Hormonal therapy for bleeding gastrointestinal mucosal vascular abnormalities: a promising alternative.
Recurrent bleeding from an obscure gastrointestinal source is a common but often frustrating clinical challenge. Frequently these bleeds can be attributed to vascular anomalies in the upper or lower gastrointestinal tract. Traditional management has included surgical resection and endoscopic fulguration. However, these methods are often ineffective when vascular lesions are diffuse, difficult to identify, or endoscopically inaccessible. Hormone therapy with a combination of oestrogen and progesterone represents a promising alternative. Since initial reports of success in patients with epistaxis from hereditary haemorrhagic telangiectasia, growing evidence supports its role in reducing bleeding from gastrointestinal vascular anomalies. Existing literature is critically reviewed and management strategies incorporating hormone therapy are suggested.


Naturalistic Effects of Five Days of Bedtime Caffeine Use on Sleep, Next-Day Cognitive Performance, and Mood.
Background: Disruptive effects of caffeine on sleep have previously been reported, although measures of next-day mood and performance have rarely been included. The present study aims to evaluate the effects of caffeine on sleep and associated next-day effects in a naturalistic field setting. Methods: Nineteen participants (daily caffeine intake 0-141 mg), assessed as good sleepers, took part in a randomized, placebo-controlled, double-blind, 2-week crossover study to assess the effects of bedtime caffeine use (250 mg) on sleep and next-day cognitive performance and mood, which were assessed on a mobile phone in the morning and afternoon. Sleep was assessed objectively (actiwatch) and subjectively (sleep diary). Results: Caffeine's effects on sleep were largely restricted to the first day of administration, with actigraphically measured reduced sleep efficiency, increased activity score and fragmentation index, decreased self-rated sleep quality, and an increased occurrence of participants waking early; only decreased sleep efficiency remained over the week. Effects on next-day performance and mood were evident over the whole week, although despite disrupting sleep, accuracy on a working memory task was higher after caffeine than placebo administration. Conclusions: Caffeine disrupted sleep, although when assessing next-day performance, which may have been affected by the presence of residual caffeine, performance appeared better after caffeine compared to placebo, although this was most likely due to prevention of the effects of overnight withdrawal from caffeine rather than representing a net benefit. Furthermore, partial tolerance developed to the effects of caffeine on sleep.


Modulation of allostery of pyruvate kinase by shifting of an ensemble of microstates.
Since the introduction of the concepts of allostery about four decades ago, much advancement has been made in elucidating the structure-function correlation in allostery. However, there are still a number of issues that remain unresolved. In this review we used mammalian pyruvate kinase (PK) as a model system to understand the role of protein dynamics in modulating cooperativity. PK has a triosephosphate isomerase (TIM) (alpha/beta)(8) barrel structural motif. PK is an ideal system to address basic questions regarding regulatory mechanisms about this common (alpha/beta)(8) structural motif. The simplest model accounting for all of the solution thermodynamic and kinetic data on ligand-enzyme interactions involves two conformational states, inactive E(T) and active E(R). These conformational states are represented by domain movements. Further studies provide the first evidence for a differential effect of ligand binding on the dynamics of the structural elements, not major secondary structural changes. These data are consistent with our model that allosteric regulation of PK is the consequence of perturbation of the distribution of an ensemble of states in which the inactive E(T) and active E(R) represent the two extreme end states. Sequence differences and ligands can modulate the distribution of states leading to alterations of functions. The future work includes: defining the network of functionally connected residues; elucidating the chemical principles governing the sequence differences which affect functions; and probing the nature of mutations on the stability of the secondary structural elements, which in turn modulate allostery.


Impact of a Cancer Urgent Care Clinic on Regional Emergency Department Visits.
Did the creation of an urgent care clinic specifically for patients with cancer affect emergency department visits among adults newly diagnosed with cancer? We applied an interrupted time series analysis to adjusted monthly emergency department visits made by adults age 18 years or older who were diagnosed with cancer between 2009 and 2016 at a comprehensive cancer center. Cancer registry patients were linked to a longitudinal regional database of emergency department and hospital visits. Because the urgent care clinic was closed on weekends, we took advantage of the natural experiment by comparing weekend visits as a control group. Our primary outcome was emergency department visits within 180 days after a cancer diagnosis, compiled as adjusted monthly rates of emergency department visits per 1,000 patient-months. We analyzed subsequent hospitalizations as a secondary outcome. The rate of weekday emergency department visits was increasing at a rate of 0.43 visits (95% CI, 0.29 to 0.57 visits) per month before May 2012, then fell in half to a rate of 0.19 visits (95% CI, 0.11 to 0.28 visits) per month (P = .007) after the urgent care clinic was established. In contrast, the weekend visit rate was growing at a rate of 0.08 visits (95% CI, -0.03 to 0.19 visits) per month before May 2012 and 0.05 (95% CI, -0.02 to 0.13 visits; P = .533) afterward. By the end of 2016, there were 15.3 fewer monthly weekday emergency department visits than expected (P = .005). Trends in weekday hospitalizations were not significantly changed. Although only one in eight emergency department-visiting patients also used the urgent care clinic, the growth rate of emergency department visits fell by half after the urgent care clinic was established.


Measurement and modeling of out-of-field doses from various advanced post-mastectomy radiotherapy techniques.
More and more advanced radiotherapy techniques have been adopted for post-mastectomy radiotherapies (PMRT). Patient dose reconstruction is challenging for these advanced techniques because they increase the low out-of-field dose area while the accuracy of out-of-field dose calculations by current commercial treatment planning systems (TPSs) is poor. We aim to measure and model the out-of-field radiation doses from various advanced PMRT techniques. PMRT treatment plans for an anthropomorphic phantom were generated, including volumetric modulated arc therapy with standard and flattening-filter-free photon beams, mixed beam therapy, 4-field intensity modulated radiation therapy (IMRT), and tomotherapy. We measured doses in the phantom where the TPS calculated doses were lower than 5% of the prescription dose using thermoluminescent dosimeters (TLD). The TLD measurements were corrected by two additional energy correction factors, namely out-of-beam out-of-field (OBOF) correction factor K OBOF and in-beam out-of-field (IBOF) correction factor K IBOF, which were determined by separate measurements using an ion chamber and TLD. A simple analytical model was developed to predict out-of-field dose as a function of distance from the field edge for each PMRT technique. The root mean square discrepancies between measured and calculated out-of-field doses were within 0.66 cGy Gy-1 for all techniques. The IBOF doses were highly scattered and should be evaluated case by case. One can easily combine the measured out-of-field dose here with the in-field dose calculated by the local TPS to reconstruct organ doses for a specific PMRT patient if the same treatment apparatus and technique were used.


Templating fullerenes by domain boundaries of a nanoporous network.
We present a new templating approach that combines the templating properties of nanoporous networks with the dynamic properties and the lattice mismatch of domain boundaries. This templating approach allows for the inclusion of guests with different sizes without the need for a strict molecular design to tailor the nanoporous network. With this approach, nonperiodic patterns of functional molecules can be formed and studied. We show that domain boundaries in a trimesic acid network are preferred over pores within the network as adsorption sites for fullerenes by a factor of 100-200. Pristine fullerenes of different sizes and functionalized fullerenes were templated in this way.


Complement-mediated 'bystander' damage initiates host NLRP3 inflammasome activation.
Complement activation has long been associated with inflammation, primarily due to the elaboration of the complement anaphylotoxins C5a and C3a. In this work, we demonstrate that the phagocytosis of complement-opsonized particles promotes host inflammatory responses by a new mechanism that depends on the terminal complement components (C5b-C9). We demonstrate that during the phagocytosis of complement-opsonized particles, the membrane attack complex (MAC) of complement can be transferred from the activating particle to the macrophage plasma membrane by a 'bystander' mechanism. This MAC-mediated bystander damage initiates NLRP3 inflammasome activation, resulting in caspase-1 activation and IL-1β and IL-18 secretion. Inflammasome activation is not induced when macrophages phagocytize unopsonized particles or particles opsonized with serum deficient in one of the terminal complement components. The secretion of IL-1β and IL-18 by macrophages depends on NLRP3, ASC (also known as PYCARD) and caspase-1, as macrophages deficient in any one of these components fail to secrete these cytokines following phagocytosis. The phagocytosis of complement-opsonized particles increases leukocyte recruitment and promotes T helper 17 cell (TH17) biasing. These findings reveal a new mechanism by which complement promotes inflammation and regulates innate and adaptive immunity.


The anxiolytic effect of aromatherapy on patients awaiting ambulatory surgery: a randomized controlled trial.
The aim of this study was to determine if aromatherapy could reduce preoperative anxiety in ambulatory surgery patients. A total of 109 preoperative patients were randomly assigned to experimental (bergamot essential oil) and control (water vapor) conditions and their responses to the State Trait Anxiety Inventory and vital signs were monitored. Patients were stratified by previous surgical experience, but that did not influence the results. All those exposed to bergamot essential oil aromatherapy showed a greater reduction in preoperative anxiety than those in the control groups. Aromatherapy may be a useful part of a holistic approach to reducing preoperative anxiety before ambulatory surgery.


Progressive abnormalities in skeletal muscle and neuromuscular junctions of transgenic mice expressing the Huntington's disease mutation.
Huntington's disease (HD) is a neurodegenerative disorder with complex symptoms dominated by progressive motor dysfunction. Skeletal muscle atrophy is common in HD patients. Because the HD mutation is expressed in skeletal muscle as well as brain, we wondered whether the muscle changes arise from primary pathology. We used R6/2 transgenic mice for our studies. Unlike denervation atrophy, skeletal muscle atrophy in R6/2 mice occurs uniformly. Paradoxically however, skeletal muscles show age-dependent denervation-like abnormalities, including supersensitivity to acetylcholine, decreased sensitivity to mu-conotoxin, and anode-break action potentials. Morphological abnormalities of neuromuscular junctions are also present, particularly in older R6/2 mice. Severely affected R6/2 mice show a progressive increase in the number of motor endplates that fail to respond to nerve stimulation. Surprisingly, there was no constitutive sprouting of motor neurons in R6/2 muscles, even in severely atrophic muscles that showed other denervation-like characteristics. In fact, there was an age-dependent loss of regenerative capacity of motor neurons in R6/2 mice. Because muscle fibers appear to be released from the activity-dependent cues that regulate membrane properties and muscle size, and motor axons and nerve terminals become impaired in their capacity to release neurotransmitter and to respond to stimuli that normally evoke sprouting and adaptive reinnervation, we speculate that in these mice there is a progressive dissociation of trophic signalling between motor neurons and skeletal muscle. However, irrespective of the cause, the abnormalities at neuromuscular junctions we report here are likely to contribute to the pathological phenotype in R6/2 mice, particularly in late stages of the disease.


Beyond money: Nonmonetary prosociality across adulthood.
Empirical evidence suggests that self-reported prosociality and donations increase with age. The majority of this research was conducted using monetary donations as outcome measures. However, on average older adults hold a significant advantage in financial and material assets compared to younger adults, effectively lowering the subjective cost of small monetary donations. Are older adults also more prosocial when donating a nonmonetary resource that is of equal or even higher value for them compared to younger age groups? A first study (N = 160, 20-74 years) combined data from self-report measures, affective responses, and hypothetical donation decisions to compute a single prosociality factor. Conceptually replicating findings from Hubbard, Harbaugh, Srivastava, Degras, and Mayr (2016) on monetary donations, results suggest that nonmonetary prosociality also increases with age. However, these differences depended on the domain of the donation. Data from two further behavioral studies (Study 2: N = 156, 18-89 years; Study 3: N = 342, 19-88 years) that were analyzed using Bayesian statistics provided evidence that older adults are not more prosocial than younger and middle-aged adults when donating a small amount of their time (in service of a donation to charity). In summary, the three studies suggest that older adults are not consistently more likely to behave prosocially than younger or middle-aged adults in nonmonetary domains. These findings point to the importance of moving research on prosociality and aging beyond financial donations and further explore the role of resources and perceived costs of prosociality. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Hydrocephalus, a rare manifestation of sarcoidosis.
A 36-week-pregnant woman developed a symptomatic hydrocephalus. Chest imaging showed bihilar lymphadenopathy and histological examination of a mediastinal lymph node revealed non-caseating granulomas. After delivery, her neurologic complaints progressed. Placement of a ventriculoperitoneal drain (VPD) did not reduce the symptoms. However, steroids resulted in rapid disappearance of the hydrocephalus. Hydrocephalus is a very rare manifestation of sarcoidosis. The diagnosis relies on the ability of clinicians to recognize this disorder. This case shows how a difference in opinion of the several specialists involved can lead to a delay in diagnosis and treatment.


Bony labyrinth morphometry reveals hidden diversity in lungless salamanders (Family Plethodontidae): Structural correlates of ecology, development, and vision in the inner ear.
Lungless salamanders (Family Plethodontidae) form a highly speciose group that has undergone spectacular adaptive radiation to colonize a multitude of habitats. Substantial morphological variation in the otic region coupled with great ecological diversity within this clade make plethodontids an excellent model for exploring the ecomorphology of the amphibian ear. We examined the influence of habitat, development, and vision on inner ear morphology in 52 plethodontid species. We collected traditional and 3D geometric morphometric measurements to characterize variation in size and shape of the otic endocast and peripheral structures of the salamander ear. Phylogenetic comparative analyses demonstrate structural convergence in the inner ear across ecologically similar species. Species that dwell in spatially complex microhabitats exhibit robust, highly curved semicircular canals suggesting enhanced vestibular sense, whereas species with reduced visual systems demonstrate reduced canal curvature indicative of relaxed selection on the vestibulo-ocular reflex. Cave specialists show parallel enlargement of auditory-associated structures. The morphological correlates of ecology among diverse species reveal underlying evidence of habitat specialization in the inner ear and suggest that there exists physiological variation in the function of the salamander ear even in the apparent absence of selective pressures on the auditory system to support acoustic behavior.


Absorbable suture for band tightening of scleral buckling in pseudophakic rhegmatogenous retinal detachment: a modified surgical technique and a 6-month follow-up.
Rhegmatogenous retinal detachment (RRD) is a separation of the neurosensory retina from the retinal pigment epithelium as a result of liquid vitreous passing through a retinal break. Scleral buckling surgery (SB) is a conventional treatment for RRD. In SB, a silicon explant is used to indent the sclera, reduce vitreous traction, and close the retinal break, and an encircling band is used circumferentially, leading to myopia. This study aimed to evaluate the functional and biometric outcomes after SB with absorbable band-tightening sutures in patients with pseudophakic RRD. In this prospective interventional study, we included pseudophakic eyes with RRD treated surgically with SB and a temporary encircling band using a 6-0 absorbable Vicryl suture to tighten the band, instead of conventional permanent suture tightening. Anterior chamber depth (ACD), axial length (AL), intraocular pressure (IOP), spherical equivalent refractive error (SER), and best-corrected distance visual acuity (BCDVA) were measured preoperatively and at 1 day, 2 weeks, 3 months, and 6 months postoperatively. We included 30 eyes of 30 patients with a mean (standard deviation [SD]) age of 66.1 (10.5) years who underwent SB with an absorbable band-tightening suture for pseudophakic RRD. Significant increases in AL and ACD were observed at 2 weeks after surgery, with a significant decline in values thereafter; however, at the 6-month follow-up, the values were significantly higher than those at baseline (all P < 0.05). Based on the Vicryl tension and its hydrolysis, mean (SD) SER at 2 weeks postoperatively was significantly more myopic than at baseline (-5.8 [1.6] D versus +1.3 [1.8] D). However, the mean (SD) SER decreased significantly throughout the 6-month follow-up (all P < 0.05), and it reached -1.8 (0.9) D, which was comparable with the mean baseline SER (P = 0.140). The participants experienced significant improvement in BCDVA throughout the follow-up period (all P < 0.05). Using an absorbable suture to tighten the encircling band in patients with pseudophakic RRD can reduce postoperative myopia without adversely affecting the anatomical or functional outcomes. Future comparative studies with larger sample sizes and longer postoperative follow-up are needed to verify these findings.


Rapid improvement of myasthenia gravis after plasma exchange.
Neuromuscular transmission and the staircase phenomenon in the adductor pollicis muscle were studied in six patients with myasthenia gravis before and 24 hours after single plasma exchanges given in short series over one to four weeks. An improvement in neuromuscular transmission was observed in all patients but one within 24 hours, suggesting that an immunological block of receptor sites is reversible or that acetylcholine receptors are rapidly resynthesized. In addition to a neuromuscular transmission defect, two of the patients also showed evidence of impaired excitation-contraction coupling with a negative staircase phenomenon and reduced posttetanic twitch potentiation. This condition became normal after plasma exchange, which may indicate that a reversible immunological impairment of the sarcoplasmic reticulum was present. Improvement lasted up to several months. The anti-acetylcholine receptor antibody titers were lowered in response to single plasma exchanges, but actual titer levels showed poor correlation with clinical and electrophysiological changes.


Lack of differential motor outcome with subthalamic nucleus region stimulation in Parkinson's disease.
Deep brain stimulation (DBS) has emerged as a viable therapy for Parkinson's disease (PD). The impact of subthalamic nucleus (STN) lead placement (lateral versus medial) on motor outcome, however, has not been systematically evaluated. Forty-eight patients with PD underwent STN-DBS surgery and were evaluated postoperatively for 48 weeks for motor improvement as measured by the Unified Parkinson's Disease Rating Scale (UPDRS) part III (standardized motor examination) and levodopa equivalent daily dose (LEDD). Postoperative MRI was used to identify the location of the active stimulating contact and motor outcome was analyzed. STN-DBS was associated with significant improvement in motor outcome as determined by a reduction in the UPDRS part III subscore from 34.44 ± 1.29 at baseline to 18.76 ± 1.06 at end visit (p<0.0001) and a reduction in LEDD from 1721 ± 152 mg/day at baseline to 1134 ± 119 mg/day at end visit (p=0.0024). Patients with stimulating contacts in the medial STN compared to the lateral STN did not demonstrate any significant differences in motor outcome (UPDRS, p=0.5811; LEDD, p=0.7341). No significant differences were found in motor outcome between patients with STN stimulation compared to stimulation of surrounding fiber tracts (p=0.80). No significant difference in stimulation voltage was noted with respect to lead location. Our study did not find a significant effect for the location of active contact and motor outcome neither within the subregions of the STN nor between the STN and surrounding fibers. Further research is needed to better understand the neurophysiological basis for these results.


Mobilization and selection of peripheral blood hematopoietic progenitors in children with systemic sclerosis.
Autologous transplant of lymphocyte-depleted peripheral blood stem cells has been proposed for treatment of patients with severe autoimmune disease. However, until now, no data are available on the safety and feasibility of both stem cell collection and selection in pediatric patients with these disorders. We report on three children affected by systemic sclerosis with lung involvement, who received chemotherapy and granulocyte colony-stimulating factor (G-CSF) to mobilize autologous peripheral blood progenitors. The priming regimen consisted of cyclophosphamide (CY, 4 g/m(2)) and G-CSF (lenograstim, 10 microg/kg/day starting 2 days after cyclophosphamide administration until stem cell collection). Leukapheresis was performed when WBC and CD34+ cell count were at least 2 x 10(9)/L and 0.03 x 10(9)/L, respectively. In the first patient, positive selection of CD34+ cells was performed through the Ceprate SC stem cell concentrator (CellPro, Bothell, WA, USA). In the remaining 2 children, progenitor cells were also purged with negative selection of CD4+ and CD8+ lymphocytes performed by means of the Isolex 300i device (Baxter). All patients tolerated the priming regimen well and did not present any sign of autoimmune disease exacerbation. Collection was successful in all children and the number of CD34+ cells before selection ranged between 10.7 x 10(6) and 17.6 x 10(6)/kg of patient body weight. The selection of haematopoietic stem cells in the 3 patients resulted in at least 2. 6-log T-cell depletion of the cell content, with a recovery of the initial value of CD34+ cells comprised between 21 and 44%. After, a preparative regimen consisting of CY (200 mg/kg over 4 days) and Campath-1 G in vivo (10 mg/day for 2 consecutive days), patients were transplanted using cryopreserved lymphocyte-depleted progenitor cells. In all cases, a prompt hematopoietic engraftment was observed. Taken together these data suggest that mobilization, collection and selection of hematopoietic progenitors are safe and feasible in children with autoimmune disease.


Organogels derived from tetranitrated crown ethers.
[reaction: see text] The 3,3',4'4'-tetranitrodibenzocrown ethers TNDB24C8 and TNDB30C10 form organogels with chloroalkanes at 3% w/v. Atomic force microscopy and scanning electron microscopy have been used to characterize the superstructure of the gels. Gels prepared using TNDB30C10 and CHCl(3) are more fibrous and are ordered into elongated domains attributable to exposed parts of intermingled fibers. Differential scanning calorimetry shows that the gel aids in the formation of supercooled CHCl(3) (DeltaT = 21 K, DeltaH(av) = 19.0 +/- 1.5 kJ mol(-)(1)) and that the gel liquefies at 307 K.


Solid-Liquid Thermal Transport and Its Relationship with Wettability and the Interfacial Liquid Structure.
Experiments and atomistic simulations have suggested the existence of a direct correlation between the wetting properties of a surface and heat transfer across it. In this investigation, molecular dynamics simulations of surface wettability and solid-liquid thermal transport were conducted in order to better understand the relationship between the surface chemistry and thermal transport. The wettability transparency of graphene-coated surfaces was considered in order to investigate heat transfer across a complex interface with similar wettability as a bare surface. The results indicate that the relationship between the interfacial heat transfer and wettability is not universal. The density depletion length was found to reconcile the thermal boundary conductance calculations for different bare and graphene-coated silicon surfaces.


Sexual pleasure during condom-protected vaginal sex among heterosexual men.
Public health condom promotion efforts increasingly focus on the importance of sexual pleasure; however, little is known about sexual event-specific factors that may increase or decrease perceptions of sexual pleasure when condoms are used. To examine event-level factors associated with ratings of sexual pleasure during condom-protected vaginal intercourse. Data were collected in 2008 from 1,875 men during a prospective daily diary study of sexual behavior and condom use. Sexual pleasure was assessed during condom-protected vaginal intercourse considering situational, relational, intrapersonal, and behavioral predictors. Analyses were generalized estimating equation ordinal regression. Event-specific perceptions of sexual pleasure (three categories: not at all enjoyable to extremely enjoyable). Vaginal intercourse was reported on 29.8% (N = 8,876/29,714) of diary days; complete condom use was reported for 59.1% (5,249/8,876) of all vaginal intercourse events. This was confusing by using the word "all sexual events." Higher sexual pleasure ratings during complete condom use were associated with older age, manual stimulation of one's genitals, receiving oral sex, and performing oral sex. Sexual pleasure ratings also increased in association with intercourse duration, intercourse intensity, ejaculation, erection perception, and condom comfort. Sexual pleasure ratings were lower with erection difficulty and partner discomfort during sex. These data advance understanding of sexual pleasure during condom use, suggesting that sexual pleasure increases in conjunction with specific relational, physiological, and condom perceptions. These findings offer points upon which clinicians and health educators can engage men in an ongoing dialogue about augmenting sexual pleasure in the context of condom use.


Improving the Energy Cost of Incline Walking and Stair Ascent With Ankle Exoskeleton Assistance in Cerebral Palsy.
Many individuals with cerebral palsy (CP) experience gait deficits resulting in metabolically-inefficient ambulation that is exacerbated by graded walking terrains. The primary goal of this study was to clinically-validate the accuracy and efficacy of adaptive ankle exoskeleton assistance during steady-state incline walking and stair ascent in individuals with CP. Exploratory goals were to assess safety and feasibility of using adaptive ankle exoskeleton assistance in real-world mixed-terrain settings. We used a novel battery-powered ankle exoskeleton to provide adaptive ankle plantar-flexor assistance during stance phase. Seven ambulatory individuals with CP completed the study. Adaptive controller accuracy was 85% for incline walking and 81% for stair-stepping relative to the biological ankle moment. Assistance improved energy cost of steady-state incline walking by 14% (p = 0.004) and stair ascent by 21% (p = 0.001) compared to walking without the device. Assistance reduced the muscular demand for the soleus and vastus lateralis during both activities. All participants were able to safely complete the real-world mixed-terrain route, with adaptive ankle assistance resulting in improved outcomes compared to walking with the device providing zero-torque; no group-level differences were found compared to walking without the device, yet individuals with more impairment exhibited a marked improvement. Adaptive ankle exoskeleton assistance can improve the energy cost of steady-state incline walking and stair ascent in individuals with CP. As the first study to demonstrate safety and performance benefits of ankle assistance on graded terrains in CP, these findings encourage further investigation in free-living settings.


The KBG syndrome: Case report.
The KBG syndrome is a rare autosomal dominant condition, first described by Hermann et al. in 1975. Fundamental findings are: mild development delay, short stature, craniofacial dysmorphism and skeletal anomalies. A 32 years old woman, Caucasian race, weight 57 Kg, affected by KBG syndrome was sent to our clinics for preoperative anaesthesia evaluation. She was schedules for left ossicular reconstruction under general anaesthesia for bilateral hearing loss. A psycho-motor retardation was associated to morphological anomalies such as short neck, hyperlordosis without neck extension imparirment, craniofacial anomalies and dento-skeletal abnormalities. An echocardiography showed the presence of interatrial defect with left-to-right shunt. The patient was sent to a cardiac surgery centre. Perioperative evaluation of patients affected by KBG syndrome must take into consideration the management of difficult airways, due to the associated craniofacial dysmorphism. The possible presence of cardiac anomalies in the KBG syndrome is currently being evalueted. In this report the finding of cardiomegaly and congestion of the pulmonary circulation was attributed to presence of an interatrial defect with left-to-right shunt. The risk of cardiopulmonary failure led us to ask for a cardiac surgery consult. Perioperative management of these patients should be extremely accurate, even in the case of minor surgery, and should include also chest X-rays and echocardiography evaluation.


A highly efficient transient protoplast system for analyzing defence gene expression and protein-protein interactions in rice.
SUMMARY The transient assay system based on mesophyll or cultured cell-derived protoplasts has been exploited in several plant species and has become a powerful tool for rapid gene functional analysis and biochemical manipulations. However, the system has not been widely used in rice owing to the difficulties in large-scale isolation of viable rice protoplasts from leaves or suspension-cultured cells. Here, we describe a significantly improved method to isolate a large number of protoplasts from stem and sheath tissues of both young and mature plants. High-level coexpression of multiple constructs and efficient suppression of exogenous and endogenous genes were observed in the stem- and sheath-derived protoplasts. A transient green fluorescent protein and luciferase-based reporter system for defence-related genes expression analysis has been established, which is useful for screening and characterizing genes involved in rice defence signalling pathways. Furthermore, a protoplast-based bimolecular fluorescence complementation (BiFC) system for the detection of protein-protein interactions in living rice cells was developed. The YFP complementation of two split-YFP halves mediated by homodimerization of the GUS and SPIN1, a cell-death related protein, was observed in transfected protoplasts. In combination with genetic, genomic and proteomic approaches, the established versatile protoplast transient assay system will facilitate large-scale functional analysis of defence-related genes in rice.


The minimal clinically important difference after simple decompression for ulnar neuropathy at the elbow.
Establishing minimally clinically important difference (MCID) for patient-reported outcomes questionnaires is an important component of outcomes research to understand treatment effectiveness from the patient's perspective. For patients with ulnar neuropathy at the elbow (UNE), these assessments are vital to examine how much change in the questionnaire scores equate to patient satisfaction. We calculated the change in scores of Michigan Hand Outcomes Questionnaire (MHQ), Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, and Carpal Tunnel Questionnaire (CTQ) from preoperative to 3, 6, and 12 months after ulnar nerve simple decompression procedure. We used the anchor-based approach of receiver operating characteristic curves to determine the MCID. On average, MCID of 10, 12, and 7 points were identified for pain, function, and activities of daily living domains of the MHQ. Similarly, DASH, CTQ-symptom severity scale, and CTQ-function severity scale had an average MCID of 7, 0.7, and 0.3, points respectively. At the 3, 6, and 12 months' time points, an MCID of 9, 8, and 13 points for pain; 12, 12, and 12 points for function; and 6, 8, and 6 points for activities of daily living domains of the MHQ were identified; similarly an MCID of 8, 7, and 7 points for DASH; 0.4, 0.7, and 0.7 points for CTQ-symptom severity scale; and 0.3, 0.3, and 0.4 points for CTQ-function severity scale were established. The smaller MCIDs of MHQ, DASH, and even smaller MCIDs of CTQ found in our study indicate that a small change in the scores identified satisfied patients. Simple decompression surgery for UNE produced patient satisfaction with only a small change in their questionnaire scores. The implications of this finding are that simple decompression surgery for UNE is a highly effective procedure and that the outcomes questionnaires used are highly responsive, which minimizes sample size requirements for future research studies relating to UNE. Therapeutic II.


Gaucher disease: a membranous enzymopathy.
Inhibitors and activators of acid beta-glucosidase activity were used as probes to characterize the components of the active site of the membrane bound enzyme, acid beta-glucosidase. Three components of the active site were defined: (1) a catalytic site, (2) an aglycon binding site, and (3) a hydrophobic binding site (Fig. 5A). Similar studies on the residual acid beta-glucosidase in homozygotes with Type 1 Ashkenazi Gaucher disease suggested that this enzyme's hydrophobic site was more hydrophilic than that of the normal enzyme. The defect in this membranous enzymopathy could have resulted from a single base substitution in the structural gene leading to the insertion of a more hydrophilic amino acid in the hydrophobic domain of the gene product. Alternatively, a base substitution which altered the conformation of the enzyme could render the hydrophobic site more hydrophilic. The following consequences of such a mutation would be expected. The mutation would not affect substrate binding to the catalytic site, since the formation of the enzyme-substrate complex (ie, the Km) would not be altered. If the HS site became more hydrophilic, its efficiency for removing the product would be reduced, resulting in a lower substrate turnover (ie, a "Vmax mutation"). Consequently, the binding of glucosyl psychosine, taurocholate, and phosphatidyl serine to the hydrophobic site would be less efficient, resulting in a greater alpha Ki value. Finally, the binding of taurocholate to the HS would be reduced, and this lipid's enhancement of acid beta-glucosidase inhibition by OBG also would be decreased. Since these results are based on kinetic data, confirmation of the hypothesis will require the preparation of homogenous beta-glucosidase from normal and Type 1 Ashkenazi Gaucher sources for amino acid sequencing of the peptides containing the catalytic site as well as the other components of the active site. Such peptides might be identified by their ability to bind radiolabeled inhibitors and/or activating compounds.


Common neural substrates for the addictive properties of nicotine and cocaine.
Regional brain activation was assessed by mapping of Fos-related protein expression in rats trained to self-administration of intravenous nicotine and cocaine. Both drugs produced specific overlapping patterns of activation in the shell and the core of the nucleus accumbens, medial prefrontal cortex, and medial caudate areas, but not in the amygdala. Thus, the reinforcing properties of cocaine and nicotine map on selected structures of the terminal fields of the mesocorticolimbic dopamine system, supporting the idea that common substrates for these addictive drugs exist.


Identification and characterization of the Tuber borchii D-mannitol dehydrogenase which defines a new subfamily within the polyol-specific medium chain dehydrogenases.
A novel NADP(+)-dependent D-mannitol dehydrogenase and the corresponding gene from the plant symbiotic ascomycete fungus Tuber borchii was identified and characterized. The enzyme, called TbMDH, is a homotetramer with two zinc atoms per subunit. It catalyzed both D-fructose reduction and D-mannitol oxidation, although it showed the highest substrate specificity and catalytic efficiency for D-fructose. Co-factor specificity was restricted to NADP(H) and the reaction proceeded via a sequential ordered Bi Bi mechanism. The carbon responsive transcriptional pattern showed that Tbmdh is up-regulated when mycelia are transferred to a culture medium containing D-mannitol or D-fructose. The phylogenetic analysis showed TbMDH to be the first example of a fungal D-mannitol-2-dehydrogenase belonging to the medium-chain dehydrogenase/reductases (MDRs). The enzyme identified a new group of proteins, most of them annotated in databases as hypothetical zinc-dependent dehydrogenases, forming a distinct subfamily among the polyol dehydrogenase family.


Correlation between Harris hip score and gait analysis through artificial intelligence pose estimation in patients after total hip arthroplasty.
Recently, open pose estimation using artificial intelligence (AI) has enabled the analysis of time series of human movements through digital video inputs. Analyzing a person's actual movement as a digitized image would give objectivity in evaluating a person's physical function. In the present study, we investigated the relationship of AI camera-based open pose estimation with Harris Hip Score (HHS) developed for patient-reported outcome (PRO) of hip joint function. HHS evaluation and pose estimation using AI camera were performed for a total of 56 patients after total hip arthroplasty in Gyeongsang National University Hospital. Joint angles and gait parameters were analyzed by extracting joint points from time-series data of the patient's movements. A total of 65 parameters were from raw data of the lower extremity. Principal component analysis (PCA) was used to find main parameters. K-means cluster, X-squared test, Random forest, and mean decrease Gini (MDG) graph were also applied. The train model showed 75% prediction accuracy and the test model showed 81.8% reality prediction accuracy in Random forest. "Anklerang_max", "kneeankle_diff", and "anklerang_rl" showed the top 3 Gini importance score in the Mean Decrease Gini (MDG) graph. The present study shows that pose estimation data using AI camera is related to HHS by presenting associated gait parameters. In addition, our results suggest that ankle angle associated parameters could be key factors of gait analysis in patients who undergo total hip arthroplasty.


[Postpoliomyelitic progressive amyotrophy].
Two clinical cases of post-poliomyelitic progressive amyotrophy (PPA) are described. One patient had serological tests of the blood and cerebrospinal fluid for viruses of poliomyelitis, measles, simple herpes and tick-borne encephalitis which were negative. The authors suggest that PPA develops in patients with a peculiar genetic predisposition and altered homeostasis and is a degenerative-dystrophic disease of the motor nerve.


Two-Dimensional Ketone-Driven Metal-Organic Coordination on Cu(111).
Two-dimensional metal-organic nanostructures based on the binding of ketone groups and metal atoms were fabricated by depositing pyrene-4,5,9,10-tetraone (PTO) molecules on a Cu(111) surface. The strongly electronegative ketone moieties bind to either copper adatoms from the substrate or codeposited iron atoms. In the former case, scanning tunnelling microscopy images reveal the development of an extended metal-organic supramolecular structure. Each copper adatom coordinates to two ketone ligands of two neighbouring PTO molecules, forming chains that are linked together into large islands through secondary van der Waals interactions. Deposition of iron atoms leads to a transformation of this assembly resulting from the substitution of the metal centres. Density functional theory calculations reveal that the driving force for the metal substitution is primarily determined by the strength of the ketone-metal bond, which is higher for Fe than for Cu. This second class of nanostructures displays a structural dependence on the rate of iron deposition.


[Methods for defining the indications for indirect revascularization of eye].
The paper deals with the problem of treating ischemic diseases of the organ of vision by crossing the external branches of the carotid arteries. Methods based on the results of objective studies and verified in numerous operations are proposed. Experience gained in more than 250 indirect revascularizations of the eye demonstrates a high efficacy of the methods for defining the indications for ligature or crossing of the facial branches of the external carotid artery, thus recommending these methods for practical application.


How to Achieve Therapeutic Response in Erlotinib-Resistant Head and Neck Squamous Cell Carcinoma? New Insights from Stable Isotope Labeling with Amino Acids in Cell Culture-Based Quantitative Tyrosine Phosphoproteomics.
Resistance to cancer chemotherapy is a major global health burden. Epidermal growth factor receptor (EGFR) is a proven therapeutic target for multiple cancers of epithelial origin. Despite its overexpression in >90% of head and neck squamous cell carcinoma (HNSCC) patients, tyrosine kinase inhibitors such as erlotinib have shown a modest response in clinical trials. Cellular heterogeneity is thought to play an important role in HNSCC therapeutic resistance. Genomic alterations alone cannot explain all resistance mechanisms at play in a heterogeneous system. It is thus important to understand the biochemical mechanisms associated with drug resistance to determine potential strategies to achieve clinical response. We investigated tyrosine kinase signaling networks in erlotinib-resistant cells using quantitative tyrosine phosphoproteomics approach. We observed altered phosphorylation of proteins involved in cell adhesion and motility in erlotinib-resistant cells. Bioinformatics analysis revealed enrichment of pathways related to regulation of the actin cytoskeleton, extracellular matrix (ECM)-receptor interaction, and endothelial migration. Of importance, enrichment of the focal adhesion kinase (PTK2) signaling pathway downstream of EGFR was also observed in erlotinib-resistant cells. To the best of our knowledge, we present the first report of tyrosine phosphoproteome profiling in erlotinib-resistant HNSCC, with an eye to inform new ways to achieve clinical response. Our findings suggest that common signaling networks are at play in driving resistance to EGFR-targeted therapies in HNSCC and other cancers. Most notably, our data suggest that the PTK2 pathway genes may potentially play a significant role in determining clinical response to erlotinib in HNSCC tumors.


4-1BB and OX40 dual costimulation synergistically stimulate primary specific CD8 T cells for robust effector function.
CD40, 4-1BB, and OX40 are costimulatory molecules belonging to the TNF/nerve growth factor superfamily of receptors. We examined whether simultaneous costimulation affected the responses of T cells using several different in vivo tracking models in mice. We show that enforced dual costimulation through 4-1BB and OX40, but not through CD40, induced profound specific CD8 T cell clonal expansion. In contrast, the response of specific CD4 T cells to dual costimulation was additive rather than synergistic. The synergistic response of the specific CD8 T cells persevered for several weeks, and the expanded effector cells resided throughout lymphoid and nonlymphoid tissue. Dual costimulation through 4-1BB and OX40 did not increase BrdU incorporation nor an increase in the number of rounds of T cell division in comparison to single costimulators, but rather enhanced accumulation in a cell-intrinsic manner. Mechanistically speaking, we show that CD8 T cell clonal expansion and effector function did not require T help, but accumulation in (non)lymphoid tissue was predominantly CD4 T cell dependent. To determine whether this approach would be useful in a physiological setting, we demonstrated that dual costimulation mediated rejection of an established murine sarcoma. Importantly, effector function directed toward established tumors was CD8 T cell dependent while being entirely CD4 T cell independent, and the timing of enforced dual costimulation was exquisitely regulated. Collectively, these data suggest that simultaneous dual costimulation through 4-1BB and OX40 induces a massive burst of CD8 T cell effector function sufficient to therapeutically treat established tumors even under immunocompromising conditions.


Validating the Manchester Acute Coronary Syndromes (MACS) and Troponin-only Manchester Acute Coronary Syndromes (T-MACS) rules for the prediction of acute myocardial infarction in patients presenting to the emergency department with chest pain.
The Manchester Acute Coronary Syndromes (MACS) rule and the Troponin-only MACS (T-MACS) rule risk stratify patients with suspected acute coronary syndrome (ACS). This observational study sought to validate and compare the MACS and T-MACS rules for assessment of acute myocardial infarction (AMI). Prospectively collected data from twoEDs in Australia and New Zealand were analysed. Patients were assigned a probability of ACS based on the MACS and T-MACS rules, incorporating high-sensitivity troponin T, heart-type fatty acid-binding protein, ECG results and clinical symptoms. Patients were then deemed very low risk, low risk, intermediate or high risk if their MACS probability was less than 2%, between 2% and 5%, between 5% and 95% and greater than 95%, respectively. The primary endpoint was 30-day diagnosis of AMI. The secondary endpoint was 30-day major adverse cardiac event (MACE) including AMI, revascularisation or coronary stenosis (>70%). Sensitivity, specificity and predictive values were calculated to assess the accuracy of the MACS and T-MACS rules. Of the 1244 patients, 114 (9.2%) were diagnosed with AMI and 163 (13.1%) with MACE. The MACS and T-MACS rules categorised 133 (10.7%) and 246 (19.8%) patients, respectively, as very low risk and potentially suitable for early discharge from the ED. There was one false negative case for both rules making sensitivity 99.1% (95.2%-100%). MACS and T-MACS accurately risk stratify very low risk patients. The T-MACS rule would allow for more patients to be discharged early. The potential for missed MACE events means that further outpatient testing for coronary artery disease may be required for patients identified as very low risk.


Improving low-performing high schools: searching for evidence of promise.
Noting that many of the nation's high schools are beset with major problems, such as low student reading and math achievement, high dropout rates, and an inadequate supply of effective teachers, Steve Fleischman and Jessica Heppen survey a range of strategies that educators have used to improve low-performing high schools. The authors begin by showing how the standards-based school reform movement, together with the No Child Left Behind Act requirement that underperforming schools adopt reforms supported by scientifically based research, spurred policy makers, educators, and researchers to create and implement a variety of approaches to attain improvement. Fleischman and Heppen then review a number of widely adopted reform models that aim to change "business as usual" in low-performing high schools. The models include comprehensive school reform programs, dual enrollment and early college high schools, smaller learning communities, specialty (for example, career) academies, charter high schools, and education management organizations. In practice, say the authors, many of these improvement efforts overlap, defying neat distinctions. Often, reforms are combined to reinforce one another. The authors explain the theories that drive the reforms, review evidence of their reforms' effectiveness to date, and suggest what it will take to make them work well. Although the reforms are promising, the authors say, few as yet have solid evidence of systematic or sustained success. In concluding, Fleischman and Heppen emphasize that the reasons for a high school's poor performance are so complex that no one reform model or approach, no matter how powerful, can turn around low-performing schools. They also stress the need for educators to implement each reform program with fidelity to its requirements and to support it for the time required for success. Looking to the future, the authors suggest steps that decision makers, researchers, and sponsors of research can take to promote evidence-based progress in education.


Penalized maximum-likelihood image reconstruction using space-alternating generalized EM algorithms.
Most expectation-maximization (EM) type algorithms for penalized maximum-likelihood image reconstruction converge slowly, particularly when one incorporates additive background effects such as scatter, random coincidences, dark current, or cosmic radiation. In addition, regularizing smoothness penalties (or priors) introduce parameter coupling, rendering intractable the M-steps of most EM-type algorithms. This paper presents space-alternating generalized EM (SAGE) algorithms for image reconstruction, which update the parameters sequentially using a sequence of small "hidden" data spaces, rather than simultaneously using one large complete-data space. The sequential update decouples the M-step, so the maximization can typically be performed analytically. We introduce new hidden-data spaces that are less informative than the conventional complete-data space for Poisson data and that yield significant improvements in convergence rate. This acceleration is due to statistical considerations, not numerical overrelaxation methods, so monotonic increases in the objective function are guaranteed. We provide a general global convergence proof for SAGE methods with nonnegativity constraints.


A novel inhibitor of signal transducers and activators of transcription 3 activation is efficacious against established central nervous system melanoma and inhibits regulatory T cells.
Activation of signal transducers and activators of transcription 3 (STAT3) has been identified as a central mediator of melanoma growth and metastasis. We hypothesized that WP1066, a novel STAT3 blockade agent, has marked antitumor activity, even against the melanoma metastasis to brain, a site typically refractory to therapies. The antitumor activities and related mechanisms of WP1066 were investigated both in vitro on melanoma cell lines and in vivo on mice with subcutaneously syngeneic melanoma or with intracerebral melanoma tumors. WP1066 achieved an IC(50) of 1.6, 2.3, and 1.5 mumol/L against melanoma cell line A375, B16, and B16EGFRvIII, respectively. WP1066 suppressed the phosphorylation of Janus-activated kinase 2 and STAT3 (Tyr705) in these cells. Tumor growth in mice with subcutaneously established syngeneic melanoma was markedly inhibited by WP1066 compared with that in controls. Long-term survival (>78 days) was observed in 80% of mice with established intracerebral syngeneic melanoma treated with 40 mg/kg of WP1066 in contrast to control mice who survived for a median of 15 days. Although WP1066 did not induce immunologic memory or enhance humoral responses to EGFRvIII, this compound reduced the production of immunosuppressive cytokines and chemokines (transforming growth factor-beta, RANTES, MCP-1, vascular endothelial growth factor), markedly inhibited natural and inducible Treg proliferation, and significantly increased cytotoxic immune responses of T cells. The antitumor cytotoxic effects of WP1066 and its ability to induce antitumor immune responses suggest that this compound has potential for the effective treatment of melanoma metastatic to brain.


Mitochondria-dependent regulation of Kv currents in rat pulmonary artery smooth muscle cells.
Voltage-gated K(+) (Kv) channels are important in the regulation of pulmonary vascular function having both physiological and pathophysiological implications. The pulmonary vasculature is essential for reoxygenation of the blood, supplying oxygen for cellular respiration. Mitochondria have been proposed as the major oxygen-sensing organelles in the pulmonary vasculature. Using electrophysiological techniques and immunofluorescence, an interaction of the mitochondria with Kv channels was investigated. Inhibitors, blocking the mitochondrial electron transport chain at different complexes, were shown to have a dual effect on Kv currents in freshly isolated rat pulmonary arterial smooth muscle cells (PASMCs). These dual effects comprised an enhancement of Kv current in a negative potential range (manifested as a 5- to 14-mV shift in the Kv activation to more negative membrane voltages) with a decrease in current amplitude at positive potentials. Such effects were most prominent as a result of inhibition of Complex III by antimycin A. Investigation of the mechanism of antimycin A-mediated effects on Kv channel currents (I(Kv)) revealed the presence of a mitochondria-mediated Mg(2+) and ATP-dependent regulation of Kv channels in PASMCs, which exists in addition to that currently proposed to be caused by changes in intracellular reactive oxygen species.


Personal Nonverbal Repertoires in facial displays and their relation to individual differences in social and emotional styles.
ABSTRACTResearch on individual differences in the occurrence of relatively frequent facial displays is scarce. We examined whether (1) individuals' spontaneous facial expressions show a relatively frequent pattern of AUs (referred to as Personal Nonverbal Repertoires or PNRs), and (2) whether these patterns are associated with self-reported social and emotional styles. We videotaped 110 individuals during 10 minutes in 2 different contexts and manually FACS coded 18 AUs. Subsequently, participants completed questionnaires regarding individual differences in social and emotional styles: BIS/BAS, interpersonal orientation, conflict handling style, and emotion regulation (reliably reduced to 4 factors: Yielding, Forcing, Compromising and Extraversion). We found five patterns of PNRs: Smiling (AU6,12), Partial Blinking, Drooping (AU41, 63), Tensed (AU1 + 2, 4, 7, 23), and Eyes widening (AU5). Three PNRs showed weak to moderate correlations with individual differences in social and emotional styles (based on EFA): Smiling is associated with Compromising and Extraversion, Drooping with Yielding, and Partial Blinking is negatively correlated with Extraversion. These findings suggest that some of an individual's frequent facial action patterns are associated with specific styles in social and emotional interactions.


Antibodies to the mycobacterial 65-kd heat-shock protein are reactive with synovial tissue of adjuvant arthritic rats and patients with rheumatoid arthritis and osteoarthritis.
The expression of 65-kd mycobacterial heat-shock protein (HSP)-related antigens in synovial membrane from rats and humans with arthritis was studied using three monoclonal antibodies and one polyclonal antiserum directed to antigens of mycobacteria. The antibodies labeled synovial tissue sections from both adjuvant arthritis (AA) rats and from patients with either rheumatoid arthritis (RA) or osteoarthritis (OA); especially the synovial lining cells appeared to be positive. The cytoplasmic staining patterns in rats and humans were essentially the same and were not related to the extent of inflammation ie, the size of lymphoid infiltration. In control tissues no cytoplasmic staining was observed. The results suggest a role for a 65-kd HSP or a cross-reactive molecule in the immunopathologic process of arthritic disease.


Plant Endemism Centres and Biodiversity Hotspots in Greece.
Biodiversity hotspots (BH) cover a small fraction of the Earth's surface, yet host numerous endemics. Human-induced biodiversity loss has been increasing worldwide, despite attempts to halt the extinction crisis. There is thus an urgent need to efficiently allocate the available conservation funds in an optimised conservation prioritization scheme. Identifying BH and endemism centres (EC) is therefore a valuable tool in conservation prioritization and planning. Even though Greece is one of the most plant species-rich European countries, few studies have dealt with the identification of BH or EC and none has ever incorporated phylogenetic information or extended to the national scale. Consequently, we are unaware of the extent that Special Areas of Conservation (SAC) of the Natura 2000 network efficiently protect Greek plant diversity. Here, we located for the first time at a national scale and in a phylogenetic framework, the areas serving as BH and EC, and assessed the effectiveness of the Greek SAC in safeguarding them. BH and EC are mainly located near mountainous areas, and in areas supposedly floristically impoverished, such as the central Aegean islands. A critical re-assessment of the Greek SAC might be needed to minimize the extinction risk of the Greek endemics, by focusing the conservation efforts also on the BH and EC that fall outside the established Greek SAC.


Is gender a predictive factor for satisfaction among patients undergoing sympathectomy to treat palmar hyperhidrosis?
Video-assisted thoracic sympathectomy (VATS) is currently the procedure of choice for the definitive treatment of primary hyperhidrosis because it is an effective, safe, and minimally invasive method. The aim of VATS treatment is to improve the quality of life through the reduction of excessive sudoresis. The purpose of this study was to assess the quality of life after VATS for treating palmar hyperhidrosis according to gender. A total of 1044 patients who submitted to the surgical treatment for palmar hyperhidrosis from June 2000 to February 2008 were retrospectively evaluated. The patients were divided into two groups according to gender [719 (68.8%) females and 325 (31.2%) males]. There are no statistically significant differences between genders with regard to the quality of life in palmar hyperhidrosis patients (p = 0.726). In the interview that was performed 30 days after surgery, the quality of life in the two groups had improved, with no statistical difference between the groups. Patients with palmar hyperhidrosis present with an improvement in the quality of life after VATS regardless of gender.


Analysis of synaptic gene expression in the neocortex of primates reveals evolutionary changes in glutamatergic neurotransmission.
Increased relative brain size characterizes the evolution of primates, suggesting that enhanced cognition plays an important part in the behavioral adaptations of this mammalian order. In addition to changes in brain anatomy, cognition can also be regulated by molecular changes that alter synaptic function, but little is known about modifications of synapses in primate brain evolution. The aim of the current study was to investigate the expression patterns and evolution of 20 synaptic genes from the prefrontal cortex of 12 primate species. The genes investigated included glutamate receptors, scaffolding proteins, synaptic vesicle components, as well as factors involved in synaptic vesicle release and structural components of the nervous system. Our analyses revealed that there have been significant changes during primate brain evolution in the components of the glutamatergic signaling pathway in terms of gene expression, protein expression, and promoter sequence changes. These results could entail functional modifications in the regulation of specific genes related to processes underlying learning and memory.


PopED lite: An optimal design software for preclinical pharmacokinetic and pharmacodynamic studies.
Optimal experimental design approaches are seldom used in preclinical drug discovery. The objective is to develop an optimal design software tool specifically designed for preclinical applications in order to increase the efficiency of drug discovery in vivo studies. Several realistic experimental design case studies were collected and many preclinical experimental teams were consulted to determine the design goal of the software tool. The tool obtains an optimized experimental design by solving a constrained optimization problem, where each experimental design is evaluated using some function of the Fisher Information Matrix. The software was implemented in C++ using the Qt framework to assure a responsive user-software interaction through a rich graphical user interface, and at the same time, achieving the desired computational speed. In addition, a discrete global optimization algorithm was developed and implemented. The software design goals were simplicity, speed and intuition. Based on these design goals, we have developed the publicly available software PopED lite (http://www.bluetree.me/PopED_lite). Optimization computation was on average, over 14 test problems, 30 times faster in PopED lite compared to an already existing optimal design software tool. PopED lite is now used in real drug discovery projects and a few of these case studies are presented in this paper. PopED lite is designed to be simple, fast and intuitive. Simple, to give many users access to basic optimal design calculations. Fast, to fit a short design-execution cycle and allow interactive experimental design (test one design, discuss proposed design, test another design, etc). Intuitive, so that the input to and output from the software tool can easily be understood by users without knowledge of the theory of optimal design. In this way, PopED lite is highly useful in practice and complements existing tools.


Self-tuning adaptive control for an industrial weigh belt feeder.
An industrial weigh belt feeder is used to transport solid materials into a manufacturing process at a constant feedrate. It exhibits nonlinear behavior because of motor friction, saturation, and quantization noise in the measurement sensors. To overcome the nonlinearities, a simple yet effective method of controller autotuning, an indirect self-tuning regulator, was designed and implemented for an industrial weigh belt feeder. Implementation issues are discussed and experimental results show the effectiveness of the adaptive controller for several different reference inputs. Also, the performance of the indirect self-tuning regulator is compared with that of a fuzzy logic controller for the same application.


Resident-as-teacher: a suggested curriculum for emergency medicine.
Resident teaching is a competency that must be recognized, developed, and assessed. The ACGME core competencies include the role of physician as educator to "educate patients and families" and to "facilitate the learning of students and other health care professionals." Residents spend a significant proportion of their time in teaching activities, and students report achieving much of their clinical learning from their interactions with residents. Although many residents enjoy their critical role as teacher, many do not feel well prepared to teach. This article summarizes a preliminary curriculum of modules for a resident teacher-training program for emergency medicine residents. The goal of these modules is to provide learning objectives and an initial structure through which residents could improve basic teaching skills. Many of these skills are adaptable to residents' interactions with each other and with students, other healthcare professionals, and patients. Each module and corresponding teaching exercises can be found at http://www.saem.org.


Can prostate specific antigen derivatives and pathological parameters predict significant change in expectant management criteria for prostate cancer?
A prior report established that pretreatment criteria based on clinical and biopsy pathology parameters can predict men who harbor small volume prostate cancer who might be followed expectantly. However, some of these men will exhibit disease progression with time and will need definitive therapy. To detect those in whom disease may progress, repeat prostate biopsies are performed at yearly intervals. Therefore, we determined whether biomarkers could be used to determine those in whom disease is likely to progress and thus those who require definitive therapy. Initial and repeat biopsy information along with transrectal ultrasound measurements of gland volume, total prostate specific antigen (PSA), %free PSA (%fPSA) and total PSA velocity were evaluated in 78 men, 45 from the prior study, in whom disease was being managed expectantly. Univariate and multivariate logistic regression analyses determined variables that predicted a favorable tumor burden based on biopsy pathology status at each subsequent repeat biopsy. A Cox proportional hazards model was produced using 67 of 78 evaluable cases having adequate temporal data to predict hazard ratios for conversion from favorable to unfavorable tumor burden status. At time zero for 78 patients %fPSA, total PSA, and gland volume univariately and multivariately differentiated unfavorable and favorable tumor burden groups (p <0.05). The receiver operator characteristic area under the curve (ROC-AUC) was 83%. At the first followup biopsy 17 of 67 (25.4%) men converted to unfavorable tumor burden status. The %fPSA, PSA velocity and gland volume univariately distinguished these 2 groups (p <0.05) with 82% ROC-AUC. At second repeat biopsy 6 of 36 (16.7%) men converted to unfavorable tumor burden status and the ROC-AUC was 76%. Of the 14 men who had a third repeat biopsy all demonstrated favorable tumor burden status. A Cox proportional hazards model stratified the 67 of 78 men into high (48) and low risk (19) groups based on %fPSA at a 20% cutoff (p <0.01). Classification and regression tree analysis using logistic regression multivariately selected variables predicted favorable tumor burden status with an accuracy that ranged from 75% to 84% during our study. PSA velocity, %fPSA and gland volume information improves the prediction of men undergoing expectant management who are more likely to have small volume disease based on a 12-core biopsy interpretation within the time of our observations. %fPSA proved to be a valuable marker to stratify the 2 risk groups. Therefore, based on these factors it may be possible to consider deferment of repeat prostate biopsy until adverse results are detected. This rational approach to the management of prostate cancer in older men with small volume cancer seems to be a reasonable strategy.


Bronchoscopic device intervention in chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease is a heterogeneous syndrome associated with varying degrees of parenchymal emphysema and airway inflammation resulting in decreased expiratory flow, lung hyperinflation, and symptoms leading to decreased exercise tolerance and quality of life. Impairment in lung function and quality of life persists following guideline-based medical therapy, thus surgical and minimally invasive bronchoscopic approaches were developed to address this unmet need. We offer a narrative review of the available technologies. Although lung volume reduction surgery has been shown to improve survival in appropriately selected patients, it is infrequently performed. Less invasive bronchoscopic procedures have thus been explored including endobronchial valves, coils, lung sealant, thermal vapor, and other airway approaches. Selection criteria including severity of physiologic and radiographic impairment, degree of lung hyperinflation, presence of intact fissures, type of symptoms, and presence of comorbidities are critical in selecting appropriate candidates. Recent advances in minimally invasive approaches to lung volume reduction have offered alternatives to surgical approaches. Two endobronchial valve devices are Food and Drug Administration approved for clinical use, and investigations into alternative bronchoscopic therapies to treat both emphysema and chronic bronchitis have been performed or are currently underway. Notably, each of these treatments requires unique selection criteria and thus a personalized approach to treatment.


An unusual missile-type head injury caused by a stone: case report and medicolegal perspectives.
Missile head injury is predominantly caused by firearms; however, small blunt objects such as a stone can be propelled into the air and cause a low-velocity-type missile injury, as described in this case report. Since the cerebral damage in low-velocity missile injuries is usually focal, there might not be disturbance of consciousness until secondary brain damage occurs; therefore, adequate medical supervision is necessary to prevent and treat potentially fatal complications in a timely manner. This is a rare case of a penetrating missile wound of the head, most likely caused by the use of a stone propelled by a slingshot that penetrated the skull and lacerated the brain with the stone embedded within the substance of the brain. The deceased died at home 2 days later from focal suppurative meningitis with cerebral abscess formation and a subdural hemorrhage.


Transition readiness in adolescents and young adults with chronic rheumatic disease in Oman: today's needs and future challenges.
In Oman, the ""transition" of health care of adolescents to adult care occurs at a young age, like many other GCC countries for cultural reasons. In order to address this concern, this study was conducted to determine the transition readiness skills of adolescents and young adults with childhood onset rheumatic diseases using a cross-cultural adaptation of the UNC TRxANSITION scale. We used a professionally translated/back translated, provider-administered UNC TRxANSITION Scale. This 32-question scale measures HCT in 10 domains including knowledge about diagnosis or treatment, diet, reproductive health, school/work, insurance, ability to self-manage and identification of new health providers. The maximum transitional score of 10, was categorized as low (1-4), moderate (4 - 7) and high (7 -10) transitional readiness scores. We enrolled 81 Omani adolescents and young adults (AYA) with chronic childhood onset rheumatic diseases. The cohort consisted of 79% females, with mean age of 15.8 years (± 3.53) and mean disease duration of 6.95 years (± 4.83). Our cohort's overall mean score is low 5.22 (±1.68). Only 14.8% of the cohort achieved a high transition score (≥7). Significant direct relationship was observed between age and the mean transition readiness score (r = .533, P < .001). The mean transition readiness score in the younger age group (10-13 years) was 4.07 (±1.29), the middle age group (14-18 years) was 5.43 (±1.27), while the older age group (19-21 year), was 6.12 (±1.81). Mean transition score of youngest age group was found to be significantly lower than the other two age groups (p = .003). Overall, the transition readiness of AYA in Oman is low compared to other western countries indicating the need to initiate a health care transition preparation program for patients with chronic diseases across the country. In addition, we need to establish regional guidelines to address the transfer and transition policies to be in line to international recommendations. As transition continues after transfer, and is preferably guided by adolescent developmental status rather than chronological age, it would be preferable to refer to the transition and transfer policies 9rather than transitional age policy) to be in line to international recommendations.


Milestones in the development of a vestibular implant.
Bilateral vestibular deficits exist and their prevalence is more important than believed by the medical community. Their severe impact has inspired several teams to develop technical solutions in an attempt to rehabilitate patients. A particularly promising pathway is the vestibular implant. This article describes the main milestones in this field, mainly focusing on work conducted in human patients. There have been substantial research efforts, first in animals and more recently in humans, toward the development of vestibular implants. Humans have demonstrated surprising adaptation capabilities to the artificial vestibular signal. Today, the possibility of restoring vestibular reflexes, particularly the vestibulo-ocular reflex, and even achieving useful function in close-to-reality tasks (i.e. improving visual abilities while walking) have been demonstrated in humans. The vestibular implant opens new perspectives, not only as an effective therapeutic tool, but also pushes us to go beyond current knowledge and well-established clinical concepts.


[Experimental-morphological study of the anti-inflammatory action of ozone-perfluorane complex application].
By ozone treatment of perfluorane with the help of ozone medical plant UOTA-60-01 of the firma Medozon (Russia) the ozone-perfluorane complex was received with ozone concentration 120+/-15 ug/ml. In experiments on rats with infected skin wounds it was shown that wound drainage with ozone-perfluorane complex led to 1 month period of inflammatory-necrotic process subsiding and partial or complete wound epithelization. In animals with infected defects of femoral bone under the influence of ozone-perfluorane complex in the bone wound there was seen consequent (from the beginning of experiment to each successive term) inflammation intensity reduction. In the forefront the processes of reparative osteogenesis, differentiation and secondary rebuilding of newly formed bone structures came out. Local use of ozone-perfluorane complex in the region of infected apical periodontium in experiments on dogs gave expressed positive effect with sharp reduction of inflammatory infiltrate intensity and extension in periodontal tissues and full disappearance of destructive manifestations; the processes of injured apical periodontal tissues organization were developed with signs of their sclerotization. As the result of reparative osteogenesis process activation the intensive formation of new bone tissue happened that led to periodontal groove constriction in the periapical region.


Factors Related to Water Filter Use for Drinking Tap Water at Home and Its Association With Consuming Plain Water and Sugar-Sweetened Beverages Among U.S. Adults.
To examine factors associated with water filter use (WFU) for drinking tap water at home and its association with consuming plain water and sugar-sweetened beverages (SSBs). Quantitative, cross-sectional study. The 2018 SummerStyles survey data. U.S. adults (≥18 years; N=4042). Outcomes were intake of plain water (tap/bottled water) and SSBs. Exposure was WFU (yes, no, not drinking tap water at home). Covariates included sociodemographics, weight status, Census regions, and home ownership status. We used multivariable logistic regressions to estimate adjusted odds ratios (AOR) and 95% confidence interval (CI) for consuming tap water, bottled water, or total plain water >3 cups/day (vs. ≤3 cups) and SSBs ≥1 time/day (vs. <1 time) by WFU. Overall, 36% of adults reported using a filter for drinking tap water at home; 14% did not drink tap water at home. Hispanics had significantly higher odds of using a water filter (AOR=1.50, 95% CI=1.14-1.98) vs non-Hispanic White. Factors significantly associated with lower odds of WFU were lower education (AOR=.69, 95% CI=.55-.86 for ≤high school; AOR=.78, 95% CI=.64-.95 for some college, vs college graduate), not being married (AOR=.81, 95% CI=.66-.98, vs married/domestic partnership), and lower household income (AOR=.68, 95% CI=.68-.90 for <$35,000, vs ≥$100,000). Using a water filter was associated with higher odds of drinking >3 cups/day of tap water (AOR=1.33, 95% CI=1.13-1.56) and lower odds of SSBs ≥1 time/day (AOR=.76, 95% CI=.62-.92). Not drinking tap water at home was associated with higher odds of drinking >3 cups/day bottled water (AOR=3.46, 95% CI=2.70-4.44). WFU was associated with higher tap water intake and lower SSB intake among U.S. adults. WFU was higher among Hispanics, but lower among those with lower education and income and not married adults. Although WFU was associated with healthful beverage habits, additional considerations for WFU may include source water quality, oral health, cost, and proper use.


Dietary iron intake and body iron stores are associated with risk of coronary heart disease in a meta-analysis of prospective cohort studies.
The link between iron intake as well as body iron stores and coronary heart disease (CHD) has been contentiously debated, and the epidemiologic evidence is inconsistent. We aimed to quantitatively summarize the literature on the association between dietary iron intake/body iron stores and CHD risk by conducting a meta-analysis of prospective cohort studies. PubMed was used to find studies published through June 2013 in peer-reviewed journals. Embase or a hand search of relevant articles was used to obtain additional articles. The pooled RRs of CHD incidence and mortality with 95% CIs were calculated by using either a random-effects or fixed-effects model, as appropriate. Twenty-one eligible studies (32 cohorts) including 292,454 participants with an average of 10.2 y of follow-up were included. Heme iron was found to be positively associated with CHD incidence (RR: 1.57; 95% CI: 1.28, 1.94), whereas total iron was inversely associated (RR: 0.85; 95% CI: 0.73, 0.999). Neither heme-iron nor total iron intakes were significantly associated with CHD mortality. Both transferrin saturation and serum iron were inversely related to CHD incidence [RR (95% CI): 0.76 (0.66, 0.88) and 0.68 (0.56, 0.82), respectively], but only transferrin saturation was inversely associated with CHD mortality (RR: 0.85; 95% CI: 0.73, 0.99). In conclusion, total iron intake and serum iron concentrations were inversely associated with CHD incidence, but heme iron intake was positively related to CHD incidence. Elevated serum transferrin saturation concentration was inversely associated with both CHD incidence and mortality. Future research is needed to establish the causal relation and to elucidate potential mechanisms.


Hierarchical Sandwich-Like Structure of Ultrafine N-Rich Porous Carbon Nanospheres Grown on Graphene Sheets as Superior Lithium-Ion Battery Anodes.
A sandwich-like, graphene-based porous nitrogen-doped carbon (PNCs@Gr) has been prepared through facile pyrolysis of zeolitic imidazolate framework nanoparticles in situ grown on graphene oxide (GO) (ZIF-8@GO). Such sandwich-like nanostructure can be used as anode material in lithium ion batteries, exhibiting remarkable capacities, outstanding rate capability, and cycling performances that are some of the best results among carbonaceous electrode materials and exceed most metal oxide-based anode materials derived from metal orgainc frameworks (MOFs). Apart from a high initial capacity of 1378 mAh g(-1) at 100 mA g(-1), this PNCs@Gr electrode can be cycled at high specific currents of 500 and 1000 mA g(-1) with very stable reversible capacities of 1070 and 948 mAh g(-1) to 100 and 200 cycles, respectively. At a higher specific current of 5000 mA g(-1), the electrode still delivers a reversible capacity of over 530 mAh g(-1) after 400 cycles, showing a capacity retention of as high as 84.4%. Such an impressive electrochemical performance is ascribed to the ideal combination of hierarchically porous structure, a highly conductive graphene platform, and high-level nitrogen doping in the sandwich-like PNCs@Gr electrode obtained via in situ synthesis.


A Novel Outbred Mouse Model to Study Lung Memory Immunological Response Induced by Pertussis Vaccines.
Lung tissue resident memory (TRM) T cells can provide rapid and effective protective immunity against respiratory pathogens such as Bordetella pertussis We assessed an outbred CD1 mouse model and i.m. immunization to study vaccine-induced immune memory, using pertussis vaccines as an example. The phenotypes of cells from the lungs of CD1 mice that had been primed with either i.m. whole-cell B. pertussis (wP), acellular B. pertussis (aP) vaccines or buffer (unvaccinated) and challenged with B. pertussis were determined using flow cytometry and immunohistology. We observed a rapid and high increase of CD4+T cells expressing TRM markers by flow cytometry, supported by immunohistology observations, in lungs from wP-immunized mice. Priming mice with wP vaccine induced a more potent CD4+ response in lungs following B. pertussis challenge than priming with aP vaccine, although both were less potent than that observed in primoinfected mice. We also observed for the first time, to our knowledge, that CD8+ and γδ+ TRM-like T cell responses were induced in lungs of wP-primed mice postinfection. This novel outbred CD1 mouse model with i.m. immunization that enabled us to study vaccine-induced B. pertussis-specific memory T cells in lungs could be useful for evaluating candidate parenteral vaccines against B. pertussis or others pulmonary pathogens.


Effects of estrogen receptor expression on growth and transformation of cells overexpressing neu.
The mechanism by which breast cancers progress to hormone independence does not always require the loss of estrogen receptor(ER) expression or function. Cellular alterations that disturb the normal pathway of estrogen-regulated growth may contribute to a state of hormone independence. We and others have described an inverse relationship between estrogen stimulation of ER(+) breast cancer cell lines and their expression of neu. Amplification and overexpression of neu are known to enhance cellular transformation and increase the metastatic potential of cancer cells. Clinically, they are also correlated with more aggressive tumor phenotypes. Therefore, expression of neu may represent a key regulatory point in estrogenic control of cellular growth and transformation. In this communication we demonstrate that the presence of E2/ER can repress transformation of NIH/3T3 cells by the neu oncogene. Furthermore, we have investigated the effects of E2/ER on growth and transformation of an ER(+), neu-overexpressing breast cancer cell line. We report that the presence of E2/ER in these cells leads to repression of the transformed phenotype (as measured by anchorage-independent growth) while stimulating cellular proliferation (in monolayer culture) and propose a model for the role of neu in progression to hormone independence based on these results.


A reverse metabolic approach to weaning: in silico identification of immune-beneficial infant gut bacteria, mining their metabolism for prebiotic feeds and sourcing these feeds in the natural product space.
Weaning is a period of marked physiological change. The introduction of solid foods and the changes in milk consumption are accompanied by significant gastrointestinal, immune, developmental, and microbial adaptations. Defining a reduced number of infections as the desired health benefit for infants around weaning, we identified in silico (i.e., by advanced public domain mining) infant gut microbes as potential deliverers of this benefit. We then investigated the requirements of these bacteria for exogenous metabolites as potential prebiotic feeds that were subsequently searched for in the natural product space. Using public domain literature mining and an in silico reverse metabolic approach, we constructed probiotic-prebiotic-food associations, which can guide targeted feeding of immune health-beneficial microbes by weaning food; analyzed competition and synergy for (prebiotic) nutrients between selected microbes; and translated this information into designing an experimental complementary feed for infants enrolled in a pilot clinical trial ( http://www.nourishtoflourish.auckland.ac.nz/ ). In this study, we applied a benefit-oriented microbiome research strategy for enhanced early-life immune health. We extended from "classical" to molecular nutrition aiming to identify nutrients, bacteria, and mechanisms that point towards targeted feeding to improve immune health in infants around weaning. Here, we present the systems biology-based approach we used to inform us on the most promising prebiotic combinations known to support growth of beneficial gut bacteria ("probiotics") in the infant gut, thereby favorably promoting development of the immune system.


[Predicting of the effectiveness of radiotherapy and chemoradiotherapy for cancer patients].
Studies carried out on samples of tumor and non-tumor tissue indicate that markers of radiosensitivity for predicting individual patient response to the planned radiation therapy may be the indicators of apoptosis and molecular profiles read from the DNA of patients. At present there is developed a technology for rapid and economical determining of indicators for the reasonable use of radiation therapy in the radiological practice in patients with breast cancer, bladder cancer and malignant glioblastomas by means of an evaluation of radiosensitivity of the DNA of blood.


Urinary continence appears to enhance social participation and intimate relations in adolescents with myelomeningocele.
The majority of adults with myelomeningocele (MMC) in Western Sweden use incontinence pads. There is an ongoing discussion as to whether continence improves the quality of life (QoL) in individuals with MMC as it has been hard to establish that an increase in QoL measured by generic health-related quality of life (HRQoL) instruments is achieved by continence surgery. The hypotheses are that patients who are actively involved in a urotherapy/urology program are more continent than patients who are not and that urinary continence is one of the conditions required to enable social participation and physical intimacy. All 25 individuals in Western Sweden with MMC (15 males) aged 16-18 years were involved in this cross-sectional, prospectively designed study of urinary and fecal continence. During interviews, questions were asked about the following: clean intermittent catheterization (CIC) and bowel regimens, the need for reminders or help from an assistant, social participation, and physical intimacy with a partner. In the group, overall 17 of 25 (68%) had achieved urinary continence, 19 of 25 (76%) had a medical history of fecal continence, and 14 of 25 (56%) had no prescription for incontinence pads. Those who were urinary continent (17) included all nine patients who had received continence surgery in addition to six patients taking anticholinergics and two following the CIC procedure only. Urinary incontinence due to sphincter insufficiency was found in eight individuals, all of whom declined surgical treatment. All individuals (25/25) physically catheterized themselves, and 15/25 (60%) performed the fecal elimination regimen independently. Twelve individuals participated actively in social life, and eight of them had, or had had, a partner. All these 12 were urinary continent, and all but one were able to follow a fecal elimination regimen independently. Three of the 12 said they were fecal incontinent but knew how to become continent by following the prescribed fecal elimination regimen. Studies in this patient group have shown that incontinence means that it's harder to live a healthy adult life. Children too worry about incontinence episodes at school, and 70% consider urinary incontinence a problem. A limitation in the study is the small population, something often seen in rare diseases. With standardized follow-up, active treatment strategy and uro/bowel therapy, the urinary continence rate in adolescents with MMC at the study center is high compared with adults with MMC in Sweden. It appears that urinary continence is important in enabling successful participation in social life and in intimate physical relations with others.


Time-dependent axonal impairment in experimental model of brain oedema.
Clinically very serious condition of ischaemia and brain injury which are often associated with brain oedema is frequently accompanied by the impairment of the structural integrity of axons. We wondered whether the brain oedema (without ischemia brain injury) can induce structural axonal impairment. Brain oedema was induced by osmotic blood-brain barrier opening with 20% mannitol applied selectively into the internal carotid. Axonal changes were recognized as signs of myelin disintegration (oedematous vesicles, varicosity, myelin fragmentation) at histological sections stained with Black Gold in hippocampal areas CA1 and CA3 and in the dentate gyrus and cerebral cortex at time intervals of one hour, one day, three days and one week after the oedema induction. Impairment of the structural integrity was identified in myelin sheets in all areas studied in all experimental groups. Whereas in the control group axon were of the uniform diameter, in the experimental groups various forms of myelin disintegration were observed. The progression of myelin damage depended on the time elapsed after the oedema induction. Opening the blood-brain barrier with an osmotic insult induces brain oedema which represents a factor triggering axonal impairment accompanied with myelin changes. The development of axonal changes initiated by brain oedema only (without ischemia brain injury) is a novel observation.


Predictors of impaired renal function among HIV infected patients commencing highly active antiretroviral therapy in Jos, Nigeria.
Kidney disease is a common complication of human immunodeficiency virus (HIV) infection even in the era of antiretroviral therapy, with kidney function being abnormal in up to 30% of HIV-infected patients. We determined the predictors of impaired renal function in HIV-infected adults initiating highly active antiretroviral therapy (HAART) in Nigeria. This was a retrospective study among HIV-1 infected patients attending the antiretroviral clinic at the Jos University Teaching Hospital (JUTH), between November 2005 and November 2007. Data were analysed for age, gender, weight, WHO clinical stage, CD4 count, HIV-1 RNA viral load, HBsAg and anti-HCV antibody status. Estimated glomerular filtration rate (eGFR) was calculated using the Cockcroft-Gault equation. Statistical analysis was done using Epi Info 3.5.1. Data for 491 (294 females and 197 males) eligible patients were abstracted. The mean age of this population was 38.8±8.87 years. One hundred and seventeen patients (23.8%; 95% CI, 20.2-27.9%) had a reduced eGFR (defined as <60 mL/min), with more females than males (28.6% vs. 16.8%; P=0.02) having reduced eGFR. Age and female sex were found to have significant associations with reduced eGFR. Adjusted odds ratios were 1.07 (95% CI, 1.04, 1.10) and 1.96 (95% CI, 1.23, 3.12) for age and female sex, respectively. Older age and female sex are independently associated with a higher likelihood of having lower eGFRs at initiation of HAART among our study population. We recommend assessment of renal function of HIV-infected patients prior to initiation of HAART to guide the choice and dosing of antiretroviral drugs.


Expression of novel-transposon-containing mRNAs in human T cells.
The HERV-H family of endogenous retrovirus like elements is the largest such human family known. Using an HERV-H LTR probe, 6 and 4.5 kb transcripts were detected by Northern blot analysis which were induced in normal peripheral T cells after treatment with phytohaemaglutinin (PHA). Expression was not evident 30 min after treatment with phorbol ester, was increased within 3-4 h after treatment, reached a maximum after 8 h and then declined to low levels 24 h after treatment. Expression was inhibited totally by cycloheximide (10 micromolar) and by the immunosuppressant cyclosporin A (1 microgram/ml). Using probes specific for the U3 and U5 regions of the HERV-H LTR, in combination with internal HERV-H probes, evidence was obtained that the 6 and 4.5 kb transcripts are polyadenylated from an HERV-H LTR. A cDNA library was constructed from T cells which had been treated with PHA for 8 h and a 1.7 kb clone was isolated using the HERV-H LTR probe. The insert contained a novel tandem array of an Alu, a LINE-1 element, two endogenous retroviral LTRs and an A-T-rich sequence. The A-T-rich sequence contained multiple copies of AUUUA mRNA regulatory motifs. Because of its high expression level, defined transcription kinetics, novel cassette-like composition and the presence of conserved mRNA stabilization sequences, we hypothesize that the transcript may play a biological role during T cell activation.


Cerebral density and perfusion measured among heart disease patients with and without stroke.
This investigation was designed to clarify the chronic effects of cardiogenic emboli on cerebral perfusion and tissue densities within remaining noninfarcted brain. Local cerebral perfusion and tissue densities were measured by xenon-contrasted CT scanning and compared by cross-sectional designs among normal volunteers without heart disease (Group C, n = 44), normal volunteers with heart disease (Group N, n = 20), patients with heart disease and lacunar infarctions (Group L, n = 31) and patients with heart disease associated with cardiogenic cerebral embolism (Group E, n = 12). In Group E, remaining cortical and subcortical gray and white matter perfusion were reduced compared to Groups C and N (p = 0.01), but did not differ from Group L, who had similar profiles of risk factor for stroke. In Group E, perfusion was reduced within the thalamus ipsilateral to cortical infarctions (p < 0.05). There were no differences in remaining tissue densities between Groups E and L. It is concluded that reduced cerebral perfusion in noninfarcted regions among patients with cardiogenic emboli appears to be related to atherosclerosis of small cerebral vessels in a similar manner to patients with lacunes, but thalamo-cortical disconnections also contribute to cerebral hypoperfusion.


Thrombus formation in the left atrial appendage in the course of atrial fibrillation.
Thromboembolism in patients with nonvalvular atrial fibrillation is secondary to emboli arising from atrial cavities, particularly left atrial appendage. Stroke Prevention Atrial Fibrillation (SPAF) III study showed washing flow, left appendage ejection fraction, natural echocontrast, and left appendage volume and morphology, as risk parameters of thromboembolism. The authors examined 69 patients by transesophageal echocardiography, subdividing them into 3 groups: 26 patients in sinus rhythm in Group A (Gr.A), 22 patients in atrial fibrillation without thrombi in the left atrial appendage in Group B (Gr.B), 21 patients with tromboembolism and with thrombus in the left atrial appendage (Gr.C). Atrial volume in sinus rhythm (SR) patients (41.9 +/- 23.4 cm3) was lower than the one in Gr.B (86.2 +/- 47.9 cm3, p < 0.001) and Gr.C (78.6 +/- 28.5 cm3, p < 0.01), whereas no difference was found between Gr.B and Gr.C (86.2 vs. 78.6 cm3; p > 0.05). No difference was found between Gr.A and Gr.B left atrial appendage fraction (31.8% versus 29.1%, p > 0.05), whereas it was found related to Gr.C (31.8% versus 15.4% p < 0.01). Flow velocity within left atrial appendage was significantly higher in Gr.A in relation to the other two groups (p < 0.001); flow velocity in Gr.B was lower than in Gr.A but higher than in Gr.C and in all cases such differences were statistically significant (p < 0.001). Gr.A flow duration was approximately twice as much compared to the one in Gr.B (616.8 +/- 94.1 msec vs. 483.3 +/- 172.6 msec, p < 0.01), whereas it was approximately four times higher compared to the one in Gr.C (616.8 +/- 94.1 msec vs. 165.7 +/- 53.7 msec; p < 0.001). Such duration, if related to the corresponding cardiac cycle, indicates the percentage of time during which blood flows through a cycle within the left atrial appendage; this value is about 85% of cardiac cycle in Gr.A, while it is 65% in Gr.B (p < 0.01) and about 21% in Gr.C (p < 0.001). Such results add a new parameter to the ones suggested in the SPAF III study for the evaluation of TE risk, that is flow duration measurement within the left atrial appendage, and its ratio to the cardiac cycle. The availability to measure this parameter, by recording the transesophageal pulse wave sample volume positioned in the atrial appendage, makes the evaluation of TE risk more reliable.