Effect of high vacuum and aspiration on phacoemulsification efficiency and chatter using a transversal ultrasound machine.
To examine the role of high vacuum and aspiration settings on efficiency using a transversal ultrasound (US) machine. John A. Moran Eye Center Laboratory, University of Utah, Salt Lake City, Utah, USA. Experimental study. Porcine lens nuclei were incubated in formalin for 2 hours and then cut into 2.0 mm cubes. Phacoemulsification was performed using the Whitestar Signature machine. Settings were bottle height 50 cm, on-time 6 milliseconds, and off-time 6 milliseconds. One hundred percent power was used for all 240 runs. Tested parameters were aspiration of 50 mL/min and 60 mL/min and vacuum of 500, mm Hg, 600 mm Hg, and 650 mm Hg. With continuous US, increasing aspiration from 50 mL/min to 60 mL/min significantly increased efficiency (23%). Increasing vacuum from 500 mm Hg to 650 mm Hg and from 600 mm Hg to 650 mm Hg significantly increased efficiency (20.2% and 13.6%, respectively). Higher vacuum and aspiration parameters did not influence the incidence of chatter events. In the micropulse US group, there was no significant efficiency increase with increasing vacuum or aspiration levels. There was a significant efficiency increase of continuous over micropulse US at an aspiration setting of 60 mL/min and vacuum settings of 600 mm Hg and 650 mm Hg. As aspiration and vacuum increased, efficiency increased under continuous transverse US. No significant efficiency improvement occurred at high aspiration and vacuum settings under micropulse US. At 60 mL/min aspiration and more than 600 mm Hg vacuum, continuous power was significantly more efficient than micropulse transverse US.


UBIAD1 alleviates ferroptotic neuronal death by enhancing antioxidative capacity by cooperatively restoring impaired mitochondria and Golgi apparatus upon cerebral ischemic/reperfusion insult.
Neuronal death due to over-oxidative stress responses defines the pathology of cerebral ischemic/reperfusion (I/R) insult. Ferroptosis is a form of oxidative cell death that is induced by disruption of the balance between antioxidants and pro-oxidants in cells. However, the potential mechanisms responsible for cerebral I/R-induced ferroptotic neuronal death have not been conclusively determined. UBIAD1, is a newly identified antioxidant enzyme that catalyzes coenzyme Q10 (CoQ10) and vitamin K2 biosynthesis in the Golgi apparatus membrane and mitochondria, respectively. Even though UBIAD1 is a significant mediator of apoptosis in cerebral I/R challenge, its roles in ferroptotic neuronal death remain undefined. Therefore, we investigated whether ferroptotic neuronal death is involved in cerebral I/R injury. Further, we evaluated the functions and possible mechanisms of UBIAD1 in cerebral I/R-induced ferroptotic neuronal death, with a major focus on mitochondrial and Golgi apparatus dysfunctions. Ferroptosis occurred in cerebral I/R. Ferroptotic neuronal death promoted cerebral I/R-induced brain tissue injury and neuronal impairment. UBIAD1 was expressed in cerebral tissues and was localized in neurons, astrocytes, and microglia. Under cerebral I/R conditions overexpressed UBIAD1 significantly suppressed lipid peroxidation and ferroptosis. Moreover, upregulated UBIAD1 protected against brain tissue damage and neuronal death by alleviating I/R-mediated lipid peroxidation and ferroptosis. However, UBIAD1 knockdown reversed these changes. Enhanced UBIAD1-mediated ferroptosis elevated the antioxidative capacity by rescuing mitochondrial and Golgi apparatus dysfunction in cerebral I/R-mediated neuronal injury. They improved the morphology and biofunctions of the mitochondria and Golgi apparatus, thereby elevating the levels of SOD, T-AOC and production of CoQ10, endothelial nitric oxide synthase (eNOS)-regulated nitric oxide (NO) generation as well as suppressed MDA generation. The neuroprotective agent, UBIAD1, modulates I/R-mediated ferroptosis by restoring mitochondrial and Golgi apparatus dysfunction in damaged brain tissues and neurons, thereby enhancing antioxidative capacities. Moreover, the rescue of impaired mitochondrial and Golgi apparatus as a possible mechanism of regulating ferroptotic neuronal death is a potential treatment strategy for ischemic stroke.


Adsorption and desorption of phenylarsonic acid compounds on metal oxide and hydroxide, and clay minerals.
Adsorption and desorption of p-arsanilic acid (p-ASA) and roxarsone (ROX) on six soil minerals, including hematite (α-Fe2O3), goethite (α-FeOOH), ferrihydrite (Fe(OH)3), aluminum oxide (α-Al2O3), manganese oxide (γ-MnO2), and kaolinite, were studied, and the impact of solution matrices on their adsorption was systematically evaluated. Adsorption of p-ASA/ROX on the metal (hydro)oxide and clay minerals occurred quickly (mostly within 2 h), and could be well described by the pseudo second-order kinetic model. The apparent maximum adsorption capacities of α-Fe2O3, α-FeOOH, Fe(OH)3, α-Al2O3, γ-MnO2, and kaolinite (at an initial pH of 7.0) for p-ASA were 1.7, 0.9, 2.5, 0.08, 1.1, and 0.02 μmol/m2, while those for ROX were 1.6, 0.7, 2.4, 0.1, 0.5, and 0.05 μmol/m2, respectively. Besides adsorbing p-ASA/ROX, γ-MnO2 also caused their oxidation. Experimental results suggest that formation of inner-sphere complexes through the arsonic acid group is the primary mechanism for adsorption of p-ASA/ROX on iron (hydro)oxides and γ-MnO2, while outer-sphere complexation plays a critical role in their adsorption on α-Al2O3 and kaolinite. Adsorption of p-ASA/ROX on the metal (hydro)oxide and clay minerals was affected by solution pH, co-existing metal ions (Ca2+, Mg2+, Al3+, Cu2+, Fe3+, and Zn2+), oxyanions (H2PO4-, HCO3-, and SO42-), and humic acid. The solid-to-liquid partition coefficients of p-ASA during the desorption from α-Fe2O3, α-FeOOH, Fe(OH)3, α-Al2O3, γ-MnO2, and kaolinite were 0.47, 2.69, 4.38, 0.03, 30.4, and 0.1 L/g, while those of ROX were 0.28, 1.68, 3.48, 0.02, 4.0, and 0.02 L/g, respectively. Agricultural soils with lower contents of organic carbon exhibited higher adsorption capacities towards p-ASA/ROX, which indicates that soil minerals play a key role in the adsorption of phenylarsonic acid compounds while organic matter could have strong inhibitory effect. These findings could help better understand and predict the transport and fate of p-ASA/ROX in surface soils with low contents of organic matter.


Current and projected heatwave-attributable occupational injuries, illnesses, and associated economic burden in Australia.
The costs of global warming are substantial. These include expenses from occupational illnesses and injuries (OIIs), which have been associated with increases during heatwaves. This study estimated retrospective and projected future heatwave-attributable OIIs and their costs in Australia. Climate and workers' compensation claims data were extracted from seven Australian capital cities representing OIIs from July 2005 to June 2018. Heatwaves were defined using the Excess Heat Factor. OIIs and associated costs were estimated separately per city and pooled to derive national estimates. Results were projected to 2030 (2016-2045) and 2050 (2036-2065). The risk of OIIs and associated costs increased during heatwaves, with the risk increasing during severe and particularly extreme heatwaves. Of all OIIs, 0.13% (95% empirical confidence interval [eCI]: 0.11-0.16%) were heatwave-attributable, equivalent to 120 (95%eCI:70-181) OIIs annually. 0.25% of costs were heatwave-attributable (95%eCI: 0.18-0.34%), equal to $AU4.3 (95%eCI: 1.4-7.4) million annually. Estimates of heatwave-attributable OIIs by 2050, under Representative Concentration Pathway [RCP]4.5 and RCP8.5, were 0.17% (95%eCI: 0.10-0.27%) and 0.23% (95%eCI: 0.13-0.37%), respectively. National costs estimates for 2030 under RCP4.5 and RCP8.5 were 0.13% (95%eCI: 0.27-0.46%) and 0.04% (95%eCI: 0.66-0.60), respectively. These estimates for extreme heatwaves were 0.04% (95%eCI: 0.02-0.06%) and 0.04% (95%eCI: 0.01-0.07), respectively. Cost-AFs in 2050 were, under RCP4.5, 0.127% (95%eCI: 0.27-0.46) for all heatwaves and 0.04% (95%eCI: 0.01-0.09%) for extreme heatwaves. Attributable fractions were approximately similar to baseline when assuming theoretical climate adaptation. Heatwaves represent notable and preventable portions of preventable OIIs and economic burden. OIIs are likely to increase in the future, and costs during extreme heatwaves in 2030. Workplace and public health policies aimed at heat adaptation can reduce heat-attributable morbidity and costs.


Cervical intraepithelial neoplasia III treatments by carbon dioxide laser.
162 women underwent one or more carbon dioxide laser conservative treatments for lesions of severe dysplasia and cervical intraepithelial neoplasia (CIN III) between 1982 and 1987. Therapy involved destruction of lesions by vaporisation in 45% of cases and excisional conisation in 55% (32% performed with a hand-held apparatus and 23% colposcopically guided). Rates of cure were, respectively, 93, 96.1 and 94.4%, with an overall rate of 2.5% for dropouts. Recurrences (rates, respectively, of 8.5, 5.8 and 5.5%) were associated with human papilloma virus in 92% of cases. The increasing numbers of very young women affected, as well as the spread of intraepithelial and condylomatous neoplastic lesions along the endocervical canal, are major reasons for the use of colposcopically guided carbon dioxide laser treatment.


Cytosolic delivery of the immunological adjuvant Poly I:C and cytotoxic drug crystals via a carrier-free strategy significantly amplifies immune response.
Co-delivery of chemotherapeutics and immunostimulant or chemoimmunotherapy is an emerging strategy in cancer therapy. The precise control of the targeting and release of agents is critical in this methodology. This article proposes the asynchronous release of the chemotherapeutic agents and immunostimulants to realize the synergistic effect between chemotherapy and immunotherapy. To obtain a proof-of-concept, a co-delivery system was prepared via a drug-delivering-drug (DDD) strategy for cytosolic co-delivery of Poly I:C, a synthetic dsRNA analog to activate RIG-I signaling, and PTX, a commonly used chemotherapeutics, in which pure PTX nanorods were sequentially coated with Poly I:C and mannuronic acid via stimulating the RIG-I signaling axis. The co-delivery system with a diameter of 200 nm enables profound immunogenicity of cancer cells, exhibiting increased secretion of cytokines and chemokines, pronounced immune response in vivo, and significant inhibition of tumor growth. Also, we found that intracellularly sustained release of cytotoxic agents could elicit the immunogenicity of cancer cells. Overall, the intracellular asynchronous release of chemotherapeutics and immunomodulators is a promising strategy to promote the immunogenicity of cancer cells and augment the antitumor immune response.


UNILATERAL ACUTE IDIOPATHIC MACULOPATHY IN A PATIENT WITH HAND-FOOT-MOUTH DISEASE: A CASE REPORT.
To demonstrate a rare cause of acute, focal chorioretinitis. Review of slit-lamp fundoscopy, color fundus photography, spectral-domain optical coherence tomography, and fluorescein angiography. Slit-lamp examination revealed parafoveal microaneurysms, parafoveal intraretinal hemorrhages, and outer segment irregularity in the left eye. Fundus photographs demonstrated retinal hemorrhages and a greyish-whitish sheen in the central parafoveal area. Optical coherence tomography was notable for a small pocket of outer segment and retinal pigment epithelium disruption and irregularity in the central foveal area of the left eye. Fluorescein angiography revealed increased focal macular leakage within a larger central area of leakage and staining. Unilateral acute idiopathic maculopathy and, specifically, coxsackievirus-related chorioretinitis should be considered in the differential diagnosis of atypical maculopathy.


Anti-Tumor Strategies by Harnessing the Phagocytosis of Macrophages.
Macrophages are essential for the human body in both physiological and pathological conditions, engulfing undesirable substances and participating in several processes, such as organism growth, immune regulation, and maintenance of homeostasis. Macrophages play an important role in anti-bacterial and anti-tumoral responses. Aberrance in the phagocytosis of macrophages may lead to the development of several diseases, including tumors. Tumor cells can evade the phagocytosis of macrophages, and "educate" macrophages to become pro-tumoral, resulting in the reduced phagocytosis of macrophages. Hence, harnessing the phagocytosis of macrophages is an important approach to bolster the efficacy of anti-tumor treatment. In this review, we elucidated the underlying phagocytosis mechanisms, such as the equilibrium among phagocytic signals, receptors and their respective signaling pathways, macrophage activation, as well as mitochondrial fission. We also reviewed the recent progress in the area of application strategies on the basis of the phagocytosis mechanism, including strategies targeting the phagocytic signals, antibody-dependent cellular phagocytosis (ADCP), and macrophage activators. We also covered recent studies of Chimeric Antigen Receptor Macrophage (CAR-M)-based anti-tumor therapy. Furthermore, we summarized the shortcomings and future applications of each strategy and look into their prospects with the hope of providing future research directions for developing the application of macrophage phagocytosis-promoting therapy.


Medication self-management in predominantly African American and Caribbean American people with epilepsy: The role of medication beliefs and epilepsy knowledge.
Suboptimal medication adherence is common in people with epilepsy (PWE) and disproportionally prevalent among racially/ethnically diverse patients. Understanding reasons and risks of suboptimal adherence is critical to developing interventions that reduce negative health outcomes. This cross-sectional study characterized common barriers to medication self-management, prevalence of negative medication beliefs, and gaps in epilepsy knowledge among predominantly African American and Caribbean American PWE and examined their interrelationships. Sixty-three PWE (Age = 42.1 ± 13.2; 60% female; 79% Black; 19% Hispanic/Latino) completed validated self-report questionnaires about medication self-management, medication beliefs, and epilepsy knowledge. Correlations and t-tests examined interrelationships. Four barriers to medication self-management were common, including not taking antiseizure medications at the same time every day, forgetting doses, not planning refills before running out, and spreading out doses when running low. More than half the sample believed medications were overused by prescribers. Nearly one-third believed medications were harmful, and nearly a quarter believed their antiseizure medications were minimally necessary with almost half reporting elevated concerns about negative consequences of antiseizure medications. Poorer medication self-management was associated with stronger beliefs that medications in general are harmful/overused by prescribers. Individuals who were "accepting" of their antiseizure medications (i.e., high perceived necessity, low concerns) were less likely to spread out time between doses when running low compared to non-accepting counterparts. Knowledge gaps related to the cause of seizures/epilepsy, chronicity of epilepsy treatment, and seizure semiology/diagnosis were common. Nevertheless, epilepsy knowledge was unrelated to medication self-management and medication beliefs. In these PWE, the most prevalent reasons for suboptimal medication self-management were behaviorally mediated and potentially modifiable. Negative medication beliefs and misconceptions about epilepsy and its treatment were common. Results further suggest that interventions addressing negative medication beliefs will be more effective than knowledge-based psychoeducation alone to improve medication self-management in this patient population.


Relative dose intensity and 1-year psoas muscle index reduction rate as prognostic factors in gastric cancer patients with postoperative adjuvant chemotherapy.
Higher relative dose intensity (RDI) of chemotherapy improves the clinical outcomes of various cancers. The psoas muscle index (PMI) is related to sarcopenia, and patients with low PMI have worse prognoses. However, few studies have demonstrated its clinical relevance in gastric cancer. This retrospective study included 188 stage II/III gastric cancer patients who had undergone curative gastrectomy between January 2013 and March 2017, 124 of whom had received postoperative S-1 adjuvant chemotherapy. Per receiver operating characteristic analysis, patients were divided into high and low RDI groups, between which relapse-free survival differed marginally significantly and disease-specific survival differed significantly. In patients who received adjuvant chemotherapy, multivariate analysis found that high RDI and low PMI reduction rate 1 year after surgery were significantly associated with better relapse-free survival. Low RDI can be predicted by a combination of low preoperative PMI and non-distal gastrectomy, whereas high PMI reduction rate at 1 year can be affected by non-distal gastrectomy. High RDI with preserved psoas muscle up to 1 year after gastrectomy may be associated with prognoses in gastric cancer requiring postoperative adjuvant chemotherapy. Since RDI and PMI reduction rate can be predicted preoperatively, respectively, interventional consideration is possible for optimal adjuvant therapy in gastric cancer.


Clinical pseudophakic cystoid macular edema. Risk factors for development and duration after treatment.
To characterize the incidence, duration, and risk factors for and outcome of cystoid macular edema (CME) after cataract surgery and investigate the effects of treatment regimens on visual outcome and duration. University-based comprehensive ophthalmology practice. This study included 1659 consecutive cataract surgeries performed by residents between 2001 and 2006. Cases were classified according to the presence of CME. Subset analysis excluded patients with diabetes mellitus (DM). The CME groups were analyzed according to type of treatment to compare duration of CME and final best corrected visual acuity. The incidence of postoperative CME was 2.35% (39/1659), and history of retinal vein occlusion (RVO) was predictive of postoperative CME (odds ratio [OR], 47.12; P<.001). When patients with DM were excluded, the incidence of CME was 2.14% (29/1357) and history of RVO (OR, 31.75; P<.001), epiretinal membrane (ERM) (OR, 4.93; P<.03), and preoperative prostaglandin use (OR, 12.45; P<.04) were predictive of postoperative CME. Patients with DM and/or intraoperative complications did not have an increased risk for CME when treated with prophylactic postoperative nonsteroidal antiinflammatory drugs (NSAIDs) for 3 months. Groups treated with NSAIDs plus a steroid had significantly shorter resolution times than the untreated group (P = .004). A history of RVO, ERM, and preoperative prostaglandin use were associated with an increased risk for pseudophakic CME. Treatment with NSAIDs plus steroids was associated with faster resolution of CME than no treatment. Treating high-risk patients with NSAIDs after cataract surgery decreases the incidence of postoperative CME to that of patients who are not at high risk.


Erysipelas and acute myocarditis: an unusual combination.
Myocarditis is a rare disease with variable clinical presentation and diverse electrocardiographic and echocardiographic features. Viral infection is the most common cause, but myocarditis can also be caused by bacterial infection. The most frequently involved bacterial agent is group A Streptococcus, which is also an etiologic agent of erysipelas. We present the case of a man aged 46 years with left-leg erysipelas who developed myocarditis. Cardiac magnetic resonance played an essential role in diagnosis. This case is, to our knowledge, the first description of an association between erysipelas and myocarditis.


Report of two cases of gastric cancer after bariatric surgery: lymphoma of the bypassed stomach after Roux-en-Y gastric bypass and gastrointestinal stromal tumor (GIST) after vertical banded gastroplasty.
We report two new cases of gastric cancer diagnosed after a bariatric operation. The first case is a 66-year-old male who 3 years after gastric bypass suffered from a perforation of the fundus that was found to be secondary to a diffuse large B-cell lymphoma of the distal stomach. The second case is a 47-year-old woman who presented 12 years after a vertical banded gastroplasty with a gastric pouch outlet obstruction caused by a gastrointestinal stromal tumor (GIST). Based on the few reports of cancer in the literature, analysis of these cases suggests that the main risk of gastric cancer after bariatric surgery comes from the delayed diagnosis of malignancy.


Feasibility and efficacy of thrombolysis in acute ischemic stroke: A study from National Institute of Neurological and Allied Sciences, Kathmandu, Nepal.
Stroke is the major cause of morbidity and mortality worldwide. The number of stroke patients receiving recombinant tissue plasminogen activator (rt-PA), also known as Alteplase, in the developing world is extremely low. We aim to study the feasibility and efficacy of thrombolysis for the 1(st) time in our country. In this retrospective study (July 2012-August 2015), acute ischemic stroke patients who were thrombolyzed within 3 h of stroke onset were included. Their demographic profiles, clinical profiles, risk factors, type of thrombolytic used, and outcomes were systematically recorded and analyzed. A total of 9 patients were thrombolyzed. The mean time from the onset of stroke symptoms to first dose of rt-PA (onset to treatment) was 1.2 h. Six patients had good neurological outcome as measured by modified Rankin Scale (mRS). The median mRS at discharge was 3. Thrombolysis-related post treatment complication was noted in 44.4%, of which nonfatal intracranial bleed occurred only in 2 patients (22.2%). None of the patients receiving intravenous tenecteplase had thrombolysis-related complications, and none of the patients had fatal intracranial bleed. This study clearly demonstrates the beginning of a feasible and effective thrombolysis in the treatment of acute ischemic stroke in Nepal.


Firing rate dynamics in recurrent spiking neural networks with intrinsic and network heterogeneity.
Heterogeneity of neural attributes has recently gained a lot of attention and is increasing recognized as a crucial feature in neural processing. Despite its importance, this physiological feature has traditionally been neglected in theoretical studies of cortical neural networks. Thus, there is still a lot unknown about the consequences of cellular and circuit heterogeneity in spiking neural networks. In particular, combining network or synaptic heterogeneity and intrinsic heterogeneity has yet to be considered systematically despite the fact that both are known to exist and likely have significant roles in neural network dynamics. In a canonical recurrent spiking neural network model, we study how these two forms of heterogeneity lead to different distributions of excitatory firing rates. To analytically characterize how these types of heterogeneities affect the network, we employ a dimension reduction method that relies on a combination of Monte Carlo simulations and probability density function equations. We find that the relationship between intrinsic and network heterogeneity has a strong effect on the overall level of heterogeneity of the firing rates. Specifically, this relationship can lead to amplification or attenuation of firing rate heterogeneity, and these effects depend on whether the recurrent network is firing asynchronously or rhythmically firing. These observations are captured with the aforementioned reduction method, and furthermore simpler analytic descriptions based on this dimension reduction method are developed. The final analytic descriptions provide compact and descriptive formulas for how the relationship between intrinsic and network heterogeneity determines the firing rate heterogeneity dynamics in various settings.


Photochemical degradation in natural attenuation of characteristics of petroleum hydrocarbons (C10-C40) in crude oil polluted soil by simulated long term solar irradiation.
Photodegradation process plays an important role in the natural attenuation of petroleum hydrocarbons (PHs) in oil contaminated soil. The photodegradation characteristics of PHs (C10-C40) in topsoil of crude oil contaminated soil irradiated by simulated sunlight in 280 d without microbial action were investigated. The results showed that photodegradation rate of PHs was increased with increasing the light intensity and decreased with increasing the initial concentration of PHs. Moreover, the photodegradation capacity of tested PHs was relevant to the length of carbon chain. The photodegradation rates of C10-C20 were higher than that of C21-C40 in photoperiod. C21-C40 showed an obvious trend of photodegradation after 56 d, although their photodegradation rates were less than 20% at the early stage. And, the redundancy analysis indicated that lighting time was the primary factor for photodegradation of PHs under abiotic conditions. The photodegradation rate was well interpreted by a two-stage, first-order kinetic law with a faster initial photolysis rate. The EPR spectrums showed that simulated solar irradiation accelerated the generation of superoxide radicals, which could react with PHs in soil. Also, the function groups in PHs polluted soil were changed after light exposure, which might imply the possible photodegradation pathway of PHs.


Microglia: Rheostats of space radiation effects in the CNS microenvironment.
Microglia are innate immune cells within the brain that arise from a distinct myeloid lineage. Like other tissue resident macrophages, microglia respond to injury or immune challenges and participate in reparative processes such as phagocytosis to preserve normal function. Importantly, they also participate in normal homeostatic processes including maintenance of neurogenic niches and synaptic plasticity associated with development. This review highlights aspects of microglial biology and how repeated insults that occur with age, neurodegenerative disease and possibly radiation exposure may heighten microglial responses and contribute to their dysfunction, creating a situation where their normal reparative mechanisms are no longer sufficient to maintain brain health. These ideas are discussed in the context of an evolving literature focused on microglial responses as possible targets for mitigation of late CNS radiation effects that represent potential risks for future exploration of deep space environments.


Dipeptide metabolism in the isolated perfused rat kidney.
Renal handling of glycyl-proline was studied in the isolated perfused rat kidney. Glycyl-proline disappeared from the perfusate as a function of time. The dipeptide was freely filtered at the glomerulus but only 6% of the filtered load was excreted in the urine as the intact peptide. More than 90% of the filtered dipeptide was reabsorbed as the intact peptide and/or its hydrolytic products. Non-filtration mechanisms were also involved to a significant extent in the clearance of the peptide. Hydrolysis at intratubular, intracellular and peritubular sites all contribute to the disappearance of the dipeptide from the perfusate, though the relative contributions of each mechanism are not known. Significant metabolic conversions, especially the conversion of glycine to serine, were also observed during perfusion.


Effect of Fluoride on Small Intestine Morphology and Serum Cytokine Contents in Rats.
This study aimed to determine the effect of excessive fluoride (F) on the morphological characteristics of the small intestine and the contents of serum cytokines in rats. A total of 48 3-week-old healthy female Sprague-Dawley rats were randomly divided into four groups (n = 12). The control group was given deionized distilled water, while the F treatment groups were treated with water containing 25, 50, and 100 mg F-/L. After 70 days of treatment, the duodenum, the jejunum, and the ileum were collected to measure the developmental parameters and the distribution of intestinal glycoproteins, goblet cells, and mast cells through Pannoramic Viewer, Periodic Acid-Schiff (PAS) staining, Alcian blue and periodic acid-Schiff (AB-PAS) staining, and toluidine blue staining, respectively. The contents of cytokines, namely, interleukin (IL)-1β, IL-2, IL-6, and tumor necrosis factor (TNF)-α, in serum were detected via enzyme-linked immunosorbent assay (ELISA). Results showed that the villus height, crypt depth, villus height to crypt depth ratio, goblet cells, glycoproteins, and mast cells of the small intestine significantly decreased (P < 0.05 or P < 0.01) in the F treatment group. The contents of IL-1β, IL-2, IL-6, and TNF-α were significantly lower in the F treatment group than in the control group (P < 0.05 or P < 0.01). In summary, excessive F intake impaired intestinal development and immune function by decreasing the developmental parameters and the distribution of immune cells, glycoproteins, and cytokines.


Remodeling of abdominal aortic aneurysm sac following endovascular aortic repair: association with clinical, surgical, and genetic factors.
After successful endovascular aortic repair (EVAR), abdominal aortic aneurysms (AAA) sac will undergo negative remodeling (i.e., shrinkage) as a measure of successful exclusion. Determinants of shrinkage after EVAR are not fully known. In 84 post-EVAR patients, time course of AAA diameter after repair and occurrence of endoleaks (ELs) have been correlated with clinical history, medications, anthropometric data, vascular anatomy, and matrix metalloprotease (MMP) genetic variants (namely MMP-1 rs1799750, MMP-3 rs35068180, MMP-9 rs2234681, rs917576, rs917577, MMP-12 rs652438, and TIMP1 rs4898). During follow-up, 41 ELs were detected in 37 patients (44%, 10.4 events/100 pt./y), accounting for AAA dilation or reduced shrinkage (P < .001). High-flow ELs (type 1 and/or 3) occurrence was associated with warfarin use, MMP9 rs17577 polymorphism, and unfavorable anatomy, while low-flow type 2 ELs occurred more often in TIMP1 rs4898 non-T carriers. In EL-free patients, AAA diameter decreased for the first three years, (-4, -3 and - 2 mm/year respectively) and remained stable thereafter. Shrinkage between two measurements (n = 120) was associated with smaller AAA diameter at the baseline, peripheral arterial disease (PAD), patients' older age at intervention, and G-/G- genotype in MMP1 rs1799750 (binary logistic regression, P = .0001). Aneurysmal sac shrinking occurs for few years after EVAR, only in patients without EL, and is related to older age, PAD, smaller aneurysm size and putative lower MMP1 expression while EL occurrence prevents such a remodeling and is mainly related to local-acting factors like unfavorable anatomy, anticoagulation, and MMP9 and TIMP1 genetic polymorphisms.


Effect of molsidomine on coronary collateral blood flow in acute myocardial ischemia.
The actions of molsidomine, a new antianginal agent, on coronary collateral blood flow and myocardial oxygen consumption were studied in anesthetized dogs with acute ligation of the distal third of the left anterior descending coronary artery. Molsidomine (50 and 100 microgram/kg, i.v.) produced a significant decrease in myocardial oxygen consumption, however no change occurred in collateral blood flow. These results suggest that the beneficial actions of molsidomine in myocardial ischemia are primarily due to a decrease in oxygen demand.


What kind of simple fasting index should be used to estimate insulin sensitivity in humans?
The hyperinsulinemic euglycemic glucose clamp method is the gold standard for measuring insulin resistance. However it is complex, and simple indexes have been developed. Some of them are based on formulae that calculate the product or the addition of fasting plasma insulin and glucose values whereas others are based on their ratios. We calculated several simple indexes of insulin resistance and compared them to hyperinsulinemic euglycemic clamp data in 111 subjects with a wide range of insulin resistance. We showed that indexes using insulin and glucose ratios in their formulae are poorly correlated with clamp measurements and give false evaluations, particularly in glucose-intolerant and type 2 diabetic subjects. Thus, whatever the glucose profile of study subjects, we suggest the use of a simple index based on the product or the addition of fasting plasma insulin and glucose values instead of their ratios to obtain insulin resistance evaluations close to the hyperinsulinemic euglycemic clamp technique.


Analysis of telomerase as a diagnostic biomarker of cervical dysplasia and carcinoma.
Telomerase expression is a potentially important marker of high-grade cervical dysplasia and squamous cell carcinoma (SCC). The routine practice of cervical cytology is limited by problems of false negative diagnoses as well as by poor specificity for clinically significant lesions in patients with low-grade cytologic abnormalities. Telomerase is widely expressed in most SCCs as well as in a high proportion of high-grade squamous intraepithelial lesions. Histochemical studies have confirmed that telomerase is expressed in the lower portions of normal or metaplastic squamous mucosa but that telomerase positive cells extend into the upper epithelial layers in cases of high-grade dysplasia. Since the cervical smear samples the uppermost cell layers of the cervical mucosa, but does not normally include cells derived from the lower layers of the squamous mucosa, the detection of telomerase in exfoliated cells of the cervical smear may have specificity for clinically significant lesions. The analysis of hTR, hTERT, and telomerase activity are complicated by a number of technical factors that may lead to either false negative or false positive test results. Thus, the practical application of telomerase analysis as a diagnostic adjunct for cervical cytopathology may depend on the development of more reliable and sensitive assay systems, possibly formatted for cytochemical applications.


Contribution of the anterior longitudinal ligament to ossification and growth of the vertebral body: an immunohistochemical study using the human fetal lumbar vertebrae.
Using 15 mid-term human fetuses, we examined the role of the spine anterior and posterior longitudinal ligaments (ALL, PLL) in ossification of the lumbar vertebral body. By 18 weeks, a pair of calcified tissue or cortical walls had developed on the anterior and posterior sides of the ossification center. These calcified cortical walls were more highly eosinophilic than trabecular or woven bone in the ossification center. Vimentin-positive osteoblasts were arranged in line along the outer surface of the walls. However, few CD68-positive osteoclasts were evident around the walls, suggesting that the calcification in the walls was similar to periosteal ossification. The anterior cortical wall was connected tightly with the ALL by fiber bundles, but the posterior wall was separated from the PLL by the basivertebral (central) vein and loose tissues. Notably, by 30 weeks, the anterior cortical wall had become attached to and incorporated into the ALL. Thus, the ALL seemed to act as an active periosteum for ossification. Although our materials were limited in number and stage, we hypothesized that, in contrast to the PLL, the mature anterior cortical wall corresponds to a calcified fibrocartilage adjacent to the ALL and forms a bone-ligament interface maintaining an ossification potential.


HOXC8: a predictive glioma biomarker that induces epithelia-mesenchymal transition.
The transcription factor Homeobox C8 (HOXC8) is overexpressed and regulates many important genes involved in the proliferation and invasion of many malignant tumors. However, the function of HOXC8 in gliomas remains unclear. Based on the Chinese Glioma Genome Atlas (CGGA) set, HOXC8 expression is negatively correlated with overall survival (OS). Small interfering RNA (si-HOXC8) was used to downregulate the mRNA and protein expression levels of HOXC8 to assess glioma cell proliferation, migration and invasion. Patients with higher HOXC8 levels showed poorer prognosis. DAVID analysis results indicated that HOXC8 was related to cell cycle, cell adhesion and immune response. In U251 and LN229 glioma cells treated with small interfering RNA for HOXC8 (si-HOXC8) for gene knockdown, significantly lower cell capacity of growth, migration and invasion was observed. Moreover, HOXC8 knockdown could reduce the protein expression of classical epithelial mesenchymal transition (EMT) related markers. HOXC8 may play an important role in glioma proliferation, migration and invasion. These findings indicated that HOXC8 may constitute a novel target for glioma treatment.


Severe hypertension and massive proteinuria in a newborn with renal artery stenosis.
Renal vein thrombosis and the congenital nephrotic syndrome have been associated with nephrotic-range proteinuria/nephrotic syndrome and hypertension in the newborn period. We describe a newborn with severe hypertension and proteinuria secondary to unilateral renal artery stenosis. Proteinuria completely disappeared with blood pressure control (with sodium nitroprusside and an angiotensin-converting enzyme inhibitor). Although renin was not measured, we speculate that proteinuria might have been induced by a high renin state, and was controlled by the angiotensin-converting enzyme inhibitor.


Eosinophils: 'new' roles for 'old' cells.
Prominent blood and tissue eosinophilia is manifested in a number of inflammatory states, particularly in allergic diseases. Eosinophils are a source of numerous cytokines and growth factors, thus in principle they can display both pro-inflammatory and anti-inflammatory activities as well as immunoregulatory ones. In this review, we will discuss the cross-talk between eosinophils and other cell types that they come in contact with in the inflammatory milieu, such as mast cells, fibroblasts and endothelial cells. 'New' roles for eosinophils in cancer and novel activatory signals will also be described.


Early maladaptive schemas are associated with self-injury thoughts and behavior in adolescents.
Early maladaptive schemas (EMSs) and self-harm have been firmly linked in adults, but research on these associations in adolescents remains scarce. Additionally, the links between EMSs and functions of self-injury has not been previously studied in this age group. Thus, the aim of the present study was to investigate the associations of EMSs with self-harm thoughts and behavior, as well as with self-harm functions, among adolescents in specialized health care. The participants were recruited from first-visit 12-22-year-old adolescent patients entering specialized mental health care or pediatric care. For 118 participants, complete data were available for the Young Schema Questionnaire Short Form 2-Extended (YSQ) when entering care and the Ottawa Self-Injury Inventory Functions scale (OSI-F) one year later. YSQ was used to measure the participants' EMSs and OSI-F their self-harm thoughts and behavior. The associations of EMSs and self-harm were investigated in three groups: no self-harm, self-harm thoughts only, and both self-harm thoughts and behavior. The associations of EMSs with self-injury behavior functions were assessed in four categories: Internal Emotional Regulation, External Emotional Regulation, Social Influence, and Sensation Seeking. Additionally, EMSs' associations with addictive features of self-injury behavior were assessed. The magnitudes of effect sizes of differences between the self-harm groups were evaluated with Cliff's Delta. The associations of EMSs with self-injury functions were analyzed with general linear modeling and with self-injury addictive features using logistic regression. The differences between the self-harm groups were significant for the majority of the EMSs. The stronger the EMSs were, the more severe the manifestations of self-harm. The effect sizes ranged from small to large depending on the EMS. Considering self-injury functions, Internal Emotional Regulation was associated with Self-Sacrifice EMS (p = 0.021), and External Emotional Regulation both with Abandonment (p = 0.040) and Unrelenting Standards (p = 0.012) EMSs. Being addicted to self-injury was associated with Abandonment (p = 0.043) and Dependence (p = 0.025) EMSs. The present study shows that significant associations between EMSs and both self-harm thoughts and behavior exist also in adolescents. Stronger EMSs are linked to more severe self-harm. Knowledge of these associations may help to improve the understanding and treatment of adolescents suffering from self-harm.


Susceptibility to IDDM is marked by MHC supratypes rather than individual alleles.
107 patients with insulin-dependent diabetes mellitus (IDDM) were typed for HLA A, B, C-, and DR antigens, and for complement C4A, C4B, and Bf alleles, and the results were compared with those of a combined reference group of 332 appropriately matched healthy subjects. Supratypes (allelic combinations) were identified from the phenotype of each group, and it was shown that the frequency of several supratypes is increased in patients with IDDM, in particular supratypes (A1 Cw7) B8 C4AQ0 C4B1 BfS DR3 (P = 0.0001), (A30 Cw-) B18 C4A3 C4BQ0 BfF1 DR3 (P = 0.0003), (A2 Cw3) B62 C4AR C4B2.9 BfS DR4 (P = 0.0002), and three other supratypes including DR4. It was also shown that increases in the frequency of individual alleles are secondary to increases in supratype frequency. Moreover, supratypes appeared to interact; the presence of two relevant supratypes being particularly important. The absolute risk of IDDM was approximately 0.5 in subjects who were homozygous for B18 C4A3 C4BQ0 BfF1 DR3. We concluded that genetic susceptibility is best recognized by MHC supratypes rather than isolated alleles, and that supratype combinations make the identification of even greater disease risk possible.


Lung antibacterial defense mechanisms in infant and adult rats: implications for the pathogenesis of group B streptococcal infections in the neonatal lung.
We investigated factors that may contribute to lung infections in infants by studying the intrapulmonary responses to aerosols of three different types of organisms--group B streptococcus with and without type-specific capsule, Pseudomonas aeruginosa, and Staphylococcus aureus--in infant (12-h-old or 24-36-h-old) and adult (150 g, 6-w-old) rats. After aerosol exposure, the lung clearance rate of each organism varied inversely with the age of the animals, and the magnitude of the clearance defect was related more strongly to animal age than to the bacterial species. Fewer alveolar macrophages from infant animals phagocytosed each type of organism in vivo, and the rate of neutrophil accumulation in the lungs of infant animals was delayed. The neonatal lung functioned effectively, however, as an antibacterial barrier, as newborn animals survived an aerosolized inoculum that exceeded the LD50 by the subcutaneous route.


Antibacterial and immunomodulator activities of virgin coconut oil (VCO) against Staphylococcus aureus.
Antibiotics have components to inhibit infections against Staphylococcus aureus, but they depend on judicious use to minimize the incidence of resistance forms. Strategies to improve the current situation include research in finding a new antimicrobial from virgin coconut oil (VCO). The saturated fatty acid, lauric acid (LA) (C12) contain in VCO was reported to have antibacterial activities. This study developed antimicrobial of VCO as an antimicrobial and immunomodulatory agent. Staphylococcus aureus used in this study had been isolated and identified from the mastitis milk crossbreed Etawa goat from Riau, Indonesia. The susceptibility of S. aureus to VCO was tested using the broth dilution method. The inhibition mechanisms of S. aureus had been studied by scanning electron microscopy (SEM) after treatment with VCO, and potential of VCO, which is known in phagocytosis macrophage. In vitro test confirmed the inhibitory effect of VCO on the growth of S. aureus at the concentration of 200 μl (equal to 0.102 % LA). Based on the result of the phagocytosing assay, VCO could increase the ability of the macrophage cells to phagocyte S. aureus significantly at a concentration of 200 μL (equal to 0.102% LA). This study concluded that the VCO could inhibit the growth of S. aureus with destructive mechanisms of bacterial cell walls and increase the ability of the phagocytic immune cells.


[Results of radiation therapy of recurrent gastric cancer].
Thirty-six cases with recurrent gastric carcinoma were treated with radiation at the National Cancer Center Hospital between 1962 and 1983. There are 17 local, 12 peritoneal and 7 lymph node recurrences, and the 50% survival months were 7.2, 5.1, and 3.8 months respectively. The survival rates of these patients were 17% at one year, 5% at two year, and 3% at three year. As a conclusion, it was suggested that combined radiation therapy with some anticancer drugs should be effective procedure to prolong the life of patients with recurrent gastric carcinoma.


JMJD2A sensitizes gastric cancer to chemotherapy by cooperating with CCDC8.
Jumonji domain-containing protein 2A (JMJD2A) of the JMJD2 family of histone lysine demethylases has been implicated in tumorigenesis. However, its expression and role in gastric cancer (GC) drug resistance remain unknown. Here, we investigated the role of JMJD2A in GC chemotherapeutic susceptibility and its clinical relevance in GC. We selected 12 relevant genes from previously identified gene signatures that can predict GC susceptibility to docetaxel, cisplatin, and S-1 (DCS) therapy. Each gene was knocked down using siRNA in GC cell lines, and cell viability assays were performed. JMJD2A expression in GC cell lines and tissues was assessed using qRT-PCR and immunohistochemistry, respectively. A JMJD2A downstream target related to drug susceptibility was examined using whole-gene expression array and immunoprecipitation. Among the 12 candidate genes, down-regulation of JMJD2A showed the maximum effect on GC susceptibility to anti-cancer drugs and increased the IC50 values for 5-FU, cisplatin, and docetaxel 15.3-, 2.7-, and 4.0-fold, respectively. JMJD2A was universally expressed in 12 GC cell lines, and its overexpression in GC tissue was positively correlated with tumor regression in 34 DCS-treated patients. A whole-gene expression array of JMJD2A-knockdown GC cells demonstrated a significant decrease in the expression of pro-apoptotic coiled-coil domain containing 8 (CCDC8), a downstream target of JMJD2A. Direct interaction between CCDC8 and JMJD2A was verified using immunoprecipitation. CCDC8 inhibition restored drug resistance to docetaxel, cisplatin, and S-1. Our results indicate that JMJD2A is a novel epigenetic factor affecting GC chemotherapeutic susceptibility, and JMJD2A/CCDC8 is a potential GC therapeutic target.


Oxygen-evolving photosynthetic cyanobacteria for 2D bismuthene radiosensitizer-enhanced cancer radiotherapy.
The local hypoxic tumor environment substantially hampers the therapeutic efficiency of radiotherapy, which typically requires the large X-ray doses for tumor treatment but induces the serious side effects. Herein, a biomimetic radiosensitized platform based on a natural in-situ oxygen-evolving photosynthetic cyanobacteria combined with two-dimensional (2D) bismuthene with high atomic-number (Z) components, is designed and engineered to effectively modulate the radiotherapy-resistant hypoxic tumor environment and achieve sufficient radiation energy deposition into tumor. Upon the exogenous sequential irradiation of 660 nm laser and X-ray beam, continuous photosynthetic oxygen evolution by the cyanobacteria and considerable generation of reactive oxygen species by the 2D bismuthene radiosensitizer substantially augmented the therapeutic efficacy of radiotherapy and suppressed the in vivo tumor growth, as demonstrated on both LLC-lung tumor xenograft-bearing C57/B6 mice model and 4T1-breast tumor xenograft-bearing Balb/c mice model, further demonstrating the photosynthetic hypoxia-alleviation capability and radiosensitization performance of the engineered biomimetic radiosensitized platform. This work exemplifies a distinct paradigm on the construction of microorganism-enabled tumor-microenvironment modulation and nanoradiosensitizer-augmented radiotherapy for efficient tumor treatment.


Author Correction: Anti-amnesic and anti-cholinesterase activities of α-asarone against scopolamine-induced memory impairments in rats.
Correction to: Eur Rev Med Pharmacol Sci 2022; 26 (17): 6344-6350. DOI: 10.26355/eurrev_202209_29660-PMID: 36111936-published online on September 15, 2022. After publication, the authors applied some corrections to the Acknowledgement section as the Grant Code was incorrect. The section has been amended as follows: - The authors extend their appreciation to the Deanship of Scientific Research at King Khalid University for funding this work through Large Groups Project under grant number (RGP.2/125/44). There are amendments to this paper. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/29660.


Long-term cimetidine and anticholinergic therapy in patients with gastrinoma.
Two patients with gastrinomas were treated with cimetidine and an anticholinergic drug for greater than 20 months after exploratory laparotomy disclosed no solitary resectable tumor. Both have done well, and thus this therapy is recommended as a safe and effective alternative to total gastrectomy in reliable patients. Additional therapeutic methods are needed to control tumor growth.


Alterations in High-Frequency Neuronal Oscillations in a Cynomolgus Macaque Test of Sustained Attention Following NMDA Receptor Antagonism.
A growing body of evidence indicates that neuronal oscillations in the gamma frequency range (30-80 Hz) are disturbed in schizophrenic patients during cognitive processes and may represent an endophenotype of the disease. N-methyl-D-aspartate (NMDA) receptor antagonists have been used experimentally to induce schizophrenia-like symptoms including cognitive deficits in animals and humans. Here we characterized neuronal oscillations and event-related potentials (ERPs) in Cynomolgus macaques fully trained to perform a continuous performance test (CPT) in the presence and absence of the NMDA antagonist phencyclidine (PCP). Macaques (n=8) were trained to touch 'target' stimuli and ignore 'distractor' stimuli presented randomly on a touchscreen. Subsequently, all subjects were implanted with epidural EEG electrodes over frontal (FC) and parietal cortices (PC) and later tested under vehicle (saline, i.m.) or acute PCP (0.1-0.3 mg/kg, i.m.) conditions. Compared with vehicle treatment, PCP produced a significant dose-dependent decrease in CPT performance accuracy and increased reaction times. Furthermore, PCP elevated the amplitudes of 'low' (30-50 Hz) and 'high' (51-80 Hz) gamma oscillations in FC and PC around target presentations for all correct responses. The CPT accuracy was inversely correlated with the gamma band amplitude in the presence of PCP. Additionally, PCP delayed the N100 peak latency in FC, and prolonged and suppressed the cognitively relevant P300 component of mean ERPs in FC and PC, respectively. The NMDA receptor antagonist-induced alteration in neuronal oscillations and ERPs may contribute to the observed cognitive deficits in macaques, and enhance our understanding of EEG recordings as a translatable biomarker.


Role of TNF-alpha in lung tight junction alteration in mouse model of acute lung inflammation.
In the present study, we used tumor necrosis factor-R1 knock out mice (TNF-alpha R1KO) to understand the roles of TNF-alpha on epithelial function in models of carrageenan-induced acute lung inflammation. In order to elucidate whether the observed anti-inflammatory status is related to the inhibition of TNF-alpha, we also investigated the effect of etanercept, a TNF-alpha soluble receptor construct, on lung TJ function. Pharmacological and genetic TNF-alpha inhibition significantly reduced the degree of (1) TNF-alpha production in pleural exudates and in the lung tissues, (2) the inflammatory cell infiltration in the pleural cavity as well as in the lung tissues (evaluated by MPO activity), (3) the alteration of ZO-1, Claudin-2, Claudin-4, Claudin-5 and beta-catenin (immunohistochemistry) and (4) apoptosis (TUNEL staining, Bax, Bcl-2 expression). Taken together, our results demonstrate that inhibition of TNF-alpha reduces the tight junction permeability in the lung tissues associated with acute lung inflammation, suggesting a possible role of TNF-alpha on lung barrier dysfunction.


Bidentate ligands by supramolecular chemistry--the future for catalysis?
In this Frontier Article we give our view on recent developments in transition-metal catalyst development that evolve from a combination of supramolecular strategies and traditional ligand design and development.


Composition and Flowering Quality of Cacahuacintle Maize Populations from the High Valleys of Mexico.
Cacahuacintle is one of the maize types with great demand for pozole preparation; however, little is known about the variation in chemical composition and flowered grain quality among populations. Physicochemical characteristics, flowered grain quality, pasting properties, and starch microstructure were evaluated in 33 populations of Cacahuacintle maize collected in Valles Altos, Mexico. The seeds samples of corn were obtained in 2017 from local farmers in the states of Mexico, Puebla, and Tlaxcala. Results were analyzed under a completely randomized design, and the ANOVA, Tukey test, and principal components were obtained. The ANOVA showed significance (p ≤ 0.05) in 18 of the 22 variables evaluated. The TE-6, AM-7, and CA-6 populations were outstanding for the good quality of their protein, pasting viscosity, and flowered grain quality. Nine populations collected in Calimaya, estate of Mexico, and Serdan Valley, state of Puebla, presented excellent physical, pasting, and flowery grain characteristics, with reduced protein content and lysine and tryptophan values typical of maize with normal endosperm. The softness of the endosperm grain, starch microstructural, and pasting characteristics of Cacahuacintle maize populations have a fundamental role in reducing the time and increasing the flowered grain volume, properties that were different from those observed in the Chalqueño, included as dent maize check. Variations in grain quality among Cacahuacintle maize populations is an important genetic resource for the improvement of the nutritional and flowering quality of Cacahuacintle maize.


Medical management of neurogenic bladder in patients with spina bifida: A scoping review.
Neurogenic bladder is a common source of morbidity in patients with spina bifida and can cause renal damage. Medical management may include imaging, urodynamic studies (UDS), laboratory testing, clean intermittent catheterization (CIC), and medication. There is ongoing debate regarding the optimal management regimen. Approaches are described by two paradigms: proactive and expectant management. In a proactive approach, invasive interventions like CIC and UDS are initiated before the onset of renal abnormalities. In expectant management, UDS, CIC, and medications are started after abnormalities are identified. In this scoping review, we aim to comprehensively review existing literature on outcomes of proactive and expectant management of neurogenic bladder in patients with spina bifida. We searched multiple databases and screened articles for inclusion using PRISMA-ScR guidelines. Included studies reported clinical outcomes of any aspect of proactive or expectant neurogenic bladder management in patients with spina bifida. Ultimately, 74 articles were included for review including 67 cohort studies, 4 cross-sectional studies, 2 sequential cohort studies, and 1 randomized control trial. Eleven studies directly compared management strategies. There was substantial heterogeneity in study designs, management protocols, and reported outcomes. Most studies addressed multiple simultaneous aspects of management without specifically analyzing individual aspects. However, some commented on individual aspects of management including UDS (13), CIC (32), imaging (7), and medication (5). Although there was no consensus about optimal management, all direct comparisons of paradigms supported a proactive approach. Our review identified a broad body of literature about optimal management of neurogenic bladder. Existing studies vary greatly in terms of treatment protocols, measured outcomes, and management recommendations. Overall, studies that directly compare management are scarce but favor proactive management. Given the implications on clinical outcomes, it is crucial to focus future work on directly comparing management strategies and isolating the effects of different individual management elements.


Proximal and remote sensing in plant phenomics: 20 years of progress, challenges, and perspectives.
Plant phenomics (PP) has been recognized as a bottleneck in studying the interactions of genomics and environment on plants, limiting the progress of smart breeding and precise cultivation. High-throughput plant phenotyping is challenging owing to the spatio-temporal dynamics of traits. Proximal and remote sensing (PRS) techniques are increasingly used for plant phenotyping because of their advantages in multi-dimensional data acquisition and analysis. Substantial progress of PRS applications in PP has been observed over the last two decades and is analyzed here from an interdisciplinary perspective based on 2972 publications. This progress covers most aspects of PRS application in PP, including patterns of global spatial distribution and temporal dynamics, specific PRS technologies, phenotypic research fields, working environments, species, and traits. Subsequently, we demonstrate how to link PRS to multi-omics studies, including how to achieve multi-dimensional PRS data acquisition and processing, how to systematically integrate all kinds of phenotypic information and derive phenotypic knowledge with biological significance, and how to link PP to multi-omics association analysis. Finally, we identify three future perspectives for PRS-based PP: (1) strengthening the spatial and temporal consistency of PRS data, (2) exploring novel phenotypic traits, and (3) facilitating multi-omics communication.


Suppression of the tonoplast sugar transporter StTST3.2 improves quality of potato chips.
Which sugar transporter regulates sugar accumulation in tubers is largely unknown. Accumulation of reducing sugar (RS) in potato (Solanum tuberosum L.) tubers negatively affects the quality of tubers undergoing the frying process. However, little is known about the genes involved in regulating RS content in tubers at harvest. Here, we have identified two tonoplast sugar transporter (TST) 3-type isoforms (StTST3.1 and StTST3.2) in potato. Quantitative real-time PCR results indicate that StTST3.1 and StTST3.2 possess distinct expression patterns in various potato tissues. StTST3.2 was found to be the expressed TST3-type isoform in tubers. Further subcellular localization analysis revealed that StTST3.2 was targeted to the tonoplast. Silencing of StTST3.2 in potato by stable transformation resulted in significantly lower RS content in tubers at harvest or after room temperature storage, suggesting StTST3.2 plays an important role in RS accumulation in tubers. Accordingly, compared with the unsilenced control, potato chips processed from StTST3.2-silenced tubers exhibited lighter color and dramatically decreased acrylamide production at harvest or after room temperature storage. In addition, we demonstrated that silencing of StTST3.2 has no significant effect on potato growth and development. Thus, suppression of StTST3.2 could be another effective approach for improving processing quality and decreasing acrylamide content in potato tubers.


[The use of hydrophobic PALL BB22-15MS filters in cross-infection prevention during anesthesia].
Microbiological testing evaluations of hygienic procedure properties using PALL BB22-15MS filters to prevent contamination of "single use" breathing circuits during anesthesia. Prospective study. Two operating rooms in a University hospital. One hundred and thirty eight patients underwent general anesthesia for urologic surgery procedures. Patients with positive tests for HIV, B and C hepatitis and those considered to be at risk for HIV infection were excluded. The study was divided into five phases on the basis of times of usage of the same circuit for an increasing number of patients: in phase I, microbiological tests were performed on 4 circuits used on 4 different patients; in phase II the same tests were performed on 2 circuits each used on two different groups of three patients; in phase III, a circuit was used on a group of 15 patients and another on a group of 16 patients and the results were analysed; in phase IV a circuit used in a group of 32 patients was evaluated and phase V involved the analysis of a circuit that was used in a group of 65 patients. A filter was left in place between the patient and the circuit's Y-piece during all phases of anesthesia. The level of microbial contamination of breathing circuits was analysed in order to evaluate the reliability of the procedure. All analysed circuits remained uncontaminated. Staphylococcus hominis was revealed in respiratory circuit no. 6 of phase II, probably as a consequence of secondary contamination. Our results confirm that this procedure with the routine placement of a PALL BB22-15MS filter at the circuit's Y-piece can provide an adequate level of protection against cross-infections during anesthesia. The hygienic protocol proposed may allow the change of the anesthetic breathing only once a month.


Maternal age, parity, and pregnancy estrogens.
Total estrogens (TE), estradiol (E2), estriol (E3), and human placental lactogen (hPL) were determined by radioimmunoassay in the blood of 126 pregnant women during their 26th and 31st weeks of pregnancy and the results were studied in relation to maternal age and parity. Total estrogens and E2 were lowest among the youngest women (less than 20 years) and highest among women aged 20-24 years, whereas older women (25+ years) had, on the average, intermediate values. For E3 the pattern was qualitatively similar to that of TE and E2 but less striking, and no maternal age pattern was evident with respect to hPL. Within maternal age groups, TE and E2 were higher among women in the first, than among those in their second, full-term pregnancy; the difference was about seven percent for TE (P = 0.14) and about 14 percent for E2 (P = 0.05). No parity patterns were evident with respect to E3 and hPL. There were fairly strong correlations between the determinations of the same hormone in the same woman during the 26th and 31st weeks of pregnancy; Pearson correlation coefficients were 0.60 for TE, 0.78 for E2, 0.60 for E3, and 0.72 for hPL. Since the risk of breast cancer increases apparently monotonically with maternal age at birth, the present data are equivocal with respect to the hypothesis linking levels of pregnancy estrogens to risk of breast cancer in the offspring. However, the data are compatible with hypotheses linking excessive pregnancy-estrogen exposure to conditions more common among first-born individuals, including testicular cancer and cryptorchidism.


Formative assessment and student understanding of structure-function.
The structure and function relationship is a core concept identified by physiology faculty. Prior research has shown this may be a difficult concept for students to understand. Formative written assessments, such as short answer essay questions, allow students to demonstrate their thinking by encouraging students to use their diverse ideas to construct their responses. Varying the context of a question, such as the inclusion of a scenario, may be used to provide insight into the different stages of students' emerging biological expertise. Short answer questions based on the core concept structure↔function were administered to students in a junior level General Physiology course and a sophomore level Human Anatomy and Physiology course at a large southeastern public university. Questions were based on the integumentary, muscular, digestive, and cardiovascular systems. Student responses were scored with a conceptual rubric developed for each question prompt as well as each organ system represented in the question prompts. Students were interviewed to determine if their responses to the short answer questions accurately reflected their thinking. Less than half of the student responses in this study demonstrated a conceptual understanding of the structure-function relationship. Students demonstrated different conceptual understanding of structure↔function concepts depending on the question prompt with a scenario versus the question prompt without a scenario. The question prompts with scenarios versus non-scenarios provided a different context, which may have influenced student explanations. These results suggest that instructors should provide students with questions in varying contexts to allow students to demonstrate their heterogeneous ideas about a concept.NEW & NOTEWORTHY Formative assessment provides feedback to both students and instructors about the process of learning. The core concept structure-function provides a foundation upon which many topics in anatomy and physiology can be built across all levels of organization. This study contributes to existing research about student conceptual understanding of the core concepts. Implications for practitioners include the design of formative assessments and a suite of questions to be used to gauge student understanding of structure-function.


Definitive radiation treatment for early stage carcinoma of the soft palate and uvula: the indications for iridium 192 implantation.
From 1971 to 1984 59 T1 and T2 carcinomas of the soft palate and uvula were treated definitively by irradiation at the Henri Mondor hospital. Included are ten patients previously irradiated to the oropharyngeal area for either a carcinoma of the soft palate or another malignancy. Sixteen patients were treated by external irradiation alone, 14 by Iridium 192 implantation, and 29 by a combination of the two. Two techniques of implantation were used: the guide gutter technique (33 patients) and the plastic tube technique (10 patients). Clinically negative neck nodes (51/59) either received prophylactic telecobalt therapy (39/51) or were surveilled (12/51). Clinically involved nodes (8/59) were managed either by external irradiation alone (4/8) or combined with neck dissection (4/8). Local failure was 25% (4/16) after exclusive telecobalt therapy, 18% (5/19) after combined telecobalt therapy and implantation, and 0% (0/14) after Iridium 192 implantation alone. No local failures were seen with the plastic tube technique (0/10) as compared to 15% (5/33) for guide gutters. Only two nodal failures were observed (2/59: 3%). Crude 5-year disease-free survival was 33%. Severe complications were limited to one osteonecrosis, one soft tissue necrosis, and one partial palatal incompetence. Salivary impairment was reduced when implantation was used for part or all of the treatment. We recommend 45 Gy external radiation followed by 30 Gy from Iridium 192 implantation using the plastic tube method unless there has been prior oropharyngeal irradiation, in which case we give 60 Gy from implantation alone. For clinically negative neck nodes, we recommend 45 Gy prophylactic external neck irradiation. For clinically positive lymph nodes, this should be followed by either a 25 to 30 Gy boost to the involved nodes or a neck dissection.


Failure Rate and Clinical Outcomes of Anterior Cruciate Ligament Reconstruction Using Autograft Hamstring Versus a Hybrid Graft.
To compare the revision rate and subjective outcome measures of autograft hamstring versus a soft tissue hybrid graft combining both autograft hamstring and tibialis allograft for isolated anterior cruciate ligament (ACL) reconstruction. A single-center retrospective, nonrandomized, comparative study of isolated ACL reconstruction revision rates for subjects who underwent arthroscopic reconstruction of the ACL using autograft hamstring or a soft tissue hybrid graft using both autograft hamstring and tibialis allograft was performed. Patients with isolated ACL tears were included and underwent anatomic single-bundle reconstruction using an independent tunnel drilling technique and a minimum of 24 months' follow-up. The primary outcome assessed was the presence or absence of ACL rerupture. Secondary clinical outcomes consisted of the International Knee Documentation Committee, University of California at Los Angeles (UCLA) ACL quality of life assessment, and the visual analog pain scale. Between February 2010 and April 2013, 95 patients with isolated ACL tears between ages 18 and 40 met the inclusion criteria and were enrolled. Seventy-one autograft hamstring and 24 soft tissue hybrid graft ACL reconstructions were performed during the course of this study. The follow-up period was 24 to 32 months (mean 26.9 months). There were no statistically significant differences in patient demographics or Outerbridge classification. No statistically significant differences in ACL retears (5.6% auto, 4.2% hybrid; P = .57) were found between groups. Clinical International Knee Documentation Committee and UCLA ACL quality of life assessment improvement scores revealed no statistically significant differences in autograft and hybrid graft reconstructions (41 ± 11, 43 ± 13; P = .65) (38 ± 11, 40 ± 10; P = .23). The mean pain level decreased from 8.1 to 2.8 in the autograft group and 7.9 to 2.5 in the hybrid group (P = .18). The use of a hybrid soft tissue graft has a comparable rerupture rate and clinical outcome to ACL reconstruction using autograft hamstring. Level III, retrospective comparative study.


Breast Cancer Screening: Is There Room for De-escalation?
Breast cancer screening is highly controversial and different agencies have widely varying guidelines. Yet it is currently used extensively in the USA and frequently the thought is "the more, the better." The purpose of this review is to objectively assess the risks and benefits of screening mammography and consider whether there may be areas where it could be de-escalated. Over the past few years, there have been several meta-analyses that are concordant, and it is now agreed that the main benefit of screening mammography is about a 20% reduction in breast cancer mortality. This actually benefits about 5% of patients with mammographically detected tumors. We now appreciate that the main harm of screening is overdiagnosis, i.e. detection of a cancer that will not cause the patient any harm and would not have ever been detected without the screening. This currently represents about 20 to 30% of screening detected cancers. Finding extra cancers with more intense screening is not always good, because in this situation, the risk of overdiagnosis increases and the benefit decreases. In some groups, the risk of overdiagnosis approaches 75%. Our goal should be not only to find more cancers, but to avoid finding cancers that would never have caused the patient any harm and lead to unnecessary treatment. The authors suggest some situations where it may be reasonable to de-escalate screening.


Activation of beta-adrenergic receptor induces Na(+)-dependent inward currents in acutely dissociated motoneurons of bullfrog spinal cord.
Effects of adrenergic drugs on single motoneurons acutely dissociated from the lumbar enlargement of adult bullfrogs were examined. The dissociated large cells were identified as motoneurons by retrograde labeling with a fluorescent dye. Adrenaline caused membrane depolarization with a decrease in input resistance. Under whole-cell voltage clamp conditions at a holding potential of -70 mV, adrenergic drugs induced inward currents in a dose-dependent manner. Adrenaline was more potent than noradrenaline. Under K(+)-free conditions, adrenaline (10(-6)-10(-5) M) induced inward currents which were blocked by propranolol (10(-6) M) but not by phentolamine (10(-5) M). CoCl2 (1 mM) did not affect the currents. Substitution of choline+ in the recording solution for Na+ abolished the currents, but tetrodotoxin (TTX, 10(-6) M) had no effect on them. The adrenaline-induced currents exhibited a characteristic voltage-dependency: the conductance became large at hyperpolarized membrane potential (-150 to -30 mV) and approached zero at the depolarized membrane potential (greater than -30 mV), but was never reversed up to 30 mV, suggesting that the currents are different from non-specific cation currents. Substitution of isethionate- for Cl- in the recording solution had no effect on the voltage-dependency of the adrenaline-induced currents, whereas substitution of choline+ for Na+ apparently attenuated the voltage-dependency of the currents. These results indicate that adrenaline induces Na(+)-dependent inward currents through activation of beta-adrenergic receptors in bullfrog motoneurons.


The effects of zinc sulphate on vagal-induced mast cell changes and ulcers in the rat stomach.
The effects of zinc sulphate pretreatment on the formation of gastric ulcers, changes in intragastric pressure and changes in the gastric mucosal mast cell count induced by electrical vagal stimulation were studied in anaesthetized rats. Vagal stimulation produced a high gastric glandular ulcer incidence and ulcer index, increased the intragastric pressure, and reduced the number of granulated mast cells in the gastric mucosa and submucosa. Pretreatment with zinc sulphate (22, 44 ot 88 mg/kg), injected i.p. 48 h beforehand, reversed the changes in these parameters in a dose-related manner. These observations suggest that the inhibitory effects of zinc sulphate on mucosal mast cell degranulation may account for its ability to antagonise vagal-induced gastric glandular ulceration. The mechanisms involved in the aetiology of this type of gastric ulcer are discussed in the light of these results.


Docosahexaenoic acid (DHA) accretion in the placenta but not the fetus is matched by plasma unesterified DHA uptake rates in pregnant Long Evans rats.
Maternal delivery of docosahexaenoic acid (DHA, 22:6n-3) to the developing fetus via the placenta is required for fetal neurodevelopment, and is the only mechanism by which DHA can be accreted in the fetus. The aim of the current study was to utilize a balance model of DHA accretion combined with kinetic measures of serum unesterified DHA uptake to better understand the mechanism by which maternal DHA is delivered to the fetus via the placenta. Female rats maintained on a 2% α-linolenic acid diet free of DHA for 56 days were mated, and for balance analysis, sacrificed at 18 days of pregnancy, and fetus, placenta and maternal carcass fatty acid concentration were determined. For tissue DHA uptake, pregnant dams (14-18 days) were infused for 5 min with radiolabeled 14C-DHA and kinetic modeling was used to determine fetal and placental serum unesterified DHA uptake rates. DHA accretion rates in the fetus were determined to be 38 ± 2 nmol/d/g, 859 ± 100 nmol/d/litter and 74 ± 3 nmol/d/pup, which are all higher (P < 0.05) than the fetal serum unesterified DHA uptake rates of 16 ± 6 nmol/d/g, 239 ± 145 nmol/d/litter and 14 ± 8 nmol/d/pup. No differences (p > 0.05) in placental DHA accretion rates versus serum unesterified DHA uptake rates were observed as values varied only 6-35% between studies. No differences in placental accretion and uptake rates suggests that serum unesterified DHA is a significant pool for the maternal-placental transfer of DHA, and lower fetal DHA uptake compared to accretion supports remodeling of placental DHA for delivery to the fetus.


Involvement of neuronal tachykinin-like receptor at 86C in Drosophila disc repair via regulation of kynurenine metabolism.
Neurons contribute to the regeneration of projected tissues; however, it remains unclear whether they are involved in the non-innervated tissue regeneration. Herein, we showed that a neuronal tachykinin-like receptor at 86C (TkR86C) is required for the repair of non-innervated wing discs in Drosophila. Using a genetic tissue repair system in Drosophila larvae, we performed genetic screening for G protein-coupled receptors to search for signal mediatory systems for remote tissue repair. An evolutionarily conserved neuroinflammatory receptor, TkR86C, was identified as the candidate receptor. Neuron-specific knockdown of TkR86C impaired disc repair without affecting normal development. We investigated the humoral metabolites of the kynurenine (Kyn) pathway regulated in the fat body because of their role as tissue repair-mediating factors. Neuronal knockdown of TkR86C hampered injury-dependent changes in the expression of vermillion in the fat body and humoral Kyn metabolites. Our data indicate the involvement of TkR86C neurons upstream of Kyn metabolism in non-autonomous tissue regeneration.


Stepwise impact of urban wastewater treatment on the bacterial community structure, antibiotic contents, and prevalence of antimicrobial resistance.
Bacteria, antibiotics, and antibiotic resistance determinants are key biological pollutants in aquatic systems, which may lead to bacterial infections or prevent the cure of bacterial infections. In this study, we investigated how the wastewater treatment processes in wastewater treatment plants (WWTPs) affect these pollutants. We found that the addition of oxygen, polyaluminum chloride (PAC), and polyacrylamide (PAM), as well as ultraviolet (UV) disinfection could significantly alter the bacterial communities in the water samples. An overall shift from Gram-negative bacteria to Gram-positive bacteria was observed throughout the wastewater treatment steps, but the overall bacterial biomass was not reduced in the WWTP samples. The antibiotic contents were reduced by the WWTP, but the size of the reduction and the step when antibiotic degradation occurred differed among antibiotics. Ciprofloxacin, sulfamethoxazole and erythromycin could be removed completely by the WWTP, whereas cephalexin could not. The removal of ciprofloxacin, cephalexin, and erythromycin occurred in the anaerobic digester, whereas the removal of sulfamethoxazole occurred after the addition of PAC and PAM, and UV disinfection. Antimicrobial resistance determinants were highly prevalent in all of the samples analyzed, except for those targeting vancomycin and colistin. However, wastewater treatment was ineffective at removing antimicrobial resistance determinants from wastewater. There were strong correlations between intI1, floR, sul1, and ermB, thereby suggesting the importance of integrons for the spread of these antimicrobial resistance genes. In general, this study comprised a stepwise analysis of the impact of WWTPs on three biological pollutants: bacteria, antibiotics, and antimicrobial resistance determinants, where our results suggest that the design of WWTPs needs to be improved to address the threats due to these pollutants.


Analysis of mitochondrial length heteroplasmy in monozygous and non-monozygous siblings.
The segregation of mitochondrial genomes and the inheritance of mitochondrial DNA are constant matters of debate. To obtain more information about this issue and to answer the question whether or not it is possible to distinguish mitochondrial DNA (mtDNA) samples from monozygous individuals by analysing heteroplasmic length variants, 290 monozygous and 121 dizygous twin pairs and 34 sets of multiples were studied by RFLP and partly by direct sequencing. A factor D describing the respective pattern of length variants in a given sample was also calculated. The results show that monozygous individuals exhibit a significantly lower median and closer distribution of D than non-monozygous siblings. Thus, a differentiation of mtDNA samples from monozygous twins by this trait is not possible. The high percentage of heteroplasmic individuals, the low median of the D values and the unexpectedly very similar distribution of length variants in monozygotic individuals support the existence of a relatively wide bottleneck or the assumption of a regeneration of length heteroplasmy following a tight bottleneck and agree with a random segregation of mtDNA genomes in dividing oocytes.


Conservative management of placenta accreta. A case report.
Placenta accreta is a rare complication of pregnancy. Traditional therapy has centered upon total abdominal hysterectomy to prevent serious hemorrhagic and infectious sequelae. Conservative management, however, may preserve reproductive function without jeopardizing maternal welfare.


Identifying academic motivation profiles and their association with mental health in medical school.
Academic motivation (AM), motivation in relation to formal studies that as a construct of the self-determination theory (SDT), is frequently assessed by the Academic Motivation Scale (AMS). However, the scoring of AMS in itself is not fully consistent with the SDT theory as only scores of the subscales can be calculated resulting in seven different score means instead of positioning the individual on the self-determination continuum. There have been few attempts at a person-centered approach to AMS scoring, especially among medical students. Our study aimed to find distinct academic motivation profiles and demonstrate their concurrent criterion validity with mental health variables (psychological distress, life satisfaction) among medical students. The AMS-28 college version, the General Health Questionnaire (GHQ-12), and the Single-Item Measure of Life Satisfaction were administered among medical freshmen. Academic motivation profiles were generated by two methods: 1) two-step cluster analysis, and 2) quantile analysis. The sample consisted of 189 participants (mean age = 19.38 ± 2.03 years, 72% females). The cluster analyses revealed three fairly distinct profiles of self-determination: 'High' (n = 59; mean im = 5.48 ± 0.60; mean em = 6.07 ± 0.41; mean am = 1.57 ± 0.95), 'Moderate' (n = 111; mean im = 4.5 ± 1.06; mean em = 4.41 ± 0.87; mean am = 1.25 ± 0.36), and 'Low' (n = 19; mean im = 4.22 ± 1.02; mean em = 4.03 ± 1.16; mean am = 3.07 ± 1.30). The creation of deciles allowed the identification of those who were most intrinsically (n = 14, 7.4%), extrinsically (n = 10, 5.3%), and least motivated (amotivated) (n = 18, 9.5%). 'Low' self-determination/amotivation was associated with increased psychological distress and decreased life satisfaction. Our results provide means to position medical students on the SDT continuum based on 'Low', 'Moderate', or 'High' levels of self-determination toward their studies. These AM profiles predict the mental health of medical freshmen, which supports the validity of the outcomes and highlight the risks of amotivation for psychological morbidity. The limitations and implications are discussed.


[Effects of SH-compounds on changes in the antioxidant enzyme activity in various tissues during acute pancreatitis].
In rats with experimental acute pancreatitis, activity of the antioxidant defense enzyme in pancreatic and liver tissues increases, while that in the blood erythrocytes decreases. Preliminary administration of SH-compounds, especially unithiol, favored an increase in the activity of superoxide dismutase, catalase, and glutathione peroxidaze.


Virtual trajectory and stiffness ellipse during multijoint arm movement predicted by neural inverse models.
We predict the virtual trajectories and stiffness ellipses during multijoint arm movements by computer simulations. A two-link manipulator with four single-joint muscles and two double-joint muscles is used as a model of the human arm. Physical parameters of the model are derived from several experimental data. Among them, special emphasis is put on low values of the dynamic hand stiffness recently measured during single-joint and multijoint movements. The feedback-error-learning scheme to acquire the inverse dynamics model and the inverse statics model is utilized for this prediction. The virtual trajectories are much more complex than the actual trajectories. This indicates that planning the virtual trajectory is as difficult as solving the inverse dynamics problem for medium and fast movements, and simply falsifies the advocated computational advantage of the virtual trajectory control hypothesis. Thus, we conclude that learning inverse models is essential even in the virtual trajectory control framework. Finally, we propose a new computational model to learn the complicated shape of the virtual trajectories by integrating the virtual trajectory control and the feedback-error-learning scheme.


[Testosterone substitution with special regard to prostate cancer].
Testosterone substitution is used to treat the symptoms of low testosterone in men who do not produce enough natural testosterone. Hypogonadism is associated with a range of disease states that have significant effects on morbidity and mortality and also affect quality of life. The regular investigation of PSA, prostate, and ultrasound is necessary.


Intertrochanteric displacement osteotomy in the treatment of femoral neck fractures.
A total of 51 patients with displaced femoral neck fractures of Garden grade III or IV was treated by intertrochanteric displacement osteotomy. Of these, 42 patients had complete follow-up and 31 fractures (73.8%) united. The results were satisfactory in 66.6% and poor in 33.4%. The poor results were mainly due to non-union, chronic osteomyelitis and stiffness of the hip or knee. A high intertrochanteric osteotomy with adequate displacement is recommended in fresh, displaced femoral neck fractures.


Adaptive growth and remodeling of transplanted hearts in children.
We aimed to evaluate the adaptive growth and remodeling behavior of the transplanted heart in pediatric heart-transplant recipients by comparing donor body surface area (BSA) and cardiac dimensions during transplantation with the corresponding parameters of the recipient over a period of time. A retrospective review of medical and echocardiographic records of 167 children (8.65 ± 5.98, median 9; range 0-17 years) who underwent orthotopic heart transplantation between 1987 and March 2010 was done. In the first 30 days post-transplantation, right- and left-ventricular end-diastolic diameters, volumes, and myocardial mass were found to be significantly increased (z score 3.96, p < 0.000) in relation to the recipients' BSA. Within the first year of post-transplantation, there was a significant reduction in the right-ventricular diameter (z score, -1.0 to +1.6, p = 0.000), left-ventricular diameter (z score -1.0 to +1.9, p = 0.000), right-ventricular end-diastolic volume (z score -1.3 to +1.9, p = 0.000) and left-ventricular end-diastolic volume (z score -1.3 to +1.8, p = 0.000), right-ventricular mass (z score, -1.4 to +1.7, p = 0.000) and left-ventricular mass (z score, -1.4 to +1.8, p = 0.000). During subsequent follow-up periods of 2-5 and 6-10 years, the aforementioned cardiac dimensions and volumes increased appropriately in accordance to the BSA (p = 0.000). In all the cardiac dimensions and volumes measured, donor-recipient mismatch did not influence the continuous growth of the measured parameters, which was in accordance to the recipients' BSA over time. Kaplan-Meier survival analysis showed a survival rate of 61.7% at 10 years. There is no statistically significant difference in survival rate among patients with varying donor-recipient weight ratios and donor-recipient BSA ratios (p = 0.53). This study demonstrates that the transplanted heart undergoes remodeling processes and grows adaptively, in accordance to the BSA, over a period of time.


Retinal detachment after phacoemulsification cataract extraction.
To estimate the incidence of retinal detachment (RD) after phacoemulsification cataract extraction in an unselected group of patients. Herlev University Hospital, Copenhagen, Denmark. This retrospective review comprised 6521 cataract patients who had phacoemulsification over a 3-year period. The incidence of postoperative RD and the risk factors were assessed. During the 15- to 52-month observation period, 22 cases of RD in 21 patients were observed, with an estimated risk (Kaplan-Meier) of 0.41% (95% confidence limit, 0.25%-0.57%) at 52 months. The results confirmed recognized preoperative risk factors for RD such as an axial length greater than 25.0 mm (P<.001), age younger than 65 years (P<.001), and male sex (P<.02). In 18 eyes, the retina was reattached after 1 operation. The incidence of RD after phacoemulsification cataract extraction in an unselected group of patients was low. A long axial length, young age, and male sex were confirmed as risk factors.


Development and Validation of a Liquid Chromatography High-Resolution Mass Spectrometry (LC-HRMS) Bioanalytical Method for Quantifying Cannabinoids in Whole Blood: Application for Determining Recent Cannabis Use.
Cannabis legalization is expanding rapidly throughout the United States, but there is no reliable means of establishing recent use. To develop and validate a bioanalytical method for determination of Δ9-tetrahydrocannabinol (Δ9-THC), cannabinol, 11-hydroxy-Δ9-THC, 11-nor-9-carboxy-Δ9-THC, and 8β,11-dihydroxy-Δ9-THC in whole blood microsamples by liquid chromatography high-resolution mass spectrometry (LC-HRMS). Cannabinoid extraction from whole blood was performed using a mixture of n-hexane/ethyl acetate (90:10, v/v). Chromatographic separation was performed with a C18 column using a binary mobile phase gradient of water and acetonitrile, each with 0.1% formic acid. Detection was performed by positive ion mode heated electrospray ionization with full scan MS on an Orbitrap mass spectrometer. A clinical study was performed in 30 subjects to identify recent cannabis use based on analysis of cannabinoids in blood samples up to 200 min post-smoking. Acceptable linearity of all calibration curves was observed (r2>0.99) for all analytes over a 1-100 ng/mL concentration range, with acceptable accuracy. Limit of detection (LOD) was 0.5 ng/mL. Accuracy and precision met acceptance criteria for all analytes. Repeatability (CV) was <5% at low (3 ng/mL) and high (90 ng/mL) concentrations. In the clinical study, the ratios between 11-nor-9-carboxy-Δ9-THC and Δ9-THC fell immediately after smoking and returned to near baseline levels by 200 min post-smoking, which is consistent with recent use. The developed LC-HRMS bioanalytical method is suitable for quantification of five key cannabinoids in whole capillary blood microsamples and can be used in conjunction with a test for determining recent cannabis use.


Intracellular hydrogen peroxide produced by 6-hydroxydopamine is a trigger for nigral dopaminergic degeneration of rats via rapid influx of extracellular Zn2.
To elucidate the mechanism and significance of 6-hydroxydopamine (6-OHDA)-induced Zn2+ toxicity, which is involved in neurodegeneration in the substantia nigra pars compacta (SNpc) of rats, we postulated that intracellular hydrogen peroxide (H2O2) produced by 6-OHDA is a trigger for intracellular Zn2+ dysregulation in the SNpc. Intracellular H2O2 level elevated by 6-OHDA in the SNpc was completely inhibited by co-injection of GBR 13069 dihydrochloride (GBR), a dopamine reuptake inhibitor, suggesting that 6-OHDA taken up through dopamine transporters produces H2O2 in the intercellular compartment of dopaminergic neurons. When the SNpc was perfused with H2O2, glutamate accumulated in the extracellular compartment and the accumulation was inhibited in the presence of N-(p-amylcinnamoyl)anthranilic acid (ACA), a blocker of the transient receptor potential melastatin 2 (TRPM2) channels. In addition to 6-OHDA, H2O2 also induced intracellular Zn2+ dysregulation via AMPA receptor activation followed by nigral dopaminergic degeneration. Furthermore, 6-OHDA-induced nigral dopaminergic degeneration was completely inhibited by co-injection of either HYDROP, an intracellular H2O2 scavenger or GBR into the SNpc. The present study indicates that H2O2 is produced by 6-OHDA taken up through dopamine transporters in the SNpc, is retrogradely transported to presynaptic glutamatergic terminals, activates TRPM2 channels, accumulates glutamate in the extracellular compartment, and induces intracellular Zn2+ dysregulation via AMPA receptor activation, resulting in nigral dopaminergic degeneration prior to movement disorder. It is likely that intracellular H2O2, but not extracellular H2O2, is a key trigger for nigral dopaminergic degeneration via intracellular Zn2+ dysregulation.


Electrostatic self-assembly sandwich-like 2D/2D NiFe-LDH/MXene heterostructure for strong microwave absorption.
MXene has great application potential in electromagnetic (EM) wave absorbers because of its high attenuation ability; however, self-stacking and excessively high conductivity are major obstacles to its widespread use. To address these issues, a NiFe layered double hydroxide (LDH)/ MXene composite with two-dimensional (2D)/2D sandwich-like heterostructure was constructed through electrostatic self-assembly. The NiFe-LDH not only acts as an intercalator to prevent self-stacking of the MXene nanosheets, but also serves as a low-dielectric choke valve to optimize impedance matching. At a thickness of 2 mm and filler loading of 20 wt%, the minimum reflection loss (RLmin) value could reach -58.2 dB, and the absorption mechanism was analyzed based on multiple reflection, dipole/interfacial polarization, impedance matching, and synergy between dielectric and magnetic losses. Furthermore, the simulation of the radar cross section (RCS) further confirmed the efficient absorption properties and application prospects of the present material. Our work demonstrates that designing sandwich structures based on 2D MXene is an effective way to improve the performance of EM wave absorbers.


Toxicological data of some antibiotics and pesticides to fish, mosquitoes, cyanobacterial mats and to plants.
This article provides toxicological data of antibiotics to fish and mosquito (El-Nahhal and El-dahdaouh, 2015) (doi: 10.5132/eec.2015.01.03 [1]), to cyanobacteria (El-Nahhal and Alshanti, 2015)(dx.doi.org/10.4172/2161-0525.1000274 [2]) and pesticides to plants (El-Nahhal and Hamdona, 2015) (doi.10.1186/s40064-015-1148-7 [3]). The data provided herein described the experimental procedure and calculation of the appropriate toxicity parameters, lethal concentrations (LC50) required to kill 50% of tested animal, percentage growth inhibition, relative toxicity (RT) and Mixture toxicity index. Moreover, the data enable the readers to perform future experiments and open future discussion with other authors elsewhere and generate future research guidelines which benefit the young scientific community around the globe in the field of mixture toxicity.


A new experimental model for studies of drug actions on myocardial metabolism. Application to a study of the influence of POCA.
In order to study myocardial metabolism by external detection, quantitative information on the metabolism of a gamma-emitting iodinated fatty acid (IHA) was obtained from time-activity curves of radioactivity in different compartments. A 4-compartment mathematical model was then developed; compartments 0, 1, 2, and 3 correspond respectively to vascular IHA, intracellular IHA, esterified forms, and iodide resulting from mitochondrial oxidation of IHA. We applied this model to a study of the influence of an inhibitor of fatty acid oxidation, POCA (2-[5(4 chlorophenyl) pentyl]-oxirane-2-carboxylate). Isolated rat hearts were perfused for 20 min with Krebs liquid containing increasing concentrations of POCA. IHA was then injected as a bolus at the entrance of the coronary network. The level of cardiac radioactivity was recorded for 30 min and the division into the 4 compartments was simulated at different concentrations of POCA. The drug appeared to increase the myocardial retention of IHA and slow down the speed of degradation and storage; the variations were dose-dependent. These results correspond to those obtained by intracellular analysis. The proposed method, which is reliable and sensitive, is an interesting experiment for pharmacological studies of cardiac metabolism.


Aminergic nuclei in the hypothalamus of the roach Leuciscus rutilus.
In the hypothalamus of the roach (Leuciscus rutilus) green and yellow fluorescent cells were found in the nucleus recessus lateralis (NRL) and the nucleus recessus posterioris (NRP) and green fluorescent cells in the nucleus recessus preopticus (NRPO). The green fluorescence indicates the presence of noradrenaline or dopamine and the yellow one the presence of 5-hydroxytryptamine. The cells of the NRL and NRP contained electron dense granules averaging 70 nm in diameter. The NRL is divided into two parts. These and the NRP are connected by large fluorescent tracts. The NRL and NRP send axons towards the nucleus lateralis tuberis (NLT) and the NRPO sends axons towards the nucleus preopticus (NPO). It could not be established whether the aminergic nuclei described are the origin of the fluorescent fibers in the hypophysis of the roach.