Improvement in upper limb function in children with dystonia following deep brain stimulation.
Childhood dystonia can severely impact upper limb function. Deep brain stimulation (DBS) has been shown to be effective in reducing dystonic symptoms in childhood. Functional recovery following DBS is however not well understood. To explore changes in upper limb function following DBS in paediatric dystonia. Upper limb outcomes, using the Melbourne Assessment of Unilateral Upper Limb Function, are reported in 20 cases of childhood dystonia (unilateral n = 1, four limb n = 19) at 6 and 12 months following DBS. Improvement in at least in one upper limb was seen in the majority of cases (n = 17, 85%) at 12 months following DBS. Deterioration of scores in both upper limbs was seen in 3 children with progressive disorders. Grouping the children aetiologically, a significant improvement in the dominant hand was obtained for the primary dystonia/dystonia-plus group at both six (p = 0.018) and twelve months (p = 0.012). In secondary dystonia due to a static disorder, improvement was also seen at 6 (p = 0.043) and 12 months (p = 0.046) in the non-dominant hand. No significant change was found in the group of children with progressive disorders. DBS has the potential to alter upper limb function in children with primary and secondary dystonia. The dominant hand improved most in children with primary dystonias, with greater improvement in the non-dominant hand in secondary-static cases.


Association of Protein Intake with Recurrence and Survival Following Primary Treatment of Ovarian Cancer.
Malnutrition is common during treatment of ovarian cancer, and 1 in 3 patients report multiple symptoms affecting food intake after primary treatment. Little is known about diet posttreatment in relation to ovarian cancer survival; however, general recommendations for cancer survivors are to maintain a higher level of protein intake to support recovery and minimize nutritional deficits. To investigate whether intake of protein and protein food sources following primary treatment of ovarian cancer is associated with recurrence and survival. Intake levels of protein and protein food groups were calculated from dietary data collected ∼12 mo postdiagnosis using a validated FFQ in an Australian cohort of women with invasive epithelial ovarian cancer. Disease recurrence and survival status were abstracted from medical records (median 4.9 y follow-up). Cox proportional hazards regression was used to calculate adjusted HRs and 95% CIs for protein intake and progression-free and overall survival. Among 591 women who were progression-free at 12 mo follow-up, 329 (56%) subsequently experienced cancer recurrence and 231 (39%) died. A higher level of protein intake was associated with better progression-free survival (>1-1.5 compared with ≤1 g/kg body weight, HRadjusted: 0.69, 95% CI: 0.48, 1.00; >1.5 compared with ≤1 g/kg, HRadjusted: 0.61, 95% CI: 0.41, 0.90; >20% compared with ≤20% total EI from protein, HRadjusted: 0.77, 95% CI: 0.61, 0.96). There was no evidence for better progression-free survival with any particular protein food sources. There was a suggestion of better overall survival among those with higher total intakes of animal-based protein foods, particularly dairy products (HR: 0.71; 95% CI: 0.51, 0.99 for highest compared with lowest tertiles of total dairy intake). After primary treatment of ovarian cancer, a higher level of protein intake may benefit progression-free survival. Ovarian cancer survivors should avoid dietary practices that limit intake of protein-rich foods.


[Combination antifungal therapy for invasive fungal disease in children with hematologic disease].
To evaluate antifungal combination strategy in children with hematologic diseases and invasive fungal disease( IFD). A retrospective clinical study was performed based on 67 childhood patients with hematologic diseases and IFD who firstly accepted combination antifungal therapy for ≥ 7 days during January 2012 and December 2014. Of them, 11 cases received combination of echinocandin with azole, 10 cases received combination of echinocandin with amphotericin B, and 46 cases received combination of azole with amphotericin B. Overall response rate was 79.1%. Univariate analysis revealed that granulocyte recovery (P=0.031), status of underling disease (P=0.023) and the duration of the therapy (P=0.046) were significantly associated with efficacy. Multivariate analysis showed that the independent prognostic factor was the duration of combination antifungal therapy (OR=0.229, 95% CI 0.061- 0.863, P=0.029). The response rates of echinocandin combined with azole, echinocandin combined with amphotericin B and azole combined with amphotericin B were 81.8%, 60.0% and 82.6%, respectively (P>0.05), and 12-week survival rates were 81.8%, 80.0% and 86.5%, respectively (P>0.05). The drug- related adverse reactions occurred 59 times in 34 patients. BUN increasing, hypokalemia and abnormal liver functions were considered the main side effects. For IFD in children with hematologic disease, to extend the duration of treatment (≥ 14 days) could significantly improve the curative effect. Combinations of echinocandin with azole, echinocandin with amphotericin B and azole with amphotericin B can be used as a combination treatment options. Combination of Azole with amphotericin B is efficacious, safe and economic treatment option considering efficacy, survival rate, cost and dosage form.


Afferent projections in the spinal accessory nerve to the facial motoneurons of the cat.
Stimulation of the accessory nerve evoked polysynaptic excitatory postsynaptic potentials (EPSPs) in the facial nucleus (FN) neurons of anesthetized cats. From the experiments with severance of C1-C3 dorsal roots, it is suggested that accessory afferents enter the brainstem through the accessory nerve. It was also found that stimulation of the solitary tract nucleus produced exclusively monosynaptic EPSPs in the FN neurons and the afferent volleys are most likely to be relayed at the solitary tract nucleus.


Severe Neuromuscular Scoliosis Implicated by Dysfunction of Intrathecal Baclofen Pump: Case Report and Review of the Literature.
Complex spinal deformities are a common issue in pediatric patients with an underlying neurologic diagnosis or syndrome. Management of neuromuscular scoliosis is an awesome responsibility, because these patients present with the most challenging pathologies of the deformed spine. Along with surgical correction of the underlying deformity, an intrathecal baclofen (ITB) pump is considered effective in managing the associated spasticity. We present the case of an 11-year-old female who sustained an episode of severe ischemic encephalopathy accompanied by hydrocephalus and severe spastic quadriplegia. An ITB pump was inserted to manage spasticity. Two years later, a very severe decompensated spinal curvature developed. In addition, malfunction of the pump was noted, and the decision was made to perform revision along with open hemilaminectomy at the L3-4 level. The inability of cerebrospinal fluid (CSF) to access the pump was verified intraoperatively, with the absence of CSF glow through the intrathecal space demonstrating blockage of CSF flow. The association of cerebral palsy and relevant disorders with the relentless progression of scoliosis is analyzed, along with the possible offending mechanisms. The efficacy of an ITB pump in controlling intractable spasticity associated with neuromuscular scoliosis is reviewed, as well as its potential to accentuate the clinical progression of neuromuscular scoliosis. Although this is an extremely infrequent situation, we must always bear in mind the possibility that malfunction of an ITB pump could be related to obstruction of CSF flow, owing to the extreme severity of the curves established during the course of, most likely untreated, neuromuscular scoliosis.


Total body mass, fat mass, fat-free mass, and skeletal muscle in older people: cross-sectional differences in 60-year-old persons.
To evaluate body composition parameters, including fat-free mass (FFM), appendicular skeletal muscle mass (ASMM), relative skeletal muscle mass (RSM) index, body cell mass (BCM), BCM index, total body potassium (TBK), fat mass, percentage fat mass (FM), and their differences between age groups and to evaluate the frequency of sarcopenia in healthy older subjects Cross-sectional, nonrandomized study. Outpatient clinic. Ninety-one healthy men and 100 healthy women age 60 and older. FFM, ASMM, FM, and percentage fat mass by whole-body dual-energy x-ray absorptiometry; TBK, BCM, and TBK/FFM ratio by whole body potassium-40 counter. All lean body mass parameters were significantly (P <.05) lower in subjects age 80 and older than in those age 70 to 79, except ASMM in women. Mean FFM was 4.2 kg (7.3%) lower in men age 80 and older than in those younger than 70 and 2.9 kg (6.8%) lower in women age 80 and older than in those younger than 70. The skeletal muscle mass, reflected by ASMM, decreased more than FFM. This suggests that nonskeletal muscle mass is proportionally preserved during aging. Forty-five percent of men and 30% of women were sarcopenic by definition of BCM index and 11.0% of men and women by definition of RSM index. Significant age-related differences exist in body composition of older men and women between age 60 and 95. The greater decrease in TBK and BCM than the decrease in FFM and skeletal muscle mass suggests changing composition of FFM with age. Lack of agreement between two independent sarcopenia indexes suggests that further refinement in the definition of a sarcopenia index is necessary.


Association of pre-operative interleukin-6 levels with Interagency Registry for Mechanically Assisted Circulatory Support profiles and intensive care unit stay in left ventricular assist device patients.
Inflammatory mechanisms are associated with worse prognosis in end-stage heart failure (ESHF) patients who require left ventricular assist device (LVAD) support. Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles describe patient condition at pre-implant and outcome. This study assessed the relationship among inflammation patterns and INTERMACS profiles in LVAD recipients. Thirty ESHF patients undergoing LVAD implantation as bridge to transplant were enrolled. Blood and urine samples were collected pre-operatively and serially up to 2 weeks post-operatively for assessment of inflammatory markers (plasma levels of interleukin [IL]-6, IL-8, IL-10, and osteopontin, a cardiac inflammatory-remodeling marker; and the urine neopterin/creatinine ratio, a monocyte activation marker). Multiorgan function was evaluated by the total sequential organ failure assessment (tSOFA) score. Outcomes of interest were early survival, post-LVAD tSOFA score, and intensive care unit (ICU) length of stay. Fifteen patients had INTERMACS profiles 1 or 2 (Group A), and 15 had profiles 3 or 4 (Group B). At pre-implant, only IL-6 levels and the IL-6/IL-10 ratio were higher in Group A vs B. After LVAD implantation, neopterin/creatinine ratio and IL-8 levels increased more in Group A vs B. Osteopontin levels increased significantly only in Group B. The tSOFA score at 2 weeks post-LVAD and ICU duration were related with pre-implant IL-6 levels. The INTERMACS profiles reflect the severity of the pre-operative inflammatory activation and the post-implant inflammatory response, affecting post-operative tSOFA score and ICU stay. Therefore, inflammation may contribute to poor outcome in patients with severe INTERMACS profile.


Multifocal choroiditis and panuveitis: immunomodulatory therapy.
To report our analysis of the efficacy of immunomodulatory therapy on the course of 19 patients with multifocal choroiditis and panuveitis (MCP). Retrospective, noncomparative, interventional case series. Nineteen patients with multifocal choroiditis with panuveitis evaluated on the Ocular Immunology and Uveitis Service of the Massachusetts Eye and Ear Infirmary from 1978 to 2000. Fifteen patients were treated with systemic immunomodulatory therapy; 4 patients (who refused therapy) were treated with systemic steroids. All patients were analyzed for control of inflammation, visual acuity outcome, and tolerance of immunomodulatory therapy. Control of inflammation and visual acuity. Nineteen patients with bilateral MCP with a mean follow-up of 72.7 months were studied. Fifteen were treated with immunomodulatory agents, whereas 4 patients received only systemic steroids; these 4 developed serious systemic steroid-related complications, and 12 others had cataract and/or glaucoma related to chronic topical, regional, or systemic steroid use before immunomodulatory therapy. Two patients who refused immunomodulatory therapy lost considerable vision in three of their four eyes. Of the 15 patients treated with immunomodulatory drugs, 7 patients lost considerable vision in one eye on steroid therapy but maintained good vision in the other eye once immunomodulatory therapy was instituted. No patient lost vision in any eye once he or she was treated with immunomodulatory treatment. Immunomodulatory therapy controls inflammation and preserves vision in patients with multifocal choroiditis and panuveitis.


Exploitation of Bacillus subtilis as a robust workhorse for production of heterologous proteins and beyond.
Bacillus subtilis, belonging to the type species of Bacillus, is a type of soil-derived, low %G+C, endospore-forming Gram-positive bacterium. After the discovery of B. subtilis 168 that displayed natural competence, this bacterium has been intensively considered to be an ideal model organism and a robust host to study several basic mechanisms, such as metabolism, gene regulation, bacterial differentiation, and application for industrial purposes, such as heterologous protein expression and the overproduction of an array of bioactive molecules. Since the first report of heterologous overproduction of recombinant proteins in this strain, the bulk production of a multitude of valuable enzymes, especially industrial enzymes, has been performed on a relatively large scale. Since B. subtilis can non-specifically secrete recombinant proteins using various signal peptides, it has tremendous advantages over Gram-negative bacterial hosts. Along with the report of the complete genome sequence of B. subtilis, a number of genetic tools, including diverse types of plasmids, bacterial promoters, regulatory elements, and signal peptides, have been developed and characterized. These novel genetic elements tremendously accelerated genetic engineering in B. subtilis recombinant systems. In addition, with the development of several complex gene expression systems, B. subtilis has performed a number of more complex functions. This ability enables it to be a substantial chassis in synthetic biology rather than just a workhorse for the overproduction of recombinant proteins. In this review, we review the progress in the development of B. subtilis as a universal platform to overproduce heterologous diverse high-value enzymes. This progress has occurred from the development of biological parts, including the characterization and utilization of native promoters, the fabrication of synthetic promoters and regulatory elements, and the assembly and optimization of genetic systems. Some important industrial enzymes that have been produced in large quantities in this host are also summarized in this review. Furthermore, the ability of B. subtilis to serve as a cellular tool was also briefly recapitulated and reviewed.


Analysis of the factors that influence the C=N stretching frequency of polyene Schiff bases. Implications for bacteriorhodopsin and rhodopsin.
In this study quantum mechanical calculations of force constants and normal mode analysis are used to elucidate the factors that influence the C=C and C=N stretching frequencies in polyenes and in protonated Schiff bases. The C=N stretching frequency is found to depend on both the C=N stretching force constant and the C=N-H bending force constant. Due to the contributions of these two modes, the C=N stretching frequency is particularly sensitive to the magnitude of the Schiff base counterion interactions and to the hydrogen bonding environment of the Schiff base nitrogen. Models for chromophore-protein interactions in the retinal binding site and for the photochemical transformations of bacteriorhodopsin and rhodopsin are evaluated in light of these results.


Incidence of de-novo breast cancer in women chronically immunosuppressed after organ transplantation.
In mice, retrovirus-associated breast cancers are promoted by immune mechanisms, and immunosuppression during the premalignant phase reduces the incidence of breast cancer and prolongs life. If some women likewise have immune promotion of breast cancer, the incidence of breast cancer in patients receiving therapeutic immunosuppression should be lower than that in a comparable cohort of non-immunosuppressed women. We examined the incidence of de-novo breast cancer arising in women receiving immunosuppressive therapy after kidney or heart transplantation, comparing the figures with published rates. In 25,914 immunosuppressed women followed for 1-11 years there were 86 cases of breast cancer compared with 113.8 expected (p = 0.009). Incidence was particularly low in the first transplant year with relative risk 0.49, rising to 0.84 in subsequent years. For all other major cancers the incidence was higher in the immunosuppressed women. If, as in mice, the reduced incidence of breast cancer is a direct effect of immunosuppression, these observations raise the possibility of therapeutic manipulation of specific immune mechanisms that promote tumour growth.


Gastroesophageal reflux in neurologically impaired children: partial or total fundoplication?
It is difficult to give guidelines when approaching gastroesophageal disease in neurologically impaired children. Indication for surgery has been increasing over recent years, but there is no consensus on the surgical technique of choice. Nothing has been written specifically comparing the results of different procedures in these patients, so far. We retrospectively compare the short- and long-term results of two different types of fundoplication in a series of children operated on for documented gastroesophageal reflux disease at our institution. One group (group A) of 27 patients, operated on between 1977 and 1993, underwent Nissen fundoplication, the other (group B), formed of 20 patients all of whom were operated on between 1993 and 1995, underwent Thai fundoplication. We compared the results in terms of positive outcome (recovery) and negative outcome (minor and major complication), computing the relative odds of group A versus group B in terms of risk of complication, and we compared the mean operative time and the length of hospital stay by means of a student's t-test analysis. Our results show that there is no statistical difference between the two procedures in terms of relative risk of complication and success rate. The duration of surgery and hospital stay were significantly shorter in group B. The Thal procedure can, therefore, be proposed as first choice in the management of these patients.


Oxidative stress as regulator of neuronal impairment after exposure to hospital effluents in Danio rerio.
The variety of activities carried out within hospitals results in their final discharges being considered hotspots for the emission of emerging pollutants. Hospital effluents contain different substances capable of altering the health of ecosystems and biota, furthermore, little research has been done to elucidate the adverse effects of these anthropogenic matrices. Taking this into account, herein we aimed to establish whether exposure to different proportions (2 %, 2.5 %, 3 %, and 3.5 %) of hospital effluent treated by hospital wastewater treatment plant (HWWTP) can induce oxidative stress, behavioral alterations, neurotoxicity, and disruption of gene expression in Danio rerio brain. Our results demonstrate that the hospital effluent under-study induces an anxiety-like state and alters swimming behavior, as fish exhibited increased freezing episodes, erratic movements and traveled less distance than the control group. In addition, after exposure we observed a meaningful rise in biomarkers related to oxidative damage, such as protein carbonyl content (PCC), lipoperoxidation level (LPX), hydroperoxide content (HPC), as well as an increase in enzyme antioxidant activities of catalase (CAT), and superoxide dismutase (SOD) upon short-term exposure. Moreover, we discovered an inhibition of acetylcholinesterase (AChE) activity in a hospital effluent proportion-dependent manner. Regarding gene expression, a significant disruption of genes related to antioxidant response (cat, sod, nrf2), apoptosis (casp6, bax, casp9), and detoxification (cyp1a1) was observed. In conclusion, our outcomes suggest that hospital effluents enhance the emergence of oxidative molecules, and promote a highly oxidative environment at the neuronal level that favors the inhibition of AChE activity, which consequently explains the anxiety-like behavior observed in D. rerio adults. Lastly, our research sheds light on possible toxicodynamic mechanism by which these anthropogenic matrices may trigger damage in D. rerio brain.


Increasing air humidity influences hydraulic efficiency but not functional vulnerability of xylem in hybrid aspen.
Climate models predict greater increases in the frequency than in the amount of precipitation and a consequent rise in atmospheric humidity at high latitudes by the end of the century. We investigated the responses of hydraulic and relevant anatomical traits of xylem to elevated relative humidity of air on a 1-yr-old coppice of hybrid aspen (Populus×wettsteinii) growing in the experimental stand at the Free Air Humidity Manipulation site in Eastern Estonia. The hydraulic conductivity of stems was measured with a high pressure flow meter; artificial cavitation in the stem segments was induced by the air injection method. Specific conductivity of xylem decreased from 4.42 in the control to 3.94kgm-1s-1MPa-1 in the humidification treatment, while the trend was well correlated with increasing wood density. Humidified trees exhibited smaller leaf area at the same xylem cross-sectional area, resulting in 34% higher average Huber values compared to the control. Control and humidity-treated trees differed by neither native embolism level nor susceptibility to dehydration-induced cavitation. Increasing atmospheric humidity reduces the hydraulic efficiency of hybrid aspen trees expressed on a xylem area basis and causes substantial changes in resource allocation between photosynthetic and water transport tissues. This climate trend does not influence stem vulnerability to cavitation.


Comparative cytotoxicity of N-substituted N'-(4-imidazole-ethyl)thiourea in precision-cut rat liver slices.
In order to more rationally design thiourea-containing drugs and drug candidates, specifically thiourea-containing histamine H3 receptor antagonists, it is necessary to develop structure-toxicity relationships (STRs). For this purpose, the cytotoxicity of a series of thiourea-containing compounds was tested in precision-cut rat liver slices. A concentration of 1000 microM of N-p-bromophenyl, N'-(4-imidazole-ethyl)thiourea (8) or N-p-nitrophenyl, N'-(4-imidazole-ethyl)thiourea (9) was found to cause cytotoxicity, evidenced as LDH leakage, resulting in more than 95% LDH leakage after 6h. N-p-Methoxyphenyl, N'-(4-imidazole-ethyl)thiourea (6) caused 40.6 +/- 19.7% LDH leakage after 6h. Control levels of cell death (1% methanol as control vehicle) were below 20% in 6h. After 6h of exposure, N-p-chlorophenyl, N'-(4-imidazole-ethyl)thiourea (7), 8, and 9 were already found to cause significant cytotoxicity at a concentration of 100 microM. At 200 microM, 9 was found to cause significantly more cytotoxicity than 7 and 8. N-Naphthyl, N'-(4-imidazole-ethyl)thiourea (12) was found to cause significant cytotoxicity towards precision-cut rat liver slices after 6h of exposure to a concentration of 500 microM. All other N-substituted, N'-(4-imidazole-ethyl)thiourea tested in this study were not found to be cytotoxic towards precision-cut rat liver slices within the 6h of exposure up to a concentration of 1000 microM. Intracellular glutathione (GSH) content and mitochondrial MTT reduction activity were also examined after exposure of slices to N-substituted, N'-(4-imidazole-ethyl)thiourea. Both of these markers, however, were not found to provide additional information regarding the possible mechanisms of cytotoxicity, i.e. GSH depletion or reduced mitochondrial activity since these markers did not clearly precede LDH leakage. A correlation was found between cytotoxicity towards precision-cut rat liver slices and Vmax/Km values for the formation of sulfenic acids from N-substituted N'-(4-imidazole-ethyl)thiourea by hepatic rat flavin-containing monooxygenases (FMO). The compound with the highest Vmax/Km value for the formation of sulfenic acids, 9, was also the most cytotoxic. Compounds with a significantly lower Vmax/Km value, 7, 8, and 12, were less cytotoxic than 9. Compounds with a Vmax/Km value for the formation of sulfenic acids lower than 0.0788 ml/(minmg) were found not to be cytotoxic towards precision-cut rat liver slices for concentrations up to 1000 microM at an exposure time of 6h. It is concluded, from this study, that N-phenyl substituted N'-(4-imidazole-ethyl)thiourea-containing electron-withdrawing p-substituents are cytotoxic towards precision-cut rat liver slices. Cytotoxicity is increased with increasing electron-withdrawing capacity of the p-substituent. A correlation was found to exist between Vmax/Km value for the formation of sulfenic acids by rat liver FMO enzymes and cytotoxicity.


Measurement of tumor cell activity in short-term primary culture. Clinical significance in women with ovarian cancer.
In vitro activity was determined by primary culture of tumor samples obtained at surgery from 63 patients with Stage III ovarian cancer. These patients had completed at least 24 months of follow-up. Proliferative activity was measured after 3-hour culture by 3H-thymidine incorporation and metabolic activity by 3H-uridine incorporation. A large range of individual tumor activity was found; no correlation was present between proliferative and metabolic activity in the same tumor, the distribution of tumors with high and low activity was similar between histologic types, and the activity was not higher in undifferentiated tumors. There was a strong association between in vitro activity of the tumor and patient outcome (both clinical status and survival). On the basis of in vitro activity, a subset of patients was identified within subgroups with known amount of residual tumor; proliferative activity was a better predictor of good outcome in patients with no residual disease, whereas metabolic activity was better in those with more extensive disease. In these patients, a tumor showing high proliferative and/or metabolic activity (greater than 5000 cpm) was associated with poor survival.


The effect of egg size variability on thermoregulation of Mallard (Anas platyrhynchos) offspring and its implications for survival.
There is a range of egg size phenotypes in Mallards (Anas platyrhynchos) that has a large genetic component. It was hypothesized that egg size variation could play an important role in survival of newly hatched ducklings during their first few days out of the nest when they are most susceptible to thermal stress and starvation. Precocial young must be physiologically capable of maintaining homeothermy in order to spend adequate time foraging. Duckling size at hatching was highly correlated with egg mass, and those hatching from heavier eggs were able to maintain homeothermy at colder environmental temperatures than those from lighter eggs. Heavy ducklings had significantly lower mass-specific cooling rates, but lower critical temperature did not vary significantly among ducklings of different size. Although insulation and energy reserves were not proportionally greater in larger ducklings, those hatching from heavier eggs can survive starvation longer than those from lighter eggs. The relative cold tolerance of young from light and heavy eggs will affect the ratio of time spent foraging to time spent being brooded by the female parent. Although there is no direct evidence that selection is acting on egg size, variation in this trait within a population could be maintained by fluctuating environmental conditions at hatch.


Correction to: Incidence, mortality, and temporal patterns of oropharyngeal cancer in China: a population-based study.
In the original publication of this article [1], the number of death cases in 'Materials and methods' section is incorrect.


Sequelae following sural nerve biopsy in type 1 diabetic subjects.
To detect post-operative sequelae of sural nerve biopsy. A questionnaire mailed to type 1 diabetic patients (n = 24; male/female 23/1; reply n = 23) 2 years after biopsy. Type 1 diabetic patients (age 56 [11]; median [interquartile range]) had a long duration of diabetes (DM; 20 [19] years) and all had neuropathy. Three out of 24 patients developed infection (two superficial and one deep) and one had a post-operative bleeding. Less frequent pain among the patients were reported from one centre. About one-third or more of the patients still complained of pain, mostly mild, in the biopsy area and paraesthesia in the foot 2 years after surgery. More than two-thirds of the patients were reluctant for further biopsy; a crucial information in drug trial planning. Sequelae of a sural nerve biopsy occur in type 1 DM. The risk for wound infections should be considered.


Scanning electron microscope study of Sendai virus fusion between HeLa cells and chick erythrocytes.
Chick erythrocytes were fused with HeLa cells by Sendai virus and preparations examined by scanning electron microscopy at different times after fusion. Heterokaryons were usually formed by fusion of erythrocyte ghosts with HeLa cells. Occasionally whole erythrocytes were engulfed but there was no evidence that free nuclei fused. Initial inter-cell attachments were usually, and possibly always, made at the site of an attached virus particle. This study helps to correlate topographical findings with previous two-dimensional studies with the transmission electron microscope and may also provide a model system for the fusion of parasitised erythrocytes with eukaryotic cells.


Rational design of small molecule inhibitors targeting the Rac GTPase-p67(phox) signaling axis in inflammation.
The NADPH oxidase enzyme complex, NOX2, is responsible for reactive oxygen species production in neutrophils and has been recognized as a key mediator of inflammation. Here, we have performed rational design and in silico screen to identify a small molecule inhibitor, Phox-I1, targeting the interactive site of p67(phox) with Rac GTPase, which is a necessary step of the signaling leading to NOX2 activation. Phox-I1 binds to p67(phox) with a submicromolar affinity and abrogates Rac1 binding and is effective in inhibiting NOX2-mediated superoxide production dose-dependently in human and murine neutrophils without detectable toxicity. Medicinal chemistry characterizations have yielded promising analogs and initial information of the structure-activity relationship of Phox-I1. Our studies suggest the potential utility of Phox-I class inhibitors in NOX2 oxidase inhibition and present an application of rational targeting of a small GTPase-effector interface.


External heating of stents by radio waves: pilot studies in rabbit aorta.
This experiment was designed to assess the feasibility of radio frequency energy delivered by a prototype radio frequency generator inductive heating device (REVAX) positioned external to the body, for transient heating of stents after arterial implant. Twenty-one New Zealand White rabbits underwent stenting of their infrarenal aorta. Nine rabbits were stented and immediately placed in the REVAX for external stent heating with internal temperature probes in place. Twelve rabbits were stented and 3 days later either heated or placed in the generator as a sham for 20 min. The animals were terminated 28 days later. The REVAX was able to heat the aortic stents in a controlled fashion; in Phase II experiments, the stent temperature was raised to 42 degrees C for 20 min. In Phase I mild necrosis was noted at the stent struts. In Phase II, necrosis and mineralization of the media was seen at the stent struts, and evidence of neointimal suppression was observed. This study demonstrated that external heating of stents in a blood vessel in a live animal via radio frequency energy is feasible. Further studies will be needed to assess whether any specific heating regimen might inhibit fibrocellular neointimal hyperplasia.


Long-term results of two unconventional agents in steroid-dependent nephrotic children.
Children with steroid-dependent minimal change nephrotic syndrome are prone to serious steroid side effects. Alternative therapies, such as oral cyclophosphamide, may also have serious side effects. We conducted this novel prospective study to compare the long-term efficacies of levamisole and I.V. pulse cyclophosphamide as therapies with potentially fewer side effects. This study included 40 children with idiopathic steroid-dependent minimal change nephrotic syndrome (age 3-15 years; 31 boys and 9 girls). The patients were randomized into two equal groups. One group received levamisole 2.5 mg/kg on alternate days (levamisole group) while the other group received I.V. cyclophosphamide 500 mg/m2/month for six months (cyclophosphamide group). Prednisolone was gradually withdrawn. After stopping treatment, the number of patients that maintained remission was five (25%) in each group at six months, four (20%) versus two (10%) at one year and three (15%) versus one (5%) at two years in the levamisole and cyclophosphamide groups respectively, and one (5%) in each group at three and four years. The overall side effects were mild and both drugs were well tolerated. In view of the results, we recommend trial of levamisole before adopting other therapies with more serious side effects in such patients.


Can we predict intensive care relatives at risk for posttraumatic stress disorder?
To identify the relatives of the intensive care unit (ICU) patients at risk for developing symptoms of posttraumatic stress disorders. A multidisciplinary hospital ICU. Prospective single center observational study. Relatives of patients admitted in the ICU (May06-Nov06) who consented to answer the questionnaire participated in the study. Anxiety was assessed by using the Hospital Anxiety and Depression Scale (HAD) and vulnerability to posttraumatic disorder (PTSD) by using the Impact of Event Scale Revised (IES-R) which was administered on the fifth day of admission and at two months following discharge or death. During admission, 48% of the relatives had a HAD score >11 and 72% showed IES-R score >26. There was no association of HAD with gender, patient outcome, working status, age of the patient, or mode of payment of the bills. There was significant association of IES-R >26 with trauma admission, HAD score >11 and mode of payment with the relatives of insured being more stressed as compared to those who settled their bills personally. A total of 35% relatives showed symptoms of posttraumatic stress reaction consistent with a high risk of PTSD after two months. Death in the hospital resulted in elevated HAD and IES-R score during admission and at the two month follow-up. Persistence of stress symptoms was more in school drop outs, working relatives, parents and those with initial anxiety score >11. HAD score greater than 11 was the only factor at admission which could statistically predict a higher PTSD score on follow-up. Adequate counseling of this group of relatives may prevent lasting psychological sequelae of an ICU admission in the relatives of critically ill.


High-Density Vertical Transistors with Pitch Size Down to 20 nm.
Vertical field effect transistors (VFETs) have attracted considerable interest for developing ultra-scaled devices. In particular, individual VFET can be stacked on top of another and does not consume additional chip footprint beyond what is needed for a single device at the bottom, representing another dimension for high-density transistors. However, high-density VFETs with small pitch size are difficult to fabricate and is largely limited by the trade-offs between drain thickness and its conductivity. Here, a simple approach is reported to scale the drain to sub-10 nm. By combining 7 nm thick Au with monolayer graphene, the hybrid drain demonstrates metallic behavior with low sheet resistance of ≈100 Ω sq-1 . By van der Waals laminating the hybrid drain on top of 3 nm thick channel and scaling gate stack, the total VFET pitch size down to 20 nm and demonstrates a higher on-state current of 730 A cm-2 . Furthermore, three individual VFETs together are vertically stacked within a vertical distance of 59 nm, representing the record low pitch size for vertical transistors. The method pushes the scaling limit and pitch size limit of VFET, opening up a new pathway for high-density vertical transistors and integrated circuits.


19F-nuclear magnetic resonance: measurements of [O2] and pH in biological systems.
19F-nuclear magnetic resonance (NMR) has been used to determine both intracellular pH and oxygen concentrations in cell suspensions. Oxygen concentrations in Paracoccus denitrificans and insulinoma cells, RINm5F, in the NMR probe can be monitored directly by 1/T1 measurements of perfluorotripropylamine (FTPA)/lecithin emulsion added to the suspensions. With FTPA oxygen monitoring, we investigated the relative aeration capabilities of two types of NMR chambers. Both normal and transformed eucaryotic cells can be maintained in either chamber for at least 1-2 h at cytocrits of up to 20-25%, with 30% oxygen saturation and cell viabilities of 90-95%. Similar concentrations of procaryotes were maintained aerobic with high FTPA concentrations in the more efficient of the two NMR chambers. A new precursor molecule for the 19F-NMR pH indicator difluoromethylalanine, the para-chlorophenyl ester, has been tested and used in RINm5F cells and P. denitrificans, neither of which hydrolyzes methyl esters.


Transcriptional response reveals translation machinery as target for high pressure in Lactobacillus sanfranciscensis.
The effect of sublethal hydrostatic pressure on the transcriptome of Lactobacillus sanfranciscensis was determined using a shot-gun-microarray. Among the 750 spots that passed quality analysis 42 genes were induced, while six were repressed when cells were incubated at 45 MPa for 30 min. The nature of genes and their differential expression clearly indicate cellular efforts to counteract a decrease in translational capacity. The majority of high pressure affected genes were found to encode either translation factors (EF-G, EF-TU), ribosomal proteins (S2, L6, L11), genes changing translational accuracy or molecular chaperones (GroEL, ClpL). These data agree with previously reported effects observed in in vitro studies as well as with physiological and proteomic data. This study provides in vivo evidence to identify ribosomes and impaired translation among primary targets for high pressure treatment. The observed induction of heat as well as cold shock genes (e.g. hsp60, gyrA) may be explained as a result of high pressure affected protein synthesis.


Effects of pre-exercise carbohydrate feedings on muscle glycogen use during exercise in well-trained runners.
The purpose of this study was to examine the effects of pre-exercise glucose and fructose feedings on muscle glycogen utilization during exercise in six well-trained runners (VO2max = 68.2 +/- 3.4 ml X kg-1 X min-1). On three separate occasions, the runners performed a 30 min treadmill run at 70% VO2max. Thirty minutes prior to exercise each runner ingested 75 g of glucose (trial G), 75 g of fructose (trial F) or 150 ml of a sweetened placebo (trial C). During exercise, no differences were observed between any of the trials for oxygen uptake, heart rate or perceived exertion. Serum glucose levels were elevated as a result of the glucose feeding (P less than 0.05) reaching peak levels at 30 min post-feeding (7.90 +/- 0.24 mmol X l-1). With the onset of exercise, glucose levels dropped to a low of 5.89 +/- 0.85 mmol X l-1 at 15 min of exercise in trial G. Serum glucose levels in trials F and C averaged 6.21 +/- 0.31 mmol X l-1 and 5.95 +/- 0.23 mmol X l-1 respectively, and were not significantly different (P less than 0.05). There were also no differences in serum glucose levels between any of the trials at 15 and 30 min of exercise.


A high-resolution melting approach for the simultaneous differentiation of five human babesiosis-causing Babesia species.
Six species of apicomplexan parasites of the genus Babesia, namely B. microti, B. divergens, B. duncani, B. motasi, B. crassa-like and B. venatorum, are considered to be the primary causal agents of human babesiosis in endemic areas. These six species possess variable degrees of virulence for their primary hosts. Therefore, the accurate identification of these species is critical for the adoption of appropriate therapeutic strategies. We developed a real-time PCR-high-resolution melting (qPCR-HRM) approach targeting 18S ribosomal RNA gene of five Babesia spp. based on melting temperature (Tm) and genotype confidence percentage values. This approach was then evaluated using 429 blood samples collected from patients with a history of tick bites, 120 DNA samples mixed with plasmids and 80 laboratory-infected animal samples. The sensitivity and specificity of the proposed qPCR-HRM method were 95% and 100%, respectively, and the detection limit was 1-100 copies of the plasmid with the cloned target gene. The detection level depended on the species of Babesia analyzed. The primers designed in this study ensured not only the high interspecific specificity of our proposed method but also a high versatility for different isolates from the same species worldwide. Additionally, the Tm obtained from the prepared plasmid standard is theoretically suitable for identifying isolates of all known sequences of the five Babesia species. The developed detection method provides a useful tool for the epidemiological investigation of human babesiosis and pre-transfusion screening.


Highly efficient ultra-broad beam silicon nanophotonic antenna based on near-field phase engineering.
Optical antennas are a fundamental element in optical phased arrays (OPA) and free-space optical interconnects. An outstanding challenge in optical antenna design lies in achieving high radiation efficiency, ultra-compact footprint and broad radiation angle simultaneously, as required for dense 2D OPAs with a broad steering range. Here, we demonstrate a fundamentally new concept of a nanophotonic antenna based on near-field phase-engineering. By introducing a specific near-field phase factor in the Fraunhofer transformation, the far-field beam is widened beyond the diffraction limit for a given aperture size. We use transversally interleaved subwavelength grating nanostructures to control the near-field phase. A Bragg reflector is used at the end of the grating to increase both the efficiency and the far-field beam width. The antenna has a compact footprint of 3.1 µm × 1.75 µm and an ultra-broad far-field beam width of 52° and 62° in the longitudinal and transversal direction, respectively, while the radiation efficiency reaches 82% after incorporating a bottom reflector to further improve the directionality. This unprecedented design performance is achieved with a single-etch grating nanostructure in a 300-nm SOI platform.


[Necrotising enterocolitis. Report of 3 cases (author's transl)].
A review of clinical, pathological findings in 3 cases of necrotising enterocolitis is presented, as well as considerations about pathogenesis. The authors stress the benefits of hyperbarie oxygen in the treatment of the disease.


Repeated Spiral Drawings in Essential Tremor: a Possible Limb-Based Measure of Motor Learning.
To investigate changes in tremor severity over repeated spiral drawings to assess whether learning deficits can be evaluated directly in a limb in essential tremor (ET). A motor learning deficit in ET, possibly mediated by cerebellar pathways, has been established in eye-blink conditioning studies, but not paradigms measuring from an affected, tremulous limb. Computerized spiral analysis captures multiple characteristics of Archimedean spirals and quantifies performance through calculated indices. Sequential spiral drawing has recently been suggested to demonstrate improvement across trials among ET subjects. One hundred and sixty-one ET and 80 age-matched control subjects drew 10 consecutive spirals on a digitizing tablet. Degree of severity (DoS), a weighted, computational score of spiral execution that takes into account spiral shape and line smoothness, previously validated against a clinical rating scale, was calculated in both groups. Tremor amplitude (Ampl), an independent index of tremor size, measured in centimeters, was also calculated. Changes in DoS and Ampl across trials were assessed using linear regression with slope evaluations. Both groups demonstrated improvement in DoS across trials, but with less improvement in the ET group compared to controls. Ampl demonstrated a tendency to worsen across trials in ET subjects. ET subjects demonstrated less improvement than controls when drawing sequential spirals, suggesting a possible motor learning deficit in ET, here captured in an affected limb. DoS improved independently of Ampl, showing that DoS and Ampl are separable motor physiologic components in ET that may be independently mediated.


First Serological & Molecular Study of Coxiella burnetii in Stray, Domestic Cats, and Their Owners in Iran.
Coxiella burnetii, the agent of Q fever, is recognized as a worldwide zoonosis a wide host and potentially complex reservoir systems. Infected ruminants are the main source of infection for humans, but cats also represent a potential source of infection. The prevalence of C burnetii in cats in Iran is unknown and the risks of transmission to humans are undetermined. This study aimed to determine the prevalence of C burnetii in domestic cats and their owners. An Enzyme-linked immunosorbent assay was used for detection of anti-C burnetii antibodies in both cats and humans. Cats serum samples and humans serum samples (n = 85) were tested with indirect ELISA. C burnetii was diagnosed using real time- polymerase chain reaction. Antibodies were detected in 19 sera of 85 (22.35%) samples in stray cats, 9 sera of 78 (11.53%) samples of domestic cats and 4 sera of 78 (5.12%) samples of their owners. This first study of C burnetii prevalence in cats in Iran has indicated that positive samples can be found throughout the country and these results confirm that Iranian cats have been exposed to C burnetii. Moreover, this study demonstrates that cat owners, breeders and veterinary personnel might be at higher risk of exposure of C burnetii.


[Oral contraception and hormone replacement therapy: management of their thromboembolic risk in the perioperative period].
Many women scheduled for surgery are using either oral contraception (OC) or hormone replacement therapy (HRT). These two treatments are associated with a significant albeit moderately increased risk of venous thromboembolic events which might increase the risk associated with surgery. Record of French and English references from Medline((R)) database. Data were selected including prospective and retrospective studies, reviews, and case reports. Thromboembolism induced by these two pharmacologic classes is similar and close to that produced by pregnancy. The increased risk is usually small, especially after the first year of administration of either class of drug, for progestogen-only contraception drugs and for transdermal HRT. The increased risk should be compared with the occurrence of undesired pregnancy after discontinuation of OC or the occurrence of climateric symptoms after discontinuation of HRT. Maintaining OC during the perioperative period is legitimate and strengthening prophylaxis is justified during the first year of combined OC administration. Stressful climateric symptoms can lead to maintain HRT and strengthening prophylaxis is justified during the first year of oral HRT. Transdermal HRT may not need to be stopped and probably does not require any additional antithrombotic measure. The increased thromboembolic risk is to be compared with the risks of stopping either treatment. In most cases, these two treatments can be maintained and antithrombotic prophylaxis is moderately strengthened in particular cases.


A randomized controlled trial of bedside ultrasound RUSH process to improve the quality of anesthesia for elderly emergency surgery patients.
The rapid ultrasound in shock examination (RUSH process) is an assessment of patient's heart function, volume status, and vasculature, which can help anesthesiologist understand the patient's physical condition. In this study, the RUSH process was applied to elderly emergency surgery patients to evaluate whether it is beneficial to maintain the patient's vital signs stable during the operation. In this randomized controlled clinical study one hundred elderly patients who needed general anesthesia and emergency surgery from January 2021 to July 2021 were randomly divided into RUSH group (Group-A, n=52) and control group (Group-B, n=48). The main result include the area under the intraoperative blood pressure curve (AUC), liquid input, urine output, lactic acid levels, number of vasoactive drugs used. There were no significant differences in patients' basic information, preoperative blood pressure, intraoperative blood loss, intraoperative fluid input, intraoperative blood transfusion, and urine output. Intraoperative systolic blood pressure less than 90mmHg AUC of Group-A is less than Group-B(P<0.05), diastolic blood pressure less than 60mmHg AUC of Group-A is less than Group-B(P<0.05). After the operation, the blood gas analysis lactic acid level in Group-A was lower than that in Group-B(P<0.05). Group-A used more vasoactive drugs than Group-B(P<0.05). The bedside ultrasound RUSH process is of great significance for anesthesiologist to understand the preoperative physical condition of elderly emergency surgery patients, and is beneficial to maintain the stability of intraoperative vital signs.


Network pharmacology-based approach of novel traditional Chinese medicine formula for treatment of acute skin inflammation in silico.
Matrix metalloproteinase-9 (MMP-9) appears to play an important role in acute skin inflammation. Subantimicrobial dose of tetracycline has been demonstrated to inhibit the activity of MMP-9 protein. However, long-term use tetracycline will induce side effect. The catalytic site of MMP-9 is located at zinc-binding amino acids, His401, His405 and His411. We attempted to search novel medicine formula as MMP-9 inhibitors from traditional Chinese medicine (TCM) database by using in silico studies. We utilized high-throughput virtual screening to find which natural compounds could bind to the zinc-binding site. The quantitative structure-activity relationship (QSAR) models, which constructed by scaffold of MMP-9 inhibitors and its activities, were employed to predict the bio-activity of the natural compounds for MMP-9. The results showed that Celacinnine, Lobelanidine and Celallocinnine were qualified to interact with zinc-binding site and displayed well predictive activity. We found that celallocinnine was the best TCM compound for zinc binging sites of MMP-9 because the stable interactions were observed under dynamic condition. In addition, Celacinnine and Lobelanidine could interact with MMP-9 related protein that identified by drug-target interaction network analysis. Thus, we suggested the herbs Hypericum patulum, Sedum acre, and Tripterygium wilfordii that containing Celallocinnine, Celacinnine and Lobelanidine might be a novel medicine formula to avoid the side effect of tetracycline and increase the efficacy of treatment.


Expression of p27((Kip1)), cyclin D3 and Ki67 in BPH, prostate cancer and hormone-treated prostate cancer cells.
p27((Kip1)), cyclin D3 and Ki67 are the markers of DNA damage and cell proliferation. The goal of the current study was to analyze expression of the markers in benign and malignant prostate cancer tissues. Activity of p27((Kip1)), cyclin D3 and Ki67 was immunohistochemically evaluated in different cells of BPH, prostate cancer (PCa) and hormonally treated prostate cancer (HTPCa) tissues. The tissue samples were derived by means of TURP or radical prostatectomy. Intensity of the expression was compared between the groups, and association was sought with clinical parameters. Total expression of p27((Kip1)) was significantly higher in BPH as compared with PCa. Epithelial marker expression was higher in HTPCa than in PCa. Intensity of the expression in epithelial, vascular and ductal cells was negatively associated with the tumor stage and Gleason grades. Total Ki67 activity was positively correlated with patient age and serum PSA level. There was significantly higher expression in PCa and hormone-escaped PCa (HEPCa) as compared with BPH. Epithelial and vascular marker expression was positively associated with tumor stage and Gleason grades. There was a positive correlation between cyclin D3 and serum PSA level. With the increase of Gleason grades, cyclin D3 expression increased significantly. Expression of p27((Kip1)) negatively correlated with Ki67 and cyclin D3, while the latter two markers correlated positively. p27((Kip1)) is down-regulated, whereas Ki67 and cyclin D3 are up-regulated in PCa. Intensity of the markers' expression is associated with tumor stage and grades. Hormonotherapy of PCa causes activation of p27((Kip1)). HEPCa is characterized by increased Ki67 expression.


3-(4-Methyl-phen-yl)-4-[(thio-semi-carba-zono)meth-yl]-1,2,3-oxa-diazol-3-ium-5-olate 1,4-dioxane hemisolvate.
The asymmetric unit of the title compound, C11H11N5O2S·0.5C4H8O2, contains one 3-(p-tol-yl)sydnone 4-thio-semi-carba-zone mol-ecule and a half mol-ecule of 1,4-dioxane, which lies abount an inversion centre. The sydnone ring is almost planar, with a maximum deviation of 0.002 (1) Å, and forms a dihedral angle of 46.31 (5)° with the benzene ring. In the crystal, the two components are linked into a tape along [01-1] by N-H⋯O and N-H⋯S hydrogen bonds. The crystal structure is further stabilized by C-H⋯O and C-H⋯π inter-actions, forming a three-dimensional network.


Anterior segment optical coherence tomography characteristics of conjunctival papilloma as compared to papilliform ocular surface squamous neoplasia.
To describe the anterior segment optical coherence tomography (AS-OCT) appearance of conjunctival papilloma and identify differentiating features from papilliform ocular surface squamous neoplasia (OSSN). A retrospective chart review of individuals clinically diagnosed with conjunctival papilloma (n = 10) or papilliform OSSN (n = 10) based on slit lamp features. Data on demographics, tumour characteristics, and primary treatment were collected. AS-OCT features were assessed including epithelial thickness and reflectivity, a corrugated epithelial surface, presence of an overhanging edge, presence of intrinsic spaces and posterior shadowing. Histopathology was available in 5 papilloma and 3 OSSN specimens. Overall, the majority of individuals in both groups were white males. OSSN lesions were more likely to involve the limbus (80% vs.10%, p = 0.005) and the bulbar conjunctiva (100% vs. 20%, p < 0.001) compared to papillomas. On AS-OCT, maximum epithelial thickness was thicker in papilloma compared to OSSN (936 ± 533 vs. 637 ± 207 µm, p = 0.009). The feature that best differentiated papilloma from OSSN was an overhanging edge (100% vs. 0%, p < 0.001), where the epithelial lesion was seen on top of underlying normal epithelium. Other features more common in papilloma compared to OSSN included a corrugated epithelial surface (70% vs.10%, p = 0.02), the presence of intrinsic spaces (100% vs. 50%, p = 0.03), and posterior shadowing (100% vs. 40%, p = 0.01). AS-OCT shows differentiating features between papilloma and OSSN with an overhanging edge as a distinctive AS-OCT feature of papilloma.


Developmentally regulated expression of a cell surface class I nuclease in Leishmania mexicana.
Leishmania mexicana, like other trypanosomatid parasites, is a purine auxotroph and must obtain these essential nutrients from its sandfly and mammalian hosts. A single copy gene encoding its unique externally oriented, surface membrane, purine salvage enzyme 3'-nucleotidase/nuclease, was isolated. Structural features of the deduced protein included: an endoplasmic reticulum-directed signal peptide, several conserved class I catalytic and metal co-factor (Zn(2+)) binding domains, transmembrane anchor sequence and a C-terminal cytoplasmic tail. 3'-Nucleotidase/nuclease gene (mRNA) and protein (enzyme activity) expression were examined in three different L. mexicana developmental forms: procyclic promastigotes, metacyclic promastigotes and amastigotes. Results of both approaches demonstrated that the 3'-nucleotidase/nuclease was a stage-specific enzyme, being expressed by promastigote forms (stages restricted to the insect vector), but not by amastigotes (which produce disease in mammalian hosts). Starvation of these parasites for purines resulted in the significant up-regulation of both 3'-nucleotidase/nuclease mRNA and enzyme activity in promastigotes, but not in amastigotes. These results underscore the critical role that the 3'-nucleotidase/nuclease must play in purine salvage during the rapid multiplicative expansion of the parasite population within its insect vector. To our knowledge, the L. mexicana 3'-nucleotidase/nuclease is the first example of a nutrient-induced and developmentally regulated enzyme in any parasitic protozoan.


Nursing impact on chronic disease Medicaid health home patients: A qualitative study.
Managing individuals with chronic health conditions in the primary care setting continues to be a significant challenge in the US health care system. This issue is further compounded for low-income individuals with both mental health and physical health chronic conditions. The Affordable Care Act provides opportunities to launch chronic disease Medicaid health homes (MHH) to address the existing health care gaps. Within a multidisciplinary team, the nurse serves an integral role as the main care manager and coordinator aimed to improve patient experiences, health outcomes, and lowering health care costs. The aim of this qualitative study is to assess the nurse's perception of their MHH role and how they may impact patient health care utilization patterns. The qualitative study included a focus group of eleven nurses and individual interviews with seven nurses. Six themes were identified that focus on how nurses can use a wide range of effective communication strategies and interpersonal skills to establish and maintain a nurse-patient relationship. The six themes provided insight as to nurses' perceived role in an MHH and how they impact patient health outcomes. The overarching message addressed connecting with the patient and taking the time to find out what was important to them. Nurses were able to impact patient health care utilization patterns.


[Ascariasis in the intrahepatic biliary duct: about a case in pediatrics].
Twenty five percent of the world population is affected by Ascaris lumbricoides. Hepatobiliary ascariasis occurs in areas with high endemicity and great amount of parasitic load, generating intense inflammation to fibrosis. We report a twoyear- old patient that consults about abdominal distension and cough of one month of evolution associated with 72 hours of fever. Abdominal ultrasound is performed, which shows bile duct, stomach, small intestine with ascaris and chest x-ray with interstitial inflammatory infiltrate, associated with hyperleukocytosis with hypereosinophilia and elevated gamma-glutamyl transpeptidase. Antibiotic, anthelminthic treatment is administered, without achieving the elimination of the bile duct parasites, requiring their removal by percutaneous cholangiography.


6 α-Hydroxy-4[14], 10[15]-guainadien-8β, 12-olide induced cell cycle arrest via modulation of EMT and Wnt/β-catenin pathway in HER-2 positive breast cancer cells.
Cyathocline purpurea has potential biological activities and has been widely used in traditional Chinese and Ayurvedic medicine. The aim of the present study is to elucidate the anticancer effect of its 6 α-hydroxy-4[14], 10[15]-guainadien-8β, 12-olide (SRCP1) against HER-2 positive subtype of breast carcinoma. Anticancer effect of SRCP1 was assessed by cell viability, senescence, apoptosis, cell cycle, DNA synthesis, and gene expression assays. The activity was further validated by the molecular docking study. SRCP1 inhibits human HER-2 positive breast cancer growth via inhibition of DNA synthesis in a dose-dependent manner. SRCP1 induces cell cycle arrest at G2/M phase, late apoptosis, and necrosis. Further, it induces senescence causing reduction in migration via down-regulation of EMT. A remarkable increase in the number of necrotic cells and Annexin-V staining revealed that exposure to SRCP1 triggers late apoptosis. Treatment with SRCP1 increased E-cadherin, p21, p53, ER-α expression and decreased β-catenin, MMP-9, snail1, TNF-α expression. SRCP1 showed binding affinity towards an active site of the HER-2 receptor. Our results of molecular docking and biological assays demonstrated the potent anticancer activity of SRCP1 in MDA-MB-453 cells via multiple pathways including EMT, TNF-α, and Wnt/β-catenin signaling.


Pseudohyperkalemia: Three Cases and a Review of Literature.
Hyperkalemia is a potentially fatal complication requiring prompt diagnosis and management. However, pseudohyperkalemia, defined as an artificial rise in serum potassium (Sk), is also an important diagnosis because management differs. Pseudohyperkalemia can result from multiple factors, including excessive potassium leakage from cells of the forearm during blood collection due to release from exercising the muscle during fist clenching, while washout is prevented by tourniquet application, hemolysis, problems with sample transport, preanalysis or contamination, cell damage and metabolic changes, familial conditions that permit excessive potassium ion (K+) leak from erythrocytes after blood sampling, and leukocytosis or thrombocytosis. In this review, we will discuss the major causes of pseudohyperkalemia, how to avoid certain diagnostic pitfalls, and comment on the clinical importance of recognizing these false readings. We will review three clinical cases seen in our nephrology and hypertension clinic that illustrate some of these problems.


Solitary cystic metastatic lymph node of occult human papillomavirus-related oropharyngeal cancer mimicking second branchial cleft cyst: A case report.
Human papillomavirus (HPV)-related oropharyngeal cancer is becoming more common, the primary cancer AQ4 usually occult and appearing only as cystic cervical lymph node (LN) metastasis. Distinguishing between a benign cystic lesion and cystic LN metastasis is challenging given their similar radiologic and histologic appearances. A 54-year-old man presented with a bulging cystic mass measuring 6.4cm on the right side of neck. Postexcision diagnosis was second branchial cleft cyst. After 2 years, the cystic mass recurred, and HPV-related tonsillar squamous cell carcinoma with cystic metastatic LNs was confirmed after wide tonsillectomy and neck dissection. The previous cystic lesion proved to be a cystic metastatic LN from the same malignancy with additional p16 immunostain. The patient was treated with adjuvant concurrent chemoradiation therapy. The patient was followed up in the outpatient department with no evidence of recurrence after 1 year. When an adult has a cystic mass in the upper neck, we must rigorously exclude it as a cystic metastatic LN of occult HPV-related oropharyngeal cancer. Additional p16 staining might be helpful.


Recent exploration of nanoemulsions for drugs and cosmeceuticals delivery.
Nanoemulsions (NEs) have been explored as nanocarriers for the delivery of many drugs and cosmeceuticals. The extraordinary expansion of using NEs is due to their capability to conquer the main challenges of conventional delivery systems such as short residence time with low patient acceptance, poor stability, low aqueous solubility, permeability, and hence bioavailability. This review recapitulated the most recent pharmaceutical and cosmeceutical applications of NEs as effective delivery nanocarriers. The outputs of our research studies and the literature review on the latest NEs applications were assessed to highlight the NEs components, preparations, applications, and the improved quality and elegance of the used product. NEs are stable submicronic translucent dispersions with narrow droplet size distribution. They exhibited excellent ability to efficiently encapsulate therapeutics of diverse nature of drugs and cosmeceuticals. NE formulations showed superiority over conventional delivery approaches with overabundances of advantages through different routes of administration. This novel technology exhibited better aesthetic appeal, higher bioavailability, and a longer duration compared to the conventional delivery systems. This novel technology holds promise for different therapeutics fields. However, the success of NEs use advocated the development of robust formulations, proper choice of equipment, ample process characterization, and assurance of their efficacy, stability, safety and cosmetic appeal.


Baseline Intraoperative Left Ventricular Diastolic Function Is Associated with Postoperative Atrial Fibrillation after Cardiac Surgery.
Detailed understanding of the association between intraoperative left atrial and left ventricular diastolic function and postoperative atrial fibrillation is lacking. In this post hoc analysis of the Posterior Left Pericardiotomy for the Prevention of Atrial Fibrillation after Cardiac Surgery (PALACS) trial, we aimed to evaluate the association of intraoperative left atrial and left ventricular diastolic function as assessed by transesophageal echocardiography (TEE) with postoperative atrial fibrillation. PALACS patients with available intraoperative TEE data (n = 402 of 420; 95.7%) were included in this cohort study. We tested the hypotheses that preoperative left atrial size and function, left ventricular diastolic function, and their intraoperative changes were associated with postoperative atrial fibrillation. Normal left ventricular diastolic function was graded as 0 and with lateral e' velocity 10 cm/s or greater. Diastolic dysfunction was defined as lateral e' less than 10 cm/s using E/e' cutoffs of grade 1, E/e' 8 or less; grade, 2 E/e' 9 to 12; and grade 3, E/e' 13 or greater, along with two criteria based on mitral inflow and pulmonary wave flow velocities. A total of 230 of 402 patients (57.2%) had intraoperative diastolic dysfunction. Posterior pericardiotomy intervention was not significantly different between the two groups. A total of 99 of 402 patients (24.6%) developed postoperative atrial fibrillation. Patients who developed postoperative atrial fibrillation more frequently had abnormal left ventricular diastolic function compared to patients who did not develop postoperative atrial fibrillation (75.0% [n = 161 of 303] vs. 57.5% [n = 69 of 99]; P = 0.004). Of the left atrial size and function parameters, only delta left atrial area, defined as presternotomy minus post-chest closure measurement, was significantly different in the no postoperative atrial fibrillation versus postoperative atrial fibrillation groups on univariate analysis (-2.1 cm2 [interquartile range, -5.1 to 1.0] vs. 0.1 [interquartile range, -4.0 to 4.8]; P = 0.028). At multivariable analysis, baseline abnormal left ventricular diastolic function (odds ratio, 2.02; 95% CI, 1.15 to 3.63; P = 0.016) and pericardiotomy intervention (odds ratio, 0.46; 95% CI, 0.27 to 0.78, P = 0.004) were the only covariates independently associated with postoperative atrial fibrillation. Baseline preoperative left ventricular diastolic dysfunction on TEE, not left atrial size or function, is independently associated with postoperative atrial fibrillation. Further studies are needed to test if interventions aimed at optimizing intraoperative left ventricular diastolic function during cardiac surgery may reduce the risk of postoperative atrial fibrillation.


Induction of hemosome formation and hemoglobin biosynthesis in HeLa cells.
Tissue cultures of HeLa cells in Hank's medium suspension, previously mixed with a solution containing reticulocyte polysomes and/or free globin, hemoglobin and blood plasma from bled rabbits, were homogenized, and an electrophoretic pattern of hemoglobin band was obtained from the supernatant; hemoglobin denatures under the tissue culture conditions. HeLa cells show typical hemosomes, identidical to those found in immature erythrocytes of embryos, and adult mammals with hemolytic anemias. When HeLa cell suspensions are mixed with solutions void of anemic blood plasma, or containing normal rabbit blood plasma, anomalous organelles are formed in the cells, and no hemoglobin biosynthesis occurs.


Hepatectomy-induced apoptotic extracellular vesicles stimulate neutrophils to secrete regenerative growth factors.
Surgical resection of the cancerous tissue represents one of the few curative treatment options for neoplastic liver disease. Such partial hepatectomy (PHx) induces hepatocyte hyperplasia, which restores liver function. PHx is associated with bacterial translocation, leading to an immediate immune response involving neutrophils and macrophages, which are indispensable for the priming phase of liver regeneration. Additionally, PHx induces longer-lasting intrahepatic apoptosis. Herein, we investigated the effect of apoptotic extracellular vesicles (aEVs) on neutrophil function and their role in this later phase of liver regeneration. A total of 124 patients undergoing PHx were included in this study. Blood levels of the apoptosis marker caspase-cleaved cytokeratin-18 (M30) and circulating aEVs were analyzed preoperatively and on the first and fifth postoperative days. Additionally, the in vitro effects of aEVs on the secretome, phenotype and functions of neutrophils were investigated. Circulating aEVs increased at the first postoperative day and were associated with higher concentrations of M30, which was only observed in patients with complete liver recovery. Efferocytosis of aEVs by neutrophils induced an activated phenotype (CD11bhighCD16highCD66bhighCD62Llow); however, classical inflammatory responses such as NETosis, respiratory burst, degranulation, or secretion of pro-inflammatory cytokines were not observed. Instead, efferocytosing neutrophils released various growth factors including fibroblast growth factor-2 and hepatocyte growth factor (HGF). Accordingly, we observed an increase of HGF-positive neutrophils after PHx and a correlation of plasma HGF with M30 levels. These data suggest that the clearance of PHx-induced aEVs leads to a population of non-inflammatory but regenerative neutrophils, which may support human liver regeneration. In this study, we show that the surgical removal of a diseased part of the liver triggers a specific type of programmed cell death in the residual liver tissue. This results in the release of vesicles from dying cells into the blood, where they are cleared by circulating immune cells. These respond by secreting hepatocyte growth factors that could potentially support the regeneration of the liver remnant.


A comparison of peripheral vasoconstrictor responses and cardiovascular autonomic function tests in diabetic patients.
Venous occlusion plethysmography has been used to measure sympathetic vasoconstrictor responses in the feet and hands to a deep breath and body cooling and to assess blood flow variability. Measurements were made in 14 non-diabetic control subjects and 52 diabetic patients, 30 of whom had evidence of peripheral neuropathy. All the measurements were significantly reduced in the feet of patients with neuropathy. Vasoconstrictor responses were not significantly impaired in the hands of these patients. Cardiovascular autonomic function was assessed in the same subjects by standard tests of reflex heart rate responses and compared to sympathetic vasoconstrictor function as determined by the response to a deep breath. Eighteen of the 30 diabetic patients with peripheral neuropathy had impairment of both cardiovascular and sympathetic vasoconstrictor function. Five had normal vasoconstrictor but impaired cardiovascular responses and two had normal cardiovascular but impaired vasoconstrictor function. It may therefore be important to assess both systems in diabetic patients.


[Activity of the psychologist within the inpatient psychotherapy of behavior disordered children and adolescents].
The author, after discussing the problem of cooperation between the physician and psychologist within the framework of psychotherapeutic activity, deals with the special functions of psychologists. Work done in this respect at the Dresden Medical Academy's department for psychotherapy of malbehaving children and juveniles of normal intelligence is described. Also outlined in this paper are the role played by the psychologist in the use of various methods of therapy and his cooperation in the continuing education and training of nurses, the psychometric control of the course of therapy, and the rehabilitation of children and juveniles.


Classification and measurement of pain in the spinal cord-injured population.
Comprehensive review and systematic analyses. The purpose of this review was to summarize studies reporting on the psychometric properties of measures commonly utilized in spinal cord injury (SCI) pain research to better inform clinicians and researchers on the selection of appropriate pain-related instruments. Vancouver, British Columbia, Canada. A detailed literature search was completed to extrapolate articles that described the psychometric properties of pain measures specifically used in SCI populations. Psychometric properties data of the identified measures such as reliability coefficients, type and magnitude of validity correlations, responsiveness as well as logistical factors (that is, interpretability, acceptability and feasibility) were extracted from manuscripts in accordance with similar projects designed to review outcome measures. Five different pain classification schemas, six self-report measures of pain, and two measures of pain impact on functioning were selected based on our inclusion criteria. The majority of the studies identified in these areas reported inter- and intra-rater reliability information. Of the little validity data found for pain screening measures, it was difficult to compare due to the variability of the descriptors used. No data on sensitivity was identified. We propose a call to SCI researchers to consistently apply psychometric analyses to SCI pain data measures. Greater rigor for assessing psychometric information in SCI pain studies will better inform the SCI research community of the applicability of generic measures to SCI pain investigations.


Greenhouse gas emissions from waste stabilisation ponds in Western Australia and Quebec (Canada).
Waste stabilisation ponds (WSPs) are highly enriched environments that may emit large quantities of greenhouse gases (GHG), including CO2, CH4 and N2O. However, few studies provide detailed reports on these emissions. In the present study, we investigated GHG emissions from WSPs in Western Australia and Quebec, Canada, and compared emissions to WSPs from other climatic regions and to other types of aquatic ecosystems. Surface water GHG concentrations were related to phytoplankton biomass and nutrients. The CO2 was either emitted or absorbed by WSPs, largely as a function of phytoplankton dynamics and strong stratification in these shallow systems, whereas efflux of CH4 and N2O to the atmosphere was always observed albeit with highly variable emission rates, dependent on treatment phase and time of the day. The total global warming potential index (GWP index, calculated as CO2 equivalent) of emitted GHG from WSPs in Western Australia averaged 12.8 mmol m(-2) d(-1) (median), with CO2, CH4 and N2O respectively contributing 0%, 96.7% and 3.3% of the total emissions, while in Quebec WSPs this index was 194 mmol m(-2) d(-1), with a relative contribution of 93.8, 3.0 and 3.2% respectively. The CO2 fluxes from WSPs were of the same order of magnitude as those reported in hydroelectric reservoirs and constructed wetlands in tropical climates, whereas CH4 fluxes were considerably higher compared to other aquatic ecosystems. N2O fluxes were in the same range of values reported for WSPs in subtropical climate.


Enhanced lytic efficacy of multiple bolus injections of tissue plasminogen activator in dogs.
The purpose of this study was to compare the lytic efficacy of tissue plasminogen activator (tPA) following different dosing regimens. Radiolabelled clots from dog whole blood were inserted into an extracorporeal jugular loop in anesthetized dogs. Clot size (counts/min) was continuously recorded. tPA was administered as a single 1 min bolus of 0.4 mg/kg, as four multiple bolus injections of 0.1 mg/kg each at 30 min intervals, or as an initial bolus (0.04 mg/kg) followed by a 30 min infusion of 0.36 mg/kg (10%/90%, bolus/infusion). Multiple injections of the same total dose of tPA resulted in 76% and 51% greater clot lysis than single bolus injection or bolus/infusion regimen, respectively, measured 120 min after initial dosing. There were no differences in fibrinogen, plasminogen or alpha-2-antiplasmin between the different treatment groups at 120 min.


Pulmonary function after anterior double thoracotomy approach versus posterior surgery with costectomies in idiopathic thoracic scoliosis.
The surgical approach in the treatment of idiopathic thoracic scoliosis depends on the type of curve involved. In anterior correction, the rib hump is corrected by derotating the thoracic spine. In posterior scoliosis surgery, additional rib hump resection is sometimes necessary to achieve an optimal cosmetic result. The aim of this study was to compare pulmonary function in these two patient groups. Forty patients in the anterior group (A) were treated with standard double thoracotomy, with an anterior derotation spondylodesis and a primary stable dual-rod system. The posterior group (P) included 29 patients who were treated with a pedicle screw-based posterior instrumentation spondylodesis, with additional rib hump resection. Pulmonary function was evaluated preoperatively, on the 12th postoperative day, and at 3, 6, 12 and 24 months during the follow-up. The patients' mean age was 15 years in group A and 19 in group P with a standard deviation 8.7 years and a significant difference. With regard to body height or weight there were no significant differences between the two groups. In group A, the deterioration in pulmonary function immediately after the operation (from [Formula: see text] 75.3 %/71.3 % preoperatively to 38.5 %/36.1 % postoperatively) was clearer than in group P ([Formula: see text] 71.6 %/65.7 % preoperatively to 47.7 %/48.4 % postoperatively). During a follow-up period of 3 months, the values improved in both groups in comparison with the values immediately after the operation. Up to the 2 year follow-up, pulmonary function in the posterior and anterior groups corresponded to the preoperative values, with no significant differences. There was a trend toward moderately increased values in the posterior group and moderately decreased values in the anterior group at the 2-year follow-up examination, in comparison with the preoperative baseline, but without a statistically significant difference. Two major complications occurred in the anterior group, with reintubation and several bronchoscopy examinations due to atelectasis. The severe deterioration in group A is caused by the substantial trauma with double thoracotomy in contrast to rib hump resection. For patients with severe restrictive pulmonary distress, posterior instrumentation in combination with rib hump resection would be preferable to an anterior procedure involving double thoracotomy. Respiratory physiotherapy exercise should be administered in order to minimise postoperative pulmonary distress. In conclusion opening of the chest wall leads to deterioration of pulmonary function with improvement to the preoperative values after 6 months in the posterior and after 24 months in the anterior group.


Public health and medical education: a natural alliance for a new regional medical school.
A century ago, the Flexner Report challenged U.S. medical schools to critically evaluate their curricula in order to nurture physicians equipped to meet the needs of an evolving society. Recently, medical educators have been charged to increase the emphasis on prevention, care of populations, public health, and community medicine. The Commonwealth Medical College (TCMC) is a new MD-granting medical school inspired by and founded in response to a community need. The founders' vision was to recruit and train physicians to fill workforce needs in Northeast Pennsylvania. In its first few years, TCMC embarked on two major public health initiatives, the Regional Health Assessment and the Community Health Research Projects (CHRPs). The results of the health assessment have been used to guide TCMC's curricular development and research agenda. The CHRPs foster commitment to community involvement, regional engagement, and participatory research. TCMC partners with various organizations and community physicians to ensure that students learn (1) to apply knowledge and skills acquired through the course of their studies to public health research in varied settings; (2) the fundamentals of community engagement, collaboration, and service-based practice; and (3) to address the different needs of patient subgroups and populations. These programs provide opportunities for students to be active participants in community capacity building while achieving specific competencies in public health. Existing partnerships with community organizations are enhanced, strengthening the regional focus of the school. This model of incorporating public health into medical education can potentially be replicated in other institutions in the U.S. and internationally.


Anabolic function of phenylalanine hydroxylase in Caenorhabditis elegans.
In humans, liver phenylalanine hydroxylase (PAH) has an established catabolic function, and mutations in PAH cause phenylketonuria, a genetic disease characterized by neurological damage, if not treated. To obtain novel evolutionary insights and information on molecular mechanisms operating in phenylketonuria, we investigated PAH in the nematode Caenorhabditis elegans (cePAH), where the enzyme is coded by the pah-1 gene, expressed in the hypodermis. CePAH presents similar molecular and kinetic properties to human PAH [S(0.5)(L-Phe) approximately 150 microM; K(m) for tetrahydrobiopterin (BH(4)) approximately 35 microM and comparable V(max)], but cePAH is devoid of positive cooperativity for L-Phe, an important regulatory mechanism of mammalian PAH that protects the nervous system from excess L-Phe. Pah-1 knockout worms show no obvious neurological defects, but in combination with a second cuticle synthesis mutation, they display serious cuticle abnormalities. We found that pah-1 knockouts lack a yellow-orange pigment in the cuticle, identified as melanin by spectroscopic techniques, and which is detected in C. elegans for the first time. Pah-1 mutants show stimulation of superoxide dismutase activity, suggesting that cuticle melanin functions as oxygen radical scavenger. Our results uncover both an important anabolic function of PAH and the change in regulation of the enzyme along evolution.


Purification of human C-reactive protein by immunoaffinity chromatography using mouse monoclonal antibody.
Human C-reactive protein (CRP) was purified from sera with a high concentration of CRP by immunoaffinity chromatography using mouse monoclonal antibody (mAb) to CRP (No. 18) and ion exchange on DEAE-Sephacel. CRP bound to the immunoaffinity column was eluted by 0.5 M acetate buffer, pH 5.0 containing 1.5 M NaCl. Final recovery of CRP was 90%. No significant immunochemical differences were observed between CRP obtained by the immunoaffinity chromatography and CRP purified by the method of Hokama and Riley.


Recovery of organ-specific tissue oxygen delivery at restrictive transfusion thresholds after fluid treatment in ovine haemorrhagic shock.
Fluid resuscitation is the standard treatment to restore circulating blood volume and pressure after massive haemorrhage and shock. Packed red blood cells (PRBC) are transfused to restore haemoglobin levels. Restoration of microcirculatory flow and tissue oxygen delivery is critical for organ and patient survival, but these parameters are infrequently measured. Patient Blood Management is a multidisciplinary approach to manage and conserve a patient's own blood, directing treatment options based on broad clinical assessment beyond haemoglobin alone, for which tissue perfusion and oxygenation could be useful. Our aim was to assess utility of non-invasive tissue-specific measures to compare PRBC transfusion with novel crystalloid treatments for haemorrhagic shock. A model of severe haemorrhagic shock was developed in an intensive care setting, with controlled haemorrhage in sheep according to pressure (mean arterial pressure 30-40 mmHg) and oxygen debt (lactate > 4 mM) targets. We compared PRBC transfusion to fluid resuscitation with either PlasmaLyte or a novel crystalloid. Efficacy was assessed according to recovery of haemodynamic parameters and non-invasive measures of sublingual microcirculatory flow, regional tissue oxygen saturation, repayment of oxygen debt (arterial lactate), and a panel of inflammatory and organ function markers. Invasive measurements of tissue perfusion, oxygen tension and lactate levels were performed in brain, kidney, liver, and skeletal muscle. Outcomes were assessed during 4 h treatment and post-mortem, and analysed by one- and two-way ANOVA. Each treatment restored haemodynamic and tissue oxygen delivery parameters equivalently (p > 0.05), despite haemodilution after crystalloid infusion to haemoglobin concentrations below 70 g/L (p < 0.001). Recovery of vital organ-specific perfusion and oxygen tension commenced shortly before non-invasive measures improved. Lactate declined in all tissues and correlated with arterial lactate levels (p < 0.0001). The novel crystalloid supported rapid peripheral vasodilation (p = 0.014) and tended to achieve tissue oxygen delivery targets earlier. PRBC supported earlier renal oxygen delivery (p = 0.012) but delayed peripheral perfusion (p = 0.034). Crystalloids supported vital organ oxygen delivery after massive haemorrhage, despite haemodilution to < 70 g/L, confirming that restrictive transfusion thresholds are appropriate to support oxygen delivery. Non-invasive tissue perfusion and oximetry technologies merit further clinical appraisal to guide treatment for massive haemorrhage in the context of Patient Blood Management.


Spontaneous regression of residual low-grade cerebellar pilocytic astrocytomas in children.
Cerebellar low-grade astrocytomas (CLGAs) of childhood are benign tumours and are usually curable by surgical resection alone or combined with adjuvant radiotherapy. To undertake a retrospective study of our children with CLGA to determine the optimum schedule for surveillance imaging following initial surgery. In this report we describe the phenomenon of spontaneous regression of residual tumour and discuss its prognostic significance regarding future imaging. A retrospective review was conducted of children treated for histologically proven CLGA at Great Ormond Street Hospital from 1988 to 1998. Of 83 children with CLGA identified, 13 (15.7%) had incomplete resections. Two children with large residual tumours associated with persistent symptoms underwent additional treatment. Eleven children were followed by surveillance imaging alone for a mean of 6.83 years (range 2-13.25 years). Spontaneous tumour regression was seen in 5 (45.5%) of the 11 children. There were no differences in age, gender, symptomatology, histological grade or Ki-67 fractions between those with spontaneous tumour regression and those with progression. There was a non-significant trend that larger volume residual tumours progressed. Residual tumour followed by surveillance imaging may either regress or progress. For children with residual disease we recommend surveillance imaging every 6 months for the first 2 years, every year for years 3, 4 and 5, then every second year if residual tumour is still present 5 years after initial surgery. This would detect not only progressive or recurrent disease, but also spontaneous regression which can occur later than disease progression.


Strongyloidiasis in a young French woman raises concern about possible ongoing autochthonous transmission in Spain.
Strongyloidiasis is one of the most common geohelminth infections in tropical and subtropical areas. Accurate diagnosis remains challenging, leading to an overall underestimation of strongyloidiasis prevalence. The possibility of ongoing autochthonous transmission in some temperate areas and especially in southern Europe is still debated, and data supporting this hypothesis are scarce. The case of a young French woman, who had travelled frequently to Spain and had acquired Strongyloides stercoralis infection as revealed by gastrointestinal symptoms and hypereosinophilia, is reported here. Physicians should keep in mind the risk of being infected in some areas of southern Europe, even if low, in order to avoid the life-threatening manifestations of strongyloidiasis favoured by pathological or therapeutic immunosuppression.


Mid-Pleistocene Transitions Forced Himalayan ibex to Evolve Independently after Split into an Allopatric Refugium.
Pleistocene glaciations had profound impact on the spatial distribution and genetic makeup of species in temperate ecosystems. While the glacial period trapped several species into glacial refugia and caused abrupt decline in large populations, the interglacial period facilitated population growth and range expansion leading to allopatric speciation. Here, we analyzed 40 genomes of four species of ibex and found that Himalayan ibex in the Pamir Mountains evolved independently after splitting from its main range about 0.1 mya following the Pleistocene species pump concept. Demographic trajectories showed Himalayan ibex experienced two historic bottlenecks, one each c. 0.8-0.5 mya and c. 50-30 kya, with an intermediate large population expansion c. 0.2-0.16 mya coinciding with Mid-Pleistocene Transitions. We substantiate with multi-dimensional evidence that Himalayan ibex is an evolutionary distinct phylogenetic species of Siberian ibex which need to be prioritized as Capra himalayensis for taxonomic revision and conservation planning at a regional and global scale.


The quality control of alkaline phosphatase determinations with placental phosphatase.
Human placenta has been recommended as the source of the alkaline phosphatase used for the preparation of control or reference materials. The effect of certain inhibitors, which may be present in the reagents, on control materials containing the placental isoenzyme, is shown to differ significantly from their effect on the isoenzymes in patient's sera. This finding indicates that if control materials are used which contain only human placental alkaline phosphatase, changes in accuracy resulting from differences in reagent quality may be missed, or alternatively a change in accuracy may be indicated by the quality control results which does not apply to the patient's sera.


Clinical and genetic characterization of a Chinese patient with triple A syndrome and novel compound heterozygous mutations in the AAAS gene.
Triple A syndrome is a rare autosomal recessive disease characterized by adrenal failure, alacrima, achalasia, and progressive neurologic symptoms. Here, we describe the clinical and genetic characteristics in a Chinese patient with novel mutations in the AAAS gene. The clinical and radiologic characteristics of the patient have been fully described. The coding sequences, including exon-intron boundaries, were amplified from genomic DNA and were sequenced. The clinical and radiologic findings of the patient are fully described. The sequencing of the AAAS gene detected two novel heterozygous mutations, including a c.577C>T, p.Gln193X in exon 7 and a novel frameshift mutation c.1062_1063insAC, p.Ser355fsX416 in exon 11. The testing of parents confirmed their heterozygous carrier status. There are significant clinical variability and mutational heterogeneities in Asian patients with this syndrome. DNA analysis is very helpful in establishing the final diagnosis of triple A syndrome, although its implication in the prediction of clinical expression and the outcome of the disorder is limited.


TP53 and RAS mutations in metachronous tumors from patients with cancer of the upper aerodigestive tract.
Patients who initially develop an upper aerodigestive tract cancer have an increased risk of second primary cancers. We examined TP53 and RAS mutations and p53 protein in 21 tumors from 10 patients with upper aerodigestive tract cancer who developed a metachronous tumor, to assess the genetic changes that occur in multiple primary tumors from the same individual. Thirteen of 21 (62%) tumors were found to have mis-sense mutations of either TP53 or RAS. Six tumors had TP53 mutations in codons 5 to 8 and 10 tumors from 7 patients had mutations of codons 12 or 13 of K-RAS. Only one patient had concordance of a mutation in 2 tumors; this mutation occurred in K-RAS and was accompanied by discordance of TP53 mutation. Three patients had tumors discordant for both TP53 and RAS mutations. Smoking-related tumors had TP53 and RAS mutations which were transversions in 11 (9 G:C to T:A and 2 G:C to C:G) and transitions in 3 (2 G:C to A:T and 1 A:T to G:C). Tumors not associated with smoking contained only transitions (both G:C to A:T). p53 protein was detected by immunohistochemistry in 7 of 13 (54%) tumors and was concordant in the multiple tumors of 3 patients. Three of the 7 tumors staining for p53 also had TP53 mutations. Thus, genetic alterations are discordant in multiple primary cancers and the pattern of mutations is similar to that found in patients with a single primary tumor, supporting the concept that these cancers arise independently.


N-methyl-D-aspartate subunit expression during mouse development altered by in utero alcohol exposure.
Alcohol-related neurodevelopmental disorders are contributors to long-term learning disabilities. By using a model for fetal alcohol syndrome, we have shown that prenatal alcohol exposure results in adult learning deficits of unknown mechanisms. In the developing hippocampus, the N-methyl-D-aspartate (NMDA) receptor subunit NR2B triggers long-term potentiation, fundamental to learning and memory; this is supplemented by the less plastic NR2A subunit in the adult. To understand the mechanism of learning deficits in FAS, we evaluated NR2B and NR2A expression in embryonic and adult mice. Pregnant C57Bl6/J mice were treated on gestational day 8 with alcohol or control (saline solution). Embryos were harvested at 6 hours, 24 hours, and 10 days, and brains from adult offspring were collected at 3 months (after evaluation for learning deficit). Calibrator-normalized relative real-time polymerase chain reaction was performed for NR2B and NR2A with glyceraldehyde-3-phosphate dehydrogenase standardization. Statistical analysis included analysis of variance. At 6 hours, NR2B expression in the alcohol-exposed embryos was higher than in controls (P < .01). NR2A was not expressed in either group. By 24 hours there was no difference in NR2B (P = .3). However, at 10 days NR2B was lower in alcohol-exposed animals (P = .02). In the adult brains there was a relative decrease in NR2B (P = .03) and an increase in NR2A (P < .01). Prenatal alcohol exposure during development induces NR2B expression deregulation in the embryos that persists until adulthood, when a relative increase in the less modifiable subunit NR2A occurs. This alteration in NMDA receptor subunits may underlie the learning abnormalities in fetal alcohol syndrome.


Applications and Perspectives of Artificial Intelligence, Machine Learning and "Dentronics" in Dentistry: A Literature Review.
The aim of this study was to describe artificial intelligence, machine learning, and "Dentronics" applications and perspectives in dentistry. A literature review was carried out to identify the applications of artificial intelligence in the field of dentistry. A specialized search for information was carried out in three databases such as Scopus, PubMed, and Web of Science. Manuscripts published from January 1988 to November 2021 were analyzed. Articles were included without any restriction by language or country. Scopus, PubMed, and Web of Science were found to have 215, 1023, and 98 registered manuscripts, respectively. Duplicates (191 manuscripts) were eliminated. Finally, 4 letters, 12 editorials, 5 books, 1 erratum, 54 conference papers, 3 conference reviews, and 222 reviews were excluded. Artificial intelligence has revolutionized prediction, diagnosis, and therapeutic management in modern dentistry. Finally, artificial intelligence is a potential complement to managing future data in this area.