[Commentaries on the complication of vestibular diseases].
Handicap of the patient with vestibular disease can be measured by means of scales and questionnaires. The utility of a questionnaire developed and validated in Spanish language is commented (CEMPV). The CEMPV consists of 46 questions distributed in three scales (emotional, functional and organic) whose obtained scores are related to diverse degrees of handicap (global, emotional, functional and organic). The CEMPV is self-employed and evaluates the evolution of the patient and allows to accredit the results obtained between different investigators.


[From "Shaking Palsy" to "Parkinson's Disease": Was Charcot Correct?]
In light of contemporary knowledge, we review a classic case of "Parkinson's disease" presented by Charcot. The patient, Bachère, provided an opportunity to change the name of the disease from "Shaking palsy" to "Parkinson's disease". We also explore a total of 4 cases of "Parkinson's disease in extension", especially that of Rab. Léon, described in 2 articles (1889 and 1892) in Nouvelle Iconographie de la Salpêtrière. Although diagnosed by Charcot as a type of Parkinson's disease, and historically accepted as such, he may have been misled. English text is available


[Therapy for ROD and measurement of the bone mass].
The kidney deeply takes part in phosphorus and vitamin D metabolism. The chronic kidney disease patients usually suffer from serious bone disease. They are prescribed the glucocorticoid medication for primary kidney disease, as nephrotic syndrome and collagen renal disease, with aging. The end of therapeutic target is normal bone structure with normal bone turnover in CKD patients. The control of serum Ca and phosphorus level is important step and also another target. This issue describes the problem and the advancement of treatment and the measurement of the bone mass from this viewpoint.


A pharmacological overview of opioid mechanisms mediating analgesia and hyperalgesia.
We present a review of the opioid mechanism of analgesia and hyperalgesia and attempt to integrate some of the most recent findings in neuro-anatomy, neuro-physiology and neuropharmacology that indicate the presence of two distinct opioid systems; the one analgesic and the other hyperalgesic. The initial finding of a paradoxical effect of naloxone in which it was able to enhance the analgesic effects of nitrous oxide under certain circumstances led us to postulate the existence of such antagonistic opioid systems which appear to be important in the perception. The review details the further experimental evidence that has subsequently emerged to support our original hypothesis. This includes a hypothesis developed by other workers (viz. diffuse noxious inhibitory control system) which has attempted to explain the analgesic effects of naloxone. Recent anatomical evidence locating the hyperalgesic system in the medullary pontine region is given.


Effect of norepinephrine and vasopressin on renal kallikrein excretion in rats.
The purpose of this study was to investigate the effect of norepinephrine and vasopressin on urinary kallikrein excretion in the rat. Two studies were undertaken: (a) acute experiments in which the rats were infused with 30% dextrose in water with the addition of norepinephrine or vasopressin, (b) chronic experiments in which the drugs were infused during seven days through an osmotic minipump. In acute experiments, urinary kallikrein excretion increased without modification in urinary flow and glomerular filtration rate. In chronic experiments, urinary kallikrein excretion was not modified in norepinephrine-treated rats and decreased in vasopressin-infused animals. This decrease followed the modifications of the urine flow. In chronic experiments the dextrose infusion increased urinary kallikrein excretion. In all the groups studied a positive correlation between urine flow and urinary kallikrein excretion was observed. It is concluded that norepinephrine and vasopressin are important stimulators of the urinary kallikrein excretion only in those circumstances where it is necessary to eliminate an excess of water.


Numerical analysis of lasing characteristics in highly bend-compensated large-mode-area ytterbium-doped double-clad leakage channel fibers.
The bend-induced mode-area reduction and thermal effects are vital factors that affect the power scaling of fiber lasers. Recently, bend-compensated large-mode-area double-clad modified hybrid leakage channel fiber (M-HLCF) has been reported with a mode area greater than 1000 μm, while sustaining the single-mode behavior at 1064 nm for high-temperature environments. In this work, the lasing characteristics of a newly designed ytterbium-doped double-clad M-HLCF (YDMHLCF) have been numerically investigated for strongly pumped conditions. The doped region size is optimally found through simulations, equivalent to the size of core diameter ∼38 μm in order to achieve maximum conversion efficiency for the bent and straight cases. Numerical simulations further confirm that a 2 m long YDMHLCF exhibits slope efficiency of 78% and conversion efficiency of 79% for the straight case and also almost the same for the practical bending radius of 7.5 cm when pumped with a 975 nm laser source.


Improved Model for Starch Prediction in Potato by the Fusion of Near-Infrared Spectral and Textural Data.
In this study, visible-near-infrared (VIS-NIR) hyperspectral imaging was combined with a data fusion strategy for the nondestructive assessment of the starch content in intact potatoes. Spectral and textural data were extracted from hyperspectral images and transformed principal component (PC) images, respectively, and a partial least squares regression (PLSR) prediction model was then established. The results revealed that low-level data fusion could not improve accuracy in predicting starch content. Therefore, to improve prediction accuracy, key variables were selected from the spectral and textural data through competitive adaptive reweighted sampling (CARS) and correlation analysis, respectively, and mid-level data fusion was performed. With a residual predictive deviation (RPD) value > 2, the established PLSR model achieved satisfactory prediction accuracy. Therefore, this study demonstrated that appropriate data fusion can effectively improve the prediction accuracy for starch content and thus aid the sorting of potato starch content in the production line.


Laxative-induced diarrhoea: a continuing clinical problem.
Seven women spent an average of 127 days in hospital and were extensively investigated, including a laparotomy, before their complaints of abdominal pain, diarrhoea, and weight loss were shown to be due to excessive taking of laxatives. All denied taking laxatives and in none were the characteristic features of the effects of cathartics on the colon seen on sigmoidoscopy or radiological examination.Hypokalaemia and other electrolyte abnormalities were common and were thought to be due to a combination of severe diarrhoea and vomiting. The rectal mucosa was seen to be abnormal on biopsy only in the three patients who had taken senna preparations. The diagnosis was not easy and was finally established either by analysis of the urine and stools or by searching the patient's ward locker.


Leukemic dissemination within a glioblastoma in a patient with chronic lymphoid leukemia.
Metastasis from an extracranial tumor to a primary central nervous system tumor is a rare event, and most reported cases concern metastases to meningiomas. The authors describe the first case of leukemic cell dissemination within a glioblastoma. The patient likely presented a genetic predisposition to multiple neoplasms, and the unusual localization of leukemic cells might be partly related to the characteristic microvascular proliferation in glioblastoma.


Significance of free radical injury in laryngeal and hypopharyngeal cancers.
Laryngeal and hypopharyngeal cancer is a multifactorial disease caused by various carcinogens such as tobacco, alcohol and viruses. Likewise, oxidative stress is known to cause aberrations in the cell membrane and DNA, leading to cancer. We conducted this prospective study in order to evaluate the level of oxidative stress in laryngeal and hypopharyngeal cancer patients. Fifty patients with laryngeal and hypopharyngeal cancer and 40 control subjects were selected. Serum malondialdehyde concentrations and ferric reducing antioxidant power were assessed, in order to evaluate oxidative stress. Results were analysed by Student's t-test. Malondialdehyde levels were significantly higher and ferric reducing antioxidant power lower in the cancer patients, compared with the controls, indicating higher oxidative stress in the former. There was no statistically significant difference in malondialdehyde concentration or ferric reducing antioxidant power, comparing patients with versus without neck secondaries, and patients with early stage versus late stage tumours. Oxidative stress may have a role to play in the initiation of laryngeal and hypopharyngeal cancers, especially in patients with other risk factors such as tobacco and alcohol use.


Adaptation and decompensation of intrarenal small arteries in experimental hypertension.
In the presence of hypertension, the arterial and arteriolar vessel walls may undergo adaptive, destructive, and reparative changes. These different types of hypertensive alterations were studied simultaneously in the intrarenal vascular bed of two-kidney, one-clip hypertensive rats. After constriction of one renal artery, focal medial necrosis of the interlobular arteries developed in the untouched kidneys after the first 24 h. These earliest signs of vascular decompensation could be explained by short-lasting hypertensive episodes that were only detectable by continuous blood pressure recording in conscious animals. Two weeks after the experiment was started, owing to a widening of the media, a substantial increase in the wall-to-lumen ratio was observed in the interlobular arteries. At the same time, the frequency of focal medial necrosis began to fall significantly. Therefore we concluded that the structural vascular adaptation might be responsible for the disappearance of focal medial necrosis in spite of still rising blood pressure values. This assumption was confirmed by an additional experiment in previously chronically two-kidney, one-clip hypertensive rats: 24 h after removing the renal artery clip, a short, severely hypertensive period, induced by infusions of angiotensin II, caused hypertensive vascular lesions almost exclusively in the primarily clipped kidneys with a nonadapted vascular bed. Early intimal changes, which are known to lead to malignant nephrosclerosis, were not only absent in the beginning of two-kidney, one-clip hypertension, but also did not occur during the angiotensin-induced accelerated hypertension. Thus, even extremely high blood-pressure values per se may not be enough to initiate this crucial renal vascular disease.


Competing feedback loops shape IL-2 signaling between helper and regulatory T lymphocytes in cellular microenvironments.
Cytokines are pleiotropic and readily diffusible messenger molecules, raising the question of how their action can be confined to specific target cells. The T cell cytokine interleukin-2 (IL-2) is essential for the homeostasis of regulatory T (Treg) cells that suppress (auto)immunity and stimulates immune responses mediated by conventional T cells. We combined mathematical modeling and experiments to dissect the dynamics of the IL-2 signaling network that links the prototypical IL-2 producers, conventional T helper (Th) cells, and Treg cells. We show how the IL-2-induced upregulation of high-affinity IL-2 receptors (IL-2R) establishes a positive feedback loop of IL-2 signaling. This feedback mediates a digital switch for the proliferation of Th cells and functions as an analog amplifier for the IL-2 uptake capacity of Treg cells. Unlike other positive feedbacks in cell signaling that augment signal propagation, the IL-2/IL-2R loop enhances the capture of the signal molecule and its degradation. Thus Treg and Th cells can compete for IL-2 and restrict its range of action through efficient cellular uptake. Depending on activation status and spatial localization of the cells, IL-2 may be consumed exclusively by Treg or Th cells, or be shared between them. In particular, a Treg cell can deprive a stimulated Th cell of its IL-2, but only when the cells are located in close proximity, within a few tens of micrometers. The present findings explain how IL-2 can play two distinct roles in immune regulation and point to a hitherto largely unexplored spatiotemporal complexity of cytokine signaling.


The Captopril Prevention Project: a prospective intervention trial of angiotensin converting enzyme inhibition in the treatment of hypertension. The CAPPP Group.
The Captopril Prevention Project (CAPPP) is a prospective, randomized, multi-centre intervention trial designed to investigate whether antihypertensive treatment with the angiotensin converting enzyme (ACE) inhibitor captopril may reduce cardiovascular mortality and morbidity more than a therapeutic regimen which does not include an ACE inhibitor. Secondary objectives are to compare total mortality, the development or deterioration of ischaemic heart disease, left ventricular failure, atrial fibrillation, diabetes mellitus and possible differences in renal function in the two groups. Male and female patients with essential hypertension, aged 25-66 years, will be randomly allocated to antihypertensive treatment which will comprise either the use of the ACE inhibitor captopril or will exclude all types of ACE inhibitors. Some 275 hypertension centres and health care centres in Sweden and Finland will take part in this multi-centre trial. A total of 7000 patients will be recruited and studied for an average period of 5 years, the assumption being that a 20% difference in cardiovascular mortality between the two groups can be detected with a power of 80% at the 5% significance level (two-sided test).


Subthalamic stimulation modulates cortical control of urinary bladder in Parkinson's disease.
Subthalamic nucleus deep brain stimulation (STN-DBS) is an effective therapy for off-period motor symptoms and dyskinesias in advanced Parkinson's disease. Clinical studies have shown that STN-DBS also ameliorates urinary bladder function in Parkinson's disease patients by delaying the first desire to void and increasing bladder capacity. This study aimed at investigating the effect of STN-DBS on the neural mechanisms underlying cerebral bladder control. Using PET to measure changes in regional cerebral blood flow (rCBF), 11 patients with bilateral STN-DBS were studied during urodynamic bladder filling in STN-DBS ON and OFF condition. A filled bladder led to a significant increase of rCBF in the anterior cingulate cortex, which was further enhanced during STN-DBS OFF. A significant interaction between bladder state and STN-DBS was observed in lateral frontal cortex with increased rCBF when the bladder was filled during STN-DBS OFF. The data suggest that STN-DBS ameliorates bladder dysfunction and that this modulation may result from facilitated processing of afferent bladder information.


Ultraviolet B radiation-induced cell death: critical role of ultraviolet dose in inflammation and lupus autoantigen redistribution.
The nuclear self-Ags targeted in systemic lupus erythematosus translocate to the cell membrane of UV-irradiated apoptotic keratinocytes and may represent an important source of self-immunization. It is hard to understand how the noninflammatory milieu accompanying most apoptosis might provoke an immunogenic response leading to autoantibodies. We have found that the precise amount of keratinocyte UV exposure is crucial in determining the rate of apoptosis, the amount of inflammatory cytokine production, and the degree of autoantigen translocation. Low doses of UVB (</=15 mJ/cm(2)) promptly induced a normal, caspase-dependent apoptosis, while intermediate doses of UV-B (35 mJ/cm(2)) caused apoptosis with altered morphology, slower DNA fragmentation, and poly(ADP-ribose) polymerase degradation accompanied by increased Bcl-2. High doses of UVB (80 mJ/cm(2)) induced instead necrosis. We observed IL-1 production upon intermediate and high UVB doses. Nuclear Ag redistribution was also markedly UV dose dependent: at low doses, Sm, Ku, and DNA translocated to the surfaces of early apoptotic cells. At intermediate doses, these Ags concentrated on the cell membrane when the nucleus was still visible. At high doses, these autoantigens diffused into the cytoplasm and were released into the supernatant. Taken together, the results show that low-dose UVB induces prompt noninflammatory apoptosis. In contrast, intermediate and high doses of UVB induce proinflammatory apoptosis and necrosis, where the production of inflammatory cytokines is accompanied by exposure and release of autoantigens. The key importance of the UV dose on the fate of apoptotic keratinocytes and on their potential immunogenicity should help clarify the role of UVB in inducing systemic lupus erythematosus autoimmunity.


Telecommunications in Israeli field hospitals deployed to three crisis zones.
A field hospital overseas requires various types of communication equipment. This study presents the communications equipment used by three Israeli field hospital delegations to earthquake sites at Adapazari, Turkey, in 1999, Port-au-Prince, Haiti, in 2010 and Minamisanriku, Japan, in 2011. The delegations to Turkey and Haiti were relatively large (105-230 personnel) and were on the site early (three to four days after each event). The 55-person delegation to Japan arrived later and was established as an outpatient community hospital. Standard military VHF radios were the only effective tool up to 5 km, until cellular coverage was regained (1-2 weeks after each event). International communication was good. While short-wave communication (telephone and Internet) was used in Turkey, a direct satellite channel was set up in Haiti. In Japan, BGAN Inmarsat provided efficient Wi-Fi for all needs. Motorola walkie talkies were not efficient beyond the immediate vicinity. This paper recommends continued use of military-specification equipment alongside newer modalities, particularly in situations where infrastructure is damaged.


Stentless mitral valve replacement by conventional and minimally invasive techniques.
Stentless mitral valve (SMV) replacement is an intriguing concept to preserve the functionality of the physiological mitral valve (MV). Beginning in August 1997 to date, 51 patients, 35 females and 16 males (age: 68.3+/-8.4 years), with severe MV disease (stenosis 25, incompetence 17, mixed lesion 9) received a chordally supported SMV. SMV implantation was performed using a conventional sternotomy in 32, or a minimally invasive lateral minithoracotomy approach in 19 of the patients. Mean valve size was 29+/-1.5 mm; cross-clamp duration was 81+/-33 min. The perioperative mortality rate was comparable to conventional MV repair or replacement. Regular echocardiographic control disclosed good SMV function (Vmax 1.7+/-0.2 m/s, Pmean 3.9+/-1.2 mmHg) and well-preserved ejection fraction postoperatively, as well as at their most recent follow-up visit. SMV implantation by way of a sternotomy or lateral minithoracotomy leads to preservation of the annulo-ventricular continuity and similar to physiological hemodynamics. However, long-term durability remains to be proven.


A bimodal pattern of relatedness between the Salmonella Paratyphi A and Typhi genomes: convergence or divergence by homologous recombination?
All Salmonella can cause disease but severe systemic infections are primarily caused by a few lineages. Paratyphi A and Typhi are the deadliest human restricted serovars, responsible for approximately 600,000 deaths per annum. We developed a Bayesian changepoint model that uses variation in the degree of nucleotide divergence along two genomes to detect homologous recombination between these strains, and with other lineages of Salmonella enterica. Paratyphi A and Typhi showed an atypical and surprising pattern. For three quarters of their genomes, they appear to be distantly related members of the species S. enterica, both in their gene content and nucleotide divergence. However, the remaining quarter is much more similar in both aspects, with average nucleotide divergence of 0.18% instead of 1.2%. We describe two different scenarios that could have led to this pattern, convergence and divergence, and conclude that the former is more likely based on a variety of criteria. The convergence scenario implies that, although Paratyphi A and Typhi were not especially close relatives within S. enterica, they have gone through a burst of recombination involving more than 100 recombination events. Several of the recombination events transferred novel genes in addition to homologous sequences, resulting in similar gene content in the two lineages. We propose that recombination between Typhi and Paratyphi A has allowed the exchange of gene variants that are important for their adaptation to their common ecological niche, the human host.


Serum positive for the autoantibody against the β(1)-adrenoceptor from Chinese patients with congestive heart failure decreases I(ss) in mouse cardiac myocytes.
Autoantibodies targeting the β(1)-adrenergic receptor (AAB-β(1)) display agonist-like effects, which may have a pathogenic role in the progression of heart failure. Here, we used the electrophysiological recordings to explore the effects of AAB-β(1)-positive serum from Chinese patients with heart failure on the activity of the peak transient outward potassium current (I(to)) and the end 50 ms steady-state potassium current (I(ss)) in mouse cardiac myocytes. We found that the AAB-β(1)-positive serum had no effect on the activity of I(to), but it produced a decrease in the currents of I(ss). A low concentration of positive serum (1/100) had a small inhibitory effect on I(ss). However, positive serum at 1 : 10, 1 : 20, and 1 : 50 significantly decreased I(ss). The concentration-dependence analysis showed that the EC(50) of AAB-β(1)-positive serum was 1/60.24 and its nH was 2.86. It indicated that the AAB-β(1) could inhibit I(ss) in mouse cardiomyocyte in a concentration-dependent manner.


Perivascular delivery of blebbistatin reduces neointimal hyperplasia after carotid injury in the mouse.
Proliferation and migration of smooth muscle cells (SMC) require myosin II activity; thus, we examined whether blebbistatin, a cell-permeable selective inhibitor of myosin II ATP activity, would impair neointimal hyperplasia after vascular injury. Delivery of blebbistatin via a perivascular polymer cuff reduced neointimal formation by 73% and luminal obstruction by 75% after carotid denudation injury in C57BL/6 mice. Blebbistatin treatment was also associated with a reduction in cell density within the neointima; total number of cells (76 ± 7 to 27 ± 3 cells/high-powered field) and actin-positive cells (64 ± 4 to 24 ± 2 cells/high-powered field) in the neointima were reduced in blebbistatin-treated mice compared with vehicle-treated mice. In a model of vascular injury with an intact endothelium, implantation of a blebbistatin-secreting cuff after carotid ligation in FVB/N mice was associated with a 61% decrease in neointimal area and a significant decrease in luminal obstruction (88 ± 4% in vehicle-treated mice versus 36 ± 4% in blebbistatin-treated mice; p < 0.0001). In cultured rat aortic SMC, blebbistatin disrupted cellular morphology and actin cytoskeleton structure, and these effects were rapid and completely reversible. Blebbistatin had a dose-dependent inhibitory effect on DNA replication and cell proliferative responses to platelet-derived growth factor-BB, angiotensin II, and α-thrombin, migratory responses to serum, and migratory responses after blunt injury. In summary, perivascular delivery of blebbistatin reduced neointimal hyperplasia after carotid injury in the mouse.


Nursing home room changes: toward a decision-making model.
Although nursing home relocation has been extensively studied, very little research has investigated the more commonly occurring phenomenon of room changes within nursing homes. Room changes were monitored in four nursing homes over a one-year period. Participant observation; repeated interviews with residents, family members and nursing home staff; and event analyses were used in developing detailed case studies of the room change decision-making process. A model of the room change process and factors influencing this process is offered, involving five distinctive phases--precursors, initiation, decision, action, and outcomes.


Slipped capital femoral epiphyses: A major on-target adverse event associated with FGFR tyrosine kinase inhibitors in pediatric patients.
Fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitors (TKIs) are increasingly being used off label in pediatrics. Long-term safety data are limited, and serious toxicities unique to pediatrics may emerge. In a retrospective analysis of patients less than 18 years of age with recurrent/refractory FGFR altered gliomas treated with FGFR TKIs at MSKCC (n = 7), we observed slipped capital femoral epiphyses in three of seven patients along with increased linear growth velocity. Clinicians should closely monitor bone health and have a low index of suspicion for serious orthopedic complications including slipped capital femoral epiphyses and inform patients of related risks as part of consent when treating with FGFR TKIs.


[Hepatic portal venous gas associated with acute pancreatitis: reports of two cases and review of literature].
Hepatic portal venous gas (HPVG) is an uncommon disease entity that usually has grave prognosis. It is generally associated with bowel necrosis, and has been reported in a wide variety of conditions such as ulcerative colitis, Crohn's disease, diverticulitis, intestinal ischemia, or infarction. We experienced two cases of HPVG associated with acute pancreatitis. HPVG was found in patients with severe necrotizing pancreatitis and concurrent bowel ischemia. Despite aggressive resuscitation with fluids and broad spectrum antibiotics, each patient developed multiorgan failure, and died within few days. Acute pancreatitis is a potential cause of severe intraabdominal systemic catastrophe. Moreover, HPVG is associated with bowel ischemia in the setting of acute pancreatitis which could lead to rapid aggravation of symptom and complicated clinical course. Therefore, vigilant and aggressive management should be warranted in such condition.


Psychometric properties of the Nurses Work Functioning Questionnaire (NWFQ).
The Nurses Work Functioning Questionnaire (NWFQ) is a 50-item self-report questionnaire specifically developed for nurses and allied health professionals. Its seven subscales measure impairments in the work functioning due to common mental disorders. Aim of this study is to evaluate the psychometric properties of the NWFQ, by assessing reproducibility and construct validity. The questionnaire was administered to 314 nurses and allied health professionals with a re-test in 112 subjects. Reproducibility was assessed by the intraclass correlations coefficients (ICC) and the standard error of measurement (SEM). For construct validity, correlations were calculated with a general work functioning scale, the Endicott Work Productivity Scale (EWPS) (convergent validity) and with a physical functioning scale (divergent validity). For discriminative validity, a Mann Whitney U test was performed testing for significant differences between subjects with mental health complaints and without. All subscales showed good reliability (ICC: 0.72-0.86), except for one (ICC = 0.16). Convergent validity was good in six subscales, correlations ranged from 0.38-0.62. However, in one subscale the correlation with the EWPS was too low (0.22). Divergent validity was good in all subscales based on correlations ranged from (-0.06)-(-0.23). Discriminative validity was good in all subscales, based on significant differences between subjects with and without mental health complaints (p<0.001-p = 0.003). The NWFQ demonstrates good psychometric properties, for six of the seven subscales. Subscale "impaired decision making" needs improvement before further use.


Evaluation of vertical deviations secondary to other causes.
Distinguishing the cause of a vertical deviation can be important for management. When surgery is being considered, it is also critical to distinguish a true hypertropia from a dissociated vertical deviation (DVD). This paper reviews the clinical manifestations of DVD, true hypertropia, and primary oblique muscle dysfunction.


Ultraflat Langmuir-Blodgett assembled graphene oxide saturable-absorber films for pulsed near-infrared laser generation.
Large-scale production of ultraflat broadband saturable-absorber films is highly desired for passive mode-locked solid-state lasers. However, the current vapour deposition and spin coating routes for fabricating saturable absorbers (SAs) are suffering from the limited flexibility in substrate choice and complexity of mass production processes. Here, we demonstrate an ultraflat carboxyl-functionalized graphene oxide (GO-COOH) SA film via Langmuir-Blodgett (LB) assembly for solid state laser mode-locking. Hydrophilic carboxyl groups from GO sheets weaken the aggregation effect thus contribute to the uniform and stable dispersion of GO sheets in water. Such GO suspensions are made into an ultrathin large-area graphene-based SA film by a LB assembly process ensuring high surface uniformity. The room-temperature and highly repeated operation for GO LB films avoids the thermal damage of GO sheets and improves the membrane repeatability. Consequently, the ultrathin GO-COOH SA shows the modulation depth (2.3%) and low saturation intensity (24.7 KW cm-2) under 1064 nm laser irradiation. By inserting the GO SA into a Nd:GdVO4laser, both passive Q-switched (QS) and passive Q-switched mode-locked (QML) operations are also attained. The slope efficiency of QS laser is up to 35.6% and the maximum single pulse energy is 1.48μJ. In particular, the QML pulses can be achieved stably and repeatedly with an average output power of 1.33 W and a pulse energy of 13.2 nJ. Our strategy provides a new concept for improving the modulation stability of graphene-based SAs and promoting their industrial application in pulsed solid-state lasers.


Left ventricular periostin gene expression is associated with fibrogenesis in experimental renal insufficiency.
Cardiovascular diseases are the most important cause of death in patients with impaired kidney function. Left ventricular hypertrophy (LVH), cardiac interstitial fibrosis and cardiovascular calcifications are characteristic of chronic renal insufficiency (CRI). Periostin is a fibrogenesis- and calcification-related matricellular protein re-expressed in adult tissues undergoing remodelling in response to pathological stimuli. The role of periostin in CRI-induced LVH is unknown. Rats were 5/6-nephrectomized (NX), and after 15 weeks of disease progression high-calcium, high-phosphate or paricalcitol treatment was given for 12 weeks. Cardiac tissue and blood samples were taken to study periostin gene expression and to determine factors contributing to its reactivation, respectively. Left ventricular (LV) periostin expression was also examined in response to angiotensin II or arginine(8)-vasopressin (AVP)-induced pressure overload and in spontaneously hypertensive rats. CRI resulted in a 6.5-fold increase in LV periostin messenger RNA (mRNA) levels. Positive extracellular immunostaining for periostin was detected in areas of infiltrated inflammatory cells and fibrotic lesions. There was a significant correlation between LV periostin mRNA levels and plasma biomarkers of impaired kidney function, LVH, fibrogenesis-related proteins osteopontin and osteoactivin, and anti-calcific matrix Gla protein. Moreover, LV periostin gene expression in CRI correlated positively with systolic blood pressure (BP) and was activated rapidly in response to angiotensin II or AVP infusions. Periostin is involved in fibrotic cardiac remodelling in CRI. The re-expression of periostin is localized to the fibrotic and inflammatory lesions and is most likely the consequence of elevated BP.


Zinc sulphate in rheumatoid arthritis.
To assess the antirheumatic activity of zinc sulphate, 27 patients with active rheumatoid arthritis took part in a 6-month, randomised, double-blind, between-group trial of oral zinc sulphate versus placebo. Twelve patients on zinc and 9 on placebo completed the trial, but no significant antirheumatic activity of zinc sulphate was demonstrated.


Immediate self-rehabilitation after open Latarjet procedures enables recovery of preoperative shoulder mobility at 3 months.
To evaluate short-term clinical outcomes of shoulders treated for anterior instability by open Latarjet procedures (OLP) followed by immediate self-rehabilitation. The hypothesis was that patients would recover preoperative function at 3 months with no adverse events related to self-rehabilitation. The authors retrieved clinical and radiographic records of 307 consecutive shoulders treated by the same surgeon for anterior instability by OLP with immediate self-rehabilitation. Four shoulders did not meet eligibility criteria and 38 were lost to follow-up, leaving a study cohort of 265 shoulders. Patients performed self-rehabilitation exercises at home from the first postoperative day. Follow-ups at 1 and 3 months evaluated recurrence of instability, postoperative complications, pain, active forward elevation (AFE), passive forward elevation (PFE), external rotation (ER) and internal rotation (IR). The difference between mobility before surgery and at 3 months was 0° for AFE, 0° for PFE, 10° for ER, and 0 spine segments for IR. Thirteen shoulders (5%) which had not followed the self-rehabilitation protocol during the first month had significantly more pain and less improvements in mobility (p < 0.05). Multivariable analyses revealed that patients who adhered to self-rehabilitation in the first month had greater improvements of AFE, PFE, and IR (p < 0.05). Immediate self-rehabilitation after open Latarjet procedures enabled recovery of preoperative shoulder mobility at 3 months. Patients who did not adhere to immediate self-rehabilitation had more pain and less improvement in mobility. Furthermore, immediate self-rehabilitation was found to be independently associated with better recovery and did not cause any adverse events. Level IV.


Exploiting photoinduced reactions in polymer blends to create hierarchically ordered, defect-free materials.
Computer simulations reveal how photoinduced chemical reactions can be exploited to create long-range order in binary and ternary polymeric materials. The process is initiated by shining a spatially uniform light over a photosensitive AB binary blend, which thereby undergoes both a reversible chemical reaction and phase separation. We then introduce a well-collimated, higher intensity light source. Rastering this secondary light over the sample locally increases the reaction rate and causes formation of defect-free, spatially periodic structures. These binary structures resemble either the lamellar or hexagonal phases of microphase-separated diblock copolymers. We measure the regularity of the ordered structures as a function of the relative reaction rates for different values of the rastering speed and determine the optimal conditions for creating defect-free structures in the binary systems. We then add a nonreactive homopolymer C, which is immiscible with both A and B. We show that this component migrates to regions that are illuminated by the secondary, higher intensity light, allowing us to effectively write a pattern of C onto the AB film. Rastering over the ternary blend with this collimated light now leads to hierarchically ordered patterns of A, B, and C. The findings point to a facile, nonintrusive process for manufacturing high quality polymeric devices in a low-cost, efficient manner.


The lymphocytic choriomeningitis virus RING protein Z associates with eukaryotic initiation factor 4E and selectively represses translation in a RING-dependent manner.
Only a few host cell proteins that associate with arenaviruses have been identified. To date, the arenavirus Z protein associates with the promyelocytic leukemia protein PML and the ribosomal P proteins. The majority of PML is present in nuclear bodies which are translocated to the cytoplasm by infection with the arenavirus, lymphocytic choriomeningitis virus (LCMV). The Z protein is a small zinc-binding RING protein with an unknown function which is required for the viral life cycle. Here, we demonstrate an association between Z and the host cell translation factor, eukaryotic initiation factor 4E (eIF-4E) in infected and transfected cells. Z's association with both ribosomal proteins and this translation factor led us to investigate whether Z could modulate host cell translation. In cell culture, Z selectively represses protein production in an eIF-4E-dependent manner. Specifically, we see reduction in cyclin D1 protein production with no effect on glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in cells transfected with Z. Previous reports indicate that cyclin D1 is sensitive to eIF-4E levels, whereas GAPDH is not. Consistent with this, we observe preferential downregulation of cyclin D1 during infection and no effect on GAPDH. Further, no changes in RNA levels were observed for cyclin D1 or GAPDH transcripts. The interaction between eIF-4E and Z may provide a mechanism for slower growth observed in infected cells and a viral strategy for establishing chronic infection.


Up-regulation of cell cycle regulatory genes after renal ischemia/reperfusion: differential expression of p16(INK4a), p21(WAF1/CIP1) and p27(Kip1) cyclin-dependent kinase inhibitor genes depending on reperfusion time.
The aim of this study was to evaluate the influence of renal ischemia, cold preservation and reperfusion on the degree of renal kidney senescence. An experimental model of ex vivo renal hemoperfusion was used. Expression of p16(INK4a), p21(WAF1/CIP1) and p27(Kip1) cyclin-dependent kinase inhibitor genes (CDKIGs) was studied immunohistochemically in kidney biopsy samples at baseline and different time points after reperfusion. All three markers were up-regulated in kidney tissue after the reperfusion; however, their activation in different renal cells varied according to the reperfusion time. Expression of p16 was significantly increased in tubular cells at 180 min of reperfusion when compared with the baseline. Activation of p27 was detected in glomerular cells at 15 min and was significantly higher at 60, 120 and 180 min of reperfusion. The marker started increasing in tubular cells at 15 min and was elevated at every time point afterwards. p21 was significantly over-expressed in all renal cells after the reperfusion. It has been shown by the results of the current study that renal ischemia/reperfusion is associated with over-expression of CDKIGs indicating on substantial DNA damage and/or accelerated tissue senescence. For the first time it has been shown that tissue expression of CDKIGs is positively related with the reperfusion time.


Effects of environment and lifestyle on gastroesophageal reflux disease.
Gastroesophageal reflux disease (GERD) is comprised of a spectrum of related disorders, including hiatal hernia, reflux disease with its associated symptoms, erosive esophagitis, peptic stricture, Barrett's esophagus, and esophageal adenocarcinoma. Besides multiple pathophysiological associations among these disorders, they are also characterized by their comorbid occurrence in identical patients and by their similar epidemiologic behavior. The occurrence of GERD is shaped by marked temporal and geographic variations, suggesting the influence of environmental risk factors in the etiology of these diseases. Between 1975 and 2005, the incidence of GERD and esophageal adenocarcinoma increased fivefold in most Western countries. The incidence of GERD also appears to be rising in the most developed countries of Asia. All severe forms of GERD, such as erosive esophagitis, peptic stricture, Barrett's metaplasia, and esophageal adenocarcinoma, are more common among whites than other ethnic groups. Barrett's esophagus and esophageal adenocarcinoma tend to occur slightly more often in subjects with higher income. Overweight and obesity contribute to the development of hiatal hernia, increase intra-abdominal pressure, and promote gastroesophageal reflux. Weight gain increases reflux symptoms, whereas weight loss decreases such symptoms. Other risk factors, such as smoking, alcohol, dietary fat, or drugs, play only a minor role in shaping the epidemiologic patterns of GERD. On a population level, a high prevalence of H. pylori infection is likely to reduce levels of acid secretion and protect some carriers of the infection against reflux disease and its associated complications. Several studies have confirmed a lesser prevalence of H. pylori among subjects with than without GERD. Until recently, populations in Africa and Asia may have been protected against the development of GERD and esophageal adenocarcinoma by their higher prevalence of H. pylori infection. The study of environmental risk factors may provide an opportunity to better understand GERD and develop a means of its prevention.


Theoretical Study of Proton Coupled Electron Transfer Reactions: The Effect of Hydrogen Bond Bending Motion.
We investigate theoretically the effect of hydrogen bond bending motion on the proton coupled electron transfer (PCET) reaction, using a model system where an intramolecular hydrogen-bonded phenol group is the proton donor. It is shown that, in a two-dimensional (2D) model of the PCET reaction, the bending and stretching vibrational motions are separated, and due to the hydrogen bond configuration and anharmonicity of the potential energy surface, the bending vibration can play a role in the PCET reaction. The results are also compared with two different sets of one-dimensional models (1D-linear and 1D-curved). Due to contributions of the bending motion, the rate constants in the 2D model are larger than those in the 1D-linear model, although the differences between the total rate constants and KIEs for 2D and 1D models are not major. Results from the 1D-curved model lie between the 2D- and 1D-linear models, indicating that it can include some effect of bending motion in reducing the potential energies along the reaction path.


[The role of large granular lymphocytes of the blood in the differential diagnosis of mediastinal neoplasms].
Examined were 57 patients with teratomas, cysts, lymphoepithelial and malignant thymomas. One hundred donors of the blood served as a control. In the blood of the normal subjects, (0.315 +/- 0.014) X 10(9)/L of large granule-containing lymphocytes were revealed, in patients with benign tumours--(0.2 +/- 0.02) X 10(9)/L, with lymphoepithelial thymomas--(0.037 +/- 0.004) X 10(9)/L. The data obtained indicate the increased immune depression in the organism in development of tumour process, and depend on degree of its malignization.


Staphylococcal superantigen (TSST-1) mutant analysis reveals that t cell activation is required for biological effects in the rabbit including the cytokine storm.
Staphylococcal superantigens (sAgs), such as toxic shock syndrome toxin 1 (TSST-1), induce massive cytokine production, which may result in toxic shock syndrome (TSS) and sepsis. Recently, we reported that in vitro studies in human peripheral blood mononuclear cells (PBMC) do not reflect the immunological situation of the host, because after exposure to superantigens (sAgs) in vivo, mononuclear cells (MNC) leave the circulation and migrate to organs, e.g., the spleen, liver and lung. Our experimental model of choice is the rabbit because it is comparable to humans in its sensitivity to sAg. T cell activation has been assessed by lymphocyte proliferation and IL-2 gene expression after in vivo challenge with TSST-1 and the mutant antigens; expression of the genes of proinflammatory cytokines were taken as indicators for the inflammatory reaction after the combined treatment with TSST-1 and LPS. The question as to whether the biological activities of TSST-1, e.g., lymphocyte extravasation, toxicity and increased sensitivity to LPS, are mediated by T cell activation or activation by MHC II-only, are unresolved and results are contradictory. We have addressed this question by studying these reactions in vivo, with two TSST-1 mutants: one mutated at the MHC binding site (G31R) with reduced MHC binding with residual activity still present, and the other at the T cell binding site (H135A) with no residual function detectable. Here, we report that the mutant G31R induced all the biological effects of the wild type sAg, while the mutant with non-functional TCR binding did not retain any of the toxic effects, proving the pivotal role of T cells in this system.


Biologics and severe asthma in children.
Severe asthma can carry significant morbidity and mortality for patients, and it places a burden on families and the healthcare system. Biologic agents have revolutionized the care of patients with severe asthma in recent years. Evidence surrounding some of these therapies is limited in the pediatric population, but recent studies show that they significantly improve asthma care when used appropriately. In this review, we discuss the biologic therapies currently approved to treat severe asthma in school-age children and adolescents. Randomized controlled trials have been published in support of biologics in children and/or adolescents. These therapies have been shown to reduce the annual rate of severe asthma exacerbations by at least 40-50%, and some up to about 70%. Improvements in asthma control, lung function, oral corticosteroid use, and quality of life have also been demonstrated, although these vary by agent. Furthermore, these therapies have reassuring safety profiles in pediatric patients. With three biologic agents approved for children ages 6-11 years and five approved for adolescents ages >12 years, it can be challenging to select one. The therapy should be chosen after careful consideration of the patient's asthma phenotype and biomarkers. Additional pediatric-specific clinical trials would be helpful in developing evidence-based guidelines on biologic therapies in this population.


Enhanced antitumoral activity of oncolytic herpes simplex virus with gemcitabine using colorectal tumor models.
To enhance the oncolytic activity of herpes simplex viruses (HSVs) control of immune-suppression and immune-resistance by cancer cells is important. Myeloid-derived suppressor cells (MDSCs), which interfere with tumor-suppressive environments, are inhibited by gemcitabine (GEM) treatment. We investigated the oncolytic activity and systemic antitumor immunity induced by oncolytic HSVs in combination with GEM treatment. A mouse model with subcutaneous tumors on both sides of the lateral flanks was used. A highly attenuated HSV type 1, strain HF10, was inoculated into one side of each tumor three times following intraperitoneal injection of GEM. Histopathological changes and IFN-γ secretion of the tumor and leukocytes in the spleen were analyzed. These treatments were repeated to enhance oncolytic activity. HF10 inoculation reduced tumor growth only on the HF10-treated side. HF10 inoculation following GEM treatment resulted in greater reduction of tumor growth on the HF10-treated tumor; furthermore, reduction of tumors on the contralateral untreated side was also observed. Necrosis of the tumor was observed in areas where HSV-infected cells were detected. F4/80(+) macrophages around the tumor were eliminated, and CD4(+) T and CD8(+) T cells increased in the spleen. A single injection of GEM decreased CD11b(+) /Gr-1(+) MDSCs while retaining CD4(+) T cells and CD8(+) T cells. Repetition of this treatment regimen resulted in even greater reduction of tumor growth on both sides and complete rejection in some of the mice. Intratumoral injection of oncolytic HSVs following GEM injection reduced MDSCs. Repeated treatment with oncolytic HSVs following GEM resulted in enhanced oncolytic activity.


Cobalt Disulfide Nanoparticles Embedded in Porous Carbonaceous Micro-Polyhedrons Interlinked by Carbon Nanotubes for Superior Lithium and Sodium Storage.
Transition metal sulfides are appealing electrode materials for lithium and sodium batteries owing to their high theoretical capacity. However, they are commonly characterized by rather poor cycling stability and low rate capability. Herein, we investigate CoS2, serving as a model compound. We synthesized a porous CoS2/C micro-polyhedron composite entangled in a carbon-nanotube-based network (CoS2-C/CNT), starting from zeolitic imidazolate frameworks-67 as a single precursor. Following an efficient two-step synthesis strategy, the obtained CoS2 nanoparticles are uniformly embedded in porous carbonaceous micro-polyhedrons, interwoven with CNTs to ensure high electronic conductivity. The CoS2-C/CNT nanocomposite provides excellent bifunctional energy storage performance, delivering 1030 mAh g-1 after 120 cycles and 403 mAh g-1 after 200 cycles (at 100 mA g-1) as electrode for lithium-ion (LIBs) and sodium-ion batteries (SIBs), respectively. In addition to these high capacities, the electrodes show outstanding rate capability and excellent long-term cycling stability with a capacity retention of 80% after 500 cycles for LIBs and 90% after 200 cycles for SIBs. In situ X-ray diffraction reveals a significant contribution of the partially graphitized carbon to the lithium and at least in part also for the sodium storage and the report of a two-step conversion reaction mechanism of CoS2, eventually forming metallic Co and Li2S/Na2S. Particularly the lithium storage capability at elevated (dis-)charge rates, however, appears to be substantially pseudocapacitive, thus benefiting from the highly porous nature of the nanocomposite.


Is two-photon absorption a limitation to dark soliton switching?
It is shown that two-photon absorption does not always place a fundamental limitation on soliton devices: The steering angle, the key characteristic of switching devices based on the propagation of dark spatial solitons, is almost preserved as the intensity of the background wave decays in the presence of weak two-photon absorption.


Predissociation resonances and accurate ab initio calculations of dication HF2.
It is very interesting and challenging to investigate the electronic structures of diatomic dications, due to the nature of coulombic repulsive and bound attractive dissociation limits and their avoided diabatic interactions. Using the multi-reference configuration interaction approach, comprehensive ab initio calculations of the first 36 electronic states, corresponding to 15 dissociation limits, of dication HF2+ are reported. Good agreements for the vertical excitation energies and dissociation limits are achieved with the available references. Besides the common interesting quantities as adiabatic potential energy curves, dipole moments and spectral constants for the bound states, the nonadiabatic radial coupling matrix elements for the 1,3Π states are also presented. A showcase for the diabatic potentials of 3Π states are presented and discussed. Furthermore, predissociation states from the nonadiabatic couplings or avoided crossing of potential energy curves, known as shape resonances in collisions, are also investigated by using the WKB and scattering methods.


Proper Depth of Percutaneous Central Venous Catheter via the Great Saphenous Vein for Very Low Birth Weight Infants: A Single-Center, Prospective Cohort Study.
A proper depth of percutaneous central venous catheter (PCVC) is very important to reduce procedural time and prevent various complications in very low birth weight (VLBW) infants who require minimal handling or have a sensitive skin. The objective of this study was to suggest a formula for faster and proper insertion of PCVC in VLBWIs to prevent unintended consequences of patients' conditions. Prospective data of VLBW infants admitted from June 2015 to January 2018 who had PCVC inserted via the great saphenous vein within seven days after birth were analyzed. Correlations of length of inserted PCVC with body weight, body length, and postmenstrual age at the date of PCVC insertion were determined with a linear regression analysis. Using results of this analysis, a formula to determine the optimal insertion length of PCVC was derived. Coefficient of determination was used to assess how well outcomes were replicated by the formula. The formula to predict the proper insertion length of PCVC via the great saphenous vein at popliteal crease level was obtained as follows: Optimal Length (cm) = 3.8 × Body Weight (kg) + 11.1. With everyday movements such as flexion and extension of the lower extremities, the mean difference in catheter tip position was 7.0 ± 3.9 mm, which was not significant enough to escalate the risk of catheter tip displacement. The rate of catheter-related complications was as low as 4.9% in this study. The formula derived from this study to predict the optimal PCVC insertion length could benefit VLBW infants by reducing procedural time and lowering the risk of complications.


Recidivism, health and social functioning following release to the community of NSW prisoners with problematic drug use: study protocol of the population-based retrospective cohort study on the evaluation of the Connections Program.
The rising rate of incarceration in Australia, driven by high reoffending, is a major public health problem. Problematic drug use is associated with increasing rates of reoffending and return to custody of individuals. Throughcare provides support to individuals during imprisonment through to post-release, improving both the transition to community and health outcomes post-incarceration. The aim of this study is to evaluate the Connections Programme (CP) that utilises a throughcare approach for release planning of people in prison with a history of problematic drug use. The study protocol is described. Population-based retrospective cohort study. The study will use record linkage of the Connections dataset with 10 other New South Wales (NSW) population datasets on offending, health service utilisation, opioid substitution therapy, pregnancy, birth and mortality. The study includes all patients who were eligible to participate in the CP between January 2008 and December 2015 stratified by patients who were offered CP and eligible patients who were not offered the programme (non-CP (NCP)). Propensity-score matching will be used to appropriately adjust for the observable differences between CP and NCP. The differences between two groups will be examined using appropriate univariate and multivariate analyses. A generalised estimating equation approach, which can deal with repeat outcomes for individuals will be used to examine recidivism, mortality and other health outcomes, including perinatal and infant outcomes. Survival analysis techniques will be used to examine the effect of the CP by sex and Indigenous status on the 'time-to' health-related outcomes after adjusting for potential confounders. Ethical approval was received from the NSW Population and Health Services Research Ethics Committee, the Justice Health and Forensic Mental Health Network Human Research Ethics Committee, the Aboriginal Health and Medical Research Council Ethics Committee, the Corrective Services NSW Ethics Committee and the University of Technology Sydney Human Research Ethics Committee.


Quantitative analysis of AIDS-related virus-carrying cells by plaque-forming assay using an HTLV-I-positive MT-4 cell line.
Quantitation of acquired immune deficiency syndrome (AIDS)-related virus-bearing cells was analyzed by a newly developed plaque-forming assay. A chemically adherent HTLV-I-positive MT-4 cell monolayer was used as the cytolytic responder cells to the AIDS-virus infection. When AIDS-virus-infected cells (Molt-4/HTLV-III, H9/HTLV-III, and CEM/LAV) were seeded with MT-4 cells, plaques were observed corresponding to the number of HTLV-III-positive cells plated. Plaque formation was inhibited by the addition of anti-HTLV-III-positive serum (neutralizing antibody) to the agarose medium. These data suggest that this plaque-forming assay technique should be useful for the quantitative analysis of AIDS-virus-bearing cells.


Drug resistance and new therapies in colorectal cancer.
Colorectal cancer (CRC) is often diagnosed at an advanced stage when tumor cell dissemination has taken place. Chemo- and targeted therapies provide only a limited increase of overall survival for these patients. The major reason for clinical outcome finds its origin in therapy resistance. Escape mechanisms to both chemo- and targeted therapy remain the main culprits. Here, we evaluate major resistant mechanisms and elaborate on potential new therapies. Amongst promising therapies is α-amanitin antibody-drug conjugate targeting hemizygous p53 loss. It becomes clear that a dynamic interaction with the tumor microenvironment exists and that this dictates therapeutic outcome. In addition, CRC displays a limited response to checkpoint inhibitors, as only a minority of patients with microsatellite instable high tumors is susceptible. In this review, we highlight new developments with clinical potentials to augment responses to checkpoint inhibitors.


Postmeningitis subdural fluid collection in infants: changing pattern and indications for surgery.
Postmeningitis subdural fluid collection (PMSFC) is a classic complication of bacterial meningitis in infants. When the diagnosis was based solely on subdural puncture (SDP), its incidence was estimated to be as high as one half of the cases of meningitis, with Haemophilus influenzae as the most common causative bacterium. Knowledge concerning the diagnostic and bacteriological characteristics of PMSFC has expanded greatly since the introduction of computerized imaging and the use of the anti-H. influenzae vaccine; however, in no recent study have the authors reappraised this clinical entity with regard to diagnosis, bacteriology, and indications for surgery. The authors reviewed their cases of PMSFC in infants in which a diagnosis was made based on computerized tomography findings and confirmed with SDP. They treated PMSFC using placement of a subdural drain whenever the collection was either clinically eloquent or exerted a mass effect on the brain. In the 26 years preceding the study, the authors had treated 29 patients younger than 16 months of age for PMSFC. Eight patients required SDP only, 20 underwent surgical drainage, and five required craniotomy. In six cases, the fluid was grossly purulent; in the others, it was clear, xanthochromatic, or hemorrhagic. Cultures were positive for Streptococcus pneumoniae in only two cases. Although H. influenzae was the most common bacterium at the beginning of the series, Neisseria meningitidis has become more prevalent since vaccination against the former became widespread. Based on their data the authors estimate that 5% of N. meningitidis infections in infants are complicated by a significant PMSFC. At present, PMSFCs are most often caused by N. meningitidis. Temporary surgical drain placement is advised for all cases in which a significant mass effect is apparent on imaging.


Dynamic branching in a neural network model for probabilistic prediction of sequences.
An important function of the brain is to predict which stimulus is likely to occur based on the perceived cues. The present research studied the branching behavior of a computational network model of populations of excitatory and inhibitory neurons, both analytically and through simulations. Results show how synaptic efficacy, retroactive inhibition and short-term synaptic depression determine the dynamics of selection between different branches predicting sequences of stimuli of different probabilities. Further results show that changes in the probability of the different predictions depend on variations of neuronal gain. Such variations allow the network to optimize the probability of its predictions to changing probabilities of the sequences without changing synaptic efficacy.


The role of diffusion-weighted imaging in patients with brain tumors.
Diffusion-weighted images (DWIs) have been used to study various diseases, particularly since echo-planar techniques shorten examination time. Our hypothesis was that DWIs and tumor apparent diffusion coefficients (ADCs) could provide additional useful information in the diagnosis of patients with brain tumors. Using a 1.5-T MR unit, we examined 56 patients with histologically verified or clinically diagnosed brain tumors (17 gliomas, 21 metastatic tumors, and 18 meningiomas). We determined ADC values and signal intensities on DWIs both in the solid portion of the tumor and in the peritumoral, hyperintense areas on T2-weighted images. We also evaluated the correlation between ADC values and tumor cellularity in both gliomas and meningiomas. The ADCs of low-grade (grade II) astrocytomas were significantly higher (P =.0004) than those of other tumors. Among astrocytic tumors, ADCs were higher in grade II astrocytomas (1.14 +/- 0.18) than in glioblastomas (0.82 +/- 0.13). ADCs and DWIs were not useful in determining the presence of peritumoral neoplastic cell infiltration. The ADC values correlated with tumor cellularity for both astrocytic tumors (r = -.77) and meningiomas (r = -.67). The ADC may predict the degree of malignancy of astrocytic tumors, although there is some overlap between ADCs of grade II astrocytomas and glioblastomas.


Improved site-specific mutagenesis in Rhodococcus opacus using a novel conditional suicide plasmid.
Rhodococcus opacus PD630 is a biotechnologically important bacterium with metabolic capability for bioremediation, metal recovery, and storage of triacylglycerols. Genome editing by homologous recombination in R. opacus is hampered by a very low combined frequency of DNA transfer and recombination. To improve recombination in the species, a conjugative, conditional suicide plasmid based on the replicon derived from the Corynebacterium glutamicum plasmid pGA1 was constructed and evaluated in R. opacus. The replication of this plasmid is controlled by a dual inducible and repressible promoter system originally developed for Mycobacterium spp. Next, we demonstrated that a derivative of this plasmid containing sacB as a counterselection marker and homologous regions of R. opacus could be used for homologous recombination, and that the problem of obtaining recombinants had been solved. Like for other Corynebacteriales, the cell wall of Rhodococcus spp. contains mycolic acids which form a hydrophobic and impermeable outer layer. Mycolic acids are essential for Mycobacterium smegmatis, but not for Corynebacterium glutamicum, and the new vector was used to study if mycolic acid is essential for R. opacus. We found that accD3 that is necessary for mycolic acid synthesis could only be deleted from the chromosome in strains containing a plasmid-encoded copy of accD3. This indicates that mycolic acid is important for R. opacus viability. The conditional suicide vector should be useful for homologous recombination or for delivering gene products like recombinases or Cas proteins and gRNA to Rhodococcus and related genera, while the approach should be applicable for any plasmid needing a plasmid-encoded protein for replication. KEY POINTS: • Improved vector for homologous recombination in R. opacus. • Mycolic acid is important for survival of R. opacus like it is for Mycobacterium. • Similar conditional suicide plasmids may be constructed for other bacteria.


Cognitive decline and the default American lifestyle.
Upward trends in IQ, education, and mental work suggest that cognitive function among seniors should be rising strongly across cohorts. There is little sign of such improvement in recent decades, and some analyses find poorer function in the newer cohorts. This essay explores possible explanations of the anomaly. Major long-term trends that might increase cognitive impairment are reviewed, and their implications are considered. Physical activity is declining, food is increasingly manufactured, body fat is increasing, diabetes and metabolic syndrome are on the rise, the number of prescription drugs per person is increasing, and the proportion of the population either old or obese is growing. Technological and economic development may lower the cognitive function needed for survival. They also lower physical activity in daily life. Sedentary work, transportation, and leisure undermine the aerobic and metabolic fitness required for the brain to perform well. Some prescription drugs impair cognitive function, and others do so when taken for many years or in combination with others. The growing fraction of the population that is either old or obese may further lower physical activity norms and requirements and substitute medical intervention for health, accelerating a trend toward cognitive impairment.


Differential and correlated expressions of p16/p21/p27/p38 in mammary gland tumors of aged dogs.
The inhibitory effect of neutering on mammary gland tumor development in dogs has been well described. However, we observed that the effect of neutering on tumor malignancy may be altered by aging. Therefore, we characterized mammary tumors in aged dogs by analyzing the expression of cellular senescence markers. Expressions of p16, p38, p21, and p27 antibodies, which are senescence-associated markers, were assessed in canine mammary tumors of aged dogs via immunohistochemical analysis. In addition, correlations between those expressions were analyzed. Expression of p16 was negatively associated with strong nuclear p27 expression. Expression of p38 was observed in most of the mammary tumors examined, and negative p38 expression was related to positive p21 expression. Moreover, p21 expression was associated with p27 expression; negative p21 expression was associated with negative p27 expression, while positive p21 expression was associated with positive p27 expression. The results confirm that the p21- and p27-encoding genes have similar expression patterns in the mammary tumors of aged dogs. In the present study, we characterized the expression of cellular senescence markers in these tumors and elucidated the relationships among their expression patterns.


Utilization of psychotherapy in patients with personality disorder: the impact of gender, character traits, affect regulation, and quality of object-relations.
The aim of the study was to generate hypotheses for examining gender differences in variables with predictive value for the utilization of psychotherapy in patients with personality disorders (PDs). Personality traits, affect experience and regulation, the quality of object relations and interpersonal problems within the process of psychotherapy planning were assessed in 140 psychiatric outpatients. Besides the structured clinical interviews for DSM-IV I+II, variables were assessed with the Shedler-Westen assessment procedure (SWAP-200), the affect regulation and experience Q sort (AREQ), the quality of object-relations scale (QORS), and the Inventory of Interpersonal Problems (IIP). Correlation and group difference statistics, regression and canonical correlation analysis were performed. Predictors concerning the utilization or non-utilization of psychotherapy were a schizoid PD rating a self-report of subassertive behaviour related to interpersonal problems in women, and a narcissistic PD rating in men. Canonical correlations between predictors and quality of object relations or interpersonal problems were found in women, while in men there was merely a tendency for predictor and affect regulation to be related. The results suggest that for men it is more important to interpret the dominating affect, while for women, understanding the pathological object relation pattern is useful for successful therapy planning.


Promoting Mammography with African-American Women in the Emergency Department Using Lay Health Workers.
The objective of this study was to test the efficacy of a pilot intervention to increase mammography utilization among African-American women recruited from those waiting in the emergency department (ED)for non-urgent complaints. In a 3-armed pilot of a randomized controlled trial we compared the effects of a brief motivational interview delivered by a lay health worker with those of a culturally targeted brochure and a usual care control group. The results showed that one quarter (23%) of the sample reported having never had a mammogram prior to the study. There was no group difference by mammography status at the 3-month interview. More than one quarter of those retained in the study indicated they had received a mammogram during the study (27.4%). The conclusions from the study were that lay health workers are a valuable asset and may be used in innovative settings such as the ED to increase screening among vulnerable populations.


[CD34(+)/CD123(+) cell sorting from the patients with leukemia by Midi MACS method].
The aim of this study was to sort the CD34(+)/CD123(+) cells from the bone marrow cells of patients with acute myeloid leukemia (AML) by Midi MACS method. Firstly, the bone marrow mononuclear cells (BMMNC) were isolated from the patients with AML with Ficoll Paque, CD34(+) cells were then isolated by Midi MACS method followed by the isolation of CD34(+)/CD123(+) cells from the fraction of CD34(+) cells. The enrichment and recovery of CD34(+) and CD34(+)/CD123(+) cells were assayed by FACS technique. The results showed that the enrichment of CD34(+) cells was up to 98.73%, its average enrichment was 95.6%, and the recovery of CD34(+) was 84.6%, its average recovery was 51% after the first round sorting, by the second round sorting, the enrichment of CD34(+)/CD123(+) cells was up to 99.23%, its average enrichment was 83%. With regard to BMMNCs before sorting, the recovery of CD34(+)/CD123(+) was 34%. But, on the CD34(+) cells obtained by the first round sorting, its recovery was 56%. In conclusion, these results confirmed that the method of Midi MACS sorting can be applied to sort CD34(+)/CD123(+) cells from the bone marrow cells of AML patients, which give rise to the similar enrichment and recovery of the sorted cells with that of literature reported by the method of FACS.


Expression of pcp4a in subpopulations of CNS neurons in zebrafish.
The molecular organization of the zebrafish brain and its relation to neuroanatomical divisions are still largely unknown. In this study we have analyzed the expression of a small transcript encoding for the IQ containing polypeptide Pcp4a in developing and juvenile zebrafish. The transcript is exclusively expressed in neural structures with a pattern that is highly specific for restricted domains and cell populations throughout development, and it allows us to follow the development of these structures at different times. The expression of pcp4a characterizes the dorsocaudal telencephalon, dorsal habenula, pretectal nuclei, preglomerular complex, mammillary bodies, and deep layers of the optic tectum and is a hallmark of a subpopulation of reticulospinal neurons. In the telencephalon, comparison of the expression of pcp4a with other pallial markers showed a rostrocaudal gradient in the expression of these genes, which suggests that the dorsal telencephalon of zebrafish may be organized in distinct areas with different molecular natures. Pcp4 has been involved in modulating calcium signals and in binding to calmodulin, but its precise role in neuronal functions is not known. The analysis of pcp4a expression and localization in the zebrafish brain suggests that pcp4a may be a useful marker for sensory and some motor neuronal circuitries and for telencephalic areas processing sensory inputs.


Dentomaxillofacial characteristics of ectodermal dysplasia.
The aim of this retrospective hospital-based study was to elucidate the dentomaxillofacial characteristics of ectodermal dysplasia. Six Japanese individuals (one male and five female; age range, 12.7-27.2 years) underwent comprehensive examinations, including history recording, cephalometric analysis, panoramic radiography, and analysis of dental models. All the subjects had two or more major manifestations for clinical diagnosis of ectodermal dysplasia (e.g., defects of hair, teeth, nails, and sweat glands). They presented hypodontia (mean number of missing teeth, 9.5; range, 5-14), especially in the premolar region, and enamel dysplasia. Five subjects had bilateral molar occlusion, whereas one subject had unilateral molar occlusion. The common skeletal features were small facial height, maxillary hypoplasia, counterclockwise rotation of the mandible, and mandibular protrusion. Interestingly, the maxillary first molars were located in higher positions and the upper anterior facial height was smaller than the Japanese norm. The results suggest that vertical and anteroposterior maxillary growth retardation, rather than lack of occlusal support due to hypodontia, leads to reduced anterior facial height in individuals with ectodermal dysplasia.


Mental Health of Young Australians during the COVID-19 Pandemic: Exploring the Roles of Employment Precarity, Screen Time, and Contact with Nature.
The coronavirus disease 2019 (COVID-19) pandemic is widely understood to have contributed to mental health problems. In Australia, young people (18-24 years) have been disproportionately affected. To date, research has predominantly focused on the presence or absence of mental illness symptoms, while aspects of mental well-being have been overlooked. We aimed to explore associations between potential risk and protective factors and mental health more comprehensively, using the Complete State Model of Mental Health. An online survey of 1004 young Australians (55% female; M age = 21.23) was undertaken. Assessment of both mental illness and mental well-being enabled participants to be cross-classified into four mental health states. Those with 'Floundering' (13%) or 'Struggling' (47.5%) mental health reported symptoms of mental illness; a 'Languishing' group (25.5%) did not report symptoms of mental illness but mental well-being was compromised relative to those who were 'Flourishing' (14%) with high mental well-being. Multinomial logistic regressions were used to examine associations, adjusting for socio-demographic confounders. Protective factors associated with Flourishing mental health included being in secure employment, using screen time to connect with others, and reporting high levels of hope. Both incidental and purposive contact with nature were also associated with Flourishing, while a lack of green/bluespace within walking distance was associated with Languishing, absence of outdoor residential space was associated with Floundering, and lower neighbourhood greenness was associated with all three suboptimal mental health states. Precarious employment, financial stress, living alone, reporting decreased screen time during lockdowns, lower levels of hope, and high disruption of core beliefs were also associated with Struggling and Floundering mental health. Those who were Languishing reported somewhat less hardship and little disruption to core beliefs, but lower levels of hope compared to young people who were Flourishing. This study highlights that young adults require dedicated mental health services to deal with current burden, but should also be supported through a range of preventive strategies which target mental health risk factors, like precarious employment, and enhance protective factors, such as urban green infrastructure.


Preoxygenated hemoglobin-based oxygen carrier HBOC-201 annihilates myocardial ischemia during brief coronary artery occlusion in pigs.
Because of their ability to perfuse remote regions and deliver oxygen, hemoglobin-based oxygen carriers (HBOCs) may be considered in the treatment of several ischemic conditions such as acute coronary syndromes or high-risk percutaneous intervention. Here we studied the effects of intracoronary infusion of ex vivo preoxygenated HBOC-201 during brief total coronary artery occlusion (CAOs) on myocardial oxygenation and left ventricular (LV) function in a large animal model and investigated the influence of HBOC-201 temperature and infusion rate on these effects. Thirteen open-chest anesthetized swine were instrumented for measurement of global and regional LV function and metabolism. CAOs were induced by inflating an intracoronary balloon catheter; preoxygenated HBOC-201 (12 g/dL) was infused distally through the central lumen of the balloon catheter. Animals underwent consecutive 3-min CAOs interspersed by 30 min of reperfusion, accompanied by different HBOC-201 infusion rates (0, 15, 23, 30, 40, and 50 ml/min) and/or two infusion temperatures (18 degrees C or 37 degrees C) in random order. CAO elicited immediate loss of systolic shortening (SS) in the ischemic region (19 +/- 1% at baseline vs. -3 +/- 2% at end of CAO), resulting in decreases in maximum rate of rise in LV pressure (15 +/- 5%) and stroke volume (12 +/- 4%; all P < 0.05). Balloon deflation resulted in marked coronary reactive hyperemia (to 472 +/- 74% of baseline), increases in coronary venous concentrations of adenosine + inosine (to 218 +/- 26% of baseline; both P < 0.05) and rapid restoration of SS toward baseline. HBOC-201 ameliorated the CAO-induced changes in SS, stroke volume, reactive hyperemia, and coronary venous adenosine + inosine. The effects were temperature and flow dependent with full preservation of SS at 50 ml/min HBOC-201 of 37 degrees C. In conclusion, intracoronary preoxygenated HBOC-201 preserved myocardial oxygenation and LV function in swine during CAO in a dose- and temperature-dependent manner. In our study setting, preoxygenated HBOC-201 can match the oxygen delivery role of endogenous blood in the heart on an almost equivalent-volume basis.


Relationship Between Androgen Deprivation Therapy for Prostate Cancer and Risk of SARS-CoV-2 Infection: A Systematic Review and Meta-Analysis.
Several cohort studies have explored the relationship between androgen deprivation therapy (ADT) and the severity of coronavirus disease 2019 (COVID-19). This study aimed to characterize the relationship between ADT and the severity of COVID-19 in patients with prostate cancer. A systematic search was conducted using PubMed, Embase, and Cochrane Library databases from the inception of each database until February 31, 2020. Patients with prostate cancer who were treated with ADT were assigned to treatment group while those patients who were not treated with ADT were assigned to the control group. Outcomes were severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) positivity, hospitalization, intensive care unit (ICU) admission, and death. The risk of bias was evaluated using ROBINS-I (Risk Of Bias In Non-randomized Studies of Interventions) tool. Three studies with qualitative synthesis were included. Finally, two studies with quantitative synthesis having a total of 44,213 patients were included for the present systematic review. There was no significant difference in SARS-CoV-2 positive rate (odds ratio [OR], 0.52; 95% confidence intervals [Cis], 0.13-2.09; P = 0.362), hospitalization (OR, 0.52; 95% CIs, 0.07-3.69; P = 0.514), ICU admission (OR, 0.93; 95% CIs, 0.39-2.23, P = 0.881), or death (OR, 0.88; 95% CIs, 0.06-12.06; P = 0.934) between ADT and non-ADT groups. Qualitative and quantitative analyses of previous studies revealed no significant effect of ADT on COVID-19. However, more studies with higher quality that explore biochemical and immunological factors involved are needed to confirm this finding in the future.


Potential medication dosing errors in outpatient pediatrics.
To determine the prevalence of potential dosing errors of medication dispensed to children for 22 common medications. Using automated pharmacy data from 3 health maintenance organizations (HMOs), we randomly selected up to 120 children with a new dispensing prescription for each drug of interest, giving 1933 study subjects. Errors were defined as potential overdoses or potential underdoses. Error rate in 2 HMOs that use paper prescriptions was compared with 1 HMO that uses an electronic prescription writer. Approximately 15% of children were dispensed a medication with a potential dosing error: 8% were potential overdoses and 7% were potential underdoses. Among children weighing <35 kg, only 67% of doses were dispensed within recommended dosing ranges, and more than 1% were dispensed at more than twice the recommended maximum dose. Analgesics were most likely to be potentially overdosed (15%), whereas antiepileptics were most likely potentially underdosed (20%). Potential error rates were not lower at the site with an electronic prescription writer. Potential medication dosing errors occur frequently in outpatient pediatrics. Studies on the clinical impact of these potential errors and effective error prevention strategies are needed.


Machismo in two cultures: relation to punitive child-rearing practices.
The relationship of culture, personality traits, and punitive child-rearing practices to machismo was examined in 40 Guyanese and 40 Caucasian parents with children aged four to 12 years. Guyanese parents were found to adhere more strongly to machista attitudes and beliefs and to employ controlling, authoritarian, and punitive child-rearing techniques more often than did Caucasian parents.


Glycated hemoglobin measurement: intermethod comparison.
Clinical interpretation of changes in serial measurements of patients' HbA1c ought to be based on the knowledge of pre-analytical, analytical and intra-individual sources of variation that affect the results. The detectable change in HbA1c percentage depends on total analytical error. Since we have previously evidenced major problems in the routine use of HPLC, we compared a highly automated glycohemoglobin assay with the reference HPLC to solve the problem. The within- and between-run coefficients of variations ranged from 0.86 to 0.93%, and 2.51 to 2.12%, respectively, for the HPLC, and from 1.07 to 0.95, and 1.61 to 0.99% for the immunoturbidimetric assay. After HbA1c-assay calibration, the quality-control survey report of duplicate determinations performed on 20 consecutive days by both the HPLC and the immunologic method provided the expected mean values of control materials. The assay of 106 blood samples showed a minor yet significant bias of the immunoturbidimetric assay toward lower HbA1c. values (p 0.0001), as previously observed, although the two determination series resulted significantly correlated (r=0.96,p=0.0001). We conclude that the immunoturbidimetric assay is surely accurate, precise, and reproducible, and represents a valid alternative to the reference HPLC assay.


Calcific myonecrosis: diagnostic dilemma.
Calcific myonecrosis is a rare benign condition affecting mainly the muscles of a single leg compartment. It is thought to follow a history of trauma with a latent period of years. Patients present with a slowly growing mass. Differential diagnosis from a malignant tumour can be made from the history and the distinctive radiographical features of a fusiform lesion with predominantly peripheral calcifications. Magnetic resonance imaging may be necessary to confirm the diagnosis; treatment is largely symptomatic.


Immunotherapy with corticosteroids in anti-neural autoantibody-associated cognitive impairment: Retrospective case series.
Anti-neural autoantibody-associated cognitive impairment is an increasing phenomenon in memory clinics deserving more attention to applying immunotherapy such as methylprednisolone to improve cognition. Our study aims to investigate the usefulness of intravenous high-dosage corticosteroids in a small cohort of patients suffering from anti-neural autoantibody-associated cognitive impairment. We included in our retrospective case series seven patients presenting diverse neural autoantibodies and cognitive impairments varying from a mild impairment to dementia. We conducted neuropsychological and psychopathological investigations before and after the application of high intravenous methylprednisolone therapy over a 6-month period. Neuropsychological function was assessed by the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) test battery. Patients were also characterized by assessing their patient files for demographic and clinical data. The patients' cognitive subdomains did not improve according to CERAD in their z-scores before and after immunotherapy. We noted a non-significant trend toward an improvement in semantic fluency and verbal memory consolidation. Patients did not do worse in 4 of 12 (33%) cognitive subdomains in the CERAD test battery. Furthermore, mood dysfunction lessened as a non-significant trend in specific psychopathological features such as reduced affective symptoms, loss of drive, and ruminations. Affective symptoms, loss of drive and ruminations were reduced by 43% after immunotherapy. Our small pilot study revealed no relevant alleviation of cognitive dysfunction in patients with neural autoantibodies. However, mood dysfunction became less obvious in specific functions concerning affect, drive, and rumination. However, we do not know whether methylprednisolone affects mood dysfunction, as some patients were taking antidepressant drugs at the same time. Our results might indicate that methylprednisolone immunotherapy is associated with impeding the progression of cognitive dysfunction and reducing mood dysfunction. Further large-scale, placebo-controlled studies in a more homogeneous patient population presenting a uniform pattern of neural autoantibodies should be undertaken.


MicroRNA-200c promotes tumor cell proliferation and migration by directly targeting dachshund family transcription factor 1 by the Wnt/β-catenin signaling pathway in nasopharyngeal carcinoma.
The purpose of the present study was to determine the crucial role of microRNAs (miRNAs/miRs) involved in the proliferation and migration of nasopharyngeal carcinoma (NPC) and to investigate their underlying mechanisms. In this study, we focused on the expression and function of miR-200c in NPC. First, we found the expression level of miR-200c in NPC cells and tissues was upregulated, and it was suggested that the high expression of miR-200c accelerated the proliferation and migration of NPC cells in vitro. Notably, a result of the present study was that the cell fate determination factor dachshund family transcription factor 1 (DACH1) was identified as a direct target of miR-200c. Suppression of miR-200c expression in NPC cells increased endogenous DACH1 mRNA and protein levels, which was negatively correlated with miR-200c. Meanwhile, DACH1 was shown to regulate the Wnt/β-catenin signaling pathway. Accordingly, it was concluded that miR-200c exerted a tumor-promoting role in NPC development by targeting DACH1, which may contribute to the increase in the rates of NPC proliferation and migration. miR-200c may be a potential diagnostic and prognostic biomarker for NPC.


Potential groundwater recharge from deep drainage of irrigation water.
Knowledge of soil water dynamics in the deep vadose zone provides valuable information on the temporal and spatial variability of groundwater recharge. However, semi-arid climate can complicate how the input of water, such as irrigation, can contribute to potential groundwater recharge. This study assessed the recharge rates and their timing under irrigated cropland from a semi-arid region of northern Iran. A deep drainage (10 m) experiment was performed and in situ soil water content was measured to analyze the soil water dynamics and model hydraulic parameters using HYSDRUS-1D. The best parameters selected from inverse parameter optimization were used to calibrate model and estimate the long-term (20-year) average groundwater recharge and the influence of the root zone, unsaturated zone and the time scale on the recharge processes. The simulated annual flux ranged from 24 mm to 268 mm (mean of 110 mm) at 2-m depth and ranged between 26 mm to 207 mm (mean of 95 mm) at the 10-m depth. High fluxes, observed between December and April, may be the result of greater precipitation combined with the irrigation return flow. The May-October period showed a gradual decrease in flux at the depth of 2 m. At the depth of 10 m, the flux showed some continuity (base flux) during the long-term recharge simulation. In total, 12.7% of the input water contributed to the recharge of the groundwater. The annual soil water fluxes were almost similar irrespective of depth below the root zone and the flux rates did not show any clear relation between the different components of the water budget at any depth. This approach improved our understanding of the recharge process in the deep vadose zone in a semiarid region and can help for the development of effective management of groundwater resources.


Treatment of Nonunion of Forearm Bones Using Radial Forearm Bone Flap.
Treatment of forearm fracture nonunion is challenging. Several surgical techniques for the treatment of forearm nonunion have been reported. The aim of this prospective study was to evaluate the effects of the radial forearm bone graft technique in cases with forearm nonunion. We treated 7 patients with forearm nonunions via radial forearm bone flap and internal plate fixation. On the preoperative examination and last follow-up, the quick disabilities of the arm, shoulder, and hand (Q-DASH) score, elbow, forearm and wrist arches of motion and grip force were measured. At the final follow-up, radiographic union and patient satisfaction and return to work were assessed. The mean follow-up duration was 34 ± 23 months. The Q-DASH scores improved from 70 ± 6 points preoperatively to 13 ± 15 points at final follow-up (P < 0.01). The preopetative range of motion (ROM) was 101 ± 26 degrees; whereas the final forearm ROM was 140 ± 17 (P = 0.01). All nonunions united uneventfully (range 3-6 months). At the last follow-up, the grip force was 83% of uninjured extremity and all patients were satisfied with the outcome of the operation. Radial forearm bone flap is a safe, useful and novel technique in cases with forearm nonunion.


Administration of IL-7 to mice with cyclophosphamide-induced lymphopenia accelerates lymphocyte repopulation.
Lymphopenia was induced in mice by a single injection of cyclophosphamide. IL-7 or a control protein were administered to the mice twice daily and the cellularity and composition of the spleen, lymph node, bone marrow, and thymus were determined at various time points thereafter. In comparison to the control cyclophosphamide-treated mice, animals receiving cyclophosphamide and IL-7 had an accelerated regeneration of splenic and lymph node cellularity. There was no significant difference in the rate of recovery of the bone marrow and thymus of the control and IL-7-treated mice. Assessment of the pre-B cell compartment revealed a dramatic increase in total pre-B cell numbers in the spleen and bone marrow of the IL-7-treated mice as measured by both flow microfluorimetry and a pre-B cell colony-forming assay. This was followed in a few days by a significant increase in surface IgM+B cell numbers to levels above normal values in both the spleen and lymph node. IL-7 administration to cyclophosphamide-treated mice also resulted in an accelerated recovery of peripheral CD4+ and CD8+ cell numbers in the spleen and lymph node. The numbers of CD8+ cells were increased by twofold over normal levels in cyclophosphamide-treated mice receiving IL-7. Myeloid recovery was determined in cyclophosphamide treated mice by assessing the numbers of CFU-granulocyte-macrophage and Mac 1+ cells. There was no significant difference in myeloid recovery between cyclophosphamide-treated mice receiving IL-7 or control protein. These results suggest that administration of IL-7 after chemical-induced lymphopenia may have therapeutic benefits in shortening the period required to achieve normal lymphoid cellularity.


Endoscopic versus mini-invasive radial artery graft harvesting for purposes of aortocoronary bypass.
The aim of the study was to compare three different methods of radial artery harvesting with regard to postoperative complications and perioperative stress of the patient. A total of 60 patients admitted for coronary artery bypass surgery were randomized into three groups. Each patient underwent extraction of radial artery, all performed by a single surgeon. The radial artery was harvested by one of the following three techniques: classical technique (20 patients), mini-invasive technique (20), and endoscopic technique (20). The time required for the graft harvest was greater in the group where the endoscopic technique was used (52.6 ± 11.3 min) than with the mini-invasive (41.5 ± 7.3 min) or the classical (27.8 ± 4.6 min) technique. Postoperative blood loss into drains was higher where the classical technique was used (35.5 ± 9.4 ml) as compared to the mini-invasive (20 ± 5 ml) or the endoscopic (10 ± 7.3 ml) technique. There was no significant difference among the groups in the rate of local neurological complications, contusion of wound edge, edema of the extremity, or wound infection rate. We observed no case of ischemia of the extremity, and a single case of postoperative myocardial ischemia in the group where the classical technique was used. From a clinical point of view, the mini-invasive and the endoscopic approach are comparable, but the latter is more expensive. Both mini-invasive and endoscopic techniques prolong the operation, reduce perioperative blood loss, and require additional training time.


Immune control of mammalian gamma-herpesviruses: lessons from murid herpesvirus-4.
Many acute viral infections can be controlled by vaccination; however, vaccinating against persistent infections remains problematic. Herpesviruses are a classic example. Here, we discuss their immune control, particularly that of gamma-herpesviruses, relating the animal model provided by murid herpesvirus-4 (MuHV-4) to human infections. The following points emerge: (i) CD8(+) T-cell evasion by herpesviruses confers a prominent role in host defence on CD4(+) T cells. CD4(+) T cells inhibit MuHV-4 lytic gene expression via gamma-interferon (IFN-gamma). By reducing the lytic secretion of immune evasion proteins, they may also help CD8(+) T cells to control virus-driven lymphoproliferation in mixed lytic/latent lesions. Similarly, CD4(+) T cells specific for Epstein-Barr virus lytic antigens could improve the impact of adoptively transferred, latent antigen-specific CD8(+) T cells. (ii) In general, viral immune evasion necessitates multiple host effectors for optimal control. Thus, subunit vaccines, which tend to prime single effectors, have proved less successful than attenuated virus mutants, which prime multiple effectors. Latency-deficient mutants could make safe and effective gamma-herpesvirus vaccines. (iii) The antibody response to MuHV-4 infection helps to prevent disease but is suboptimal for neutralization. Vaccinating virus carriers with virion fusion complex components improves their neutralization titres. Reducing the infectivity of herpesvirus carriers in this way could be a useful adjunct to vaccinating naive individuals with attenuated mutants.


Saccharomyces cerevisiae Adr1p governs fatty acid beta-oxidation and peroxisome proliferation by regulating POX1 and PEX11.
Saccharomyces cerevisiae Adr1p is essential for fatty acid degradation and peroxisome proliferation. Here, the role of Adr1p was examined with respect to the transcriptional regulation of the Pip2p-Oaf1p dependent genes POX1 and PEX11. POX1 encodes the rate-limiting enzyme of peroxisomal beta-oxidation, acyl-CoA oxidase. The POX1 promoter was shown to contain a canonical Adr1p element (UAS1), within which the oleate response element (ORE) was nested. PEX11 codes for a peroxin that is critical for normal peroxisome proliferation, and its promoter was shown similarly to contain a UAS1-like element overlapping the ORE. Northern analysis demonstrated that transcriptional up-regulation of both POX1 and PEX11 was abolished in adr1 Delta mutant cells, and immunoblotting confirmed that the abundance of their gene products was dramatically reduced. Studies of an overlapping ORE/UAS1 arrangement in the CTA1 promoter revealed synergy between these elements. We conclude that overlapping ORE and UAS1 elements in conjunction with their binding factors Pip2p-Oaf1p and Adr1p coordinate the carbon flux through beta-oxidation with peroxisome proliferation.


Acetolactate synthase is the site of action of two sulfonylurea herbicides in higher plants.
Biochemical and genetic studies of a tobacco mutant resistant to the herbicides chlorsulfuron and sulfometuron methyl have demonstrated that these sulfonylurea herbicides inhibit acetolactate synthase, the first enzyme specific to the branched chain amino acid biosynthetic pathway. Resistance of this mutant is accomplished by production of a form of the enzyme that is insensitive to inhibition by the two herbicides.


Novel mechanism of gene regulation: the protein Rv1222 of Mycobacterium tuberculosis inhibits transcription by anchoring the RNA polymerase onto DNA.
We propose a novel mechanism of gene regulation in Mycobacterium tuberculosis where the protein Rv1222 inhibits transcription by anchoring RNA polymerase (RNAP) onto DNA. In contrast to our existing knowledge that transcriptional repressors function either by binding to DNA at specific sequences or by binding to RNAP, we show that Rv1222-mediated transcription inhibition requires simultaneous binding of the protein to both RNAP and DNA. We demonstrate that the positively charged C-terminus tail of Rv1222 is responsible for anchoring RNAP on DNA, hence the protein slows down the movement of RNAP along the DNA during transcription elongation. The interaction between Rv1222 and DNA is electrostatic, thus the protein could inhibit transcription from any gene. As Rv1222 slows down the RNA synthesis, upon expression of the protein in Mycobacterium smegmatis or Escherichia coli, the growth rate of the bacteria is severely impaired. The protein does not possess any significant affinity for DNA polymerase, thus, is unable to inhibit DNA synthesis. The proposed mechanism by which Rv1222 inhibits transcription reveals a new repertoire of prokaryotic gene regulation.