Mcm10 is required for oogenesis and early embryogenesis in Drosophila.
Efficient replication of the genome and the establishment of endogenous chromatin states are processes that are essential to eukaryotic life. It is well documented that Mcm10 is intimately linked to both of these important biological processes; therefore, it is not surprising that Mcm10 is commonly misregulated in many human cancers. Most of the research regarding the biological roles of Mcm10 has been performed in single-cell or cell-free in-vitro systems. Though these systems are informative, they are unable to provide information on the cell-specific function of Mcm10 in the context of the tissue and organ systems that comprise multicellular eukaryotes. We therefore sought to identify the potential biological functions of Mcm10 in the context of a complex multicellular organism by continuing our analysis in Drosophila using three novel hypomorphic alleles. Observation of embryonic nuclear morphology and quantification of embryo hatch rates reveal that maternal loading of Mcm10 is required for embryonic nuclear stability, and suggest a role for Mcm10 post zygotic transition. Contrary to the essential nature of Mcm10 depicted in the literature, it does not appear to be required for adult viability in Drosophila if embryonic requirements are met. Although not required for adult somatic viability, analysis of fecundity and ovarian morphology in mutant females suggest that Mcm10 plays a role in maintenance of the female germline. Taken together, our results demonstrate critical roles for Mcm10 during early embryogenesis, and mark the first data linking Mcm10 to female specific reproduction in multicellular eukaryotes.


Cancer cell plasticity during tumor progression, metastasis and response to therapy.
Cell plasticity represents the ability of cells to be reprogrammed and to change their fate and identity, enabling homeostasis restoration and tissue regeneration following damage. Cell plasticity also contributes to pathological conditions, such as cancer, enabling cells to acquire new phenotypic and functional features by transiting across distinct cell states that contribute to tumor initiation, progression, metastasis and resistance to therapy. Here, we review the intrinsic and extrinsic mechanisms driving cell plasticity that promote tumor growth and proliferation as well as metastasis and drug tolerance. Finally, we discuss how cell plasticity could be exploited for anti-cancer therapy.


Adverse childhood experiences, antenatal stressful life events, and marijuana use during pregnancy: A population-based study.
Cumulative exposure to adverse childhood experiences (ACEs) and antenatal stressful life events (ASLEs) are independently associated with marijuana use during pregnancy. However, research has not explored how both exposures may influence marijuana use jointly. Assessing the joint associations of ACEs and recent ASLEs on marijuana use can identify people who may benefit from early intervention. Data come from the Nevada Pregnancy Risk Assessment Monitoring System, 2017-2020 (N = 2483). We assessed eight measures of ACEs before age 18 and fourteen measures of ASLEs twelve months before giving birth. Generalized estimating equations estimated the direct and joint associations (additive and multiplicative interaction) of ACEs and ASLEs on marijuana use during pregnancy. 9.8% used marijuana during the most recent pregnancy. Compared to people who reported no ACEs, those reporting 1 ACE (adjusted prevalence ratio[aPR] = 1.96, 95% confidence interval [CI] = 1.30-2.94), 3 ACEs (aPR = 3.58, 95%CI = 2.69-4.77), and 4+ ACEs (aPR = 3.67, 95%CI = 2.36-5.72) were more likely to use marijuana. Compared to people reporting no ASLEs, those reporting 4+ ASLEs (aPR = 3.12, 95% CI = 1.64-5.92) were more likely to use marijuana. There was evidence of interaction for high ACE and ASLE exposure on an additive scale. ACEs and ASLEs were independently associated with marijuana use during pregnancy, and there was evidence of additive interaction. Screening for ACEs and ASLEs during pregnancy, referrals to appropriate behavioral health services, and trauma-informed approaches are important to address marijuana use during pregnancy.


Inhibition of the catalytic activity of hypoxia-inducible factor-1alpha-prolyl-hydroxylase 2 by a MYND-type zinc finger.
Hypoxia-induced gene expression is initiated when the hypoxia-inducible factor-1 (HIF-1) alpha subunit is stabilized in response to a lack of oxygen. An HIF-1alpha-specific prolyl-hydroxylase (PHD) catalyzes hydroxylation of the proline-564 and/or -402 residues of HIF-1alpha by an oxygen molecule. The hydroxyproline then interacts with the ubiquitin E3 ligase von Hippel Lindau protein and is degraded by an ubiquitin-dependent proteasome. PHD2 is the most active of three PHD isoforms in hydroxylating HIF-1alpha. Structural analysis showed that the N-terminal region of PHD2 contains a Myeloid translocation protein 8, Nervy, and DEAF1 (MYND)-type zinc finger domain, whereas the catalytic domain is located in its C-terminal region. We found that deletion of the MYND domain increased the activity of both recombinant PHD2 protein and in vitro-translated PHD2. The zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine augmented the activity of wild-type PHD2-F but not that of PHD2 lacking the MYND domain, confirming that the zinc finger domain is inhibitory. Overexpression of PHD2 lacking the MYND domain caused a greater reduction in the stability and function of HIF-1alpha than did overexpression of wild-type PHD2, indicating that the MYND domain also inhibits the catalytic activity of PHD2 in vivo.


Interleukin-6 downregulated vascular smooth muscle cell contractile proteins via ATG4B-mediated autophagy in thoracic aortic dissection.
Interleukin-6 (IL-6) overexpression played an important role in the pathogenesis of thoracic aortic dissection (TAD). Our previous study found enhanced autophagy accompanying with contractile proteins α smooth muscle actin (α-SMA) and smooth muscle 22α (SM22α) degradation in TAD aortic vascular smooth muscle cells (VSMCs). Autophagy is an important way for intracellular proteins degradation, while IL-6 has been found as a contributing factor of autophagy in some cancers. These indicated IL-6 might contribute to the occurrence of TAD by promoting autophagy-induced contractile proteins degradation, which has not been investigated. The aim of the present study is to verify this hypothesis and investigate the mechanism of it. We collected 10 TAD and 10 control aortic specimens from patients underwent TAD surgical repair and coronary artery bypass grafting, respectively. Quantitative real-time polymerase chain reaction was used to detect mRNA expression. Protein expression level was assessed by enzyme-linked immunosorbent assay, western blot, and immunohistochemistry. Microtubule-associated protein 1 light chain 3 beta overexpression adenovirus with green and red fluorescent protein tags and transmission electron microscopy were used to detect autophagy level in VSMCs. 3-Methyladenine (3-MA) and chloroquine were used to block autophagy in human VSMCs. Experiment results showed that the expression of IL-6 was significantly increased accompanying with up-regulated autophagy in TAD aortic wall compared with controls. In vitro results showed that IL-6 stimulation decreased the expression of VSMCs contractile proteins α-SMA and SM22α accompanying with up-regulated autophagy. Blocking autophagy with 3-MA or chloroquine inhibited IL-6 induced α-SMA and SM22α degradation. Further investigation showed that autophagy-related 4B cysteine peptidase (ATG4B) was significantly overexpressed in TAD aortic wall and played important role in IL-6 induced autophagy up-regulation. ATG4B knockdown blocked IL-6-induced autophagy and α-SMA and SM22α degradation, while ATG4B overexpression partly replaced the function of IL-6 in human VSMCs. In conclusion, our study demonstrated that IL-6 downregulated expression of VSMCs contractile proteins α-SMA and SM22α via enhancing ATG4B-mediated autophagy in TAD.


Reconsidering some standards in immediate autotransplantation of teeth: Case report with 2-year follow-up.
Dental autotransplantation (DAT) is that surgical procedure of extracting a tooth from one place (donor site) and transplanting it into another (recipient site) within the same individual. If successfully implemented, the treatment outcome will pose characteristics of a natural tooth rather than a dental prosthesis. This case report sheds light on the validity of this treatment option, and provides suggestions to reconsider some standards regarding its conventional protocols. A 24-year-old female with no history of medical conditions presented with hopelessnon-restorable lower molars with clinical signs of chronic infection. Cone-beam computed tomography (CBCT) was used to check compatibility of her third molars for DAT. After clinical and radiographical examination, patient's consent to perform DAT of impacted upper right third molar to replace the lower right first molar was obtained. Based on patient's CBCT, an individual replica of the donor tooth was fabricated. Replica helped in pre-preparing recipient site to fit the dimensions of the donor tooth before being extracted and transplanted. The extraction socket was thoroughly debrided and irrigated to ensure the removal of any lesion or infection. Immediate DAT was carried out with minimal trauma to the transplant. Follow-up for 2 years showed functional transplant with uneventful healing of periodontal and pulpal tissues. Some standards regarding DAT needs to be reconsidered. Routine prophylactic endodontic treatment is not necessary for every case of DAT even when transplanted tooth is mature. Immediate autotransplantation into an infected site can be successful if the recipient site is managed properly.


Aggregation algorithm based on consensus verification.
Distributed learning, as the most popular solution for training large-scale data for deep learning, consists of multiple participants collaborating on data training tasks. However, the malicious behavior of some during the training process, like Byzantine participants who would interrupt or control the learning process, will trigger the crisis of data security. Although recent existing defense mechanisms use the variability of Byzantine node gradients to clear Byzantine values, it is still unable to identify and then clear the delicate disturbance/attack. To address this critical issue, we propose an algorithm named consensus aggregation in this paper. This algorithm allows computational nodes to use the information of verification nodes to verify the effectiveness of the gradient in the perturbation attack, reaching a consensus based on the effective verification of the gradient. Then the server node uses the gradient as the valid gradient for gradient aggregation calculation through the consensus reached by other computing nodes. On the MNIST and CIFAR10 datasets, when faced with Drift attacks, the proposed algorithm outperforms common existing aggregation algorithms (Krum, Trimmed Mean, Bulyan), with accuracies of 93.3%, 94.06% (MNIST dataset), and 48.66%, 51.55% (CIFAR10 dataset), respectively. This is an improvement of 3.0%, 3.8% (MNIST dataset), and 19.0%, 26.1% (CIFAR10 dataset) over the current state-of-the-art methods, and successfully defended against other attack methods.


High mitochondrial priming sensitizes hESCs to DNA-damage-induced apoptosis.
Human embryonic stem cells (hESCs) are highly sensitive to DNA damage and have low survival ability relative to differentiated cells. We investigated the source of this difference by comparing damage response pathways in hESCs and differentiated cells. We found that hESCs undergo more rapid p53-dependent apoptosis after DNA damage than differentiated cells do. However, p53 localization and function are similar between hESCs and differentiated cells, suggesting that p53 alone cannot explain the difference in sensitivity. Instead, we show that mitochondrial readiness for apoptosis, known as mitochondrial priming, differs between hESCs and differentiated cells. Specifically, the balance between proapoptotic and antiapoptotic proteins is shifted closer to the apoptotic threshold in hESCs than in differentiated cells. Altering this balance in differentiated cells increases their sensitivity and results in cell death, suggesting that manipulation of mitochondrial priming could potentially alter the sensitivity of other stem cells, including cancer stem cells.


Toward autonomous wearable triboelectric systems integrated on textiles.
One of the major requirements of smart textiles is to achieve the integration of an energy source for powering embedded electronic systems. In this context, textile triboelectric nanogenerators (T-TENGs) are particularly well suited to imperceptibly play this role in the core of textiles, making them highly appealing for the development of future autonomous systems. This article reviews the wide range of topics related to T-TENGs technology starting from triboelectric generation (textile device and behavior modeling) up to the complete integration of power transfer (rectifier) circuits on textiles. The modeling part deals with the current mathematical models of the triboelectric charge transfer in order to highlight efficient power transfer circuits. Then the materials and architectures used to fabricate different types of T-TENGs are described. Finally, the methods and technologies to seamlessly integrate the power transfer circuit into textiles are discussed: from realizing electrically conductive tracks through to integrating electronic component on textiles.


Distribution and properties of protein kinase and protein phosphatase activities in synaptosomal plasma membranes and synaptic junctions.
Some characteristics of the protein kinase activity associated with a synaptosomal plasma membrane (synaptic membrane) fraction and a synaptic junction fraction have been compared. Autoradiography of the phosphorylated fractions separated on sodium dodecyl sulfate polyacrylamide gels showed that cyclic AMP stimulates the phosphorylation of five polypeptides in synaptic membranes, whereas no cyclic AMP dependency could be detected in synaptic junctions. Kinetic studies demonstrated that synaptic junctions contain a high Km and a low Km protein kinase activity while only the high Km activity could be detected in synaptic membranes. The intrinsic ATPase activity of synaptic membranes was shown to strongly interfere with measurements of protein kinase activity. Cyclic AMP binding experiments revealed a 2.6-fold enrichment of cyclic AMP binding capacity in synaptic junctions as compared to synaptic membranes. Protein phosphatase activity was not detected in synaptic junctions but was associated with synaptic membranes, where cyclic AMP was shown to either stimulate or inhibit the dephosphorylation of different polypeptides.


Effects of 4-week slackline training on lower limb joint motion and muscle activation.
To investigate the effects of four weeks of slacklining on lower limb kinematics and muscle activity following a slip of the upright stance. A randomized, gender matched study. Twenty-four young healthy adults participated in the study and were assigned to either a training or a control group. The training group completed a 4-week training program on slacklines, while the control group received no slackline training. Before and after training, participants performed single leg standing tasks on a moveable platform. During medio-lateral platform perturbation, platform displacement, lower limb joint motion (ankle, knee and hip) and surface electromyography (EMG) measurements from six lower limb muscles were recorded. In the training group, a decrease in platform mean and maximum velocity (all p<0.05) was detected, but no changes were observed for the release time and maximum deflection (all p>0.05) of the platform. Regarding lower limb kinematics, a reduced corrective action was detected in the knee joint (p<0.05), whereas only a trend towards a decrease could be observed in the ankle joint (p<0.1). EMG data revealed an enhanced activation of the rectus femoris (p<0.05), as well as a trend to increased rectus femoris to biceps femoris co-activation (p=0.06) in the preparatory phase for training group. The data strongly support that slacklining can improve postural control and enhance functional knee joint stability, which seems to be induced by enhanced preparatory muscle activation of the rectus femoris.


Fetal behaviour in growth retardation: its relationship to fetal blood flow.
The fetal behaviour of asymmetrical growth retarded fetuses was compared with that of a control group of healthy fetuses. Fetuses underwent simultaneous cardiotocographic and echographic examinations for two consecutive hours at 36-38 weeks of gestation. The distribution of gross fetal body movements, fetal breathing movements and fetal eye movements was analysed during the different fetal heart rate patterns. Furthermore, the incidence and organization of fetal behavioural states was investigated. The degree of vascular peripheral resistance was also evaluated by means of pulsed doppler ultrasonic equipment. Growth retarded fetuses were divided into two groups on the basis of the presence or absence of end diastolic flow in the fetal thoracic descending aorta. Growth retarded fetuses showed a delay in the integration of behavioural patterns and a lower coincidence of behavioural states. These findings are particularly evident in the fetuses with a severe increase of peripheral vascular resistance (absence of end diastolic flow in descending aorta). Thus, we suggest that a delay in central nervous system development is present in asymmetrical growth retarded fetuses and that there is a possible relationship of this delay to the degree of peripheral vascular resistance.


Biochemical Properties of Black and Green Teas and Their Insoluble Residues as Natural Dietary Additives to Optimize In Vitro Rumen Degradability and Fermentation but Reduce Methane in Sheep.
Black (BTL) or green (GTL) tea and their spent tea (STL) leaves can be used as natural dietary additives for ruminants. Experiment 1 used a 3 × 2 × 2 factorial arrangement, with four replicates (n = 4) to test the effects of three different inclusions of tea leaves at 0 (control), 50, and 100 g/kg DM of two different tea types (BTL and GTL) in two different total mixed diets containing either ryegrass hay (RH) or rice straw (RS) on in vitro rumen organic matter degradability (IVOMD), volatile fatty acids (VFA), pH, ammonia (NH3), and methane (CH4) outputs over a 24 h incubation time. Experiment 2 followed a 3 × 2 × 2 factorial arrangement, with eight replicates (n = 8) to study the impacts of three different STL inclusions at 0, 100, and 200 g/kg DM of two different STL types (black and green) into two different total mixed diets containing either RH or RS on the same in vitro measurements. Both types of tea leaves decreased NH3 (p < 0.001) and CH4 (p < 0.01) without affecting (p > 0.05) rumen degradability, but the effect of their STL was less remarkable. Tea leaves and their STL inclusions improved (p < 0.01 and p < 0.001, respectively) the acetate to propionate (A:P) ratio. Compared with BTL, GTL containing diets had higher IVOMD (p < 0.05) and A:P ratio (p < 0.05) but lower NH3 (p < 0.001). Reduced rumen NH3 and CH4 outputs can be useful for protein and energy use efficiency while an increased A:P ratio might lead to increased milk fat synthesis and reduced low-fat milk syndrome. The surplus or wasted tea leaf products could be used as sustainable sources of nutrients to optimize rumen function and minimize environmental impacts of feeding ruminant animals.


Interaction of inhalable volatile organic compounds and pulmonary surfactant: Potential hazards of VOCs exposure to lung.
Exposure of volatile organic compounds (VOCs) towards lung leads to pulmonary dysfunctions and various lung diseases. However, the interaction of VOCs with pulmonary surfactant (PS) that directly comes into contact with inhaled VOCs is unknown. Here, simulated PS extracted from porcine lungs (EPS) was used to study the interaction with BTEX (i.e., benzene, toluene, ethylbenzene, and p-xylene) as representatives of VOCs. Surface pressure-area (π-A) isotherms showed that in the presence of individual BTEX, EPS monolayer's phase conversion from gas to liquid expanded phase was dramatically influenced and its collapse pressure decreased greatly compared to those of EPS alone, which was attributed to the alteration of EPS monolayer's microstructure characterized by atomic force microscopy and Brewster angle microscopy. Solubilization experiments manifested that EPS and its major components (dipalmitoyl phosphatidylcholine, DPPC; bovine serum albumin, BSA) exhibited obvious solubilization effects on individual BTEX. The solubilization capacity followed an order: EPS > DPPC > BSA, which was positively correlated with hydrophobicity of individual BTEX. Synergistic solubilization test unveiled that the mixed phospholipid components were largely responsible for the solubilization capacity of EPS. These findings indicate that VOCs exposure may induce potential pulmonary health risk due to the alteration of gas-liquid interfacial properties of PS.


Expression of podocalyxin enhances the adherence, migration, and intercellular communication of cells.
Podocalyxin (PODXL) is an anti-adhesive glycoprotein expressed abundantly in the epithelial cells of kidney glomeruli. In contrast, we report herein that expression of podocalyxin(GFP) (PODXL(GFP)) in CHO cells increased the adherence to immobilized fibronectin, spreading, and migration. The transient knockdown of PODXL or the expression of PODXL lacking the cytosolic carboxyterminal domain (PODXL-Delta(451)) inhibited cell adherence. Moreover, the effect of PODXL was prevented by the ectodomain of podocalyxin (PODXL-Delta(429)), by RGD peptides, or by inhibitors of the vitronectin receptor (alphavbeta3). CHO-PODXL(GFP) also showed adherence to human vascular endothelial cells (HUVEC), exhibiting polarization of granular PODXL and emission of long and thin, spike-like, protrusions with PODXL granules progressing along. We found PODXL colocalized with beta1 integrins at membrane ruffle regions on the leading edge of the cell and a blocking beta1 mAb prevented the spreading of cells. PODXL was also associated with submembrane actin in lamellipodia ruffles, or with vinculin at cell protrusions. The proadhesive effects of PODXL were absent in sialic acid deficient O-glycomutant CHO cells. To conclude, we present evidence indicating that human PODXL enhances the adherence of cells to immobilized ligands and to vascular endothelial cells through a mechanism(s) dependent on the activity of integrins.


Short-term effect of kinesiology taping on pain, functional disability and lumbar proprioception in individuals with nonspecific chronic low back pain: a double-blinded, randomized trial.
This study aimed to evaluate the effect of kinesiology taping (KT) on lumbar proprioception, pain, and functional disability in individuals with nonspecific chronic low back pain (CLBP). Thirty individuals with nonspecific CLBP participated in this double-blinded, randomized clinical trial from July 2017 to September 2018. The participants were randomized into two groups: KT (n = 15) and placebo group (n = 15). KT was applied with 15-25% tension for 72 h, and placebo taping was used without tension. Lumbar repositioning error was measured by a bubble inclinometer at three different angles (45° and 60° flexion, and 15° extension) in upright standing. Pain and disability were assessed by the Short-Form McGill Pain Questionnaire and Oswestry Disability Index, respectively. All measurements were recorded at baseline and 3 days after taping. Pain and disability scores reduced 3 days after taping in the KT group with large effect sizes (p < 0.05). Only the total score of pain was significantly different between the groups 3 days after taping and improved more in the KT group with a large effect size (p < 0.05). However, lumbar repositioning errors were similar between the groups after 3 days (p > 0.05). Also, only constant error of 15° extension showed a moderate correlation with disability (r = 0.39, p = 0.02). KT can decrease pain and disability scores after 3 days of application. Although placebo taping can reduce pain, the effect of KT is higher than placebo taping. The findings do not support the therapeutic effect of KT and placebo taping as a tool to enhance lumbar proprioception in patients with nonspecific CLBP. The study prospectively registered on 21.05.2018 at the Iranian Registry of Clinical Trials: IRCT20090301001722N20 .


The GABA neurons and their axon terminals in rat corpus striatum as demonstrated by GAD immunocytochemistry.
Glutamic acid decarboxylase (GAD, EC 126.96.36.199), the enzyme which catalyzes the alpha-decarboxylation of L-glutamate to form the neurotransmitter gamma-aminobutyric acid (GABA), was localized immunocytochemically in rat neostriatum, pallidum and entopeduncular nucleus. A large amount of GAD-positive reaction product was observed in both the pallidum and entopeduncular nucleus in light microscopic preparations and was localized ultrastructurally to axon terminalis that surrounded dendrites and large somata. In the neostriatum the relative numbers of GAD-positive axons terminals per unit area were substantially less than in the pallidum. GAD-positive terminals predominantly formed symmetric synapses with somata, dendrites and spines, but a small number of them formed asymmetric synapses with either dendrites or spines. The presence of GAD within these terminals is consistent with results of other investigations which have indicated that the striatopallidal and striatoentopeduncular pathways as well as neostriatal local circuit neurons and/or collaterals from neostriatal projection neurons, use GABA as a neurotransmitter. GAD-positive reaction product was also localized within the somata and dendrites of neostriatal and pallidal neurons in colchicine-injected preparations. The GAD-positive somata in the pallidum were medium-sized neurons and since such cells project to the substantia nigra, our results are in agreement with those from other studies which demonstrate a GABAergic, pallidonigral pathway. In the neostriatum, GAD-positive somata were identified light microscopically as medium-sized neurons with either round or fusiform shapes. Electron microscopic examinations also showed GAD-positive reaction product within the perikaryal and dendritic cytoplasm of these neurons, as well as in dendritic spines. These findings are in accord with the results of studies which have indicated that medium-sized, spinous neurons of the neostriatum give rise to a GABAergic, striatonigral pathway. The significance of GAD localization within these neostriatal neurons is discussed in relation to recent findings which show that substance P is contained within this same class of striatonigral projection neuron.


Single-Cell Microgels for Diagnostics and Therapeutics.
Cell encapsulation within hydrogel droplets is transforming what is feasible in multiple fields of biomedical science such as tissue engineering and regenerative medicine, in vitro modeling, and cell-based therapies. Recent advances have allowed researchers to miniaturize material encapsulation complexes down to single-cell scales, where each complex, termed a single-cell microgel, contains only one cell surrounded by a hydrogel matrix while remaining <100 μm in size. With this achievement, studies requiring single-cell resolution are now possible, similar to those done using liquid droplet encapsulation. Of particular note, applications involving long-term in vitro cultures, modular bioinks, high-throughput screenings, and formation of 3D cellular microenvironments can be tuned independently to suit the needs of individual cells and experimental goals. In this progress report, an overview of established materials and techniques used to fabricate single-cell microgels, as well as insight into potential alternatives is provided. This focused review is concluded by discussing applications that have already benefited from single-cell microgel technologies, as well as prospective applications on the cusp of achieving important new capabilities.


Treatment of children and adolescents with localized parameningeal sarcoma: experience of the Intergroup Rhabdomyosarcoma Study Group protocols IRS-II through -IV, 1978-1997.
We reviewed 611 patients with parameningeal sarcoma entered on Intergroup Rhabdomyosarcoma Study Group (IRSG) Protocols-II through IV (1978-1997), to delineate treatment results and evaluate prognostic factors. Primary sites were the middle ear/mastoid (N = 138), nasopharynx/nasal cavity (N = 235), paranasal sinuses (N = 132), parapharyngeal region (N = 29), and the pterygopalatine/infratemporal fossa (N = 77). Treatment was initial biopsy or surgery followed by multiagent chemotherapy and radiation therapy (XRT). Beginning in 1977, patients with cranial nerve palsy, cranial base bony erosion, and/or intracranial extension at diagnosis were considered as having meningeal involvement. They received triple intrathecal medications, whole brain XRT, and then spinal XRT. These treatments were successively eliminated from 1980 to 1991. The 611 patients' overall survival rate at 5 years was 73% (95% confidence interval, 70-77%). Favorable prognostic factors were: age 1-9 years at diagnosis; primary tumor in the nasopharynx/nasal cavity, middle ear/mastoid, or parapharyngeal areas; no meningeal involvement; and non-invasive tumors (T1). Thirty-five of 526 patients (6.7%) with information about presence/absence of meningeal involvement at diagnosis developed central nervous system (CNS) extension at 5-164 weeks (median, 46 weeks) after starting therapy. The estimated 5-year cumulative incidence rate of CNS extension during the study period was 5-7% (P = 0.88). Biopsy, XRT to the target volume, and systemic chemotherapy are successful treatments for the large majority of patients with localized parameningeal sarcoma. Carefully defining and irradiating the initial volume should reduce the risk of CNS failure. Aggressive initial surgical management of these patients is unnecessary.


Using EEM-PARAFAC to probe NF membrane fouling potential of stabilized landfill leachate pretreated by various options.
Pretreatment processes substantially modify the organic composition of landfill leachate, which affect the fouling behavior in the post-treatment of membrane filtration. In this study, the changes in the chemical composition of stabilized landfill leachate upon various pretreatments, which encompassed coagulation/flocculation (C/F), ion exchange resins (MIEX), granular activated carbon (GAC) adsorption, and their combinations, were tracked via excitation emission matrix - parallel factor analysis (EEM-PARAFAC), and the membrane fouling potentials were assessed in the subsequent processes of nanofiltration (NF). Fluorescence components, fulvic-like (C1), protein-like (C2), and humic-like (C3), were identified and validated using EEM-PARAFAC. MIEX and C/F pretreatments were not effective to remove C1 and C2, which were associated with relatively small sized and hydrophilic molecules. GAC adsorption did not show any preference with the removal towards different components. These differences in the chemical heterogeneity among the variously pretreated leachates led to the discrepancies in membrane fluxes at a similar leachate concentration. The result also signified the importance of probing the chemical composition of pretreated leachate for the optimization of the post membrane filtration. The sum of C2 and C3 in the pretreated leachate showed a good correlation with reversible membrane fouling resistance (r = 0.93; p < 0.05), while C1 was highly correlated with irreversible membrane resistance (r = 0.872; P < 0.05). These findings provided a new insight into the applicability of fluorescence spectroscopy for tracking the changes in the membrane fouling potential of stabilized landfill leachate after various pretreatments.


Negative regulation of hepatitis B virus gene expression and replication by oxidative stress.
We present data demonstrating that hydrogen peroxide markedly decreases release of progeny hepatitis B virus particles in cultured cells. The presence of reduced glutathione prevents this effect. Hydrogen peroxide also decreases secretion of the hepatitis B virus surface and e antigens, with a concomitant decrease in the steady-state levels of the corresponding viral transcripts. This effect is specific to viral gene expression, since hydrogen peroxide at the concentration used does not have any significant effect on the overall pattern of host cell protein synthesis nor on the secretion of growth hormone from a co-transfected plasmid. Since hepatitis B virus can cause acute and chronic hepatitis and since inflammatory cells release significant amounts of reactive oxygen species, including hydrogen peroxide, this phenomenon may be of pathophysiological importance in the viral life cycle.


Misoprostol knowledge and distribution in Mexico City after the change in abortion law: a survey of pharmacy staff.
First-trimester abortion is widely available in Mexico City since legalisation in 2007, but few data exist surrounding pharmacy staff knowledge and sales practices. We describe misoprostol availability, whether a prescription is required, and knowledge of the legal status of abortion and uses for misoprostol among pharmacy staff in Mexico City. Data were collected from 174 pharmacies in Mexico City. One employee at each pharmacy was asked about availability, need for prescription, indications for misoprostol, and sociodemographic information. Our primary outcome was availability of misoprostol. We used descriptive and bivariate statistics to compare knowledge and practices by type of pharmacy and staff gender. No patients were involved in this study. Of the 174 pharmacies, 65 were chain and 109 small independent. Misoprostol was available at 61% of sites. Only 49% of independent pharmacies sold misoprostol, compared with 81.5% of chain pharmacies (p<0.05). Knowledge of indications for misoprostol use was similar. The majority (80%) of respondents knew that abortion was legal in Mexico City, and 44% reported requiring a prescription for sale of misoprostol, with no significant difference between male and female staff or by pharmacy type. Availability, requirement of a prescription, and knowledge of indications for use of misoprostol varies among pharmacies, resulting in differential access to medical abortion. Pharmacies may be a good place to target education for pharmacy staff and women about safe and effective use of misoprostol for abortion.


Endoneurosurgical resection of intraventricular and intraparenchymal lesions using the port technique.
Deep-seated intraventricular and intraparenchymal lesions have traditionally been resected via transcortical routes, often requiring the use of retractors to maintain the corridor created to reach the lesion and proceed with a bimanual microsurgical resection. A transparent cylindrical conduit (port) has been developed to resect deep-seated lesions using the endoscope or, more recently, Video Telescopic Operating Microscopy (VTOM) for visualization. We describe the surgical technique of the port technique and discuss the evolution of the concept of intraaxial brain surgery performed through a conduit. Detailed description of the ventriculoport and brainport technique with illustrative cases. Results of intraventricular and intraparenchymal port surgery have been published and document the feasibility and safety of this technique. Over the years, the technique has been improved. The port technique offers numerous potential advantages, including: 1) minimizing white matter disruption as the tip design minimizes the risk of fascicles injury during cannulation; 2) ensuring stability as the rigidity prevents inadvertent expansion of the initial diameter of the corticectomy and white fiber tract dissection throughout surgery; 3) protecting the surrounding tissues against iatrogenic injuries caused by instrument entry and reentry; 4) affording constant visualization of the tissue traversed given the transparent conduit design; 5) enabling homogeneous radial dispersion of the pressure on the surrounding tissue to minimize injury. The port technique is an option for resection of intraventricular and intraparenchymal lesions. Additional studies are required to assess its impact on adjacent cerebral tissue morphology, blood flow, and metabolism. Quality-of-life assessments are also needed. High-definition fiber tracking, new visualization techniques (VTOM), and new instrumentation will add to the progress of endoscopic port surgery. We have already seen a significant evolution of the technology even since the preparation of this article.


Improved production of teicoplanin using adsorbent resin in fermentations.
To use adsorbent resins in fermentations to eliminate toxic effects on growth, reduce feedback repression of production and assist in recovery of teicoplanin. An adsorbent resin was added to the culture broth for the adsorption of teicoplanin. Amberlite XAD-16, Diaion HP-20, charcoal and silica gel were investigated as adsorbent resins. The adsorbed teicoplanin was extracted from the resin by 80% methanol after fermentation. Antibiotic activity was quantified by the disc-agar diffusion assay against Bacillus substilis, and qualitative evaluations were based on HPLC using YMC-Pack ODS-A column. Diaion HP-20 was the most effective adsorbent resin when added at a concentration of 5% (w/v) in the inoculation stage. Addition of Diaion HP-20 in fermentations eliminated toxic effects on growth and reduced feedback repression of teicoplanin by adsorption. There was a 4.2-fold increase in the quantities of teicoplanin. Addition of adsorbent assisted in the recovery of teicoplanin by reducing the recovery steps. The results of this study provide useful information for the production of teicoplanin, a glycopeptide antibiotic produced by Actinoplanes teicomyceticus. Addition of adsorbent in fermentation increased productivity of teicoplanin by more than five times.


Metazoan Parasite Life Cycles: Significance for Fish Mariculture.
Marine fish are a nutritious and high-value food commodity, but many wild-capture fisheries are in decline. Thus, marine fish culture is expected to expand greatly in coming years. Management of disease is a major problem in this industry, and metazoan parasites are among the most significant disease agents in terms of economic loss and animal welfare. Current methods for controlling metazoan parasites are mostly reactionary and rely on chemical treatment. Such methods are ultimately unsustainable. Here, we summarise the life cycles of marine metazoan parasites and how this knowledge can be used for nonchemical management and control. To aid the sustainable growth of marine fish culture, we advocate for a renewed research focus on the basic life history characteristics of parasites.


The efficacy and safety of managing ectopic pregnancies with transvaginal ultrasound-guided local injections of absolute ethanol.
To describe the efficacy and safety of managing ectopic pregnancies (EP) with ultrasound-guided local injections of absolute ethanol (AE). 69 cases of EP following IVF performed in our clinic were treated with a local injection of 0.3 ml AE with a 23-gauge needle under transvaginal ultrasonic guidance. The efficacy was evaluated comparing serum beta-human chorionic gonadotropin (beta-hCG) levels before and after the injection. In the 60 successful cases (87%), the serum beta-hCG level decreased by 10-30% in two hours postinjection. Of these, 46 were effective with a single injection and the half-life of beta-hCG was achieved within 4 days in 45 cases. In 56 cases (including repetitive administration) serum beta-hCG levels decreased to 20 mIU/mL within 20 days. The treatment showed no side effects and could be given on an outpatient basis without anesthesia. This method was shown to be a safe, effective new approach to treating EP.


Infections after auxiliary partial liver transplantation. Experiences in the first ten patients.
In ten auxiliary partial liver transplant recipients selective bowel decontamination (SBD) was used to reduce infections due to gram-negative microorganisms and fungi. During SBD no gram-negative infections occurred. Candida peritonitis was observed in one patient. After discontinuation of SBD serious infections of gram-negative origin did occur and three fungal infections were seen. SBD seems to have a favourable effect in reducing infections by gram-negative microorganisms and fungi. Most striking was the number of enterococcal infections that occurred. Five out of ten patients developed enterococcal infections which in two cases contributed to a fatal outcome. These infections occurred after increase of the number of enterococci in faeces and concomitant positive cultures of bile, ascites or wound drains. This increase could be due to the use of SBD. Also, the kind of biliary anastomosis may play an important role in the relatively high incidence of enterococcal infections. In the postoperative period, recurrence of hepatitis B infection in the liver graft was observed in all patients with cirrhosis due to this virus. Problems caused by other viral infections or protozoal infections remained limited in these ten patients.


Opposing effects of Sca-1(+) cell-based systemic FGF2 gene transfer strategy on lumbar versus caudal vertebrae in the mouse.
Our previous work showed that a Sca-1(+) cell-based FGF2 therapy was capable of promoting robust increases in trabecular bone formation and connectivity on the endosteum of long bones. Past work reported that administration of FGF2 protein promoted bone formation in red marrow but not in yellow marrow. The issue as to whether the Sca-1(+) cell-based FGF2 therapy is effective in yellow marrow is highly relevant to its clinical potential for osteoporosis, as most red marrows in a person of an advanced age are converted to yellow marrows. Accordingly, this study sought to compare the osteogenic effects of this stem cell-based FGF2 therapy on red marrow-filled lumbar vertebrae with those on yellow marrow-filled caudal vertebrae of young adult W(41)/W(41) mice. The Sca-1(+) cell-based FGF2 therapy drastically increased trabecular bone formation in lumbar vertebrae, but the therapy not only did not promote bone formation but instead caused substantial loss of trabecular bone in caudal vertebrae. The lack of an osteogenic response was not due to insufficient engraftment of FGF2-expressing Sca-1(+) cells or inadequate FGF2 expression in caudal vertebrae. Previous studies have demonstrated that recipient mice of this stem cell-based FGF2 therapy developed secondary hyperparathyroidism and increased bone resorption. Thus, the loss of bone mass in caudal vertebrae might in part be due to an increase in resorption without a corresponding increase in bone formation. In conclusion, the Sca-1(+) cell-based FGF2 therapy is osteogenic in red marrow but not in yellow marrow.


Community-Acquired Methicillin-Resistant Staphylococcus aureus Infections in Acutely Ill Children: A Retrospective Case-Control Study.
To test if admission clinical and laboratory variables could reliably discriminate community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections from methicillin-sensitive Staphylococcus aureus (MSSA) infections in acutely ill children, and to describe the epidemiology, clinical features and outcomes among children with Staphylococcal infections admitted to the hospital. The authors conducted this retrospective case-control study comparing children with CA-MRSA and MSSA infections admitted to hospital between June 2014 and June 2017. They describe the evolving epidemiology and attempt to identify clinical and laboratory variables that can differentiate MRSA cases from MSSA controls. They used multivariate logistic regression to identify independent predictors of MRSA infection and Cox-proportional hazard analysis to compare survival times. Seventy-three children were enrolled, of which 35 had CA-MRSA and 38 had MSSA infections. Children in MRSA group were younger [median (IQR) age in months: 36 (12, 62) vs. 56 (37, 96); p = 0.032]. MRSA and MSSA groups had similar rate of skin and soft tissue involvement (SSTI) [62.9% vs. 54.1%; p = 0.449]. Median duration of illness was lower in MRSA, 6 vs. 8.5 d (p = 0.001). TLC of 8100 or less was 82% sensitive and 94% specific for MRSA sepsis at admission [AUROC = 0.64 (0.51-0.77), p = 0.04]. Mortality (8.6% vs. 10.5% p = 1.0) and length of ICU stay (7.2 vs. 9.3 d, p = 0.24) were similar in both. None of the admission variables were predictive of MRSA culture-positivity on regression analysis. The hospital-based incidence of CA-MRSA infections among children appears to be increasing. None of the admission clinical or laboratory variables could reliably identify CA-MRSA infections. As there seems to be no reliable way to differentiate children with MSSA and MRSA infections, physicians may consider empiric initiation of broad-spectrum antibiotics at admission to cover both MSSA and MRSA, especially in critically ill children with suspected Staphylococcal infections.


The design, synthesis, biological evaluation, and molecular docking of new 5-aminosalicylamide-4-thiazolinone hybrids as anticancer agents.
New 5-aminosalicylamide-4-thiazolinone hybrids (27) were efficiently synthesized, characterized, and evaluated to explore their structure-activity relationship as anticancer agents. The antiproliferative activities of the new hybrids were evaluated against eight cancer cell lines using the sulforhodamine B assay. The most potent compound (24b) possessed high selectivity on the tested cell lines in the low micromolar range, with much lower effects on normal fibroblast cells (IC50 > 50 µM). The cell lines derived from leukemia (Jurkat), cervix (HeLa), and colon (HCT116) cancers appeared to be the most sensitive, with IC50 of 2 µM. 24b is the N-ethylamide derivative with p-dimethylaminobenzylidene at position 5 of the 4-thiazolinone moiety. Other N-substituents or arylidene derivatives showed lower activity. Hybrids with salicylamides showed lower activity than with methyl salicylate. The results clearly show that the modifications of the carboxy group and arylidene moiety greatly affect the activity. Investigating the possible molecular mechanisms of these hybrids revealed that they act through cell-cycle arrest and induction of apoptosis and epidermal growth factor receptor (EGFR) inhibition. Molecular docking studies rationalize the molecular interactions of 24b with EGFR. This work expands our knowledge of the structural requirements to improve the anticancer activity of 5-aminosalicylic-thiazolinone hybrids and pave the way toward multitarget anticancer salicylates.


DExD/H-box proteins and their partners: helping RNA helicases unwind.
Members of the DExD/H-box family of RNA helicases are involved in many processes and complexes within the cell. While individual DExD/H helicase family members have been studied extensively, the mechanisms through which helicases affect multiprotein complexes are just beginning to be investigated. Because RNA helicases are both highly conserved and numerous in the cell, study of RNA helicase recruitment and modulation by cofactors is necessary for understanding the mechanisms of helicase action in vivo. This review will focus on cofactor-mediated regulation of helicase target specificity and activity.


Does preoperative chemical depilation make any difference in postoperative wound infection?
Preparation for surgery has traditionally included the removal of body hair from the intended surgical wound site. The effect of this practice on postoperative wound infection is yet to be fully elucidated. This study sought to determine if preoperative chemical depilation reduces the risk of surgical site infection (SSI). Two methods of preoperative hair removal: razor shaving and depilatory cream were compared. The eligible patients were randomized into two groups and the presence of postoperative wound infection was evaluated using the Southampton wound grading system. Data were analyzed using SPSS version 21 Chicago-Illinois, statistical significance was inferred at Pvalue ≤ 0.05. In total 100 patients were analyzed with 20 patients excluded due to co-morbidities and noncompletion of the study. The overall prevalence of SSI was 18.0% (7 (14.0%) and 11 (22.0%) in the depilatory cream and razor shaving groups, respectively). The difference in the rate of SSI was not statistically significant (P = 0.436). Hair was completely removed in 47 (94.0%) compared to 38 (76.0%) patients in the razor shaving group (P = 0.012) while skin injuries were noted in 21 (42.0%) vs 1 (2.0%) patients who had razor shaving and chemical depilation(P = <0.0001), respectively. There was no significant difference in SSI rates in patients that had preoperative chemical depilation when compared with razor shaving.


Structure-function relationships in rat brainstem subnucleus interpolaris: V. Functional consequences of neonatal infraorbital nerve section.
In a prior study (Jacquin et al., '86c), the response properties and projections of neonatally axotomized trigeminal (V) primary afferents were studied in the adult rat. Here, single-unit recording, electrical stimulation, and receptive field (RF) mapping techniques were also used to assess the functional consequences of neonatal infraorbital nerve section upon postsynaptic cells in V brainstem subnucleus interpolaris (SpVi). Of 904 cells studied, 385 were from normal adults and 519 were from neonatally deafferented adults. Infraorbital nerve section at birth resulted in: (1) a substantial reduction in those areas of SpVi containing cells with infraorbital RFs, and only a slight increase in areas solely responsive to noninfraorbital surfaces, (2) an absence of orderly topography within cells expressing regenerate primary afferent inputs, (3) a slight increase in mean discharge latency to V ganglion or thalamic shocks, (4) an increased relative percentage of cells orthodromically activated by diencephalic or cerebellar shocks, (5) a decreased relative percentage of mystacial vibrissa-sensitive local circuit neurons, with a corresponding increase in local circuit nociceptors and unresponsive cells, (6) an increased relative percentage of mystacial nociceptors, virbrissae, guard hair, and/or skin sensitive cells projecting to thalamus and/or cerebellum, (7) an increased percentage of local circuit neurons with RFs including more than one vibrissa, whereas projection neurons did not differ from normal in the number of vibrissae composing their RFs, and (8) an increased relative percentage of cells expressing interdivisional and intermodality convergence, split RFs, spontaneous activity, directional high velocity, and neuroma sensitivity. Thus neonatal nerve section produces changes in topography, inputs, projection status, and responses of surviving postsynaptic neurons. Although many of these centrally observed alterations can be attributed to altered peripheral projections in axotomized V primary afferents, others must reflect central reorganization. The central mechanisms responsible for the synthesis of deafferentation-induced RFs remain to be elucidated.


Biological and methodological features of the measurement of S100B, a putative marker of brain injury.
The S100B astroglial protein is widely used as a parameter of glial activation and/or death in several conditions of brain injury. Cerebrospinal fluid and serum S100B variations have been proposed to evaluate clinical outcomes in these situations. Here, we briefly broach some aspects, commonly not sufficiently valorized, concerning the biology and measurements of this protein. S100B has molecular targets and activities in and outside of astrocytes, and variations of intra and extracellular content are not necessarily coupled. We discuss the extracellular origin of this protein in brain tissue, as well as extracerebral sources of this protein in serum, comparing it with other available protein markers of brain damage. The superestimation of the heterodimer S100A1-B in the current clinical literature is also analyzed. We affirm that poor dualistic views that consider S100B elevation as "bad" or "good" simplify clinical practice and delay our comprehension of the role of this protein, both in physiological conditions and in brain disorders.


Measuring local RF heating in MRI: Simulating perfusion in a perfusionless phantom.
To overcome conflicting methods of local RF heating measurements by proposing a simple technique for predicting in vivo temperature rise by using a gel phantom experiment. In vivo temperature measurements are difficult to conduct reproducibly; fluid phantoms introduce convection, and gel phantom lacks perfusion. In the proposed method the local temperature rise is measured in a gel phantom at a timepoint that the phantom temperature would be equal to the perfused body steady-state temperature value. The idea comes from the fact that the steady-state temperature rise in a perfused body is smaller than the steady-state temperature increase in a perfusionless phantom. Therefore, when measuring the temperature on a phantom there will be the timepoint that corresponds to the perfusion time constant of the body part. The proposed method was tested with several phantom and in vivo experiments. Instead, an overall average of 30.8% error can be given as the amount of underestimation with the proposed method. This error is within the variability of in vivo experiments (45%). With the aid of this reliable temperature rise prediction the amount of power delivered by the scanner can be controlled, enabling safe MRI examinations of patients with implants.


Use of a modified chitosan-dextran gel to prevent peritoneal adhesions in a rat model.
Intra-abdominal adhesions are a major cause of morbidity and a significant drain on healthcare resources. Numerous anti-adhesion products have reached clinical use but none has been wholly satisfactory. This study examines the application of a modified chitosan-dextran (CD) gel to the intraperitoneal cavity to reduce adhesion formation. This is a unique synthetic gel, its active ingredients being succinyl chitosan and dextran aldehyde. Eighty adult male Wistar albino rats were randomized to undergo surgery alone or to receive CD gel at the time of surgery. Control groups using modified dextran only gel were also included. The surgical procedures comprised of laparotomy and either cecal abrasion or anastomotic simulation by enterotomy of the cecum with primary closure. At postoperative d 21 rats were euthanized by CO2 inhalation, and adhesions graded by an investigator blinded to the treatment groups, using a predetermined adhesion measurement score. Adhesions were significantly reduced in the cecal abrasion group with median adhesion scores for the treatment group of 0 versus 3 in the control group (P<0.001, Fisher's exact test). Further reduction in adhesion formation was noted in the enterotomy group with median scores of 2 versus 5 for treatment and control groups respectively (P=0.003, Fisher's exact test). Chitosan-dextran gel appears to significantly reduce the formation of intra-abdominal adhesions without adversely affecting wound healing. This is a noteworthy advancement in the safe prevention of post operative, intra-abdominal adhesions.


Mitochondrial dysfunction in the pathogenesis of endothelial dysfunction.
Cardiovascular diseases (CVDs) are a matter of concern worldwide, and mitochondrial dysfunction is one of the major contributing factors. Vascular endothelial dysfunction has a major role in the development of atherosclerosis because of the abnormal chemokine secretion, inflammatory mediators, enhancement of LDL oxidation, cytokine elevation, and smooth muscle cell proliferation. Endothelial cells transfer oxygen from the pulmonary circulatory system to the tissue surrounding the blood vessels, and a majority of oxygen is transferred to the myocardium by endothelial cells, which utilise a small amount of oxygen to generate ATP. Free radicals of oxide are produced by mitochondria, which are responsible for cellular oxygen uptake. Increased mitochondrial ROS generation and reduction in agonist-stimulated eNOS activation and nitric oxide bioavailability were directly linked to the observed change in mitochondrial dynamics, resulting in various CVDs and endothelial dysfunction. Presently, the manuscript mainly focuses on endothelial dysfunction, providing a deep understanding of the various features of mitochondrial mechanisms that are used to modulate endothelial dysfunction. We talk about recent findings and approaches that may make it possible to detect mitochondrial dysfunction as a potential biomarker for risk assessment and diagnosis of endothelial dysfunction. In the end, we cover several targets that may reduce mitochondrial dysfunction through both direct and indirect processes and assess the impact of several different classes of drugs in the context of endothelial dysfunction.


Negative pressure devices in the explanted penile prosthesis population.
Of 402 penile prosthesis implanted at our institution between 1980 and 1987, 20 required explantation due to infection, erosion, pain or tissue necrosis. Of these 20 patients 14 were available for a prospective trial using a negative pressure device in an attempt to restore potency. Among these 14 patients 11 used the device at home for a minimum of 30 days after an acceptable office demonstration. Three patients did not desire the negative pressure device after an office visit test. Of the 11 home users 10 (91 per cent) reported at least satisfactory erections and successful intercourse. Interestingly, 5 of 6 patients in whom explantation was due to infection were able to use the negative pressure device successfully. Over-all, 10 of the 14 explant patients (71 per cent) engaged in regular successful intercourse using the device. The negative-pressure device can be a useful therapy for erectile impotence even in the sometimes challenging explant population. Despite previous corporeal infection and presumed fibrosis, negative pressure devices can provide patients with a functional erection-like state.


Simultaneous bucket handle tear of both medial and lateral menisci of a knee with chronic anterior cruciate ligament deficiency.
Bucket handle meniscus tears constitute about 10% of all meniscal tears. Bucket handle tears of medial meniscus is three times more than lateral meniscus. Most of these tears are associated with anterior cruciate ligament (ACL) deficiency. Lateral meniscus lesions are more common with acute ACL deficiency, where medial meniscus lesions are more associated with chronic ACL deficiency. We identified bucket handle tears of each meniscus of a 30-year-old male patient while performing diagnostic arthroscopy during ACL reconstruction procedure. We present an ACL deficient knee with bucket handle tears of medial and lateral meniscus of the same knee and discuss the treatment.


Insertion of an E. coli lacZ gene in Acetobacter xylinus for the production of cellulose in whey.
A mini-Tn10:lacZ:kan was inserted into a wild-type strain of Acetobacter xylinus by random transposon mutagenesis, generating a lactose-utilising and cellulose-producing mutant strain designated ITz3. Antibiotic selection plate assays and Southern hybridisation revealed that the lacZ gene was inserted once into the chromosome of strain ITz3 and was stably maintained in non-selective medium after more than 60 generations. The modified strain had, on the average, a 28-fold increase in cellulose production and a 160-fold increase in beta-galactosidase activity when grown in lactose medium. beta-Galactosidase activity is present in either lactose or sucrose medium indicating that the gene is constitutively expressed. Cellulose and beta-galactosidase production by the modified strain was also evaluated in pure and enriched whey substrates. Utilisation of lactose in whey substrate by ITz3 reached 17 g l(-1) after 4 days incubation.


Heritable custom genomic modifications in Caenorhabditis elegans via a CRISPR-Cas9 system.
We adapted the CRISPR-Cas9 system for template-mediated repair of targeted double-strand breaks via homologous recombination in Caenorhabditis elegans, enabling customized and efficient genome editing. This system can be used to create specific insertions, deletions, and base pair changes in the germline of C. elegans.


Meningeal carcinomatosis from breast cancer: spinal cord vs. brain involvement.
Twenty-two patients with meningeal carcinoma due to breast cancer were retrospectively evaluated to determine what prognostic factors affected survival. Five patients survived for more than one year. The therapy in these long-term survivors was similar to that of those suffering early death. Patients with primarily brain symptoms survived a median of 21 days vs. 150 days in those with primarily spinal cord symptoms (p = 0.026). The site of involvement may be an important stratification parameter for future prospective trials.


A 30-year experience of Millin's retropubic prostatectomy: Has this classic operation derived by a President of the College in Ireland stood the test of time?
In patients with large gland volume, open prostatectomy/adenoma enucleation remains a valuable surgical option in treating large obstructing prostates. We report our series of open prostatectomies spanning 32 years from a single institution. We retrospectively reviewed all patients who underwent open prostatectomy between 1980 and 2012. Patient demographical, clinical, pre- and postoperative data and final histology were retrieved from hospital in-patient enquiry system and chart review. A total of 161 patients underwent Millin's prostatectomy by seven surgeons between 1980 and 2012. The mean blood loss was 1,381 mls (range 300-3,675 mls). One-third (34%) of patients (n = 55) received a blood transfusion. The mean weight of prostate tissue removed was 119 g (median 112 g, range 17-372 g). 6.6 % of pathological specimens revealed incidental prostate cancer, of which 78% were well differentiated (Gleason score ≤ 6). The mean weight of prostate tissue removed in patients who received a transfusion was 124 g. Trial of micturition (TOM) was performed at a mean of 9 days (median 9 days, range 5-25 days) with 94% of patients having a successful trial of voiding. 6% of cases early in the series failed to void initially, but did so at later removal of catheter while still in hospital. 45 patients (28%) of patients developed peri- or postoperative complications. There were three deaths (1.9%). Open Millin's prostatectomy popularized over half a century ago continues to be a valuable option for the surgical treatment of high-volume prostate glands with excellent outcomes for patients.


Identification and analysis of conjugated linoleic acid isomers (CLA).
CLA are predominantly found in milk, milk products, meat and meat products of ruminants. The distribution of CLA isomers in cheese and/or meat shows one major isomer C18:2 c9t11 with nearly 84% of total CLA. It is estimated that the daily intake of CLA using the German Nutrition Study is 0.35 g/d for women and 0.43 g/d for men.


Impact of a Ration Negative in Dietary Cation-Anion Difference and Varying Calcium Supply Fed before Calving on Colostrum Quality of the Dams and Health Status and Growth Performance of the Calves.
This study investigated the effect of diets negative in dietary cation-anion difference (DCAD) or restricted in Ca fed prepartum to dairy cows for three weeks on colostrum yield and composition, and the health and growth performance of their calves. Thirty-six pregnant non-lactating Holstein-Friesian cows were randomly assigned to three isoenergetic diets: (1) low Ca: 0.24% Ca, DCAD: +86 mEq/kg; (2) high Ca: 1.23% Ca, DCAD: +95 mEq/kg; and (3) low DCAD: 1.28% Ca, DCAD: -115 mEq/kg (all dry matter (DM) basis). While colostrum quality was not affected, low Ca supply prepartum tended to increase the colostrum yield compared to high Ca (low Ca = 8.81 vs. high Ca = 5.39 kg). However, calves from cows fed low DCAD showed higher serum concentrations of K, lower body weight (BW), starter feed intake and average daily weight gain before weaning compared to low Ca and high Ca calves (53.12 vs. 57.68 and 57.32 kg) but BW was similar postweaning (d 70). In addition, calves from dams fed low DCAD were more likely to develop diarrhea and had increased number of days with abnormal fecal scores. Consequently, calves from low DCAD dams had to be treated more frequently.


In vivo conversion of human HDL3 to HDL2 and apoE-rich HDL1 in the rat: effects of lipid transfer protein.
In this study we determined in vivo conversions of human 3H-labeled cholesteryl ester-labeled HDL3 [( 3H]CE-HDL3) in male rats and the effects of partially purified lipid transfer protein on the conversion processes. Zonal centrifugation techniques were used to prepare the [3H]CE-HDL3 and to follow the conversion processes. One hour after the injection, a complete conversion of HDL3 to the HDL2-density species was found. With time, [3H]CE separated with apoE-rich HDL1 and, by 18 hr, 35.9% of plasma radioactivity was associated with the apoE-rich HDL1 lipoprotein fraction. In vitro incubation of [3H]CE-HDL3 in rat plasma reproduced in part the HDL3----HDL2 conversion, but no movement of radioactivity to HDL1 was observed. Injection of the rats with partially purified lipid transfer proteins induced [3H]CE exchange between lipoproteins. The conversion of HDL3 to HDL2, however, was minimally affected. Formation of [3H]CE-HDL1, in contrast, was reduced to about one-half of that found in control animals. It is concluded that in vivo conditions are necessary for conversions of HDL3 (and HDL2) to HDL1, and that lipid transfer reactions delay this process.


Introduction--development and phylogeny of the arthropods: Darwin's legacy.
In the present essay, I first recall the genealogical concept of classification settled by Charles Darwin in the "Origin of Species". Darwin tightly linked what we now call phylogeny and development. He often insisted to take into account embryonic and larval characters, most often using as examples his favourite animals, the cirripedes. Then I discuss remaining problems, and also perspectives, to address the link between phylogeny and development in the modern terms of molecular and cladistic phylogenetics and of molecular and genetic developmental biology.


Pharmacodynamics and potential synergistic effects of Mai-Luo-Ning injection on cardiovascular protection, based on molecular docking.
As a computer-assisted approach, molecular docking has been universally applied in drug research and development and plays an important role in the investigation and evaluation of herbal medicines. Herein, the method was used to estimate the pharmacodynamics of Mai-Luo-Ning injection, a traditional Chinese compound herbal prescription. Through investigating the interactions between several important proteins in cardiovascular system and characteristic components of the formula, its effect on cardiovascular protection was evaluated. Results showed the differences in the interactions between each component and the selected target proteins and revealed the possible mechanisms for synergistic effects of various characteristic components on cardiovascular protection. The study provided scientific evidence supporting the mechanistic study of the interactions among multi-components and targets, offering a general approach to investigating the pharmacodynamics of complicated materials in compound herbal prescriptions.


Examining the Role of and Treatment Directed at IL-1β in Atherosclerosis.
The purpose of this review was to examine the role of IL-1β in the inflammatory process central to the development of atherosclerosis and to discuss current clinical evidence for treatments targeting IL-1β in coronary artery disease. IL-1β has been shown to modulate atherosclerotic plaque progression by upregulating the synthesis of adhesion molecules on endothelial cells, as well increasing activation and proliferation of vascular smooth muscle cells. Animal studies have further suggested that alterations in the balance between agonists and antagonists of IL-1β are important in promoting atherosclerosis. In humans, preliminary assessment of therapy targeting IL-1β noted early reductions in serum inflammatory biomarkers among those with systemic inflammatory or coronary artery disease. The CANTOS trial, a large randomized double-blind study found that canakinumab, a monoclonal antibody targeting IL-1β, reduced ischemic events in patients being treated for secondary prevention. Cellular, animal, and now clinical studies have suggested a role for therapies aimed at IL-1β for treatment of CAD. However, given potential side effects and costs of these medications, further study is required to determine which patients may be most suited for treatment above current standard of care.


Diagnosis and management of intradiaphragmatic extralobar pulmonary sequestration: a report of 11 cases.
Evaluate the diagnosis and management of intradiaphragmatic extralobar pulmonary sequestration (IDEPS). We retrospectively reviewed cases of bronchopulmonary sequestrations (BPS) diagnosed in our hospital from March 2011 to May 2014, in order to identify patients with IDEPS. Diagnosis of IDEPS was confirmed using prenatal Doppler ultrasound, postnatal intravascular enhanced computed tomography, and surgery. The 11 cases diagnosed with IDEPSs were confirmed with histopathology. In our first case we did not find any mass from abdominal surgery; we then turned to transthoracic surgery. Three patients underwent thoracoscopy, and seven underwent thoracotomy. IDEPS is better approached through the chest. Thoracoscopy in experienced hands a favorable approach.


Development of the First Tritiated Tetrazine: Facilitating Tritiation of Proteins.
Tetrazine (Tz)-trans-cyclooctene (TCO) ligation is an ultra-fast and highly selective reaction and it is particularly suited to label biomolecules under physiological conditions. As such, a 3 H-Tz based synthon would have wide applications for in vitro/ex vivo assays. In this study, we developed a 3 H-labeled Tz and characterized its potential for application to pretargeted autoradiography. Several strategies were explored to synthesize such a Tz. However, classical approaches such as reductive halogenation failed. For this reason, we designed a Tz containing an aldehyde and explored the possibility of reducing this group with NaBT4 . This approach was successful and resulted in [3 H]-(4-(6-(pyridin-2-yl)-1,2,4,5-tetrazin-3-yl)phenyl)methan-t-ol with a radiochemical yield of 22 %, a radiochemical purity of 96 % and a molar activity of 0.437 GBq/μmol (11.8 Ci/mmol). The compound was successfully applied to pretargeted autoradiography. Thus, we report the synthesis of the first 3 H-labeled Tz and its successful application as a labeling building block.


Punish or perish? Retaliation and collaboration among humans.
A spate of recent investigations on reciprocation and social enforcement in humans has brought together (and sometimes divided) economists, psychologists, anthropologists, social scientists and evolutionary biologists, in addition to neurologists and students of animal behavior. Experimental work on public goods and social incentives has addressed a wealth of questions on the emotional and cognitive (proximal) factors, and also on the genetic and cultural (ultimate) evolutionary mechanisms involved in this essential aspect of human nature.


Prevalence of dyssynchrony and relation with long-term outcome in patients after acute myocardial infarction.
The impact of left ventricular (LV) dyssynchrony on the long-term outcomes of patients with acute myocardial infarction (AMI) remains unknown. The purpose of the present study was to evaluate the prevalence of LV dyssynchrony after AMI and the potential relation with adverse events. A total of 976 consecutive patients admitted with AMI treated with primary percutaneous coronary intervention were evaluated. Two-dimensional echocardiography was performed <48 hours after admission. LV dyssynchrony was assessed with speckle-tracking imaging and calculated as the time difference between the earliest and latest activated segments. Patients were followed up for the occurrence of all-cause mortality (the primary end point) or the composite secondary end point (heart failure hospitalization and all-cause mortality). Within 48 hours of admission for the index infarction, mean LV dyssynchrony was 61 ± 79 ms, and 14% of the patients demonstrated a ≥130-ms time difference, defined as significant LV dyssynchrony. During a mean follow-up period of 40 ± 17 months, 82 patients (8%) reached the primary end point. In addition, 36 patients (4%) were hospitalized for heart failure. The presence of LV dyssynchrony was associated with an increased risk for all-cause mortality and hospitalization for heart failure during long-term follow-up (adjusted hazard ratio 1.06, 95% confidence interval 1.05 to 1.08, p <0.001, per 10-ms increase). Moreover, LV dyssynchrony provided incremental value over known clinical and echocardiographic risk factors for the prediction of adverse outcomes. In conclusion, LV dyssynchrony is a strong predictor of long-term mortality and hospitalization for heart failure in a population of patients admitted with ST-segment elevation AMI treated with primary percutaneous coronary intervention.


A case report of spinal toxocariasis with extensive tumor-like involvement.
Toxocariasis is a common parasitic infection worldwide. Although it can present as several clinical syndromes, neurological manifestation is rare. Only a few reports are available on spinal cord involvement of toxocariasis. We report a case that presented with gait disturbance due to progressive lower limb spasticity. The patient had had visceral toxocariasis infection 8 years before. A spine magnetic resonance image (MRI) showed syringomyelia along the entire thoracic cord with small nodular enhancing lesions in the mid-portion of the syrinx, which led to the suspicion of ependymoma. Surgical mass removal was performed. However, histopathological examination of the mass did not show any malignant cells; instead, there were numerous axonal retraction balls with an eosinophilic granular body-like appearance. The serum antibody titer against toxocariasis was borderline high. Taken together, these observations led to a diagnosis of Toxocara infection, and the patient was treated with albendazole. To the best of our knowledge, this is the first case report of tumor-like spinal toxocariasis involving extensive lesions. A solid enhancing mass with accompanied syrinx and hemorrhage might be a Toxocara infection. It can easily be diagnosed with serologic tests and simply be treated with oral albendazole if suspected.


Optimization of a model of red blood cells for the study of anti-oxidant drugs, in terms of concentration of oxidant and phosphate buffer.
The aggression of erythrocytes by an oxidative stress induces hemolysis. This paper aims to valid a model of erythrocytes in terms of composition of the phosphate buffer solution and of concentration of a well-known oxidant, AAPH. Three compositions of phosphate buffer solution are mixed with three concentrations of oxidant. The influence of these two parameters on hemolysis is independently studied by a variance analysis and a Kruskal-Wallis test when ANOVA is not available. The hemolysis rate increases with time at fixed oxidant concentration, but is not influenced by the composition of the buffer solution. The highest hemolysis rate, 90%, was only measured within 2 h with the highest oxidant concentration. If we retain this concentration of oxidant, the lower concentration of the buffer can by eliminated by a significant less hemolysis and the highest concentration of the buffer can by chosen in regard of the better precision for a similar hemolysis compared to the mean buffer. We hope to study the effect of anti-oxidant agent with such a model of erythrocytes.


When only one embryo is available, is it better to transfer on Day 3 or to grow on?
In patients with only one embryo on Day 3 post-IVF treatment, does transferring the embryo into the uterine environment achieve a higher pregnancy rate than growing the embryo on with a plan to transfer at Day 4-6? This was a retrospective cohort study conducted in patients with only one viable embryo on Day 3 post-IVF treatment. Data were extracted from a standardized IVF database and included 1384 women who fulfilled this study's selection criteria. Outcomes of these embryos were followed up and stratified into two groups: embryos transferred on Day 3 and those grown on to Day 4-6. Pregnancy rate (biochemical and clinical) and live birth rates were analysed with logistic regression and adjusted using a parsimonious model for baseline patient characteristics. Biochemical pregnancy (16.7% versus 9.5%, odds ratio [OR] 1.9, P = 0.001), clinical pregnancy (14.7% versus 6.8%, OR 2.35, P < 0.001) and live birth rates (9.7% versus 4.4%, OR 2.37, P = 0.002) were significantly higher in the Day 3 group than those in the group grown on to Day 4-6. These differences were still significant after adjusting for potential confounders (adjusted OR 2.60, 3.71, 4.08, respectively, P < 0.001). These findings support Day 3 cleavage-stage embryo transfer instead of growing on to Day 4-6 for blastocyst-stage transfer when only a single embryo is available.


Hemostatically distinct FFPs equally improve abnormal TEG variables in an in vitro dilutional coagulopathy model.
To improve fresh frozen plasma (FFP) availability, thawed plasma is stored at 4°C for up to 5 days and considered equivalent to freshly thawed FFP. However, we have shown that hemostatic potential of thawed plasma is highly variable between donors and significantly diminished during storage. We hypothesized that smaller volumes of plasma with higher hemostatic potential (FFP-H) would be needed to restore normal thrombelastogram (TEG) values compared to plasma with lower hemostatic potential (FFP-L). A dilutional coagulopathy model was established from whole blood by diluting plasma with saline to 23%, while cellular components were kept unchanged. Saline was gradually replaced with equal volumes of FFPs with distinctive hemostatic potentials, which was evaluated by the calibrated automated thrombogram. Clot formation in the presence of tissue factor was evaluated by TEG at baseline and after addition of increasing concentrations of FFP-H and FFP-L. Blood dilution with saline in the presence of tissue factor resulted in abnormal TEGs that resemble a pattern observed in severely bleeding trauma patients. All FFPs produced similar improvements in TEG variables despite different hemostatic potentials. TEG changes were solely dependent on FFP volume and reached the normal reference range when plasma concentration increased to 40%. Plasma dilution and tissue factor in whole blood results in an abnormal TEG with a hyperfibrinolytic pattern. A plasma concentration of at least 40% was necessary for TEG normalization after dilution with saline. An effect of FFPs' hemostatic potential on clot formation could not be detected by TEG in this in vitro model.


Effects of acute and chronic fluoxetine and diazepam on freezing behavior induced by electrical stimulation of dorsolateral and lateral columns of the periaqueductal gray matter.
The defensive responses induced by electrical stimulation of the dorsal periaqueductal gray matter (dPAG) of the rat have been proposed as a model of panic attacks in humans. In the present study we investigated the acute and chronic effects of fluoxetine and diazepam on freezing and escape reactions elicited by electrical stimulation of the dorsolateral (dlPAG) and lateral (lPAG) columns of the periaqueductal gray matter (PAG). The frequencies of crossing, rearing, bouts of micturition and fecal boli were also recorded. Electrodes were unilaterally implanted in the brainstem aimed at the PAG. Drug treatments were given daily for 2 weeks with fluoxetine (5, 10 and 20 mg/kg ip), a selective inhibitor of serotonin reuptake, diazepam (1, 2 and 4 mg/kg ip), or saline. Drug effects were assessed acutely (15 min after the first injection) and chronically (15 min after the 14th injection). Chronic, but not acute, administration of fluoxetine caused a significant increase in the threshold of freezing without affecting the escape response elicited by dlPAG/lPAG stimulation. This characteristic pattern of effects could not be attributed to motor deficit, since this drug did not change the number of crossings and rearings. In contrast, no significant threshold changes were observed following acute and chronic treatment with diazepam. These data give further evidence for (a) an antiaversive effect of chronic treatment with fluoxetine, which caused a selective reduction in freezing behavior and neurovegetative responses associated with fearlike reaction elicited by dlPAG/lPAG electrical stimulation; (b) the involvement of the dlPAG and lPAG in the generation and organization of defensive responses and that freezing may probably be associated with panic attacks; and (c) the lack of effect of diazepam in this model is in line with its inefficacy as a panicolytic drug. The study of the unconditioned freezing behavior evoked by dlPAG/lPAG stimulation may constitute a new and interesting model for the study of panic disorder.


CILP2: A prognostic biomarker associated with immune infiltration in colorectal cancer.
The function played by cartilage intermediate layer protein 2 (CILP2) between colorectal cancer (CRC) progression and immune response remains unclear, especially with respect to immune cell infiltration and checkpoints. Materials and Methods: We examined CILP2 expression in The Cancer Genome Atlas (TCGA) COAD-READ cohort and analyzed its relationship with clinicopathological features, mutations, survival, and immunity. Gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and gene set enrichment analyses (GSEA) were performed to determine CILP2 related pathways. To further investigate the results of TCGA analysis, validation was performed using CRC cell lines, fresh pathological tissues, and a CRC tissue microarray (TMA). Results: In both TCGA and TMA cohorts, CILP2 expression was increased in CRC tissues and was associated with patient T stage (T3 and T4), N stage (N1), pathological stage (III and IV), and overall survival. Immune cell infiltration and checkpoint analysis revealed that CILP2 expression is highly correlated with multiple immune marker genes, including PD-1. In addition, results of enrichment analysis indicated that CILP2 related genes was mainly enriched in extracellular matrix related functions. Conclusion: Elevated CILP2 expression is associated with adverse CRC clinical features and immune cells, it has potential as a biomarker detrimental to CRC survival.


Shortage of iodinated contrast media: Status and possible chances - A systematic review.
Covid-19 related lockdowns have resulted in a shortage of iodinated contrast media (ICM) in 2022. Health care providers have reacted with implementing conservation strategies to stay operational without compromising patient care. Although articles describing the implemented Interventions have been published, possible chances of the shortage have not yet been mentioned in the literature. We conducted a literature search in PubMed and Google Scholar, and analysed the background, interventions, and possible benefits of low-dose ICM regimens. We included 22 articles dealing with "ICM shortage" for the analysis. The delivery bottlenecks in the USA and Australia led to two different countermeasures, 1. reduction of the number of contrast-enhanced image-guided examinations and 2. reduction of the (single) ICM dose. Interventions from both groups have resulted in significant reduction of ICM usage; however, group 1 has contributed more to overall ICM reduction. As benefit of the ICM reduction, we revealed an increased safety for patients at risk (e.g. hypersensitivity reactions, contrast-induced acute kidney injury, thyroid toxic effects). The ICM shortage of 2022 has forced health care providers to implement conservation strategies to stay operational. Although there were already proposals for dose reduction before the corona pandemic and the associated supply bottlenecks, this situation led to the use of a reduced amount of contrast agent on a large scale. This presents a good opportunity to reconsider protocols and the use of contrast-enhanced imaging in general for future practice as it offers chances and advantages regarding costs, environmental impact, and patient safety.


Incidence of bloodstream infections: a nationwide surveillance of acute care hospitals in Switzerland 2008-2014.
Bloodstream infections are often associated with significant mortality and morbidity. We aimed to investigate changes in the epidemiology of bloodstream infections in Switzerland between 2008 and 2014. Data on bloodstream infections were obtained from the Swiss antibiotic resistance surveillance system (ANRESIS). The incidence of bloodstream infections increased throughout the study period, especially among elderly patients and those receiving care in emergency departments and university hospitals. Escherichia coli was the predominant pathogen, with Enterococci exhibiting the most prominent increase over the study period. The described trends may impact morbidity, mortality and healthcare costs associated with bloodstream infections.


Characterization of cupric glutamate extinguishing mechanism of Alexandrium sp. LC3 with two-dimensional electrophoresis and MALDI-TOF MS.
Mechanisms by which cupric glutamate, a novel algicide, extinguishes Alexandrium sp. LC3 are shown in this study. We show that cupric glutamate not only stimulated the production of malonaldehyde (MDA) and dramatically promoted cell plasma membrane permeability (p < 0.01) but also remarkably reduced sulfhydryl (SH) group content (p < 0.01). Analysis of protein expression profiles by two-dimensional electrophoresis (2-DE) indicated that only 47 protein spots were detected in both control and cupric glutamate treated cells. Three reliable spots were identified by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) as ribulose-bisphosphate carboxylase large subunit precursor, RNA polymerase beta chain, and hypothetical protein, which can be well correlated with cupric glutamate stress. Based on above results, we hypothesize that the extinguishing mechanisms include (1) the cell membrane being damaged by cupric glutamate; (2) cupric glutamate probably induced denaturation and disintegration of intracellular protein, which led to inhibition of cell growth.


Hit to lead optimization of a series of N-[4-(1,3-benzothiazol-2-yl)phenyl]acetamides as monoacylglycerol lipase inhibitors with potential anticancer activity.
A total of thirty five new N-[4-(1,3-benzothiazol-2-yl)phenyl]acetamide derivatives were synthesized and structures of all the compounds were confirmed on the basis of elemental analysis and collective use of IR, (1)H NMR, (13)C NMR and mass spectral data. Compounds were tested for their ability to inhibit human monoacylglycerol lipase (hMAGL) enzyme. Eight compounds 4, 19-21, 24-26, and 34 reduced the hMAGL activity less than 50% at 100 nM concentrations. The halogen substituted aniline derivatives 20, 21 and 24-26 were found to be most active among all the synthesized compounds having IC50 value in the range of 6.5-9 nM. Twenty five compounds were selected by NCI, USA for one dose anticancer screening. Compound 21 (NSC: 780167) and 24 (NSC: 780168) fulfilled prearranged doorstep growth inhibition criteria and further selected for NCI full panel five dose assay at 10-fold dilutions of five different concentrations (0.01, 0.1, 1, 10 and 100 μM). Both the compounds 21 and 24 were found to be most active against MCF7 and MDA-MB-468 breast cancer cell lines. The GI50 value of 32.5 nM (MCF7) and 23.8 nM (MDA-MB-468) was observed for compound 21. Compound 24 showed GI50 values of 37.1 nM against MCF7 breast cancer cell line and 25.1 nM against MDA-MB-468 breast cancer cell line.


Motives of Future Elementary School Teachers to Be Physically Active.
The aim of this study was to determine the relationship between the motives for engaging in sports activities and the self-determination index (SDI) and how this in turn predicts the intentionality of future elementary school teachers to be physically active. A total of 331 first-year students of the teacher training degree participated, 34.4% men and 65.6% women (M = 20.02; SD = 2.55). They answered the following questionnaires: "Behavioral Regulation in Exercise Questionnaire-3", "Motives for Physical Activity Measure-Revised" and "Intention to be Physically Active". Fitness, fun and care of one's appearance are the motives most valued by university students. A regression analysis (structural equation modeling) revealed that appearance and social motives were negatively related to SDI, although the model clearly predicted the intention to be physically active (R2 = 0.74). A second model, which positively related the appearance and competence motives with the intention to be active, improved the coefficient of determination (R2 = 90) and fit index. The motives for engaging in physical activity influence university students in different ways in relation to the SDI and strongly predict the intention to be physically active.


Funding the online teaching and learning in developing countries: insights from Zimbabwe.
While the outbreak of COVID-19 in December 2019 threatened educational activities in Higher Education globally, it renewed the interest in online learning and teaching in developing countries. To frame our understanding, we employed the Technological Readiness Index lens to investigate the institutional needs necessitated by the sudden uptake of online teaching and how these needs could be funded in one of the developing countries in Africa.15 Heads of Departments (HODs), working in different universities across Zimbabwe, participated in the in-depth interviews and WhatsApp discussions to generate data. Findings replicate that while HODs noted the indispensability of online teaching to embrace the Fourth Industrial Revolution (4IR), universities were confronted with trenchant institutional needs, for example, the absence of well-trained personnel, poor digital infrastructure and cyber security of which most of them emanated from inadequate funding. Considering this, the study proposes that rather than depending on traditional donor and stakeholder quota funding, governments of developing countries must liberalise internet trade markets through legal frameworks to de-monopolise the provision of internet services to reduce costs of erecting digital infrastructures and provision of services. This study, provides insights and extends scholarship on other funding strategies available for the digitalization of education in higher education.


Quantitative studies of sympathetic ganglia and spinal cord intermedio-lateral gray columns in familial dysautonomia.
In adult patients with familial dysautonomia the mean volume of superior cervical sympathetic ganglia is reduced to 34% of the normal of 222 mm3. Packing density of neurons is reduced to 37% of normal. The mean total number of ganglionic neurons is 120,000 as compared to 1,060,000 in controls. The mean totals of preganglionic neurons in the first three thoracic cord segments are 13,600 in patients and 25,150 in controls. Deficits in sympathetic neurons account for many of the clinical, pharmacological and biochemical manifestations of familial dysautonomia.


Multiform accelerated idioventricular rhythm in acute myocardial infarction.
The presence of accelerated idioventricular rhythm (AIVR) in its multiform variant in two patients with acute myocardial infarction is described. No difference was noted in the clinical evolution of this arrhythmia and the more commonly observed unifocal AIVR.


[Recurrent epidemics of gastroenteritis caused by norovirus GI.3 in a small hotel].
Recurrent cases of gastroenteritis occurred in a small hotel. The causative agent of disease could not be detected. The cause and the source of the disease were established through epidemiological investigations and laboratory diagnosis. The causative agent of the disease was norovirus GI.3. Norovirus GI was detected in the water from the well and on surfaces at the hotel. Both epidemiological investigations and laboratory diagnostics are needed in resolving epidemics. Continuous development of laboratory methods is important.


Classification of daily and near-daily headaches: proposed revisions to the IHS criteria.
The International Headache Society (IHS) headache classification, while a major advance, does not adequately classify the daily and near-daily headache disorders known as chronic daily headache (CDH). We believe that chronic daily headache is a group of disorders which includes chronic tension-type headache (CTTH), transformed migraine (TM), new daily persistent headache (NDPH), and hemicrania continua (HC). We propose specific criteria for transformed migraine, new daily persistent headache, and hemicrania continua, and have modified the criteria for chronic tension-type headache.


Wheel-running in a transgenic mouse model of Alzheimer's disease: protection or symptom?
Several studies on both humans and animals reveal benefits of physical exercise on brain function and health. A previous study on TgCRND8 mice, a transgenic model of Alzheimer's disease, reported beneficial effects of premorbid onset of long-term access to a running wheel on spatial learning and plaque deposition. Our study investigated the effects of access to a running wheel after the onset of Abeta pathology on behavioural, endocrinological, and neuropathological parameters. From day 80 of age, the time when Abeta deposition becomes apparent, TgCRND8 and wildtype mice were kept with or without running wheel. Home cage behaviour was analysed and cognitive abilities regarding object recognition memory and spatial learning in the Barnes maze were assessed. Our results show that, in comparison to Wt mice, Tg mice were characterised by impaired object recognition memory and spatial learning, increased glucocorticoid levels, hyperactivity in the home cage and high levels of stereotypic behaviour. Access to a running wheel had no effects on cognitive or neuropathological parameters, but reduced the amount of stereotypic behaviour in transgenics significantly. Furthermore, wheel-running was inversely correlated with stereotypic behaviour, suggesting that wheel-running may have stereotypic qualities. In addition, wheel-running positively correlated with plaque burden. Thus, in a phase when plaques are already present in the brain, it may be symptomatic of brain pathology, rather than protective. Whether or not access to a running wheel has beneficial effects on Alzheimer-like pathology and symptoms may therefore strongly depend on the exact time when the wheel is provided during development of the disease.


An Improved Soft Subspace Clustering Algorithm Based on Particle Swarm Optimization for MR Image Segmentation.
Soft subspace clustering (SSC), which analyzes high-dimensional data and applies various weights to each cluster class to assess the membership degree of each cluster to the space, has shown promising results in recent years. This method of clustering assigns distinct weights to each cluster class. By introducing spatial information, enhanced SSC algorithms improve the degree to which intraclass compactness and interclass separation are achieved. However, these algorithms are sensitive to noisy data and have a tendency to fall into local optima. In addition, the segmentation accuracy is poor because of the influence of noisy data. In this study, an SSC approach that is based on particle swarm optimization is suggested with the intention of reducing the interference caused by noisy data. The particle swarm optimization method is used to locate the best possible clustering center. Second, increasing the amount of geographical membership makes it possible to utilize the spatial information to quantify the link between different clusters in a more precise manner. In conclusion, the extended noise clustering method is implemented in order to maximize the weight. Additionally, the constraint condition of the weight is changed from the equality constraint to the boundary constraint in order to reduce the impact of noise. The methodology presented in this research works to reduce the amount of sensitivity the SSC algorithm has to noisy data. It is possible to demonstrate the efficacy of this algorithm by using photos with noise already present or by introducing noise to existing photographs. The revised SSC approach based on particle swarm optimization (PSO) is demonstrated to have superior segmentation accuracy through a number of trials; as a result, this work gives a novel method for the segmentation of noisy images.


[Slow onset septic arthritis by Scedosporium apiospermum after periarticular infiltration].
Fungal arthritis is usually of haematogenous origin, and mainly affects patients with impaired cellular immunity or users of intravenous drugs. The infection in immunocompetent patients is generally caused by direct inoculation of the microorganism through an invasive device. The experience of azole therapy in these patients is limited. We report a case of arthritis caused by Scedosporium apiospermum characterized by its slow onset, lack of response to posaconazole and caspofungin, and its successful resolution after surgical debridement and treatment with voriconazole. Treatment with voriconazole and surgical debridement is an effective therapy for arthritis due to S. apiospermum.


Ameloblastoma: a clinical review and trends in management.
Ameloblastoma is a rare odontogenic neoplasm of the mandible and maxilla, with multiple histologic variants, and high recurrence rates if improperly treated. The current mainstay of treatment is wide local excision with appropriate margins and immediate reconstruction. Here we review the ameloblastoma literature, using the available evidence to highlight the change in management over the past several decades. In addition, we explore the recent molecular characterization of these tumors which may point towards new potential avenues of personalized treatment.