on the chemical structure and electrical conductivity of rGO/AgNP composites was studied. Due to the strong reducibility of gallic acid, the obtained rGO/AgNPs exhibited a high electrical conductivity of 1549.2 S·m-1. Furthermore, the electrical conductivity, mechanical properties and antibacterial properties of the prepared rGO/AgNP-cellulose nanofiber films as a function of various proportions were investigated. The prepared composite film with a specific ratio of rGO/AgNPs to cellulose nanofibers as 7:3 exhibited the superior tensile strength of 28.0 MPa and the electrical conductivity of 1199.3 S·m-1. Meanwhile, compared with pure cellulose nanofiber films, rGO/AgNP-cellulose nanofiber films displayed strong antibacterial effect against Escherichia coli and Staphylococcus aureus. Therefore, this work demonstrated an effective approach for imparting structural and functional properties to cellulose nanofiber based films, which could hold great application prospects for flexible and wearable electronics.


Bipolar affective disorder--techniques and results of treatment.
Differences between bipolar and unipolar patients and the natural history of bipolar illness are discussed. Reviewing recent studies, the paper then outlines the treatment of mania, the treatment of depression, and the prophylactic treatment of bipolar illness.


Influence of tumour-associated symptoms on the prognosis of patients with renal cell carcinoma.
To evaluate the prognostic significance of symptoms related to renal cell carcinoma (RCC) in comparison with incidentally detected tumours in a group of long-term observed patients. The study included 396 patients operated for RCC between 1982 and 2001. The patients were classified according to age, gender, detection mode, pathological stage and grade, tumour size, nodal involvement and Eastern Cooperative Oncology Group (ECOG) performance status. Special attention was given to the analysis of duration and quality of symptoms. The endpoint of the study was overall survival, which was assessed with univariate and multivariate analyses using the Kaplan-Meier method, log-rank test and Cox proportional hazards model. Of the 396 patients, 135 (34%) and 261 (66%) presented with incidental and symptomatic RCC, respectively. Compared with incidental cases, symptomatic tumours had significantly larger size (p < 0.0001), and higher pathological stage (p < 0.0001) and grade (p < 0.02). Five-year survival in patients with incidental and symptomatic tumours was 88.1% and 59.4% (p < 0.0001), respectively. In relation to the quality of symptoms, the 5-year survival in patients with local and systemic symptoms was 75.4% and 44.4% (p < 0.0001), respectively. In the group of patients with a history of tumour-related symptoms shorter and longer than 3 months, the 5-year survival was 62.2% and 55.6% (p < 0.0001), respectively. Multivariate analysis found tumour size [hazard ratio (HR) 1.22, p = 0.05] tumour grade (HR 1.44, p = 0.002), tumour stage (HR 1.35, p = 0.001), presence of symptoms (HR 1.36, p = 0.004) and ECOG (HR 1.25, p = 0.005) to be independent prognostic variables. Preoperative somatic symptoms and performance status in patients with RCC provide readily available prognostic information in addition to tumour size, stage and grade.


Pathological Change of Chronic Hepatitis B Patients with Different Tongue Coatings by Circular Multi-Omics Integrated Analysis.
To compare the circular pathological changes of chronic hepatitis B (CHB) patients according to the tongue diagnosis. Totally 41 CHB patients with typical white tongue coating (WTC) or yellow tongue coating (YTC) were enrolled and 14 healthy volunteers with normal tongue manifestation served as controls. The mRNA expression of peripheral leukocytes was detected by GeneChips, and 9 genes were randomly selected for expression validation. Circular metabolites were detected by gas chromatographymass spectrometry. Biological information was analyzed based on ingenuity pathways analysis or metabolomics database and the integrated networks were constructed by ClueGO. A total of 945 and 716 differentially expressed genes were found in patients with WTC and YTC relative to healthy volunteers respectively. The biological information analysis indicated that CHB patients had obviously increased functions in cell death, apoptosis and necrosis (Z-score ⩾2, P<0.05) and decreased activation in T lymphocytes (Z-score ⩽-2, P<0.05), regardless of the tongue manifestation. Compared to patients with WTC, the YTC patients were predicted to be more active in functions related to virus replication (Z-score ⩾2, P<0.05), and the content of circular fatty acids, such as oleic acid (P=0.098) and lauric acid (P=0.035), and citric acid cycle-related metabolites were higher in the YTC patients (P<0.1). The integrated analysis based on differential genes and metabolites indicated that the most difference in the biological function network between the WTC and YTC patients was tumor necrosis factor receptor associated factor 6 mediated-nuclear factor kappa-B activation process. CHB patients with YTC had more severe inflammation and fatty acids metabolism aberrant than patients with WTC. The results facilitate the modern pathological annotation of Chinese medicine tongue diagnosis theory and provide a reference for the interpretation of pharmacological mechanisms of Chinese medicine treatment.


Can the Borg CR-10 scale for neck and low back discomfort predict future neck and low back pain among high-risk office workers?
Perceived discomfort could indicate an early sign of pain, for example, as a result of a biomechanical load on the musculoskeletal system. Assessing discomfort can, therefore, help to identify workers at increased risk of musculoskeletal disorders for targeted intervention development. We aimed: (1) to identify the optimal cut-off value of neck and low back discomfort among office workers and (2) to evaluate its predictive validity with future neck and low back pain, respectively. At baseline healthy participants (n = 100) completed questionnaires, including the Borg CR-10 discomfort scale (on a 0-10 scale), and were followed for six months, during which musculoskeletal pain was assessed monthly. Logistic regression analyses were performed to assess the associations of baseline discomfort with the onset of future neck or low back pain. Sensitivity, specificity, and the area under the receiver operating characteristics curve were estimated to identify the optimal discomfort cut-off value predicting future pain. Borg CR-10 scores ≥ 3.5 for perceived neck and low back discomfort had acceptable sensitivity and specificity to predict future neck and low back pain, respectively. Perceived discomfort at baseline as a dichotomous measure (using the ≥ 3.5 cut-off) was a statistically significant predictor of future neck pain (OR = 10.33) and low back pain (OR = 11.81). We identified the optimal cut-off value of the Borg CR-10 discomfort scale to identify office workers at increased risk of developing neck and low back pain. These findings might benefit ergonomists, primary health care providers, and occupational health researchers in developing targeted interventions.


Size-biased dispersal prior to breeding in a damselfly.
Dispersal is notoriously difficult to measure, so its potential population consequences are often unknown. If dispersal is density-dependent, it can act in population regulation. Adult damselflies Enallagma boreale (Zygoptera: Coenagrionidae) raised as larvae under a range of competitive regimes were individually measured and marked. Individuals that survived to reproductive maturity were either recovered at the natal pond or had dispersed to nearby water bodies. Dispersing individuals were heavier at emergence than those returning to the natal pond to breed. Therefore, an increased probability of dispersal does not appear to be a response to poor conditions in this species.


Patterns of morphologic alteration correlate with vision in diabetic macular oedema: a cross-sectional evaluation of patients using the SAVE II protocol.
We sought to describe and evaluate patients with clinically significant diabetic macular oedema (CSME) according to the improved SAVE II protocol and correlate findings with visual acuity and systemic parameters in the outpatient clinic for DR (diabetic retinopathy) management. This was a cross-sectional case series study of patients with CSME, regardless of prior treatment. Visual acuity testing was performed according to the Early Treatment of Diabetic Retinopathy Study (ETDRS) protocol. Optical coherence tomography (OCT) and fluorescence angiography (FA) were performed. All imaging data were evaluated according to an improved version of the SAVE grading protocol for CSME (SAVE II). The main outcome measures were SAVE II oedema types and best-corrected visual acuity. Additional parameters of a blood sample (fasting glucose, haemoglobin A1c, serum creatinine, triglycerides, cholesterol, low-density lipoproteins, and high-density lipoproteins) were taken. In total, 66 eyes of 66 patients were included. The mean age of the patients was 64.9 ± 8.2 years. Two eyes were classified as SAVE oedema type 1, 19 eyes as SAVE oedema type 2, 28 eyes as SAVE oedema type 3, and 28 eyes as SAVE oedema type 4, respectively. Central retinal thickness and laboratory parameters were not significantly different between the groups. There was a statistically significant difference in ETDRS visual acuity between the SAVE groups 2 and 4 (p < 0.001) with lower vision in group 4. There was no statistically significant difference between oedema types 2 and 3 (p = 0.065) and oedema types 3 and 4 (p = 0.13). There was a significant correlation between the four defined oedema types and visual acuity. Morphologic findings did not correlate with any of the evaluated blood parameters.


Porous SiO2 coated AlxFeyZr1-x-yO2 solid superacid nanoparticles with negative charge for polyvinylidene fluoride (PVDF) membrane: Cleaning and partial desalinating seawater.
In this work, porous SiO2 coated AlxFeyZr1-x-yO2 solid superacid nanoparticles with negative charge (CS-SAFZr) were synthesized via hydrolysis, sulfation and sulfonation, and characterized by SEM, TEM, XRD, BET and so on. The results show that the size of CS-SAFZr nanoparticles prepared under the optimum preparation conditions is around 80 nm, thickness of the porous SiO2 shell is about 20 nm, Hammett acidity is -16.197 and ion exchange capacity (IEC) is 0.98 mmol·g-1. Correspondingly, ferrum (Fe) and aluminum (Al) elements are successfully doped into the ZrO2 lattice and the doped nanoparticles present a specific surface area of 396.2 m2 g-1 with abundant hydroxyl and sulfonic acid groups on the surface. To investigate the properties of the nanoparticles as the filler, polyvinylidene fluoride (PVDF) was used as a candidate to prepare CS-SAFZr/PVDF ultrafiltration (UF) composite membranes and the performance were characterized via cleaning and desalinating seawater. Results indicate that the CS-SAFZr nanoparticles strengthen their compatibility with the membrane via hydrogen bonds and improve performances of PVDF membrane. The suspended solid and conductivity decline ratio of permeate seawater was 1.8 mg L-1 and 13.20% respectively, indicating that CS-SAFZr/PVDF membrane performs seawater cleaning and partial desalination. Therefore, CS-SAFZr nanoparticles can be a promising candidate to modify PVDF membrane for cleaning and desalinating seawater.


Long-term facilitation of amphetamine-induced rotational behavior and striatal dopamine release produced by a single exposure to amphetamine: sex differences.
Amphetamine (AMPH)-induced rotational behavior in non-lesioned rats and AMPH-stimulated dopamine (DA) release from striatal tissue fragments in vitro were used to study the long-term effects of a single injection of AMPH on activity in the mesostriatal DA system. A single injection of a low dose of AMPH (1.25 mg/kg) greatly enhanced the rotational behavior produced by a second injection of AMPH given 3-4 weeks later in intact female, ovariectomized female and castrated male rats. The effect of AMPH pretreatment in intact males differed from that in the other groups. When only 7-8 days separated the two test sessions both intact male and female rats showed sensitization of rotational behavior, but the magnitude of the change was greater in females. In addition, a single injection of 1.25 mg/kg of AMPH in vivo produced a long-lasting (3-5 weeks) enhancement of AMPH-stimulated DA release from striatal tissue in vitro. It is suggested that: (1) repeated injections of AMPH are not necessary to produce a long-lasting facilitation of behaviors mediated by the mesostriatal DA system; (2) gender and/or hormonal state influences the development of long-term changes in the mesostriatal DA system; and (3) changes in DA release from presynaptic terminals may contribute to the behavioral sensitization produced by stimulant drugs. The phenomena reported here may provide complementary in vitro and in vivo models for studying neuroplasticity in brain DA systems.


Development of venovenous extracorporeal blood purification circuits in rodents for sepsis.
Unlike pharmacologic interventions in sepsis, extracorporeal blood purification, which is widely used in septic patients, is not typically studied in experimental rodents. Most of the previous studies have performed extracorporeal blood purification in larger animals and typically use arteriovenous (AV) vascular access. We developed a venovenous (VV) purification model in the rat as an adjunct for the treatment of sepsis. Using adult male Sprague-Dawley rats, we cannulated the femoral artery or vein and the jugular vein with P50 tubing and created an AV or VV circuit. Blood flow was maintained by arterial pressure in the AV circuit, whereas in the VV circuit the blood flow was regulated using a rotary pump. The safety of this circuit was evaluated using the changes of blood interleukin 6, rectal temperature, and 7-d survival with sham extracorporeal circulation (circuit connection without treatment) compared with the control (without circuit). The main side complications of this VV circuit were compared with those of the AV circuit. The differences in interleukin 6, body temperature, and cumulative survival were not statistically significant after extracorporeal circulation. The main complications of extracorporeal circulation occurred less often with VV compared with AV therapy: massive bleeding (2.5% versus 15%, P = 0.04); clot formation (2.5% versus 15%, P = 0.04). This VV circuit has been successfully used in different septic rodent models with different techniques (hemoadsorption and hemofiltration). VV blood purification in a rodent model appears to be effective and is safer than AV circuit.


MIB-1 labeling indices in benign, aggressive, and malignant meningiomas: a study of 90 tumors.
Predicting tumor behavior in meningiomas based on histology alone has been problematic. This study retrospectively compares histology and MIB-1 (cell proliferation marker) labeling indices (LI) in benign, aggressive, and malignant meningiomas. Six histological features, including mitoses, necrosis, loss of pattern, hypervascularity/hemosiderin deposition, prominent nucleoli, and nuclear pleomorphism, were compared in 90 meningiomas (Fisher's exact test). Tumors with two or more of the above features were designated as aggressive meningiomas. Malignant meningiomas were characterized by brain invasion or metastasis. The MIB-1 LIs (% positive tumor cell nuclei) were compared between the three groups (Kruskal-Wallis test, Wilcoxon two-sample test). Of the benign meningiomas (n=37; mean age, 54 years), 41% had one of the six histological features, with nuclear pleomorphism (n=10) being the most frequent. The aggressive tumors (n=29; mean age, 61 years) were characterized by nuclear pleomorphism (n=28), mitoses (n=20), necrosis (n=16), loss of pattern (n=16), prominent nucleoli (n=6), and hypervascularity/hemosiderin deposition (n=5). Malignant tumors (n=24; mean age, 59 years) were characterized by nuclear pleomorphism (n=22), mitoses (n=21), loss of pattern (n=21), necrosis (n=21), nucleoli (n=17), and hypervascularity/hemosiderin deposition (n=3). Significant differences were found between the aggressive and malignant groups with regard to loss of pattern, necrosis, and nucleoli (P=.0043, .011, and .00029, respectively). Mean MIB-1 LIs for the benign, aggressive, and malignant groups were 1.0% (range, 0 to 5.5%),5.5% (range, 0.1 to 32.5%), and 12.0% (range, 0.3 to 32.5%), respectively. Differences in the mean MIB-1 LI between groups were statistically significant, with P values of <.0001 (benign v aggressive) and .0012 (aggressive v malignant). Mean MIB-1 LIs for recurrent versus nonrecurrent tumors were 7.1% (range, 0 to 32.5%) versus 3.8% (range, 0 to 20.9%) (P=.32). The mean MIB-1 LI for patients who were alive with or without tumor was 6.2% (range, 0 to 32.5%) versus a mean MIB-1 LI of 14.2% (range, 2.8% to 32.5%) for patients who died of or with tumor (P=.0013). In conclusion, (1) There is a statistically significant difference in the increasing MIB-1 LI means between benign, aggressive, and malignant meningiomas and between patients who were alive versus those who died; (2) there is some overlap in MIB-1 LI ranges between groups, which warrants caution in interpreting an individual MIB-1 LI in a given tumor.


Management of Impacted Third Molars.
Impacted third molars occur in a significant number of patients and often require treatment because of presence of symptoms and/or disease. Management of these teeth typically involves referral to oral and maxillofacial surgeons for diagnosis, treatment planning, and ultimate removal if indicated. Proper diagnosis and treatment planning helps optimize surgical results at each stage of the procedure, and ultimately patient outcomes. Adherence to proper surgical techniques helps minimize risks and complications associated with the procedure. Multiple alternative surgical techniques also exist for uncommon, but potentially complicated, situations that arise with some impacted third molars.


[Effect of conditioning to altitude hypoxia on mesenteric microcirculation in rats].
A long-term training of rats to high-altitude hypoxia (in an altitude chamber at the height of 6500 m, 6 hours daily, for 30 to 40 days) results in a significant hyperemia of their intestinal wall and mesentery. The number of functioning capillaries of trained rats exceeded that of control animals several times, but the blood flow was slowed down in the dilated vessels and their structure was altered. Besides an obvious increase in blood rachemia in the arteries and veins, its rarefaction is observed in the capillaries. Definite hemorheological changes, probably associated with polycythemia, and an increased hematocrite index were noted.


Mechanism of L-serine oxidation in Entamoeba histolytica.
1. The enzymatic mechanism of oxygen uptake elicited by L-serine in axenically cultivated trophozoites of Entamoeba histolytica was investigated. 2. Of 22 amino acids examined, only L-serine stimulated oxygen consumption by intact and disrupted amoebae. 3. Pyruvate, a product of serine metabolism, also stimulated oxygen consumption in the amoebae. 4. Characterization of the oxygen uptake elicited by both L-serine and pyruvate, and analysis of the products of L-serine metabolism indicate that the amino acid is first converted to pyruvate. 5. L-Serine dehydratase, which catalyzes the deamination of serine to pyruvate, was detected primarily in the soluble fraction of the amoebae. D-Serine potently inhibited the enzyme, as well as oxygen uptake in the presence of L-serine but not in the presence of pyruvate. 6. The pyruvate formed is oxidized, at least in part, by a novel pyruvate oxidase involving the uptake of molecular oxygen.


Abscess formation following spilled gallstones during laparoscopic cholecystectomy.
Our purpose was to report the occurrence of abscess following spilled gallstones during laparoscopic cholecystectomy as experienced at Good Samaritan Hospital, and to compare it to the experience of other institutions in order to identify the incidence, characteristics and possible risk factors for the development of this complication. Four case reports of abscess following spilled gallstones during laparoscopic cholecystectomy are presented. The English literature was reviewed, and characteristics of the case reports found in the literature were compared. In four years at this institution, four reports of abscess formation following laparoscopic cholecystectomy have been identified. Two occurred in elderly females and were located in the right flank in both. Two were in middle-aged men, both diabetic. One abscess was in the right flank and one in the right pleural space. Twenty-three cases were found in the literature. The average age was 65 years; there were 12 men and 11 women. The locations of abscess formation were trocar sites (most common), right subphrenic space, right flank or retroperitoneum, and pelvis. The average time to presentation was 4-5 months (range 4 days-12 months). Abscess formation following spilled gallstones during laparoscopic cholecystectomy occurs infrequently, but can be debilitating and require more than one procedure. The older population appears to be at greater risk. Future prospective studies of patients who undergo laparoscopic cholecystectomy are needed to more accurately determine the incidence of this complication and to identify the population at risk.


2,3-Di-hydro-1H-cyclo-penta-[b]naphthalene-4,9-dione.
The title compound, C13H10O2, crystallizes with two almost planar mol-ecules in the asymmetric unit. In the crystal, slipped π-π stacking inter-actions help to establish the packing with the shortest centroid-centroid separation being 3.8195 (18) Å.


Electrocardiographic Features of Immune Checkpoint Inhibitor-Associated Myocarditis.
Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events including myocarditis, whilst improving cancer-related outcomes. There is thus a clinical need to identify electrocardiographic manifestations of ICI-related myocarditis to guide clinical management. PubMed was searched for clinical studies and case reports describing electrocardiographic changes in patients with ICI-related myocarditis. A total of 6 clinical studies and 79 case reports were included. This revealed a range of presentations for patients on ICIs, including supraventricular arrhythmias, ventricular arrhythmias and heart block, and new changes of ST-T segment unrelated to coronary artery disease, ST-segment elevation or depression and T-wave abnormalities. Several patients showed low voltages in multiple leads and new onset Q-wave development. Patients with ICI-related myocarditis may develop new arrhythmia and ST-T changes, and infrequently low voltages in multiple leads.


Influences of amino acid features of glutathione S-transferase fusion proteins on their solubility.
We have previously described our strategy for high-throughput (HT) production of recombinant antigens for anti-mKIAA antibody generation, which involves using shotgun fragments generated during entire sequencing of mKIAA cDNAs. We applied this strategy to 1628 mouse KIAA (mKIAA) cDNA fragments, and 84.2% of the GST-mKIAA fusion proteins were successfully purified. The solubility of the proteins was predicted by a small-scale bacterial culture, and a large-scale culture was then performed according to the expected results. Among them, 43.8% of the proteins were purified as a soluble form and 56.2% as an insoluble form. The average yield of the soluble proteins was 0.15 nmol/mL of bacterial culture, and that of the insoluble proteins was 0.55 nmol/mL Statistical analysis of the data revealed a significant correlation between amino acid features of the recombinant proteins and their solubility. To achieve the most effective and feasible protein expression, we constructed a decision tree in which the analyzed data were reflected. The information described here may provide practical guidelines for HT production of recombinant proteins.


Effects of CO₂ Concentration and pH on Mixotrophic Growth of Nannochloropsis oculata.
This communication reports an experimental investigation of integrated CO2 bio-conversion, wastewater treatment, and biomass production by microalgae cultivation. In this regard, the effects of CO2 concentrations on mixotrophic growth kinetics of a microalgae strain (Nannochloropsis oculata) are conducted in a semi-batch photobioreactor. The concentration of CO2 in the feed stream is varied from 4 to 12 mol% by adjusting CO2-to-air ratio. The variation of pH of the synthetic wastewater culture media and nutrient uptake by the microalgae are also monitored. The experimental evaluation shows that 8 % CO2 gives the highest growth rate of N. oculata with a productivity of 0.088 g L(-1) day(-1). Under the studied conditions, the pH value of the culture media between 5.5 and 6.5 is favorable for the growth of N. oculata in mixotrophic condition. Among the nutrients available in the culture media, percentage of ammonia removal is found to be the highest (98.9 %) as compared that of other compounds such as nitrate (88.2 %) and phosphate (18.9 %). The thermochemical characteristics of the cultivated microalgae are assessed by thermogravimetric analysis in presence of air. The produced microalgae is thermally stable up to 200 °C. Following that, the microalgae biomass is sharply decomposed within 600 °C.


Phorbol ester-induced protein phosphorylation and contraction in sphincter smooth muscle of rabbit iris.
Phorbol 12,13-dibutyrate (PDBu) was employed in studies designed to determine the role of C-kinase in muscle contraction in the iris sphincter. PDBu induced MLC phosphorylation and contraction in a dose- and time-dependent manner. Maximum responses exerted by PDBu were about 50-60% of that obtained with CCh, and were totally dependent on the presence of extracellular Ca2+. PDBu had no effect on basal IP3 levels, however it blocked the CCh-stimulated accumulation of IP3. PDBu-induced effects were potentiated by ionomycin, and inhibited by the C-kinase antagonist H-7. These results provide further evidence for the involvement of C-kinase in mediating the sustained phase of the contractile response in the iris sphincter.


Human mismatch repair gene, MLH1, is transcriptionally repressed by the hypoxia-inducible transcription factors, DEC1 and DEC2.
Tumor hypoxia has been reported to cause a functional loss in DNA mismatch repair (MMR) system as a result of downregulation of MMR genes, although the precise molecular mechanisms remain unclear. In this study, we focused on the downregulation of a key MMR gene, MLH1, and demonstrated that hypoxia-inducible transcription repressors, differentiated embryo chondrocytes (DEC1 and 2), participated in its transcriptional regulation via their bindings to E-box-like motif(s) in MLH1 promoter region. In all cancer cell lines examined, hypoxia increased expression of DEC1 and 2, known as hypoxia-inducible genes, but decreased MLH1 expression in an exposure time-dependent manner at both the mRNA and protein levels. Co-transfection reporter assay revealed that DEC1 and, to greater extent, DEC2 as well as hypoxia-repressed MLH1 promoter activity. We further found that the action was remarkably inhibited by trichostatin A, and identified a possible DEC-response element in the MLH1 promoter. In vitro electrophoretic gel mobility shift and chromatin immunoprecipitation assays demonstrated that DEC1 or 2 directly bounds to the suggested element, and transient transfection assay revealed that overexpression of DEC2 repressed endogenous MLH1 expression in the cells. Hypoxia-induced DEC may impair MMR function through repression of MLH1 expression, possibly via the histone deacethylase-mediated mechanism in cancer cells.


Timing of cataract surgery in patients with giant cell arteritis.
To determine a safe timeframe and parameters for performing cataract surgery after diagnosis and treatment of giant cell arteritis (GCA). Single institution in the United States. Retrospective chart review. This retrospective study used ICD-9/10 and Current Procedural Terminology codes to identify all patients with biopsy-proven GCA who underwent cataract surgery from 2005 to 2019 at a single institution. Excluded from the study were patients whose date of biopsy diagnosis or dose of corticosteroids at the time of cataract surgery was unknown. Chart review identified 15 eyes of 10 patients that met inclusion criteria; 80% of patients were women, and mean age was 74.4 years. Two patients had a history of arteritic ischemic optic neuropathy. There were no perioperative or postoperative complications in the 15 eyes that underwent cataract surgery with varying doses of prednisone at the time of surgery (1 to 25 mg daily prednisone ± 10 to 25 mg weekly methotrexate; median prednisone dose of 10.75 mg) and varying time from biopsy diagnosis of GCA to surgery of at least 7 months (median 13.75 months). Cataract surgery seemed safe for patients with GCA on varying doses of prednisone at the time of surgery at least 7 months from time of biopsy diagnosis. There is a need for a larger cohort of data from neuro-ophthalmologists and cataract surgeons nationally to establish guidelines for safe cataract surgery in patients with GCA.


Some of the properties of flame retardant medium density fiberboard made from rubberwood and recycled containers containing aluminum trihydroxide.
The flame retardancy of medium density fiberboard (MDF) made from mixture of rubberwood fibers and recycled old corrugated containers was studied. Aluminum trihydroxide (ATH) was used as a fire retardant additive and mixed with the fibers to manufacture experimental MDF panels using wet process. Phenol formaldehyde (PF) resin in liquid, 2% based on oven dry weight of fibers, was used along with 0%, 10%, 15% and 20% of ATH. The flame retardant test was done using the limiting oxygen index (LOI) test. The other properties investigated include internal bond strength, thickness swelling and water absorption. The results showed that ATH loading increased as the LOI of MDF increased. This demonstrated that ATH could improved the fire retardant property of MDF at sufficient loading. An increase in concentration of ATH showed an increase in the IB values of MDF made without resin. MDF panels made without resin showed a progressive increase in internal bond as the composition of recycled old corrugated containers fiber increased. Addition of resin improved internal bond strength and reduced thickness swelling, and water absorption. Thickness swelling of panel increased as the composition of recycled old corrugated containers fiber increased. Scanning electron microscopy (SEM) and energy dispersive X-ray analysis (EDAX) showed that there is indication of ATH and resin filling the void space in between fibers.


Modeling the energetic cost of cancer as a result of altered energy metabolism: implications for cachexia.
Cachexia affects most patients with incurable cancer. We hypothesize that in metastatic cancer the mass of the tumor as well as its level of anaerobic energy metabolism play a critical role in describing its energetic cost, which results in elevated resting energy expenditure and glucose utilization, leading to cachexia. Prior models of cancer cachexia may have underestimated the specific energetic cost of cancer as they have not taken the range of tumor mass and anaerobic energy metabolism fully into account. We therefore modelled the energetic cost of cancer as a function of the percentage of energy the cancer produces anaerobically, based on resting energy expenditure, glucose turnover, glucose recycling, and oxygen consumption in cancer patients found in previous studies. Data from two clinical studies where tumor burden was estimated and resting energy expenditure or oxygen consumption were measured lead to a broad range of estimates of tumor cost from 190 to 470 kcal/kg tumor/day. These values will vary based of the percentage of energy the cancer produces anaerobically (from 0 to 100%), which in and of itself can alter the cost over a 2 to 3-fold range. In addition to the tumor cost/kg and the degree of anaerobic metabolism, the impact on a given individual patient will depend on tumor burden, which can exceed 1 kg in advanced metastatic disease. Considering these dimensions of tumor cost we are able to produce a 2-dimensional map of potential values, with an overall range of 100-1400 kcal/day. Quantifying the energetic cost of cancer may benefit an understanding of the tumor's causation of cachexia. Our estimates of the range of tumor cost include values that are higher than prior estimates and suggest that in metastatic disease the tumor cost could be expected to eclipse attempts to stabilize energy balance through nutrition support or by drug therapies. Tumor mass and the percentage of anaerobic metabolism in the tumor contribute to the cost of the tumor on the body and potentially lead directly to negative energy balance and increased muscle wasting.


A new post-intoxication treatment of paraoxon and parathion poisonings using an evolved PON1 variant and recombinant GOT1.
Organophosphate (OP) based pesticides are highly toxic compounds that are still widely used in agriculture around the world. According to World Health Organization (WHO) data, it is estimated that between 250,000 and 370,000 deaths occur yearly around the globe as a result of acute intoxications by pesticides. Currently available antidotal drug treatments of severe OP intoxications are symptomatic, do not reduce the level of intoxicating OP in the body and have limited ability to prevent long-term brain damage. Pesticide poisonings present a special therapeutic challenge since in many cases, such as with parathion, their toxicity stems from their metabolites that inhibit the essential enzyme acetylcholinesterase. Our goal is to develop a new treatment strategy for parathion intoxication by combining a catalytic bioscavenger that rapidly degrades the intoxicating parathion-metabolite (paraoxon) in the blood, with a glutamate bioscavenger that reduces the elevated concentration of extracellular glutamate in the brain following OP intoxication. We report on the development of a novel catalytic bioscavenger by directed evolution of serum paraoxonase 1 (PON1) that effectively detoxifies paraoxon in-vivo. We also report preliminary results regarding the utilization of this PON1 variant together with a recombinant human enzyme glutamate oxaloacetate transaminase 1 (rGOT1), suggesting that a dual PON-GOT treatment may increase survival and recovery from parathion and paraoxon intoxications.


Detection of antibody-forming cells directed against Newcastle disease virus and their immunoglobulin class by double immunoenzyme histochemistry.
Antibody-forming cells (AFCs) against Newcastle disease virus (NDV) and their immunoglobulin (Ig) class were demonstrated by a double immuno-enzyme histochemical technique. The AFCs were stained and quantified in spleen sections of chickens euthanatized at day 7 postexposure to the Roakin strain of NDV. The sections were incubated with NDV to determine the specificity of the AFCs. Bound virus was subsequently visualized with a primary monoclonal antibody (MAb), a secondary horseradish peroxidase-conjugated MAb, and 3-amino-9-ethylcarbazole as substrate. IgM and IgA were stained with MAbs and an alkaline phosphatase (AP)-conjugated secondary antibody. IgG class antibodies were demonstrated with an AP-conjugated rabbit serum. The final substrate for the three Igs was naphthol AS-MX-phosphate and fast blue BB. About 64-159/mm2 AFCs against NDV were detected. Of these virus-binding cells, about 55% produced IgM, 37% produced IgG, and the remaining 8% produced IgA.


Characterization of cyclodextrin glycosyltransferase from Bacillus firmus strain no. 37.
The enzyme cyclodextrin glycosyltransferase (CGTase), EC 18.104.22.168, which produces cyclodextrins (CDs) from starch, was obtained from Bacillusfirmus strain no. 37 isolated from Brazilian soil and characterized in the soluble form using as substrate 100 g/L of maltodextrin in 0.05 M Tris-HCl buffer, 5 mM CaCl2, and appropriate buffers. Enzymatic activity and its activation energy were determined as a function of temperature and pH. The activation energy for the production of beta- and gamma-CD was 7.5 and 9.9 kcal/mol, respectively. The energy of deactivation was 39 kcal/mol. The enzyme showed little thermal deactivation in the temperature range of 35-60 degrees C, and Arrhenius-type equations were obtained for calculating the activity, deactivation, and half-life as a function of temperature. The molecular weight of the enzyme was determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis, giving 77.6 kDa. Results for CGTase activity as a function of temperature gave maximal activity for the production of beta-CD at 65 degrees C, pH 6.0, and 71.5 mmol of beta-CD/(min x mg of protein), whereas for gamma-CD it was 9.1 mmol of gamma-CD/(min mg of protein) at 70 degrees C and pH 8.0. For long contact times, the best use of the enzymatic activity occurs at 60 degrees C or at a lower temperature, and the reaction pH may be selected to increase the yield of a desired CD.


Behaviour of fibroblasts and epidermal cells cultivated on analogues of extracellular matrix.
A porous collagen sponge can be used for supporting epidermal cells and fibroblasts in order to manufacture an artificial skin. Fibroblasts were grown on analogues of extracellular matrix containing collagen and glycosaminoglycans and/or glycoproteins. Cell replication, and also infiltration of fibroblasts, were enhanced by the presence of hyaluronic acid and/or fibronectin. Epidermal cells grown on a collagen sponge have been characterized by microscopic observations. Epidermal cells on the surface of the sponge showed an incomplete differentiation in comparison to normal skin; clumps of epidermal cells were found in the interior of the sponge. Epidermal cell replication was enhanced in the presence of collagen sponge seeded with fibroblasts.


Reversal of transplant rejection by monoclonal antiblast antibody.
The first clinical trial of an antiblast monoclonal antibody, CBL1, in the treatment of kidney allograft rejection is described. The theory that this antibody might destroy active clones of cells without major side effects was given validity by a previously described study showing prolongation of skin allograft survival in rhesus monkeys. CBL1 was used to treat kidney allograft rejections in 11 patients with a one-haplotype-identical related-donor graft who had been prestimulated with donor-specific transfusions and 8 patients with cadaver grafts who had been prestimulated with multiple transfusions. 15 of the rejections were steroid-resistant. Although CBL1 had no effect on the peripheral blood lymphocyte counts, rejections were reversed in 17 of 19 patients. There was 1 graft loss in the 11 recipients of related-donor grafts and 3 in patients with cadaver-donor grafts. Side effects associated with administration of antilymphocyte serum--ie, chills, fever, and thrombocytopenia--did not develop in any of the patients treated with CBL1. It is postulated that administration of an antiblast monoclonal antibody during rejection of a kidney kills only those cells that are reacting against the graft. This could result in the maintenance of normal lymphocyte numbers and immunological functions against other antigens.


Author Correction: A Silurian ancestral scorpion with fossilised internal anatomy illustrating a pathway to arachnid terrestrialisation.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Accessibility of emergency contraception in California's Catholic hospitals.
Access to emergency contraception (EC) is an important option for women wanting to prevent an unintended pregnancy. In California, emergency rooms (ERs) are required to provide survivors of sexual assault with information about and access to EC. This study assessed the likelihood that a woman calling a Catholic hospital in California to inquire about EC could access the medication. During September 2003, we contacted an ER staff member in each of California's Catholic hospitals (n = 45) using a mystery caller approach. Following a written script, trained female researchers asked ER staff whether they dispense EC at their facility and under what circumstances. If respondents initially stated that their facility would not dispense EC, the caller asked whether EC was available to women who had been raped. If staff confirmed that their facility would not provide EC under any circumstances including rape, callers requested a referral to another facility that would provide the medication. Sixty-six percent of staff contacted stated that their hospital would not provide EC under any circumstances, including rape. Of those that would not dispense EC, fewer than half of respondents (48%) provided a referral. Of the 14 referrals given, only about one third (n = 5) led to a facility that provides EC. Our findings suggest that access to EC in California's Catholic hospitals is minimal, even for victims of sexual assault. As many as two-thirds of these hospitals may be violating state legislation requiring hospitals to provide EC to sexual assault survivors upon request.


[Ultrastructural evaluation of carcinoembryonic antigen (CEA) using an immunocytochemical method with the peroxidase-antiperoxidase (PAP) complex technic in patients with laryngeal cancer].
Peroxidase-antiperoxidase complex method (PAP) was used to reveal the CEA antigen in the larynx carcinoma cells by means of electron microscope. Studies were carried out on the material taken from 8 patients with the larynx carcinoma. In all cases positive immunoperoxidase reaction has been observed. The product of the reaction has been found on the surface of the cells. In one case intracytoplasmic positive reaction has been noticed.


Renal access in PNL under sonographic guidance: Do we really need to insert an open end ureteral catheter in dilated renal systems? A prospective randomized study.
To evaluate the true necessity of open end ureteral catheter insertion in patients with moderate to severe pelvicalyceal system dilation treated with percutaneous nephrolithotomy (PNL) under sonographic guidance. 50 cases treated with PNL under sonographic guidance in prone position for solitary obstructing renal stones were evaluated. Patients were randomly divided into two groups; Group 1: Patients in whom a open end ureteral catheter was inserted prior to the procedure; Group 2: Patients receiving no catheter before PNL. In addition to the duration of the procedure as a whole and also all relevant stages as well, radiation exposure time, hospitalization period, mean nephrostomy tube duration, mean drop in Hb levels and all intra and postoperative complications have been evaluated. Mean size of the stones was 308.5 ± 133.2 mm2. Mean total duration of the PNL procedure in cases with open end ureteral catheter was significantly longer than the other cases (p < 0.001). Evaluation of the outcomes of the PNL procedures revealed no statistically significant difference between two groups regarding the stone-free rates (86% vs 84%). Additionally, there was no significant difference with respect to the duration of nephrostomy tube, hospitalization period and secondary procedures needed, complication rates as well as the post-operative Hb drop levels in both groups (p = 0.6830). Our results indicate that the placement of an open end ureteral catheter prior to a PNL procedure performed under sonographic access may not be indicated in selected cases presenting with solitary obstructing renal pelvic and/or calyceal stones.


Use of a Textured Insole to Improve the Association Between Postural Balance and Ankle Discrimination in Young Male and Female Dancers.
Ballet dancers require a high level of postural balance (PB) and proprioception ability during performance. As textured insoles inserted into ballet shoes were found to improve proprioception ability, and better proprioceptive acuity was associated with better PB, the aim of the present study was to investigate whether the association between ankle inversion movement discrimination (AIMD) and PB changed following wearing textured insoles in young male and female dancers. Forty-four dancers from the Australian Ballet School, ages 14-19 yrs, were tested for static and dynamic PB and AIMD under two conditions: in ballet shoes, and in ballet shoes with textured insoles inserted. Female dancers demonstrated a significant inverse relationship between AIMD and static PB in the medio-lateral direction when wearing ballet shoes, but not when wearing textured insoles. Male dancers showed a non-monotonic relationship when tested with ballet shoes only, but a significant inverse relationship between AIMD and dynamic PB in the vertical direction and with the waist/head cross-correlation acceleration in the three movement directions when they were tested with textured insoles. Male dancers demonstrated an improved association between dynamic PB and proprioception ability when using textured insoles, suggesting that the increased afferent information from the plantar surface had a beneficial effect on proprioception feedback about their PB. Conversely, for female dancers, that association was present when wearing ballet shoes, but not when using textured insoles, suggesting that the increased afferent information for female dancers who already had high proprioception ability was "overloaded" by wearing the textured insoles.


Indole-3-carbinol induction of CYP1A1, CYP1A2, and CYP3A1 activity and gene expression in rat liver under conditions of different fat content in the diet.
Wistar male rats were fed semisynthetic diet with different fat content for 6 weeks: fat-free, 10%, and 30% fat (sunflower oil and lard, 1:1). Increasing fat content was associated with an increase in ethoxyresofurin-O-dealkylase (EROD) activity of CYP1A1, methoxyresofurin-O-dealkylase (MROD) activity of CYP1A2, and 6β-testosterone-hydroxylase (6β-TH) activity of CYP3A1. EROD, MROD, and 6β-TH activities in rats on high-fat diet exceeded those in rats on fat-free diet by 64, 58, and 140%, respectively. Addition of indole-3-carbinol to the diet led to an increase in CYP1A1, CYP1A2, and CYP3A1 activities and mRNA levels, the degree of this increase was lower with increasing fat content in the diet. In rats on fat-free, 10% fat, and 30% fat diets, indole-3-carbinol induced EROD activity by 4.7, 3.2, and 2.0 times, respectively; MROD activity by 5.9, 5.6, and 5.4 times; and 6β-TH activity by 2.1, 1.9, and 1.3 times. A correlation was detected between activities of the studied cytochrome P-450 isoforms, their inducibility by indole-3-carbinol, and vitamin A and E levels in rat liver.


Sulfinylcalix[4]arene-impregnated amberlite XAD-7 resin for the separation of niobium(V) from tantalum(V).
Amberlite XAD-7 resin was impregnated with p-tert-butylsulfinylcalix[4]arene. Niobium(V) was collected on the impregnated resin in yields of more than 90% around pH 5.4, whereas tantalum(V) was negligibly collected. The collected niobium(V) was desorbed with 9 M sulfuric acid nearly quantitatively, hence the separation of niobium(V) from tantalum(V) was successfully achieved.


A Critical Role for Neocortical Processing of Threat Memory.
Memory of cues associated with threat is critical for survival and a leading model for elucidating how sensory information is linked to adaptive behavior by learning. Although the brain-wide circuits mediating auditory threat memory have been intensely investigated, it remains unclear whether the auditory cortex is critically involved. Here we use optogenetic activity manipulations in defined cortical areas and output pathways, viral tracing, pathway-specific in vivo 2-photon calcium imaging, and computational analyses of population plasticity to reveal that the auditory cortex is selectively required for conditioning to complex stimuli, whereas the adjacent temporal association cortex controls all forms of auditory threat memory. More temporal areas have a stronger effect on memory and more neurons projecting to the lateral amygdala, which control memory to complex stimuli through a balanced form of population plasticity that selectively supports discrimination of significant sensory stimuli. Thus, neocortical processing plays a critical role in cued threat memory.


HIV-1-infection in a man who has sex with men despite self-reported excellent adherence to pre-exposure prophylaxis, the Netherlands, August 2021: be alert to emtricitabine/tenofovir-resistant strain transmission.
In August 2021, a man who has sex with men was diagnosed with HIV-1 infection despite using event-driven pre-exposure prophylaxis for over 2 years with self-reported excellent adherence. Sequencing identified resistance-associated mutations (RAM) M184V and K65R, conferring resistance to emtricitabine and tenofovir, and RAM V108I and E138A. Background RAM prevalence was two of 164 (1.2%) new HIV diagnoses in Amsterdam (2017-19). We reiterate the need for frequent HIV testing among PrEP users and additional testing in case of symptoms.


In Alzheimer's disease, heme oxygenase is coincident with Alz50, an epitope of tau induced by 4-hydroxy-2-nonenal modification.
In this study, we compared the neuronal induction of the antioxidant heme oxygenase-1 (HO-1) in Alzheimer's disease with abnormalities in tau marked by antibodies recognizing either phosphorylation (AT8) or conformational change (Alz50). The epitope recognized by Alz50 shows a complete overlap with HO-1-containing neurons, but AT8 recognized these neurons as well as neurons not displaying HO-1. These findings suggest that tau phosphorylation precedes the HO-1 response and that HO-1 is coincident with the Alz50 epitope. This led us to consider whether oxidative damage plays a role in forming the Alz50 epitope. We found that 4-hydroxy-2-nonenal (HNE), a highly reactive product of lipid peroxidation, reacts with normal tau and induces the Alz50 epitope in tau. It is important that the ability of HNE to create the Alz50 epitope not only is dependent on lysine residues of tau but also requires tau phosphorylation because neither methylated, recombinant, nor dephosphorylated tau reacts with HNE to create the Alz50 epitope. Supporting the in vivo relevance of this observation, endogenous paired helical filament-tau isolated from subjects with Alzheimer's disease was immunoreactive with an antibody to a stable HNE-lysine adduct, as were all vulnerable neurons in subjects with Alzheimer's disease but not in control individuals. Together, these findings support the involvement of oxidative damage early in neurofibrillary tangle formation in Alzheimer's disease and also suggest that HNE modification contributes to the generation of the tau conformation defining the Alz50 epitope. These findings provide evidence that an interplay between phosphorylation of tau and neuronal oxidative stress-induced pathology is important in the formation of neurofibrillary tangles.


Pediatric Considerations.
The article discusses the nuances required to effectively perform the biomechanical examination in children and assess the findings. The author covers several factors in children that make the examination different in certain respects than in that of adults, including growth, osseous maturation, gait development, and interpretation of symptoms as conveyed by the child. Further delineation is made for prewalkers, foot-flat to foot-flat walkers, and heel-to-toe walkers. Segmental review of the lower extremity is covered by age bracket, with clinical pearls inserted where relevant to assist the clinician. A brief discussion of shoe wear and orthoses is made as well.


Possible involvement of a 95-kDa protein phosphorylation in phorbol 12-myristate 13-acetate-induced suppression of zymosan phagocytosis in guinea pig macrophages.
Recently, we characterized a surface antigen (Z-1) of guinea pig macrophages by monoclonal anti-Z-1 antibody. The Z-1 antigen consists of two different polypeptide chains; alpha (140 kDa) and beta (95 kDa). This antigen is closely correlated with the phagocytic activity of the cells for zymosan and presumably functions as a receptor for zymosan. In the present study, the effect of phorbol 12-myristate 13-acetate (PMA) on the function of Z-1 was examined. Incubation of ortho-[32P]phosphate-labeled macrophages with PMA greatly increased the phosphorylation of the beta subunit of Z-1 but not that of the alpha subunit. Optimal phosphorylation was observed when cells were incubated with 300 ng/ml of PMA for 60-120 min. The PMA-induced phosphorylation was markedly suppressed by treatment of the macrophages with H-7, an inhibitor of protein kinase C. A chemotactic peptide, N-formyl-Met-Leu-Phe (fMLP) also caused phosphorylation of the beta subunit. Unlike PMA, fMLP maximized the phosphorylation within 30 s. Purified Z-1 was an excellent substrate for the exogenously added protein kinase C only in the presence of both Ca2+ and phosphatidylserine. H-7 completely inhibited the in vitro phosphorylation. These data suggest that the beta subunit of Z-1 is phosphorylated by protein kinase C. The phosphorylation of Z-1 by PMA and fMLP coincided with inhibition of zymosan phagocytosis. A linear relationship was obtained between the level of phosphorylation of Z-1 and the degree of inhibition of zymosan phagocytosis induced by PMA. Thus, the results suggest that zymosan uptake is negatively regulated by protein kinase C-mediated phosphorylation of the beta subunit of Z-1.


The effect of peritoneal lavage and aprotinin in the treatment of severe acute pancreatitis.
Fifty-five patients with severe acute pancreatitis were treated with peritoneal lavage at the Dept. of Surgery at Malmö General Hospital. In a randomized study 26 of the 55 patients received in addition 500,000 KIU aprotinin in the lavage fluid every 2 h. There were no significant differences between the aprotinin- and non-aprotinin-treated groups as to mortality and clinical results. The initial concentration of alpha 1-antitrypsin in plasma was mainly within normal range with increasing values during the treatment. No differences were seen between the two groups. The initial mean level of alpha 2-macroglobulin in plasma was slightly decreased, but 17 patients showed values below normal range. The alpha 2-macroglobulin level during the lavage showed a similar course in the two groups. alpha 1-Antitrypsin and alpha 2-macroglobulin in the lavage fluids showed signs of complexation but in plasma these inhibitors did not show any signs of complexation. On admission to the hospital the mean levels of C3 and kininogen in the plasma were slightly below normal. During the lavage treatment no differences were seen between the two groups. Degradation products of C3 and kininogen were seen in both serum and peritoneal fluids. The electrophoretic patterns of C3 and kininogen normalized in serum as well as in lavage fluids during the lavage treatment without any significant differences in the two groups. High levels of immunoreactive trypsin, pancreatic elastase, PSTI, and leukocyte elastase in serum were seen equally in both groups of patients.


Combined Abl inhibitor therapy for minimizing drug resistance in chronic myeloid leukemia: Src/Abl inhibitors are compatible with imatinib.
Chronic myeloid leukemia (CML) is effectively treated with imatinib. However, reactivation of Bcr-Abl via kinase domain mutations that reduce sensitivity to imatinib can cause relapse. As combination therapy is frequently used to prevent emergence of resistance, the combination of imatinib with an inhibitor of imatinib-resistant Bcr-Abl mutants (e.g., Src/Abl inhibitors AP23848 and BMS-354825) was investigated. To test this approach, cellular proliferation and Bcr-Abl tyrosine phosphorylation assays were done on Ba/F3 cells expressing wild-type (WT) Bcr-Abl and four common imatinib-resistant mutants (Y253F, E255K, T315I, and M351T). Colony-forming assays with primary CML cells were also done. Both Src/Abl inhibitors retained full inhibitory capacity when coadministered with imatinib at concentrations above typical clinical levels. For cells expressing WT Bcr-Abl or the marginally imatinib-resistant mutant M351T, inclusion of imatinib at therapeutic levels enhanced the effects of the Src/Abl inhibitors. By comparison, for the highly imatinib-resistant mutants Y253F and E255K, inclusion of imatinib at clinical levels resulted in only a slight enhancement beyond the effects of the Src/Abl inhibitors. None of the inhibitors affected Bcr-Abl T315I cells. Colony-forming assays with primary CML cells yielded analogous results. Our results indicate that Src/Abl inhibitors are compatible with imatinib and suggest that combined Abl inhibitor therapy is a feasible treatment strategy for patients with CML.


Rapid induction and persistence of paracrine-induced cellular antiviral states arrest viral infection spread in A549 cells.
The virus/host interaction is a complex interplay between pro- and anti-viral factors that ultimately determines the spread or halt of virus infections in tissues. This interplay develops over multiple rounds of infection. The purpose of this study was to determine how cellular-level processes combine to impact the spatial spread of infection. We measured the kinetics of virus replication (VSV), antiviral paracrine signal upregulation and secretion, spatial spread of virus and paracrine antiviral signaling, and inhibition of virus production in antiviral-exposed A549 human lung epithelial cells. We found that initially infected cells released antiviral signals 4-to-7h following production of virus. However, the subsequent rapid dissemination of signal and fast induction of a robust and persistent antiviral state ultimately led to a suppression of infection spread. This work shows how cellular responses to infection and activation of antiviral responses can integrate to ultimately control infection spread across host cell populations.


Optimized profit repatriation in multinational enterprises through cross-border change of legal form and international tax management.
This article shows for the first time that the cross-border change of legal form can be used for tax-optimized profit repatriation. By means of a cross-border change of legal form of the foreign EU corporation prior to distribution into another foreign EU corporation with subsequent dividend distribution after the cross-border change of legal form has taken place, the taxation of dividends with withholding tax can be avoided. This study develops and discusses this strategy for the first time and transfers it specifically to U.S. shareholders of European corporations. Moreover, this strategy is relevant in general for all shareholders of European corporations, irrespective of their residence, to get tax-optimized profit repatriation of dividends (retained earnings) and to avoid the problem of treaty shopping, which has been significantly strengthened by the introduction of the ATAD/BEPS principal purpose test (PPT) in all EU Member States. The study extends the state of knowledge in the area of international taxation, international mergers, finance and strategy.


A new multimedia-based instruction for hip arthroplasty in clinical practice.
With the aging of the population, patients with degenerative osteoarthritis are growing. Until now, artificial joint arthroplasty (HA) is the final treatment for such joint-related disease. Because of the implementation of case payment insurance policy, patients with artificial HA in Taiwan have higher post-operative infection, dislocation and readmission than those in other countries. It is more important, nowadays, to provide patients and their family appropriate care guide for operative preparation and post-operative rehabilitation. Therefore, the purpose of this study was to develop a multimedia-based instruction (MBI) videodisc and then apply it in the care guide instruction for HA patients. The MBI videodisc in this study created combined texts, pictures, film, animations, sound, etc. by using Ulead PhotoImpact package and CyberLink PowerDirector. Thirty-three subjects in the experimental group and an equal number of subjects in the control group were recruited to evaluate the efficacy of the HA MBI videodisc in patients' learning. The results demonstrated that the HA MBI videodisc could improve patient self-care cognition in operative preparation and functional activity in post-operative rehabilitation.


Biogenesis of the mitochondrial matrix enzyme, glutamate dehydrogenase, in rat liver cells. II. Significance of binding of glutamate dehydrogenase to microsomal membrane.
1. Glutamate dehydrogenase and malate dehydrogenase solubilized from liver microsomes were able to rebind to microsomal vesicles while the corresponding dehydrogenases extracted from mitochondria showed no affinity for microsomes. 2. Competition was noticed between microsomal glutamate dehydrogenase and microsomal malate dehydrogenase in the binding to microsomal membranes. Mitochondrial malate dehydrogenase or bovine serum albumin did not inhibit the binding of microsomal glutamate dehydrogenase to microsomes. 3. Binding of microsomal glutamate dehydrogenase to microsomal membranes decreased when microsomes was preincubated with trypsin. 4. Rough microsomal glutamate dehydrogenase was more efficiently bound to rough microsomes than smooth microsomes. Conversely, smooth microsomal glutamate dehydrogenase had higher affinity for smooth microsomes than for rough microsomes. 5. A difference was noticed among the glutamate dehydrogenase isolated from rough and smooth microsomes, and from mitochondria, which suggested the possibility of minor post-translational modification of enzyme molecules in the transport from the site of synthesis to mitochondria.


Physical activity correlates in people living with HIV/AIDS: a systematic review of 45 studies.
Understanding barriers and facilitators of physical activity participation in persons living with HIV/AIDS is an essential first step in order to devise effective interventions. The present review provides a systematic quantitative review of the physical activity correlates in people with HIV/AIDS. Major electronic databases were searched till August 2016. Keywords included "physical activity" or "exercise" or "sports" and "AIDS" or "HIV". Out of 55 correlates from 45 studies (N = 13,167; mean age range = 30.5-58.3 years; 63.2% male) five consistent (i.e., reported in four or more studies) correlates were identified. Lower levels of physical activity were consistently associated with older age (6/10 studies), a lower educational level (6/7), a lower number of CD4 cells/μl (7/11), exposure to antiviral therapy (4/6), and the presence of lipodystrophy (4/4). Other important barriers were the presence of bodily pain (2/2), depression (3/3), and opportunistic infections (3/4). Facilitators were a higher cardiorespiratory fitness level (3/3), a higher self-efficacy (2/2), more perceived benefits (2/2), and a better health motivation (3/3). The current review has elucidated that participation in physical activity by people with HIV/AIDS is associated with a range of complex factors which should be considered in rehabilitation programs. Implications for Rehabilitation Health care professionals should consider HIV-related bodily pain and feelings of depression when assisting people living with HIV in inititiating and maintaining an active lifestyle. Interventions to improve self-efficacy and motivation, and to help people living with HIV in understanding the benefits of exercise, may encourage greater participation.


Causative factors affecting peripheral neuropathy in burn patients.
Peripheral neuropathy in burn patients may be frequently missed in clinical settings. Although its incidence has been reported, little is known regarding the factors that cause burn-related peripheral neuropathy. A retrospective chart review of the demographic and clinical characteristics of patients admitted to a university hospital based burn center was conducted to explore the characteristics of burn-related neuropathy and factors affecting its types or extent. The variables collected were gender, age, length of hospital stay, site and surface area of burn, type of burn, and electrodiagnostic findings. We found that flame injuries, and third degree injuries were the most common in patients with peripheral neuropathy. Axonotmesis was more common than demyelinating injury and polyneuropathy was more common than mononeuropathy. Higher degree and larger area burns were more frequently associated with axonotmesis than with demyelination. Length of hospital stay was significantly longer in patients with axonotmesis. Overall, more severe burns showed a significant association with axonotmesis and a tendency to be related to polyneuropathy.


Effects of oral bisphosphonate therapy on serum calcium in elderly veterans with poor kidney function.
Limited data exist on the use of bisphosphonates in patients with poor kidney function due to a contraindication derived from inadequate experience among patients with kidney failure, accounting for as much as 25% of nonprescribing when otherwise appropriate. To determine whether bisphosphonate use in patients with decreased renal function, as outlined in the package insert (estimated creatinine clearance [eCrCl] <35 mL/min), would result in higher rates of hypocalcemia, as suggested in previous studies. This was a retrospective cohort study of elderly veterans 65 years of age and older at the Veterans Affairs North Texas Health Care System in Dallas, Texas. We identified 3089 patients who started oral bisphosphonate therapy between August 1, 2003 and July 12, 2010. Of the 252 patients meeting the inclusion criteria, 25 and 227 patients had an eCrCl <35 mL/min and eCrCl ≥35 mL/min, respectively. Analyses of changes in serum calcium from baseline to the 1-year study end point were performed within and between each renal function group. Among the veterans with an eCrCl <35 mL/min and eCrCl ≥35 mL/min, there were decreases in median serum calcium levels from baseline to study end point from 9.8 mg/dL (interquartile range [IQR], 9.4-10.2 mg/dL) to 9.3 mg/dL (IQR, 9.0-10.0 mg/dL; P = 0.028) and 9.6 mg/dL (IQR, 9.3-9.9 mg/dL) to 9.4 mg/dL (IQR, 9.1-9.8 mg/dL; P < 0.001), respectively. However, there was no difference in Δcalcium: -0.2 mg/dL (IQR, 0-0.6 mg/dL) and 0.2 mg/dL (IQR, -0.2 to 0.5 mg/dL; P = 0.547), respectively. This exploratory assessment may suggest that, in elderly veterans, the initiation of oral bisphosphonate therapy contributed to a statistically significant decrease in serum calcium levels regardless of baseline renal function; however, the clinical impact of this change does not appear to be significant. Future studies should assess serum calcium in a larger population of patients to confirm the safety of oral bisphosphonates in poor kidney function.


Atmospheric particle-bound polycyclic aromatic compounds over two distinct sites in Pakistan: Characteristics, sources and health risk assessment.
Much attention is drawn to polycyclic aromatic hydrocarbons (PAHs) as an air pollutant due to their toxic, mutagenic and carcinogenic properties. Therefore, to understand the levels, seasonality, sources and potential health risk of PAHs in two distinct geographical locations at Karachi and Mardan in Pakistan, total suspended particle (TSP) samples were collected for over one year period. The average total PAH concentrations were 31.5 ± 24.4 and 199 ± 229 ng/m3 in Karachi and Mardan, respectively. The significantly lower concentration in Karachi was attributed to diffusion and dilution of the PAHs by the influence of clean air mass from the Arabian sea and high temperature, enhancing the volatilization of the particle phase PAHs to the gas phase. Conversely, the higher concentration (~6 times) in Mardan was due to large influence from local and regional emission sources. A clear seasonality was observed at both the sites, with the higher values in winter and post-monsoon due to higher emissions and less scavenging, and lower values during monsoon season due to the dilution effect. Diagnostic ratios and principal component analysis indicated that PAHs in both sites originated from traffic and mixed combustion sources (fossil fuels and biomass). The average total BaP equivalent concentrations (BaPeq) in Karachi and Mardan were 3.26 and 34 ng/m3, respectively, which were much higher than the WHO guideline of 1 ng/m3. The average estimates of incremental lifetime cancer risk from exposure to airborne BaPeq via inhalation indicated a risk to human health from atmospheric PAHs at both sites.