Genetic nurture versus genetic transmission of risk for ADHD traits in the Norwegian Mother, Father and Child Cohort Study.
Identifying mechanisms underlying the intergenerational transmission of risk for attention-deficit/hyperactivity disorder (ADHD) traits can inform interventions and provide insights into the role of parents in shaping their children's outcomes. We investigated whether genetic transmission and genetic nurture (environmentally mediated effects) underlie associations between polygenic scores indexing parental risk and protective factors and their offspring's ADHD traits. This birth cohort study included 19,506 genotyped mother-father-offspring trios from the Norwegian Mother, Father and Child Cohort Study. Polygenic scores were calculated for parental factors previously associated with ADHD, including psychopathology, substance use, neuroticism, educational attainment, and cognitive performance. Mothers reported on their 8-year-old children's ADHD traits (n = 9,454 children) using the Parent/Teacher Rating Scale for Disruptive Behaviour Disorders. We found that associations between ADHD maternal and paternal polygenic scores and child ADHD traits decreased significantly when adjusting for the child polygenic score (pΔβ = 9.95 × 10-17 for maternal and pΔβ = 1.48 × 10-14 for paternal estimates), suggesting genetic transmission of ADHD risk. Similar patterns suggesting genetic transmission of risk were observed for smoking, educational attainment, and cognition. The maternal polygenic score for neuroticism remained associated with children's ADHD ratings even after adjusting for the child polygenic score, indicating genetic nurture. There was no robust evidence of genetic nurture for other parental factors. Our findings indicate that the intergenerational transmission of risk for ADHD traits is largely explained by the transmission of genetic variants from parents to offspring rather than by genetic nurture. Observational associations between parental factors and childhood ADHD outcomes should not be interpreted as evidence for predominantly environmentally mediated effects.


ABO-incompatible pediatric kidney transplantation without antibody removal.
Because of the severe shortage of suitable deceased donors, ABO-incompatible living donor kidney transplantation (ABOi LDKT) is performed even in pediatric recipients in Japan. We performed pediatric ABOi LDKT using rituximab without anti-A/B antibody removal. Thirteen pediatric recipients (mean age 7.4, range 3.4-15.7, four females) whose baseline anti-A/B IgG titers were ≤ × 64 underwent ABOi LDKT without antibody removal and splenectomy between July 2013 and April 2017 at Toho University. Mycophenolate mofetil (MMF) was initiated on day - 10. Rituximab (100 mg) was administered twice. Basiliximab and triple maintenance immunosuppression (calcineurin inhibitor, MMF, and steroids) were administered. Protocol biopsy was performed at 3 months and 1 year after transplantation. We retrospectively compared the clinical outcomes between these recipients and 37 children (mean age 9.0, range 2.6-18.9, 15 female) who underwent ABO-compatible (ABOc) LDKT during the same period. The mean follow-up periods of ABOi and ABOc groups were 31.9 ± 13.5 and 28.8 ± 14.4 months, respectively. In the ABOi group, no clinical acute rejection (AR) was noted and subclinical AR was observed in four patients without evidence of acute antibody-mediated rejection. In the ABOc group, clinical and subclinical AR developed in 3 and 10 patients, respectively. No significant difference was identified for the mean eGFR between the ABOi and ABOc groups (98.3 ± 48.8 vs. 86.9 ± 39.4, P = 0.452 at 3 months; 78.2 ± 21.2 vs. 79.7 ± 21.3, at 1 year, P = 0.830). Death-censored graft survival at follow-up was 100% in the ABOi group and 94.6% in the ABOc group. Patient survival during the follow-up period in both the groups was 100%. Late-onset neutropenia (LON) requiring granulocyte colony-stimulating factor occurred more frequently in the ABOi group than in the ABOc group (4 vs. 0 patients) (P < 0.001). Pre- and post-transplantation antibody removal is not a prerequisite for successful pediatric ABOi LDKT, at least in patients with a low anti-A/B IgG antibody titer. However, LON caused by rituximab should be monitored.


MR image-based measurement of rates of change in volumes of brain structures. Part I: method and validation.
A detailed analysis procedure is described for evaluating rates of volumetric change in brain structures based on structural magnetic resonance (MR) images. In this procedure, a series of image processing tools have been employed to address the problems encountered in measuring rates of change based on structural MR images. These tools include an algorithm for intensity non-uniformity correction, a robust algorithm for three-dimensional image registration with sub-voxel precision and an algorithm for brain tissue segmentation. However, a unique feature in the procedure is the use of a fractional volume model that has been developed to provide a quantitative measure for the partial volume effect. With this model, the fractional constituent tissue volumes are evaluated for voxels at the tissue boundary that manifest partial volume effect, thus allowing tissue boundaries be defined at a sub-voxel level and in an automated fashion. Validation studies are presented on key algorithms including segmentation and registration. An overall assessment of the method is provided through the evaluation of the rates of brain atrophy in a group of normal elderly subjects for which the rate of brain atrophy due to normal aging is predictably small. An application of the method is given in Part II where the rates of brain atrophy in various brain regions are studied in relation to normal aging and Alzheimer's disease.


Correction: miRNA independent hepacivirus variants suggest a strong evolutionary pressure to maintain miR-122 dependence.
[This corrects the article DOI: 10.1371/journal.ppat.1006694.].


A triggered hyperkinesia induced in rats by lesions of the corpus striatum.
The role of the corpus striatum (caudate, putamen, and globus pallidus) in movement control has been suggested to involve the modulation of sensory traffic to downstream motor mechanisms. We report that kainic acid lesions of the posterior corpus striatum, which preferentially spare fibers of passage while destroying striatopallidal neurons, produce a stimulus-sensitive movement pattern in rats that has a highly specific sensory trigger. The triggered choreic movement pattern is not a motor pathology per se, nor a response to diffuse states of arousal or stress, but rather is activated specifically in response to oral sensory stimulation. This sensory-specific hyperkinesia may be relevant to certain human sensorimotor pathologies.


Fabrication of photoluminescent electrically conductive and flame-retardant cellulose fabric incorporating polyaniline/strontium aluminate nanocomposite for a plethora of useful applications.
The pad dry cure method was used to coat linen fibers with a smart nanocomposite that has photoluminescence, electrical conductivity, flame resistance, and hydrophobic properties. Environmentally benign silicone rubber (RTV) was utilized to encapsulate rare-earth activated strontium aluminate nanoparticles (RESAN; 10-18 nm), polyaniline (PANi) and ammonium polyphosphate (APP) into linen surface. The flame resistance of the treated linen fabrics was evaluated for their self-extinguishing capabilities. The flame-retardant qualities of linen were retained for 24 washings. Additionally, the superhydrophobicity of the treated linen has markedly improved upon increasing the concentration of RESAN. The colorless luminous film deposited onto linen surface was excited at 365 nm and emitted a wavelength of 518 nm. In accordance with the results of CIE (Commission internationale de l'éclairage) Lab and luminescence analysis, the photoluminescent linen gave rise to diverse colors, including off-white in daylight, green beneath UV radiation and greenish-yellow in a darkened room. The treated linen displayed sustained phosphorescence, as evidenced by decay time spectroscopy. The bending length and air permeability of linen were evaluated for their mechanical and comfort assessment. Finally, the coated linens exhibited remarkable antibacterial activity along with strong UV protection.


Angle Based Critical Nodes Detection (ABCND) for Reliable Industrial Wireless Sensor Networks.
Node failure in the Wireless Sensor Networks (WSN) topology may lead to economic loss, endanger people, and cause environmental damage. Node reliability can be achieved by adequately managing network topology using structural approaches, where the critical nodes are precisely detected and protected. This paper addresses the problem of critical node detection and presents two-phase algorithms (ABCND). Phase-I, a 2D Critical Node (C-N) detection algorithm, is proposed, which uses only the neighbor's Received Signal Strength Indicator (RSSI) information. In Phase II, a correlation-based reliable RSSI approach is proposed to increase the node resilience against the adversary. The proposed algorithms (ABCND) require O(log(N)) time for convergence and O(δ(logN)) for Critical Node detection, N represents the number of IoT devices, and δ is the cost required to forward the message. We compare our algorithm (ABCND) with the current state-of-the-art on C-N detection algorithms. The simulation result shows that the proposed ABCND algorithm consumes 50% less energy to detect C-N with 90% to 95% accurate Critical Nodes (C-N).


Nanophotonic coherent light-matter interfaces based on rare-earth-doped crystals.
Quantum light-matter interfaces connecting stationary qubits to photons will enable optical networks for quantum communications, precise global time keeping, photon switching and studies of fundamental physics. Rare-earth-ion-doped crystals are state-of-the-art materials for optical quantum memories and quantum transducers between optical photons, microwave photons and spin waves. Here we demonstrate coupling of an ensemble of neodymium rare-earth-ions to photonic nanocavities fabricated in the yttrium orthosilicate host crystal. Cavity quantum electrodynamics effects including Purcell enhancement (F=42) and dipole-induced transparency are observed on the highly coherent (4)I(9/2)-(4)F(3/2) optical transition. Fluctuations in the cavity transmission due to statistical fine structure of the atomic density are measured, indicating operation at the quantum level. Coherent optical control of cavity-coupled rare-earth ions is performed via photon echoes. Long optical coherence times (T2∼100 μs) and small inhomogeneous broadening are measured for the cavity-coupled rare-earth ions, thus demonstrating their potential for on-chip scalable quantum light-matter interfaces.


Association of presence and timing of invasive airway placement with outcomes after pediatric in-hospital cardiac arrest.
Little data exist regarding the association of presence of an invasive airway before cardiac arrest or early placement of an invasive airway after cardiac arrest with outcomes in children who experience in-hospital cardiac arrest. We conducted a retrospective review of patients aged 1 day to 18 years who received cardiopulmonary resuscitation (CPR) for ≥ 1 min in any of the three intensive care units (ICUs) at a tertiary care, academic children's hospital between 2002 and 2010. Specific outcomes evaluated included survival to hospital discharge, return of spontaneous circulation (ROSC), 24-h survival, and good neurological status at hospital discharge. We fitted multivariable logistic regression models to evaluate the association between the presence of an invasive airway prior to cardiac arrest and timing of placement of an invasive airway with these outcomes. Three hundred and ninety-one patients were included. Of these, 197 (51%) patients were already tracheally intubated before the occurrence of cardiac arrest. Median time to intubation was 6 min [interquartile range (IQR): 2, 12] among the 194 patients tracheally intubated following cardiac arrest. We found lower survival to hospital discharge among patients intubated prior to cardiac arrest (intubated vs. non-intubated group, 43% vs. 61%, p < 0.001). After adjusting for patient and event characteristics, presence of an invasive airway prior to cardiac arrest was not associated with a significant improvement in survival to hospital discharge [odds ratio (OR): 0.70, 95% confidence interval (CI): 0.42-1.16, p = 0.17], or good neurological outcomes (OR: 0.60, 95% CI: 0.34-1.05, p = 0.07). Similarly, early placement of an invasive airway after cardiac arrest was also not associated with an improvement in survival to hospital discharge (OR: 1.05, 95% CI: 0.78-1.42, p = 0.73), or good neurological outcomes (OR: 1.08, 95% CI: 0.77-1.53, p = 0.65). Our study demonstrates that presence of an invasive airway prior to cardiac arrest or early placement of an invasive airway after cardiac arrest is not associated with an improvement in survival to hospital discharge or good neurological outcomes. Further study of the relationship between invasive airway management and survival following cardiac arrest is warranted.


Gait Training and Ankle Dorsiflexors in Cerebral Palsy.
Investigators at University of Copenhagen, Denmark, evaluated whether 4 weeks of 30 min daily treadmill training with an incline may facilitate corticospinal transmission and improve control of the ankle joint in 16 children, aged 5-14 years, with cerebral palsy.


5'RARA submicroscopic deletion from new variant translocation involving chromosomes 15, 17, and 18, in a case of acute promyelocytic leukemia.
Submicroscopic deletions of the PML-RARA fusion genes constitute rare rearrangements in acute promyelocytic leukemia (APL). We describe a rare case of APL carrying a novel complex translocation involving chromosomes 15, 17, and 18 associated with a submicroscopic deletion of the 5' part of the RARA gene, as evidenced by fluorescence in situ hybridization (FISH). A PML/RARA dual-fusion probe did not reveal the RARA-PML fusion signal on the der(17q), usually detected in the typical t(15;17). The RARA break-apart probe showed a deletion hybridization pattern with loss of the signal corresponding to the 5' portion of the RARA gene. Reverse transcriptase-polymerase chain reaction confirmed the absence of the fusion RARA-PML transcript. The patient achieved complete remission, but died during consolidation therapy, 2 months after diagnosis. To our knowledge, this is the first reported case of APL with a complex variant t(15;17) involving chromosome 18 at band q12 and one of the very rare described cases displaying a submicroscopic deletion of the RARA 5' region. Further cases are needed to delineate the incidence of submicroscopic deletions in APL and elucidate their prognostic impact.


A high gene flow in populations of Amblyomma ovale ticks found in distinct fragments of Brazilian Atlantic rainforest.
The genetic structure of populations of the tick Amblyomma ovale from five distinct areas of the Brazilian Atlantic rainforest was evaluated via DNA sequencing and associated with the presence of domestic dogs acting as hosts at the edge of forest fragments. Ticks were collected from domestic dogs and from the environment between 2015 and 2017. Four collection areas were located in the surroundings and within the Serra do Mar State Park, São Paulo State (23°37'21"S, 45°24'43"W), where dogs were bimonthly monitored along 2 years using camera traps and GSM trackers. To determine the spatial limits of genetic structure, ticks collected upon dogs living near the Serra do Baturié, Ceará State (4°15'40"S, 38°55'54"W) were included as well. A total of 39 haplotypes of 16S rRNA and Cox 1 mitochondrial genes sequences were observed, with 27 of them coming from areas within the Serra do Mar State Park. No haplotype was shared between the Serra do Mar and the Serra do Baturié indicating isolation of tick populations at the scale of 2000 km. Although three different haplotype lineages of A. ovale occurred within the Serra do Mar State Park, no genetic structure was found across the study sites within this park, suggesting high tick gene flow across a range of 45 km. Monitoring data from domestic dogs and wild carnivores showed that these species share the same habitats at the forest edge, with dogs playing a likely limited role in tick dispersal. Our findings have important implications for understanding the genetic structure of wide spread A. ovale along Brazilian rainforest remnants, which can further be associated to tick-borne infectious agents, such as Rickettsia parkeri, and used for predicting future patterns of tick diversity in the Brazilian Atlantic rainforest.


Studies on a series of milnacipran analogs containing a heteroaromatic group as potent norepinephrine and serotonin transporter inhibitors.
A series of milnacipran analogs containing a heteroaromatic group were synthesized and studied as monoamine transporter inhibitors. Many compounds exhibited higher potency than milnacipran at NET and NET/SERT with no significant change in lipophilicity. For example, compound R-26f was about 10-fold more potent than milnacipran with IC(50) values of 8.7 and 26nM at NET and SERT, respectively.


Prospects for advanced electron cyclotron resonance and electron beam ion source charge breeding methods for EURISOL.
As the most ambitious concept of isotope separation on line (ISOL) facility, EURISOL aims at producing unprecedented intensities of post-accelerated radioactive isotopes. Charge breeding, which transforms the charge state of radioactive beams from 1+ to an n+ charge state prior to post-acceleration, is a key technology which has to overcome the following challenges: high charge states for high energies, efficiency, rapidity and purity. On the roadmap to EURISOL, a dedicated R&D is being undertaken to push forward the frontiers of the present state-of-the-art techniques which use either electron cyclotron resonance or electron beam ion sources. We describe here the guidelines of this R&D.


Early postoperative endoscopic sphincterotomy for retained common bile duct stones.
Endoscopic sphincterotomy was performed within 28 days after cholecystectomy in 20 patients with retained common bile duct stones, of whom 15 (75%) underwent endoscopic sphincterotomy within the first week of surgery. Stone extraction was successful in all patients and no immediate complications were noted. Early endoscopic sphincterotomy for retained common bile duct stones was safe and effective in the early postoperative period.


Activation of Nigrostriatal Dopamine Neurons during Fear Extinction Prevents the Renewal of Fear.
Manipulations that increase dopamine (DA) signaling can enhance fear extinction, but the circuits involved remain unknown. DA neurons originating in the substantia nigra (SN) projecting to the dorsal striatum (DS) are traditionally viewed in the context of motor behavior, but growing data implicate this nigrostriatal circuit in emotion. Here we investigated the role of nigrostriatal DA in fear extinction. Activation of SN DA neurons with designer Gq-coupled receptors exclusively activated by designer drugs (Gq-DREADD) during fear extinction had no effect on fear extinction acquisition, but enhanced fear extinction memory and blocked the renewal of fear in a novel context; a pattern of data paralleled by cFos expression in the central amygdala. D1 receptors in the DS are a likely target mediating the effects of SN DA activation. D1-expressing neurons in the medial DS (DMS) were recruited during fear extinction, and Gq-DREADD-induced DA potentiated activity of D1-expressing neurons in both the DMS and the lateral DS (DLS). Pharmacological activation of D1 receptors in the DS did not impact fear extinction acquisition or memory, but blocked fear renewal in a novel context. These data suggest that activation of SN DA neurons and DS D1 receptors during fear extinction render fear extinction memory resistant to the disrupting effects of changes in contextual contingencies, perhaps by recruiting habitual learning strategies involving the DLS. Nigrostriatal DA thus represents a novel target to enhance long-term efficacy of extinction-based therapies for anxiety and trauma-related disorders.


A double-blind, placebo-controlled trial of modafinil for cocaine dependence.
This is a randomized, double-blind, placebo-controlled study of modafinil treatment for cocaine dependence. Patients (N = 210) who were actively using cocaine at baseline were randomized to 8 weeks of modafinil (0 mg/day, 200 mg/day, or 400 mg/day) combined with once-weekly cognitive-behavioral therapy. Our primary efficacy measure was cocaine abstinence, based on urine benzoylecgonine (BE) levels, with secondary measures of craving, cocaine withdrawal, retention, and tolerability. We found no significant differences between modafinil and placebo patients on any of these measures. However, there was a significant gender difference in that male patients treated with 400 mg/day tended to be more abstinent than their placebo-treated counterparts (p = .06). Our negative findings might be explained by gender differences and/or inadequate psychosocial treatment intensity in patients with severe cocaine dependence.


Composting of seaweed waste: Evaluation on the growth of Sarcocornia perennis.
Composting represents a suitable and cheap method for handling and processing seaweeds accumulated on the coast. Within this framework, two seaweed composts were prepared, one with Undaria pinnatifida accumulated in spring-summer and other with a mixture of seaweeds accumulated in autumn-winter, both from Central Patagonian beaches. The effect of these two composts was evaluated experimentally as an amendment for the growth of Sarcocornia perennis (chickenclaws), a plant species dominating Patagonian salt marshes. Both composts were applied at 75, 50, and 25% doses with perlite. The analysis of the compost properties (phytotoxicity test, C/N, electrical conductivity, pH, and metal content) allowed characterizing both composts as matures and stables. The growth results showed that both composts allow the growth of S. perennis in all doses tested; however, Undaria compost was better in the stimulation of vegetative growth when applied in dose 50%, followed by 75% of both composts. For these reasons, both composts from seaweed waste accumulated on Patagonian coasts could be used in the growth of S. perennis and potentially other plant species, giving value to the seaweeds that currently are considered a waste that disturb these coasts and are discarded without use.


Providing information for young people in sexual health clinics: getting it right.
The need to improve the quality and availability of information on sexual health is identified as a key element in achieving the aims set out in the National Strategy for Sexual Health and HIV. Providing information about sexual health to young people poses particular challenges because of the sensitive nature of the issues and because of the difficulties that young people may face in sourcing information and asking questions of professionals.


Prophylaxis against hypocalcemia in low-birth-weight infants requiring bicarbonate infusion.
Forty-eight low-birth-weight infants with varying degrees of respiratory distress were studied with respect to serum calcium concentration and urinary calcium excretion. Serum calcium decreased over the 24-hour study period in infants who did not receive calcium infusion. The decrease was greater in those receiving bicarbonate therapy for acidosis. Continuous calcium infusion at 1 mg/kg/hr sustained relatively normal serum calcium concentration, even in those infants who required bicarbonate. Since the changes in estimated extracellular calcium could not be accounted for by urinary excretion, a shift of calcium into bone was postulated.


Efficacy vs. effectiveness--docetaxel and prednisone in hormone refractory prostate cancer.
To assess the clinical effectiveness of docetaxel and prednisone in a clinical setting and to compare the results to those seen in the pivotal clinical trial. To assess the impact of various factors on the prognosis of patients treated with docetaxel. Retrospective chart review. The primary outcome measured was survival. Survival data was analyzed through the Kaplan-Meier methodology. A multivariate analysis of prognostic variables was also conducted. Public cancer centers within the Canadian province of Alberta. Hormone refractory, metastatic prostate cancer patients initiated on docetaxel chemotherapy between September 2004 and February 2007 within the Alberta Cancer Board. Main Outcome Measured. The primary outcome measured was median survival. Among 161 patients eligible for review, median survival was 17.22 months. Chemotherapy received after docetaxel was determined to be a significant favorable prognostic factor for survival (p<0.0001). In a clinical setting, docetaxel and prednisone did not perform as well in terms of median survival, as it was shown to in prior clinical trials (17.22 vs. 18.9 months). Further investigation into the impact of docetaxel and prednisone on quality of life in clinical practice, would complement the findings of this study.


Parvimonas micra bacteremia following endoscopic retrograde cholangiopancreatography: A new route of infection.
Parvimonas micra is an anaerobic, Gram-positive coccus belonging to oral, gastrointestinal and genital flora, rarely causing infections in humans. It was mainly deemed to cause bacteremia, septic bone and cerebral infections in patients which have undergone dental procedures or with suboptimal dental hygiene. We report the first case of Parvimonas micra bacteremia following endoscopic retrograde colangiopancreatography performed due to choledocholithiasis in a patient with good oral health. Identification of P. micra was finally performed by Matrix-assisted laser desorption ionization-time of flight mass spectrometry (VITEK MS system, bioMérieux, Marcy l'Étoile, France). All cases reported in english language of Parvimonas micra infections after medical procedure are reviewed in order to alert clinicians about new possible routes of infection of this emerging pathogen.


Photodimerization systems for regulating protein-protein interactions with light.
Optogenetic dimerizers are modular domains that can be utilized in a variety of versatile ways to modulate cellular biochemistry. Because of their modularity, many applications using these tools can be easily transferred to new targets without extensive engineering. While a number of photodimerizer systems are currently available, the field remains nascent, with new optimizations for existing systems and new approaches to regulating biological function continuing to be introduced at a steady pace.


[Thrombolysis in acute ischemic stroke in centers lacking a stroke unit: referral to reference center or on-site treatment?].
To assess the clinical impact of on-site thrombolysis versus referral to another hospital in patients with ischemic stroke attended in a hospital lacking a stroke unit. Expected value decision analysis and Monte Carlo simulation. Decision analysis based on a cohort study (SIT-MOST) and a meta-analysis of randomized trials of thrombolysis versus placebo in patients with acute ischemic stroke. On-site thrombolysis (in hospitals lacking a stroke unit) versus delayed thrombolysis in a reference hospital. Neurological outcome (modified Rankin scale) three months after admission according to the delay in the administration of thrombolysis. At baseline (initial delay of 135 min, travel time 60 minutes), on-site treatment was more effective than referral to another hospital (number of patients with favorable neurological outcome 45.3% versus 41.3%). In patients seen within 45 minutes of the onset of symptoms, for every 10 patients transferred there was an additional case with an unfavorable neurological outcome that could have been avoided with on-site thrombolysis. In the Monte Carlo analysis, biased against on-site treatment by a reduction in effectiveness of 30%, on-site treatment was superior to patient referral in 77.2% of the cases. The available evidence does not support the recommendations of the national stroke strategy or some regional plans that discourage the administration of thrombolysis in hospitals without stroke units.


Effect of Awake Prone Positioning on Endotracheal Intubation in Patients With COVID-19 and Acute Respiratory Failure: A Randomized Clinical Trial.
The efficacy and safety of prone positioning is unclear in nonintubated patients with acute hypoxemia and COVID-19. To evaluate the efficacy and adverse events of prone positioning in nonintubated adult patients with acute hypoxemia and COVID-19. Pragmatic, unblinded randomized clinical trial conducted at 21 hospitals in Canada, Kuwait, Saudi Arabia, and the US. Eligible adult patients with COVID-19 were not intubated and required oxygen (≥40%) or noninvasive ventilation. A total of 400 patients were enrolled between May 19, 2020, and May 18, 2021, and final follow-up was completed in July 2021. Patients were randomized to awake prone positioning (n = 205) or usual care without prone positioning (control; n = 195). The primary outcome was endotracheal intubation within 30 days of randomization. The secondary outcomes included mortality at 60 days, days free from invasive mechanical ventilation or noninvasive ventilation at 30 days, days free from the intensive care unit or hospital at 60 days, adverse events, and serious adverse events. Among the 400 patients who were randomized (mean age, 57.6 years [SD, 12.83 years]; 117 [29.3%] were women), all (100%) completed the trial. In the first 4 days after randomization, the median duration of prone positioning was 4.8 h/d (IQR, 1.8 to 8.0 h/d) in the awake prone positioning group vs 0 h/d (IQR, 0 to 0 h/d) in the control group. By day 30, 70 of 205 patients (34.1%) in the prone positioning group were intubated vs 79 of 195 patients (40.5%) in the control group (hazard ratio, 0.81 [95% CI, 0.59 to 1.12], P = .20; absolute difference, -6.37% [95% CI, -15.83% to 3.10%]). Prone positioning did not significantly reduce mortality at 60 days (hazard ratio, 0.93 [95% CI, 0.62 to 1.40], P = .54; absolute difference, -1.15% [95% CI, -9.40% to 7.10%]) and had no significant effect on days free from invasive mechanical ventilation or noninvasive ventilation at 30 days or on days free from the intensive care unit or hospital at 60 days. There were no serious adverse events in either group. In the awake prone positioning group, 21 patients (10%) experienced adverse events and the most frequently reported were musculoskeletal pain or discomfort from prone positioning (13 of 205 patients [6.34%]) and desaturation (2 of 205 patients [0.98%]). There were no reported adverse events in the control group. In patients with acute hypoxemic respiratory failure from COVID-19, prone positioning, compared with usual care without prone positioning, did not significantly reduce endotracheal intubation at 30 days. However, the effect size for the primary study outcome was imprecise and does not exclude a clinically important benefit. ClinicalTrials.gov Identifier: NCT04350723.


Subcellular Imaging of Voltage and Calcium Signals Reveals Neural Processing In Vivo.
A mechanistic understanding of neural computation requires determining how information is processed as it passes through neurons and across synapses. However, it has been challenging to measure membrane potential changes in axons and dendrites in vivo. We use in vivo, two-photon imaging of novel genetically encoded voltage indicators, as well as calcium imaging, to measure sensory stimulus-evoked signals in the Drosophila visual system with subcellular resolution. Across synapses, we find major transformations in the kinetics, amplitude, and sign of voltage responses to light. We also describe distinct relationships between voltage and calcium signals in different neuronal compartments, a substrate for local computation. Finally, we demonstrate that ON and OFF selectivity, a key feature of visual processing across species, emerges through the transformation of membrane potential into intracellular calcium concentration. By imaging voltage and calcium signals to map information flow with subcellular resolution, we illuminate where and how critical computations arise.


Dianthusaticii, a new species from Turkey (Caryophyllaceae).
During the taxonomic revision of the Turkish Dianthus species, specimens collected from Bilecik, Seben (Bolu), and Nallıhan (Ankara) were discovered that represent a new species. Its description, images, chorology, ecology, and threat category are provided. It was compared with a closely related species, Dianthuszonatus, and differences are based on its general morphology and seed micromorphology.


Anti-glaucoma potential of Heliotropium indicum Linn in experimentally-induced glaucoma.
Heliotropium indicum is used as a traditional remedy for hypertension in Ghana. The aim of the study was to evaluate the anti-glaucoma potential of an aqueous whole plant extract of H. indicum to manage experimentally-induced glaucoma. The percentage change in intraocular pressure (IOP), after inducing acute glaucoma (15 mLkg(-1) of 5 % dextrose, i.v.), in New Zealand White rabbits pretreated with Heliotropium indicum aqueous extract (HIE) (30-300 mgkg(-1)), acetazolamide (5 mgkg(-1)), and normal saline (10 mLkg(-1)) per os were measured. IOPs were also monitored in chronic glaucoma in rabbits (induced by 1 % prednisolone acetate drops, 12 hourly for 21 days) after treatments with the same doses of HIE, acetazolamide, and normal saline for 2 weeks. The anti-oxidant property of the extract was assessed by assaying for glutathione levels in the aqueous humour. Glutamate concentration in the vitreous humour was also determined using ELISA technique. Histopathological assessment of the ciliary bodies was made. The extract significantly reduced intraocular pressure (p ≤ 0.05-0.001) in acute and chronic glaucoma, preserved glutathione levels and glutamate concentration (p ≤ 0.01-0.001). Histological assessment of the ciliary body showed a decrease in inflammatory infiltration in the extract and acetazolamide-treated group compared with the normal saline-treated group. The aqueous whole plant extract of Heliotropium indicum has ocular hypotensive, anti-oxidant and possible neuro-protective effects, which therefore underscore its plausible utility as an anti-glaucoma drug with further investigation.


IGF-1 in gynaecology and obstetrics: update 2002.
Recent discoveries on endocrine, paracrine and autocrine involvement of insulin-like growth factor-1 (IGF-1) in the proliferation of many tissues raised the attention of its role in reproduction and in the growth of various cancers as well as of benign proliferations. The intention of this article is to focus on IGF-1 in the field of gynaecology. Perimenopausal women who exhibit high IGF-1 and low IGF binding protein (IGFBP) levels, like IGFBG-3, have an increased risk of developing breast cancer. A higher risk for cervical, ovarian and endometrial cancer is related to high IGF-1 levels in post- and premenopausal women. It has been shown that myomas, by far the most common benign uterine tumor in women, grow in the presence of IGF-1, in vitro as well as in vivo. Studies show that IGF-1 is involved in the differentiation of various reproductive tissues, like endometrium and ovarian tissues. Patients suffering from polycystic ovary syndrome (PCO) frequently show insulin resistance accompanied by an increase of IGF-1 in plasma. Plasma IGF-1 levels are higher in cases of severe endometriosis, however, in endometriosis and in PCO IGF levels locally in the endometrium are reduced, what might explain infertility. Recently, it was shown that IGF facilitates the implantation of the human embryo in the endometrium during IVF. Implantation is a paradox where different immune systems have to collaborate to make implantation and survival of the pregnancy possible. IGF seems to be the starter molecule so that the two epithelia can fuse. A disturbance can result in complications during pregnancy i.e. spontaneous miscarriage, preeclampsia as well as defects of the embryo. Therefore, IGF is a useful marker in successful pregnancy as well. A better mechanistic understanding of IGF-1 action on the cellular level not only provides more elegant mechanistic explanations for the scientist, but the practitioner might find it interesting to utilize its diagnostic potential as a marker for various diseases. The relation between systemic IGF levels and local tissue IGF-1 levels has not yet been determined for all conditions.


Mechanisms of allicin exposure for the sludge fermentation enhancement: Focusing on the fermentation processes and microbial metabolic traits.
As a frequently used product with antimicrobial activity, consumed allicin might be discharged and concentrated in waste-activated sludge (WAS). However, the influence of allicin (as an exogenous pollutant) on WAS fermentation has not been clearly revealed. This study aimed to disclose the impacts of allicin on volatile fatty acid (VFA) generation during WAS fermentation. The results showed that the appropriate presence of allicin (10 mg/g TSS) significantly enhanced the VFA yield (1894 versus 575 mg COD/L in the control) with increased acetate proportion (24.3%). Further exploration found that allicin promoted WAS solubilization, hydrolysis and acidification simultaneously. Metagenomic analysis revealed that the key genes involved in extracellular hydrolysis metabolism (i.e., CAZymes), membrane transport (i.e., gtsA and ytfT), substrate metabolism (i.e., yhdR and pfkC) and fatty acid synthesis (i.e., accA and accD) were all highly expressed. Allicin also induced the bacteria to produce more signalling molecules and regulate cellular functions, thereby enhancing the microbial adaptive and regulatory capacity to the unfavourable environment. Moreover, the variations in fermentative microbes and their contributions to the upregulation of functional genes (i.e., ytfR, gltL, INV, iolD and pflD) for VFA generation were disclosed. Overall, the simultaneous stimulation of functional microbial abundances and metabolic activities contributed to VFA production in allicin-conditioned reactors.


Serotonin antagonism in the treatment of systemic hypertension: the role of ketanserin.
Serotonin has various hemodynamic effects, and may play a role in systemic hypertension. Ketanserin is a specific S2 serotonergic receptor blocker with possible adrenergic blocking activities that has clinical utility in the treatment of hypertension. The drug may have particular advantages for various patient populations.


Cerebrovascular integrity affects gradients of aging-related dopamine D1 differences in the striatum.
Extant research suggest aging-related losses of different dopaminergic markers, including presynaptic dopamine transporters as well as post-synaptic DA receptors. Given the central role of DA in neurocognitive functions, maintenance of a healthy DA system may be a key to mitigate age-related cognitive decline. Mechanisms behind DA losses in aging are however largely uncharted. Past research documented an association between dopaminergic integrity and cerebrovascular health (via white matter lesion volumes). However, it remains unclear whether proximity to lesions affected the spatial patterns of age-related D1DR differences within the striatum, and whether such differences are related to mnemonic function. Here, a large cohort of middle-aged to older healthy participants (age = 40-80 years, n = 119, 50 % women) was assessed for D1-receptor (D1DR) availability with positron emission tomography using [11C]SCH23390, and for white matter lesions using FLAIR-MRI. We found evidence for variations in degree of age-related differences along the ventro-dorsal axis, with more pronounced differences in the dorsal caudate. Further analyses revealed an association between distance to lesions and extent of D1DR losses in the caudate. Furthermore, D1DR differences in dorsal caudate (proximal to lesions) was more strongly associated with memory performance. In conclusion, the present findings suggest that maintenance of cerebrovascular health may be a key factor in promoting successful dopaminergic and memory aging.


Management of Acute Pediatric Hand Burns.
Worldwide, approximately 500,000 children are admitted to the hospital with burn injuries every year. Referral to an accredited burn center is required for burns that involve the hand regardless of age. As with most burn injuries, a multidisciplinary approach is important; however, in the younger pediatric patient, extra resources such as child life services, pediatric psychotherapy, and music therapy all play major roles alongside the nurse, physical therapists, and psychiatrists so that together with the appropriate support for the family involved, a successful outcome can be achieved.


Recent developments in the design and construction of facilities for the production of human injectables.
The pressures imposed upon pharmaceutical production managers are such that insufficient time is available to plan and develop new pharmaceutical facilities. Standards and codes of practice are available but the relevant data is not presented in a form which would enable the reader to readily access. This paper attempts to highlight the relevant extracts and to visually demonstrate some practical proprietary solutions. It is acknowledged that in some aspects the designer will find it necessary to deviate from the Code and the Standards in the interests of achieving a practical process solution. This paper will provide an awareness of the necessary design parameters such that any deviation judgements have been fully considered.


Triazene formation via reaction of imidazol-2-ylidenes with azides.
Treatment of N-heterocyclic carbenes (as their free carbenes or generated in situ) with alkyl, aryl, acyl or tosyl azides afforded the respective substituted triazenes in excellent yields.


WNT-C59, a Small-Molecule WNT Inhibitor, Efficiently Induces Anterior Cortex That Includes Cortical Motor Neurons From Human Pluripotent Stem Cells.
The recapitulation of human neural development in a controlled, defined manner from pluripotent stem cells (PSCs) has considerable potential for studies of human neural development, circuit formation and function, and the construction of in vitro models of neurological diseases. The inhibition of Wnt signaling, often by the recombinant protein DKK1, is important for the induction of cortical neurons. Here, we report a novel differentiation method using a small-molecule WNT inhibitor, WNT-C59 (C59), to efficiently induce human anterior cortex. We compared two types of small molecules, C59 and XAV939 (XAV), as substitutes for DKK1 to induce cortical neurons from PSCs in serum-free embryoid body-like aggregate culture. DKK1 and XAV inhibited only the canonical pathway of Wnt signaling, whereas C59 inhibited both the canonical and noncanonical pathways. C59 efficiently induced CTIP2+/COUP-TF1- cells, which are characteristic of the cells found in the anterior cortex. In addition, when grafted into the cortex of adult mice, the C59-induced cells showed abundant axonal fiber extension toward the spinal cord. These results raise the possibility of C59 contributing to cell replacement therapy for motor neuron diseases or insults. For a cell therapy against damaged corticospinal tract caused by neurodegenerative diseases or insults, cortical motor neurons are needed. Currently, their induction from pluripotent stem cells is considered very promising; however, an efficient protocol to induce motor neurons is not available. For efficient induction of anterior cortex, where motor neurons are located, various WNT inhibitors were investigated. It was found that one of them could induce anterior cortical cells efficiently. In addition, when grafted into the cortex of adult mice, the induced cells showed more abundant axonal fiber extension toward spinal cord. These results raise the possibility that this inhibitor contributes to a cell-replacement therapy for motor neuron diseases or insults.


Effect of noradrenaline on propofol-induced mitochondrial dysfunction in human skeletal muscle cells.
Mitochondrial dysfunction is a hallmark of both critical illness and propofol infusion syndrome and its severity seems to be proportional to the doses of noradrenaline, which patients are receiving. We comprehensively studied the effects of noradrenaline on cellular bioenergetics and mitochondrial biology in human skeletal muscle cells with and without propofol-induced mitochondrial dysfunction. Human skeletal muscle cells were isolated from vastus lateralis biopsies from patients undergoing elective hip replacement surgery (n = 14) or healthy volunteers (n = 4). After long-term (96 h) exposure to propofol (10 µg/mL), noradrenaline (100 µM), or both, energy metabolism was assessed by extracellular flux analysis and substrate oxidation assays using [14C] palmitic and [14C(U)] lactic acid. Mitochondrial membrane potential, morphology and reactive oxygen species production were analysed by confocal laser scanning microscopy. Mitochondrial mass was assessed both spectrophotometrically and by confocal laser scanning microscopy. Propofol moderately reduced mitochondrial mass and induced bioenergetic dysfunction, such as a reduction of maximum electron transfer chain capacity, ATP synthesis and profound inhibition of exogenous fatty acid oxidation. Noradrenaline exposure increased mitochondrial network size and turnover in both propofol treated and untreated cells as apparent from increased co-localization with lysosomes. After adjustment to mitochondrial mass, noradrenaline did not affect mitochondrial functional parameters in naïve cells, but it significantly reduced the degree of mitochondrial dysfunction induced by propofol co-exposure. The fatty acid oxidation capacity was restored almost completely by noradrenaline co-exposure, most likely due to restoration of the capacity to transfer long-chain fatty acid to mitochondria. Both propofol and noradrenaline reduced mitochondrial membrane potential and increased reactive oxygen species production, but their effects were not additive. Noradrenaline prevents rather than aggravates propofol-induced impairment of mitochondrial functions in human skeletal muscle cells. Its effects on bioenergetic dysfunctions of other origins, such as sepsis, remain to be demonstrated.


Primary and secondary prevention in cardiovascular disease: an old-fashioned concept?
Is the concept of primary and secondary cardiovascular prevention an old-fashioned concept that needs to be re-defined? Discussion paper. Cardiovascular prevention means reduction of absolute risk for cardiovascular disease (CVD), irrespective of clinical stage. For the calculation of an individual probability to develop CVD all factors that contribute to the risk must be taken into account, including previous CVD events.


Assessing Contaminants of Emerging Concern in the Great Lakes Ecosystem: A Decade of Method Development and Practical Application.
Assessing the ecological risk of contaminants in the field typically involves consideration of a complex mixture of compounds which may or may not be detected via instrumental analyses. Further, there are insufficient data to predict the potential biological effects of many detected compounds, leading to their being characterized as contaminants of emerging concern (CECs). Over the past several years, advances in chemistry, toxicology, and bioinformatics have resulted in a variety of concepts and tools that can enhance the pragmatic assessment of the ecological risk of CECs. The present Focus article describes a 10+- year multiagency effort supported through the U.S. Great Lakes Restoration Initiative to assess the occurrence and implications of CECs in the North American Great Lakes. State-of-the-science methods and models were used to evaluate more than 700 sites in about approximately 200 tributaries across lakes Ontario, Erie, Huron, Michigan, and Superior, sometimes on multiple occasions. Studies featured measurement of up to 500 different target analytes in different environmental matrices, coupled with evaluation of biological effects in resident species, animals from in situ and laboratory exposures, and in vitro systems. Experimental taxa included birds, fish, and a variety of invertebrates, and measured endpoints ranged from molecular to apical responses. Data were integrated and evaluated using a diversity of curated knowledgebases and models with the goal of producing actionable insights for risk assessors and managers charged with evaluating and mitigating the effects of CECs in the Great Lakes. This overview is based on research and data captured in approximately about 90 peer-reviewed journal articles and reports, including approximately about 30 appearing in a virtual issue comprised of highlighted papers published in Environmental Toxicology and Chemistry or Integrated Environmental Assessment and Management. Environ Toxicol Chem 2023;42:2506-2518. © 2023 SETAC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.


Contraceptive issues of youth and adolescents in developing countries: highlights from the Philippines and other Asian countries.
This article highlights contraceptive issues in Asia, home to some 700 million adolescents. It starts with a description of the socio-cultural milieu of adolescents in South and Southeast Asia, their knowledge and use of contraceptives, the myriad barriers to access, and the many innovative programs to broaden contraceptive availability. The reproductive health needs of adolescents in poor countries cannot be solved by merely supplying them with contraceptives--these needs can only be fully addressed in the context of gender equality, poverty alleviation and the conviction that investing in the reproductive health of adolescents is a most urgent priority. Investing in the reproductive health of adolescents will have an impact not only on birth and abortion rates, maternal health, and the spread of STI/HIV but also on the demographics and economic development of the region--and beyond.


Surface tension of amniotic fluid lipid extracts: prediction of pulmonary maturity.
The surface tension (ST)-lowering properties of an amniotic fluid lipid extract can provide a rapid and reliable means of predicting pulmonary maturity. One hundred and eleven samples from 91 patients were analyzed. A surface tension of less than 56 dynes per centimeter at 120 microliter of extract and less than 46 dynes per centimeter at 220 microliter of extract denoted pulmonary maturity. Values greater than these indicated immaturity. Among fluid samples studied within 48 hours of delivery for the presence or absence of respiratory distress syndrome (RDS) in 71 patients, there were no false positive ST values, while 7 of 22 patients with immature values developed RDS. Surface tension correlates well with the lecithin/sphingomyelin (L/S) ratio but provides clearer definition than the L/S ratio when compared to outcome. Blood and meconium contamination make the surface tension of fluid from babies with pulmonary immaturity appear mature. Identical twins with dissimilar ST values and outcome, as well as serial samples from individual patients, are analyzed and discussed.


Time-resolved absorption and magnetic circular dichroism spectroscopy of cytochrome c3 from Desulfovibrio.
The UV-visible absorption and magnetic circular dichroism (MCD) spectra of the ferric, ferrous, CO-ligated forms and kinetic photolysis intermediates of the tetraheme electron-transfer protein cytochrome c3 (Cc3) are reported. Consistent with bis-histidinyl axial coordination of the hemes in this Class III c-type cytochrome, the Soret and visible region MCD spectra of ferric and ferrous Cc3 are very similar to those of other bis-histidine axially coordinated hemeproteins such as cytochrome b5. The MCD spectra indicate low spin state for both the ferric (S = 1/2) and ferrous (S = 0) oxidation states. CO replaces histidine as the axial sixth ligand at each heme site, forming a low-spin complex with an MCD spectrum similar to that of myoglobin-CO. Photodissociation of Cc3-CO (observed photolysis yield = 30%) produces a transient five-coordinate, high-spin (S = 2) species with an MCD spectrum similar to deoxymyoglobin. The recombination kinetics of CO with heme Fe are complex and appear to involve at least five first-order or pseudo first-order rate processes, corresponding to time constants of 5.7 microseconds, 62 microseconds, 425 microseconds, 2.9 ms, and a time constant greater than 1 s. The observed rate constants were insensitive to variation of the actinic photon flux, suggesting noncooperative heme-CO rebinding. The growing in of an MCD signal characteristic of bis-histidine axial ligation within tens of microseconds after photodissociation shows that, although heme-CO binding is thermodynamically favored at 1 atm CO, binding of histidine to the sixth axial site competes kinetically with CO rebinding.


Development and validation of a nomogram for predicting dysphagia in long-term care facility residents.
Dysphagia is a common problem that can seriously affect the health of elderly residents in long-term care facilities. Early identification and targeted measures can significantly reduce the incidence of dysphagia. This study aims to establish a nomogram to evaluate the risk of dysphagia for elderly residents in long-term care facilities. A total of 409 older adults were included in the development set, and 109 were included in the validation set. Least absolute shrinkage selection operator (LASSO) regression analysis was used to select the predictor variables, and logistic regression was used to establish the prediction model. The nomogram was constructed based on the results of logistic regression. The performance of the nomogram was evaluated by receiver operating characteristic (ROC) curve, calibration, and decision curve analysis (DCA). Internal validation was performed using tenfold cross-validation with 1000 iterations. The predictive nomogram included the following variables: stroke, sputum suction history (within one year), Barthel Index (BI), nutrition status, and texture-modified food. The area under the curve (AUC) for the model was 0.800; the AUC value for the internal validation set was 0.791, and the AUC value for the external validation set was 0.824. The nomogram showed good calibration in both the development set and validation set. Decision curve analysis (DCA) demonstrated that the nomogram was clinically valuable. This predictive nomogram provides a practical tool for predicting dysphagia. The variables included in this nomogram were easy to assess. The nomogram may help long-term care facility staff identify older adults at high risk for dysphagia.


Clinical and prognostic role of matrix metalloproteinase-2, -9 and their inhibitors in breast cancer and liver diseases: A review.
Matrix metalloproteinases are a family of zinc endopeptidases with proteolytic activity against the extracellular matrix components. In particular, two members of this family named Gelatinase A and B, as amply documented in the literature, play a key role in the process of tumor growth/metastasis in breast and hepatocellular carcinoma. Their activity is regulated by Tissue Inhibitor of metalloproteinases-1 and -2, which are the physiological inhibitor of Gelatinases A and B respectively. The aim of this review is to determine the current understanding of the clinical and prognostic role of Metalloproteinases-2 and -9 and their inhibitors in the course of breast cancer and liver diseases. Forty-one articles were selected from PubMed by entering the following keywords: liver diseases, breast cancer, MMP-2, TIMP-2; all articles were read and notes were made regarding the number of enrolled patients, pathology, measures, results and these data were used to write this review. Over-expression of both gelatinases is associated with the relapse of disease, metastasis, shorter overall survival in breast cancer and hepatocellular carcinoma and invasion and progression to tumors in chronic liver diseases, and MMPs/TIMPs ratio could be useful in the follow-up of these patients.


Absence of human leukocyte antigen molecules in skin tumors and some cutaneous appendages: evidence using monoclonal antibodies.
Four highly sensitive monoclonal antibodies were assessed for their use in an immunoperoxidase technic on cutaneous sections. Three, B2, C23, and 2A1, were found to discriminate basal cell carcinomas (BCCs) from benign proliferative disorders of skin, and 2A1, a monoclonal antibody against the heavy chain component of class 1 human leukocyte antigens (HLA) for the first time directly demonstrated the absence of this structure from the malignant cell membrane. However, the deeper portions of hair follicles were also found to be unlabeled, and further study of benign follicular tumors which may histologically mimic basal cell carcinomas is suggested.


Imaging of lower extremity trauma from Boston Marathon bombing.
The goal of this study is to describe the imaging features of lower extremity blast injuries in patients encountered in the radiology departments from the Boston Marathon bombings. A total of 115 patients presented to four acute care hospitals on April 15, 2013, 43 of whom presented with lower extremity injuries and were included in this study. The imaging findings of primary, secondary, tertiary, and quaternary blast injuries were evaluated. Forty-one of 43 patients sustained secondary blast injuries to the lower extremities with 31 patients (70 %) having retained shrapnel, seven patients (16 %) having soft tissue lacerations without retained shrapnel, and ten patients (23 %) having lower extremity amputation (7 % double amputees). Eight of these patients (20 %) had lower extremity fractures, and five patients (12 %) had vascular injuries. Two of the 43 patients (5 %) had only tertiary injuries, and five of 43 patients (12 %) were noted to have lower extremity burns, consistent with quaternary blast injury. No primary blast injury occurred in the lower extremities. A vast majority of lower extremity injuries were from secondary blast injury, most commonly from retained shrapnel in 70 % of patients and 23 % of patients sustaining lower extremity amputation. Retained shrapnel in the lower extremity was most commonly ball bearings and pressure cooker fragments, and most injuries affected the leg, followed by the thigh and foot.


[Ifosfamide, cisplatin, adriamycin combination chemotherapy in gynecologic cancer].
Thirteen patients with gynecologic cancer were treated with ifosfamide (2 g X 5), cisplatin (70 mg/m2) and adriamycin (20 mg/m2) combination chemotherapy. The response rate of 7 evaluable patients was 43%, with a median duration of survival of 14 months. Six patients with non-measurable disease are currently free from disease with a median duration of survival of 18 months. This combination caused reversible myelosuppression. No hemorrhagic cystitis was observed.


Percutaneous Microwave Tumor Ablation Is Safe in Patients with Cardiovascular Implantable Electronic Devices: A Single-Institutional Retrospective Review.
The risk of electromagnetic interference between microwave (MW) ablation and cardiac implantable electronic devices (CIEDs), ie, pacemakers and defibrillators, has not been fully evaluated. Fourteen MW ablations (kidney, n = 8; liver, n = 5; lung, n = 1) were performed in 13 patients with CIEDs in normal operating mode. Electrocardiography tracings, cardiovascular complications, tumor size, tumor-to-CIED distance, and tumor-to-device lead distance were recorded. Mean tumor size was 2.9 cm, mean tumor-to-CIED distance was 26.4 cm (range, 9-30 cm), and mean tumor-to-lead distance was 12.1 cm (range, 3.5-20 cm). No device-based cardiovascular complications or class C or higher complications per Society of Interventional Radiology criteria were identified. MW ablation appears to be safe in select patients with CIEDs.


Cyphastreakausti sp. n. (Cnidaria, Anthozoa, Scleractinia), a new species of reef coral from the Red Sea.
A new scleractinian coral species, Cyphastreakausti sp. n., is described from 13 specimens from the Red Sea. It is characterised by the presence of eight primary septa, unlike the other species of the genus, which have six, ten or 12 primary septa. The new species has morphological affinities with Cyphastreamicrophthalma, from which it can be distinguished by the lower number of septa (on average eight instead of ten), and smaller calices and corallites. This species was observed in the northern and central Red Sea and appears to be absent from the southern Red Sea.


Automated detection of posterior restorations in permanent teeth using artificial intelligence on intraoral photographs.
Intraoral photographs might be considered the machine-readable equivalent of a clinical-based visual examination and can potentially be used to detect and categorize dental restorations. The first objective of this study was to develop a deep learning-based convolutional neural network (CNN) for automated detection and categorization of posterior composite, cement, amalgam, gold and ceramic restorations on clinical photographs. Second, this study aimed to determine the diagnostic accuracy for the developed CNN (test method) compared to that of an expert evaluation (reference standard). The whole image set of 1761 images (483 of unrestored teeth, 570 of composite restorations, 213 of cements, 278 of amalgam restorations, 125 of gold restorations and 92 of ceramic restorations) was divided into a training set (N = 1407, 401, 447, 66, 231, 93, and 169, respectively) and a test set (N = 354, 82, 123, 26, 47, 32, and 44). The expert diagnoses served as a reference standard for cyclic training and repeated evaluation of the CNN (ResNeXt-101-32 × 8d), which was trained by using image augmentation and transfer learning. Statistical analysis included the calculation of contingency tables, areas under the receiver operating characteristic curve and saliency maps. After training was complete, the CNN was able to categorize restorations correctly with the following diagnostic accuracy values: 94.9% for unrestored teeth, 92.9% for composites, 98.3% for cements, 99.2% for amalgam restorations, 99.4% for gold restorations and 97.8% for ceramic restorations. It was possible to categorize different types of posterior restorations on intraoral photographs automatically with a good diagnostic accuracy. Dental diagnostics might be supported by artificial intelligence-based algorithms in the future. However, further improvements are needed to increase accuracy and practicability.


Ion-dependent structure, dynamics, and allosteric coupling in a non-selective cation channel.
The selectivity filter (SF) determines which ions are efficiently conducted through ion channel pores. NaK is a non-selective cation channel that conducts Na+ and K+ with equal efficiency. Crystal structures of NaK suggested a rigid SF structure, but later solid-state NMR and MD simulations questioned this interpretation. Here, we use solution NMR to characterize how bound Na+ vs. K+ affects NaK SF structure and dynamics. We find that the extracellular end of the SF is flexible on the ps-ns timescale regardless of bound ion. On a slower timescale, we observe a structural change between the Na+ and K+-bound states, accompanied by increased structural heterogeneity in Na+. We also show direct evidence that the SF structure is communicated to the pore via I88 on the M2 helix. These results support a dynamic SF with multiple conformations involved in non-selective conduction. Our data also demonstrate allosteric coupling between the SF and pore-lining helices in a non-selective cation channel that is analogous to the allosteric coupling previously demonstrated for K+-selective channels, supporting the generality of this model.


Correction to: Impact of a mixed educational and semi-restrictive antimicrobial stewardship project in a large teaching hospital in Northern Italy.
A technical error led to incorrect rendering of the author group in this article. The correct authorship is as follows: Daniele Roberto Giacobbe1, Valerio Del Bono1, Malgorzata Mikulska1, Giulia Gustinetti1, Anna Marchese2, Federica Mina3, Alessio Signori4, Andrea Orsi5, Fulvio Rudello6, Cristiano Alicino5, Beatrice Bonalumi3, Alessandra Morando7, Giancarlo Icardi5, Sabrina Beltramini3, Claudio Viscoli1; On behalf of the San Martino Antimicrobial Stewardship Group.


Prevalence of refractive error within a Portuguese sample of optometric records.
Considering the burden of refractive error, clinical-based research methods are often used as epidemiological tools. This study aimed to generate evidence on the prevalence and distribution of refractive error in Portugal. A cross-sectional retrospective study was designed to review optometric records from Portuguese practices during July 2021. 348 optometric records were analysed. Subjects had a mean age of 44.2 ± 19.2 years (range 6-81) and 58.4% were female. The mean spherical equivalent was myopic, -0.65 ± 2.38 Diopters (D), varying from a minimum of -13.63 to a maximum of 6.25 D. According to sex, the mean spherical equivalent was -0.76 ± 2.29 D for female and -0.49 ± 2.49 D for male, with no significant difference between them (p = .307). The distribution of the spherical equivalent mean across the age groups, linearly varies from a myopic -1.62 ± 1.74 D in the age group of [6 - 29]; -1.58 ± 2.80 D in [30 - 44]; -0.09 ± 2.40 in [45 - 59] to a hyperopic 0.67 ± 1.61 D in the group of [60 - 81]. High myopia had a prevalence of 2.7% in the sample. Myopia was the most prevalent refractive error in the sample representing 41.3%. In the age group [6-29], myopia had a prevalence of 69.3%. Hyperopia had a prevalence in the sample of 29.7%. Myopia represents the most prevalent refractive error within the sample and is the prevalence is higher in the younger age groups, demonstrating a shift towards an increase of myopia in the next years.


Ultrasound-assisted dextranase entrapment onto Ca-alginate gel beads.
In this research work, dextranase has immobilized onto calcium alginate beads using a novel ultrasound method. The process of immobilization of the enzyme was carried out in a one-step ultrasound process. Effects of ultrasound conditions on loading efficiency and immobilization yield of the enzyme onto calcium alginate beads were investigated. Furthermore, the activity of the free and immobilized enzymes prepared with and without ultrasound treatment, as a function of pH, temperature, recyclability and enzyme kinetic parameters, was compared. The maximum loading efficiency and the immobilization yield were observed when the immobilized dextranase was prepared with an ultrasonic irradiation at 25 kHz, 40 W for 15 min, under which the loading efficiency and the immobilization yield increased by 27.21% and 18.77%, respectively, compared with the immobilized enzymes prepared without ultrasonic irradiation. On the other hand, immobilized enzyme prepared with ultrasonic irradiation showed Vmax and KM value higher than that for the immobilized enzyme prepared without ultrasonic irradiation, likewise, both the catalytic and specificity constants of immobilized enzyme prepared with ultrasonic irradiation were higher than that for immobilized enzyme prepared without ultrasound, indicating that, this new ultrasonic method improved the catalytic kinetics activity of immobilized dextranase at all the reaction conditions studied. Compared with immobilized enzyme prepared without ultrasound treatment, the immobilized enzymes prepared with ultrasound irradiation exhibited: a higher pH optimum, optimal reaction temperature, activation energy, and thermal stability, as well as, a higher recyclability, which, illustrating the effectiveness of the sonochemical method. To the best of our knowledge, this is the first report on the effect of ultrasound treatments on the immobilization of dextranase.


Validation of dopamine receptor DRD1 and DRD2 antibodies using receptor deficient mice.
Dopamine receptors 1 and 2 (DRD1, DRD2) are essential for signaling in the brain for a multitude of brain functions. Previous work using several antibodies against these receptors is abundant but only the minority of antibodies used have been validated and, therefore, the results of these studies remain uncertain. Herein, antibodies against DRD1 (Merck Millipore AB1765P, Santa Cruz Biotechnology sc-14001, Sigma Aldrich D2944, Alomone Labs ADR-001) and DRD2 (Abcam ab21218, Merck Millipore AB5084P, Santa Cruz Biotechnology sc-5303) have been tested using western blotting and immunohistochemistry on mouse striatum (wild type and corresponding knock-out mice) and when specific, they were further evaluated on rat and human striatum. Moreover, a DRD1 antibody and a DRD2 antibody that were found specific in our tests were used for immunoprecipitation with subsequent mass spectrometrical identification of the immunoprecipitate. Two out of nine antibodies (anti DRD1 Sigma Aldrich D2944 and anti DRD2 Merck Millipore AB5084P) against the abovementioned dopamine receptors were specific for DRD1 and DRD2 as evaluated by western blotting and immunohistochemistry and the immunoprecipitate indeed contained DRD1 and DRD2 as revealed by mass spectrometry. The observed findings may question the use of so far non-validated antibodies against the abovementioned dopamine receptors. Own observations may be valuable for the interpretation of previous results and the design of future studies using dopamine receptors DRD1 or DRD2.


On resonance phase alternated CWFP sequences for rapid and simultaneous measurement of relaxation times.
T1 and T2 relaxation times have been frequently used as probes for physical-chemical properties in several time-domain NMR applications (TD-NMR) such as food, polymers and petroleum industries. T2 measurements are usually achieved using the traditional Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence because it is a fast and robust method. On the other hand, the traditional methods for determining T1, i.e., inversion and saturation recovery, are time-consuming, driving several authors to develop rapid 1D and 2D methods to obtain T1 and T2 or T1/T2 ratio. However, these methods usually require sophisticated processing and/or high signal to noise ratio (SNR). This led us to develop simple methods for rapid and simultaneous determination of T1 and T2 using Continuous Wave Free Precession (CWFP) and Carr-Purcell Continuous Wave Free Precession (CP-CWFP) pulse sequences. Nevertheless, a drawback of these sequences is that they require specific adjustment of the frequency offset or the time interval between pulses (Tp). In this paper we present an alternative form of these sequences, named CWFPx-x, CP-CWFPx-x, where a train of π/2 pulses with phases alternated by π enable performing the experiments on-resonance and independently of Tp, when Tp<T2(∗). Moreover, a CPMG type sequence with π/2 refocusing pulses shows similar results to CP-CWFP when the pulses are alternated between y and -y axis, CPMG90y-y. In these approaches, the relaxation times are determined using the magnitude of the signals after the first pulse |M0| and in the steady-state |Mss|, as well as the exponential time constant T(∗) to reach the steady-state regime, as in conventional CWFP. CP-CWFPx-x shows the highest dynamic range to measure T(∗) among CWFP sequences and, therefore, is the best technique to measure T1 and T2 since it is less susceptible to SNR and can be performed for any T1/T2 ratio.


[Clinical experience in a case of chronic myeloid leukemia in accelerated phase treated with beta-interferon].
The Authors report an alternative approach to treatment in CML with beta-interferon in patients in whom other traditional drugs failed. The accelerated stage of the illness was well controlled with return to chronic phase.


Imaging of choroid plexus infection by Stomatococcus mucilaginosus in neutropenic patients.
We report two neutropenic patients with Stomatococcus mucilaginosus meningitis and choroid plexus involvement on neuroimaging studies. CT and MR showed abnormal enlargement of the choroid plexus in one lateral ventricle and intense enhancement. In one patient there was edema in the periventricular white matter adjacent to the involved choroid plexus; in both patients there was enhancement of the ependyma.


Presence of a distinct 24-hour melatonin rhythm in the ventricular cerebrospinal fluid of the goat.
Melatonin profiles in the cerebrospinal fluid (CSF) of conscious goats were examined under long-day (16L:8D) and short-day (8L:16D) environments. CSF melatonin, collected from the lateral ventricle, showed distinct 24 h rhythms with high concentrations being restricted to the dark phase, which averaged 1,320.6 pg/ml under 16L:8D and 660.6 pg/ml under 8L:16D. On the contrary, the nocturnal rise in CSF melatonin was totally absent in the pineal sympathetically denervated animals. Night interruption by 1 h lighting (about 400 lux at the height of goat's head) resulted in an abrupt decline of CSF melatonin to the basal level within 30 min and immediate recovery to the previous high level after reestablishment of the dark phase. The CSF/plasma ratio was 10.8-18.4 during the dark phase and 1.7-1.8 during the light phase. CSF and plasma melatonin levels were also examined after exogenous melatonin given either peripherally or intraventricularly. Continuous subcutaneous infusion of melatonin (5 micrograms/h) maintained melatonin levels in the plasma about 3 times higher than that in the CSF during its application. On the other hand, an intraventricular injection of 2 micrograms melatonin elevated plasma melatonin by 100 pg/ml within 1 min. These results indicate that turnover of CSF melatonin is fairly rapid and favor a hypothesis for direct access of pineal melatonin to the brain ventricular system in the goat.


The rate of lactate production from glucose in hearts is not altered by per-deuteration of glucose.
This study was designed to determine whether perdeuterated glucose experiences a kinetic isotope effect (KIE) as glucose passes through glycolysis and is further oxidized in the tricarboxylic acid (TCA) cycle. Metabolism of deuterated glucose was investigated in two groups of perfused rat hearts. The control group was supplied with a 1:1 mixture of [U-13C6]glucose and [1,6-13C2]glucose, while the experimental group received [U-13C6,U-2H7]glucose and [1,6-13C2]glucose. Tissue extracts were analyzed by 1H, 2H and proton-decoupled 13C NMR spectroscopy. Extensive 2H-13C scalar coupling plus chemical shift isotope effects were observed in the proton-decoupled 13C NMR spectra of lactate, alanine and glutamate. A small but measureable (∼8%) difference in the rate of conversion of [U-13C6]glucose vs. [1,6-13C2]glucose to lactate, likely reflecting rates of CC bond breakage in the aldolase reaction, but conversion of [U-13C6]glucose versus [U-13C6,U-2H7]glucose to lactate did not differ. This shows that the presence of deuterium in glucose does not alter glycolytic flux. However, there were two distinct effects of deuteration on metabolism of glucose to alanine and oxidation of glucose in the TCA. First, alanine undergoes extensive exchange of methyl deuterons with solvent protons in the alanine amino transferase reaction. Second, there is a substantial kinetic isotope effect in metabolism of [U-13C6,U-2H7]glucose to alanine and glutamate. In the presence of [U-13C6,U-2H7]glucose, alanine and lactate are not in rapid exchange with the same pool of pyruvate. These studies indicate that the appearance of hyperpolarized 13C-lactate from hyperpolarized [U-13C6,U-2H7]glucose is not substantially influenced by a deuterium kinetic isotope effect.


The efficacy and safety of intrathecal fluorescein in endoscopic cerebrospinal fluid leak repair -a systematic review.
Effective management of cerebrospinal fluid (CSF) leaks can reduce significant associated morbidity. Intrathecal fluorescein (IF) may be a valuable intra-operative adjunct to localise leak sites. Recent reports have demonstrated low doses of IF to be safe, however, no internationally accepted dose of IF has been agreed. To assess the efficacy and safety of IF used in the endoscopic management of anterior skull base CSF fistulae. A systematic review and descriptive analysis were performed of all published data in accordance to PRISMA guidelines. There were 18 included articles giving a total of 335 procedures where IF was used. Doses of IF ranged from 10mg - 150mg. IF positively identified the site of CSF fistula in 88.7% of cases (n = 297). There was a total of 25 reported peri-operative complications in all included studies (7.5%) with 5.1% (n = 17) potentially related to IF use. Of these, the complication rate was 3.9% at low IF doses (<50mg) and 80.0% at higher doses (≥50mg). Our review demonstrates that IF is effective at localising CSF fistulae with most significant complications being related to doses ≥50mg. We therefore propose that there is a potential for the licensing of IF in this field. Doses <50mg have consistently been shown to be safe while still maintaining effective localisation rates. Based on the most common doses used in this group, we recommend utilisation of a dosing below 50mg, with the most frequent range being between 10-30mg.


Results of the non-small cell lung cancer part of a phase III, open-label, randomized trial evaluating topical corticosteroid therapy for facial acneiform dermatitis induced by EGFR inhibitors: stepwise rank down from potent corticosteroid (FAEISS study, NCCH-1512).
This FAEISS study was designed to confirm the superior efficacy of reactive topical corticosteroid strategies employing serially ranking-DOWN from very strong steroid levels for the treatment of facial acneiform rash induced by epidermal growth factor receptor (EGFR) inhibitors (EGFRIs), in comparison with strategies employing serially ranking-UP from weak steroid levels. This article reports the primary results of the non-small cell lung cancer (NSCLC) part of the trial. Patients with EGFR-mutated advanced NSCLC treated with erlotinib or afatinib were enrolled in the first registration. All patients received preemptive therapy with oral minocycline and heparinoid moisturizer from the initiation of an EGFR inhibitor. Enrolled patients who developed facial acneiform rash within 2 weeks were randomized at second registration to either a ranking-UP (WEAK) group or a ranking-DOWN group. The primary endpoint was incidence of grade ≥ 2 facial acneiform rash over 8 weeks. Fifty-one patients were enrolled at the first registration and received EGFRIs (n = 30 for afatinib, n = 21 for erlotinib). However, 35 patients did not develop facial acneiform rash within 2 weeks; one patient discontinued preemptive treatment. Fifteen patients (29.4%) were enrolled in the second registration; nine were assigned to the WEAK group and six to the DOWN group. There was no significant difference in the incidence of grade ≥ 2 facial acneiform rash between the WEAK group (one patient, twice) and the DOWN group (one patient, twice; p = 0.8417). No patients developed severe facial acneiform rash within 10 weeks. In NSCLC patients who received EGFRIs, preemptive therapy of oral minocycline and heparinoid moisturizer reduced facial acneiform rash incidence. UMIN000024113.


Initial experience of robotic versus laparoscopic colectomy for transverse colon cancer: a matched case-control study.
Robotic surgery for transverse colon cancer has rarely been described. This study reports our initial experience in robotic resection for transverse colon cancer, by comparing robotic transverse colectomy (RC) to laparoscopic transverse colectomy (LC) in terms of safety, feasibility, short-term outcomes, and the surgeon's psychological stress and physical pain. The study population included the first 22 consecutive patients who underwent RC between March 2013 and December 2014 for histologically confirmed transverse colon adenocarcinoma. These patients were compared with 22 matched patients undergoing LC between December 2010 and February 2013. Patients were matched based on age, gender, body mass index (BMI), American Society of Anesthesiology (ASA) score, American Joint Committee on Cancer (AJCC) tumor stage, and tumor location (ratio 1:1). Mortality, morbidity, operative, and short-term oncologic outcomes were compared between groups. The operating surgeon's stress and pain were assessed before and after surgery on a 0-100-mm visual analog scale. The demographic and preoperative characteristics were comparable between RC and LC patients. No group difference was observed for intraoperative complications, blood loss, postoperative pain, time to flatus, time to regular diet, and hospital stay. RC was associated with longer operative time than LC (260 min vs. 225 min; p = 0.014), but the overall operative and robotic time in the RC group decreased over time reflecting the increasing experience in performing this procedure. No conversion to laparotomy was observed in the RC group, while two LC patients were converted due to uncontrolled bleeding and technically difficult middle colic pedicle dissection. Postoperative complications (Dindo-Clavien grade I or II) occurred in 11.3 % of patients with no group difference. Mortality was nil. All resections were R0, with >12 lymph nodes harvested in 90.9 % of RC and 95.5 % of LC patients. The surgeon's stress was not different between RC and LC, whereas the surgeon's hand and neck/shoulder pain were significantly lower after RC. RC for transverse colon cancer appears to be safe and feasible with short-term outcomes comparable to LC.


Protections of bovine serum albumin protein from damage on functionalized graphene-based electrodes by flavonoids.
A sensitive electrochemical sensor based on bovine serum albumin (BSA)/poly (diallyldimethylammonium chloride) (PDDA) functionalized graphene nanosheets (PDDA-G) composite film modified glassy carbon electrode (BSA/PDDA-G/GCE) had been developed to investigate the oxidative protein damage and protections of protein from damage by flavonoids. The performance of this sensor was remarkably improved due to excellent electrical conductivity, strong adsorptive ability, and large effective surface area of PDDA-G. The BSA/PDDA-G/GCE displayed the greatest degree of BSA oxidation damage at 40 min incubation time and in the pH 5.0 Fenton reagent system (12.5 mM FeSO4, 50 mM H2O2). The antioxidant activities of four flavonoids had been compared by fabricated sensor based on the relative peak current ratio of SWV, because flavonoids prevented BSA damage caused by Fenton reagent and affected the BSA signal in a solution containing Co(bpy)3(3+). The sensor was characterized by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and scanning electron microscopy (SEM). UV-vis spectrophotometry and FTIR were also used to investigate the generation of hydroxyl radical and BSA damage, respectively. On the basis of results from electrochemical methods, the order of the antioxidant activities of flavonoids is as follows: (+)-catechin>kaempferol>apigenin>naringenin. A novel, direct SWV analytical method for detection of BSA damage and assessment of the antioxidant activities of four flavonoids was developed and this electrochemical method provided a simple, inexpensive and rapid detection of BSA damage and evaluation of the antioxidant activities of samples.


Rate dependent variation in concealed bigeminy.
A 63 year old man with angina pectoris was found to have frequent extrasystoles separated by odd as well as even numbers of conducted sinus beats. Analysis of 935 conducted sinus beats showed that premature ventricular beats without interpolation were separated by odd numbers of conducted sinus beats in 117 sequences and even numbers (exceptions) in 48 sequences (p less than 2 X 10(-4)). Tabulation of cycle lengths revealed that cycles with even numbers of conducted sinus beats were characterized by a significant reduction in the preceding postextrasystolic pause (1441+/-76 msec vs. 1487 +/-59 msec; p less than .001) and second sinus cycle (720 +/- 44 msec vs. 750 +/- 38 msec; p less than .001). Premature ventricular beats were interpolated in 41 additional sequences. Interpolated extrasystoles were separated by the expected even numbers of conducted sinus beats in 39 cases and odd numbers (exceptions) in only two cases. The frequency of exceptions to the usual rules for concealed bigeminy was therefore 2/39 during interpolation and 48/117 without interpolation (p less than .01). This case demonstrates that: 1) a reduction in cycle length may be associated with exceptions to the usual rules for concealed bigeminy, and 2) the frequency of exceptions to concealed bigeminy may be altered by the presence of interpolation. Only one previous case has contained statistical documentation of these circumstances. The diagnosis of a concealed ventricular rhythm may be facilitated by careful analysis at multiple cycle lengths.


Kimura's Theory of Non-Adaptive Radiation and Peto's Paradox: A Missing Link?
Karyotype diversity reflects genome integrity and stability. A strong correlation between karyotype diversity and species richness, meaning the number of species in a phylogenetic clade, was first reported in mammals over forty years ago: in mammalian phylogenetic clades, the standard deviation of karyotype diversity (KD) closely corresponded to species richness (SR) at the order level. These initial studies, however, did not control for phylogenetic signal, raising the possibility that the correlation was due to phylogenetic relatedness among species in a clade. Accordingly, karyotype diversity trivially reflects species richness simply as a passive consequence of adaptive radiation. A more recent study in mammals controlled for phylogenetic signals and established the correlation as phylogenetically independent, suggesting that species richness cannot, in itself, explain the observed corresponding karyotype diversity. The correlation is, therefore, remarkable because the molecular mechanisms contributing to karyotype diversity are evolutionarily independent of the ecological mechanisms contributing to species richness. Recently, it was shown in salamanders that the two processes generating genome size diversity and species richness were indeed independent and operate in parallel, suggesting a potential non-adaptive, non-causal but biologically meaningful relationship. KD depends on mutational input generating genetic diversity and reflects genome stability, whereas species richness depends on ecological factors and reflects natural selection acting on phenotypic diversity. As mutation and selection operate independently and involve separate and unrelated evolutionary mechanisms-there is no reason a priori to expect such a strong, let alone any, correlation between KD and SR. That such a correlation exists is more consistent with Kimura's theory of non-adaptive radiation than with ecologically based adaptive theories of macro-evolution, which are not excluded in Kimura's non-adaptive theory. The following reviews recent evidence in support of Kimura's proposal, and other findings that contribute to a wider understanding of the molecular mechanisms underlying the process of non-adaptive radiation.


Asymmetric cell division in plants: mechanisms of symmetry breaking and cell fate determination.
Asymmetric cell division is a fundamental mechanism that generates cell diversity while maintaining self-renewing stem cell populations in multicellular organisms. Both intrinsic and extrinsic mechanisms underpin symmetry breaking and differential daughter cell fate determination in animals and plants. The emerging picture suggests that plants deal with the problem of symmetry breaking using unique cell polarity proteins, mobile transcription factors, and cell wall components to influence asymmetric divisions and cell fate. There is a clear role for altered auxin distribution and signaling in distinguishing two daughter cells and an emerging role for epigenetic modifications through chromatin remodelers and DNA methylation in plant cell differentiation. The importance of asymmetric cell division in determining final plant form provides the impetus for its study in the areas of both basic and applied science.


Choroiditis in a HIV-infected patient with disseminated cryptococcal infection: A case report and literature review.
Ocular involvement in AIDS patients is a common event mainly caused by inflammation or infection. Despite the high prevalence rate of cryptococcosis in these individuals, ocular features have been occasionally described. A 20-year-old Brazilian female with HIV infection recently diagnosed was admitted with a respiratory profile presumptively diagnosed as Pneumocystis jirovecii pneumonia; an ophthalmologic exam suggested choroiditis by this agent as well. She was complaining of headaches and blurred vision which led to cryptococcal meningitis diagnosis by a CSF positive India ink stain and Cryptococcus neoformans positive culture. Despite therapy based on amphotericin B plus fluconazole, her clinical state progressively worsened and the patient died one week later. At necropsy, disseminated cryptococcal infection was evidenced in several organs including eyes, which presented bilateral chorioretinitis. Cryptococcal ocular involvement in AIDS patients has been occasionally proved among the cases already reported. Thus, the post mortem exam is still pivotal to improve the quality of the clinical diagnosis, especially in limited-resource settings.


Analysing the Impact of Social Media on Students' Academic Performance: A Comparative Study of Extraversion and Introversion Personality.
The advent of technology in education has seen a revolutionary change in the teaching-learning process. Social media is one such invention which has a major impact on students' academic performance. This research analyzed the impact of social media on the academic performance of extraversion and introversion personality students. Further, the comparative study between these two personalities will be analysed on education level (postgraduate and undergraduate) and gender (male and female). The research was initiated by identifying the factors of social media impacting students' academic performance. Thereafter, the scale was developed, validated and tested for reliability in the Indian context. Data were collected from 408 students segregated into 202 males and 206 females. Two hundred and thirty-four students are enrolled in postgraduation courses, whereas 174 are registered in the undergraduate programme. One-way ANOVA has been employed to compare the extraversion and introversion students of different education levels and gender. A significant difference is identified between extraversion and introversion students for the impact of social media on their academic performance.


Hidden morbidity with "successful" early discharge.
This study was conducted to determine if early postnatal discharge (EDC; < or =48 hours) in well newborns had an effect on the rate of hospital readmission within the first week after hospital discharge when compared to infants who remained >48 hours after birth (later discharge, LDC). This was a retrospective medical chart review. Charts of infants born between January 1994 and December 1998, discharged as "well newborns" and treated subsequently at a primary children's hospital within 7 days of neonatal discharge, were reviewed. Infants were categorized by length of neonatal hospital stay, level of medical intervention (emergency department treatment or hospital admission), and final diagnosis. There was a significant increase in hospital readmission rate for LDC infants when compared to EDC infants. When considering jaundice alone as an admitting diagnosis, EDC infants were admitted at a higher rate than LDC infants and with higher serum bilirubin concentrations. Readmitted, jaundiced infants had been almost always breast-fed. Overall, EDC of well newborns appears to be a safe and reasonable practice. However, the risk for severe jaundice is an unresolved issue that requires a discharge strategy and early follow-up to prevent serious morbidity.


Patient-Specific Three-Dimensional Ultrasound Derived Computational Modeling of the Mitral Valve.
Several new techniques to repair the mitral valve affected by functional mitral regurgitation are in development. However, due to the heterogeneity of valve lesions between patients, predicting the outcomes of novel treatment approaches is challenging. We present a patient-specific, 3D ultrasound-derived computational model of the mitral valve for procedure planning, that faithfully mimics the pathological valve dynamics. 3D ultrasound images were obtained in three pigs induced with heart failure and which developed functional mitral regurgitation. For each case, images were segmented, and finite element model of mitral valve was constructed. Annular and papillary muscle dynamics were extracted and imposed as kinematic boundary conditions, and the chordae were pre-strained to induce valve tethering. Valve closure was simulated by applying physiologic transvalvular pressure on the leaflets. Agreement between simulation results and truth datasets was confirmed, with accurate location of regurgitation jets and coaptation defects. Inclusion of kinematic patient-specific boundary conditions was necessary to achieve these results, whereas use of idealized boundary conditions deviated from the truth dataset. Due to the impact of boundary conditions on the model, the effect of repair strategies on valve closure varied as well, indicating that our approach of using patient-specific boundary conditions for mitral valve modeling is valid.


Decline in tested and self-reported cognitive functioning after prophylactic cranial irradiation for lung cancer: pooled secondary analysis of Radiation Therapy Oncology Group randomized trials 0212 and 0214.
To assess the impact of prophylactic cranial irradiation (PCI) on self-reported cognitive functioning (SRCF), a functional scale on the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire (EORTC QLQ-C30). Radiation Therapy Oncology Group (RTOG) protocol 0214 randomized patients with locally advanced non-small cell lung cancer to PCI or observation; RTOG 0212 randomized patients with limited-disease small cell lung cancer to high- or standard-dose PCI. In both trials, Hopkins Verbal Learning Test (HVLT)-Recall and -Delayed Recall and SRCF were assessed at baseline (after locoregional therapy but before PCI or observation) and at 6 and 12 months. Patients developing brain relapse before follow-up evaluation were excluded. Decline was defined using the reliable change index method and correlated with receipt of PCI versus observation using logistic regression modeling. Fisher's exact test correlated decline in SRCF with HVLT decline. Of the eligible patients pooled from RTOG 0212 and RTOG 0214, 410 (93%) receiving PCI and 173 (96%) undergoing observation completed baseline HVLT or EORTC QLQ-C30 testing and were included in this analysis. Prophylactic cranial irradiation was associated with a higher risk of decline in SRCF at 6 months (odds ratio 3.60, 95% confidence interval 2.34-6.37, P<.0001) and 12 months (odds ratio 3.44, 95% confidence interval 1.84-6.44, P<.0001). Decline on HVLT-Recall at 6 and 12 months was also associated with PCI (P=.002 and P=.002, respectively) but was not closely correlated with decline in SRCF at the same time points (P=.05 and P=.86, respectively). In lung cancer patients who do not develop brain relapse, PCI is associated with decline in HVLT-tested and self-reported cognitive functioning. Decline in HVLT and decline in SRCF are not closely correlated, suggesting that they may represent distinct elements of the cognitive spectrum.


[Individualization of the dosimetric requirements of intracavitary irradiation in the radiotherapy of gynecologic patients].
The authors proposed a method of dosimetric planning in intracavitary irradiation taking into account the individual features of a patient, including the status of the uterus during the introduction of radiation sources into its cavity. To simulate the dynamics of a resultant uterus shift a special device was developed to obtain information required for individual planning. The proposed method is aimed at the prevention of undesirable radiation reactions and complications in healthy organs.


Effects of age on the serum concentration of alpha 1-acid glycoprotein and the binding of lidocaine in pediatric patients.
We determined the effect of age on the serum concentration of alpha 1-acid glycoprotein (alpha 1-AGP) in venous blood from 134 subjects who ranged in age from preterm neonates to 18-year-old adolescents. The mean (+/- SD) serum concentration of alpha 1-AGP, determined by radial immunodiffusion, increased significantly with age: the concentration found in neonates was less than that found in infants which, in turn, was less than that found in older children (p less than 0.001). In addition, we determined the effect of alpha 1-AGP on the free fraction of lidocaine in four groups of infants and children who received intravenous lidocaine (1.5 mg/kg). The percentage of free lidocaine correlated inversely and linearly with the serum alpha 1-AGP concentration (r2 = 0.617; p less than 0.001). The percentage of free lidocaine in the five neonates exceeded that in the older age groups. We conclude that the serum concentration of alpha 1-AGP increases while the free fraction of lidocaine decreases from early infancy to adolescence.