Statistical shape analyses of trigonocephaly patients.
Surgery is the first treatment option for patients with metopic craniosynostosis. Fronto-orbital advancement is the preferred method for correction of isolated trigonocephaly, but it is hard to understand whether surgery has been successful mainly in an early period. We aim to investigate the shape differences in the head shapes of trigonocephaly patients compared between preoperative and postoperative term. Cranial shape data were collected from the two-dimensional digital images. The Generalized Procrustes analysis was used to obtain mean shapes of the preoperative and postoperative term. The shape deformation of the frontal calvarium from preoperative to the postoperative term was evaluated using the thin-plate spline (TPS) method. There was significant cranial shape difference between preoperative and postoperative term. The high-level deformations for preoperative to postoperative term determined seen in TPS graphic. Highest deformation was observed at the bifrontal dimension especially at nasion and posterior edge of the forehead. In this study, we showed that the shape difference and structural deformation of the calvarium were correlated with the metopic craniosynostosis. The present study also shows that preoperative and postoperative head shapes of patients with trigonocephaly can be compared using the landmark-based geometrical morphometric method by taking into consideration the topographic distribution.


Age at diagnosis and outcome for women with ductal carcinoma-in-situ of the breast: a critical review of the literature.
Patients younger than 35 to 45 years old at the time of diagnosis of invasive breast cancer have been found to have a worse prognosis than older patients in many studies. However, the impact of patient age at diagnosis on the outcome of treatment with either lumpectomy and radiation therapy (RT) or mastectomy for patients with ductal carcinoma-in-situ (DCIS) of the breast has not been extensively analyzed. Articles addressing the effect of patient age at diagnosis on the outcome of treatment of DCIS with lumpectomy and RT or mastectomy were identified through the MEDLINE and CancerLit databases and reference lists of relevant articles. Studies were reviewed to determine the impact of patient age at diagnosis on clinical and pathologic features of DCIS, the influence of age on outcome after lumpectomy and RT, and the impact of age on outcome after mastectomy. DCIS in younger patients more frequently contains adverse prognostic pathologic factors and extends over a greater distance in the breast than in older patients. In series with adequate follow-up, younger patients treated with lumpectomy and RT had a significantly higher rate of local recurrence than older patients, especially for invasive local recurrences. Some studies have suggested that careful attention to margin status and excising larger volumes of tissue can reduce this difference substantially. No available data show that younger patients have better long-term cancer-free survival rates if treated by mastectomy rather than lumpectomy and RT. Successful treatment of younger patients with DCIS with lumpectomy and RT requires careful attention to patient evaluation, selection, and surgical technique. When this is done, age at diagnosis should not be a contraindication to breast-conserving therapy.


Assessment of the Wanyu River (China) based on a water, sediment and hydrobiont framework.
Due to the striving for the development of economy and agriculture, anthropogenic activities in many countries dramatically alter natural hydrology. These activities are primarily responsible for river deterioration. Thus, we need to assess the river environment and take measures for remediation. According to the survey data, the study identified the critical factors causing water quality deterioration and evaluated the aquatic biodiversity in the Wanyu River. First, based on the monitoring data of water (dissolved oxygen (DO), chemical oxygen demand (COD), total phosphorus (TP), and ammonia nitrogen (NH3-N)), sediment (copper (Cu), zinc (Zn), lead (Pb), arsenic (As), nickel (Ni), mercury (Hg), cadmium (Cd), and chromium (Cr)), and aquatic biodiversity (fish and hydrophyte), the study identified the critical factors causing river quality deterioration. Second, the study provided some recommendations that would consolidate the restoration efforts. Consequently, because of the government's efforts in building the municipal sewage treatment plant, dredging, and other measures, the river environment improved during the 2020-2021 period. The maximum concentrations of COD, NH3-N, and TP in water were reduced by 17.76%, 26.17%, and 20.93%, respectively. The sediment had no risk of heavy metal pollution in the past 2 years. And we could utilize sludge as garden soil or compost resource. However, reducing agricultural pollution, internal nutrient loading, and cost-effective restoration and evaluation represent significant challenges in the efforts to recover the river ecosystem.


Lymphocyte activation provokes modification of a lymphocyte-specific protein tyrosine kinase (p56lck).
The protein tyrosine kinase p56lck is implicated in the control of lymphocyte growth by virtue of its overexpression in some lymphoid malignancies and its transforming activity in heterologous systems. Previous studies have demonstrated that levels of lck mRNA and of p56lck decline rapidly after T cell activation. The disappearance of p56lck results primarily from post-translational conversion of p56lck to more slowly migrating forms with apparent sizes of approximately 60 kDa. This modification can be provoked by treatment of lymphocytes with PMA, and has been associated with increased serine phosphorylation of the p56lck molecule. Here we demonstrate that conversion of p56lck to p60lck is a feature of the physiologic activation of T lymphocytes by antigen-presenting cells. In addition, we show that the PMA-induced modification of p56lck proceeds via a mechanism distinct from conventional protein kinase C activation. The rapid conversion of p56lck to p60lck after antigenic stimulation is consistent with the view that this membrane-associated protein tyrosine kinase regulates some aspects of the lymphocyte activation sequence.


Dopamine Homeostasis Imbalance and Dopamine Receptors-Mediated AC/cAMP/PKA Pathway Activation are Involved in Aconitine-Induced Neurological Impairment in Zebrafish and SH-SY5Y Cells.
Aconitine is one of the main bioactive and toxic ingredients of Aconitum species. Increasingly, aconitine has been reported to induce neurotoxicity. However, whether aconitine has effects on the dopaminergic nervous system remains unclear. In this study, zebrafish embryos at 6-days postfertilization were exposed to aconitine at doses of 0.5, 1, and 2 μM for 24 h, and SH-SY5Y cells were treated with 50, 100, and 200 μM of aconitine for 24 h. Results demonstrated that aconitine treatment induced deformities and enhanced the swimming behavior of zebrafish larvaes. Aconitine exposure suppressed cell proliferation and increased the number of reactive oxygen species and apoptosis in zebrafish larvaes and SH-SY5Y cells. Aconitine altered the levels of dopamine and its metabolites by regulating the expression of genes and proteins related to dopamine synthesis, storage, degradation, and reuptake in vivo and in vitro. Moreover, aconitine activated the AC/cAMP/PKA pathway by activating the dopamine D1 receptor (D1R) and inhibiting the dopamine D2 receptor (D2R) to disturb intracellular calcium homeostasis, eventually leading to the damage of nerve cells. Furthermore, the D1R antagonist SCH23390 and D2R agonist sumanirole pretreatment effectively attenuated the excitatory state of larvaes. Sumanirole and PKA antagonist H-89 pretreatment effectively decreased intracellular Ca2+ accumulation induced by aconitine in vivo. SCH23390 and sumanirole also reduced aconitine-induced cytotoxicity by inhibiting the AC/cAMP/PKA pathway in vitro. These results suggested that dopamine homeostasis imbalance and dopamine receptors (DRs)-mediated AC/cAMP/PKA pathway activation might be vital mechanisms underlying aconitine-induced neurological injury.


Impact of Oxygenation Status on the Noninvasive Measurement of Hemoglobin.
Noninvasive monitoring of hemoglobin (SpHgb) via pulse oximetry has the potential to alert caregivers to blood loss. Previous studies have demonstrated that changes in oxygenation may impact accuracy. Twenty normal volunteers were monitored using SpHgb at sea level, during ascent to 14,000 feet, at 14,000 feet with 100% oxygen delivery, and again at sea level. Each period consisted of 15 minutes of monitoring. SpHgb measurements were compared to a blood sample using Bland Altman analysis. The loss of the SpHgb signal was also recorded. The mean difference in measured hemoglobin (Hgb) between a venous sample and SpHgb was -2.6 ± 0.96 at 14,000 feet. Ascent to 14,000 feet resulted in a predictable fall in SpO2 and was associated with loss of the SpHgb signal for half the period of observation (7.4 minutes). In the other three conditions, SpHgb signal was missing 1 to 12.6% of the time. The nadir SpO2 was not predictive of the loss of SpHgb signal. Changes in oxygenation in normal volunteers are associated with short-term SpHgb signal loss (<10 minutes), but no impact on the measured SpHgb.


Dinucleotide receptor modulation by protein kinases (protein kinases A and C) and protein phosphatases in rat brain synaptic terminals.
The diadenosine polyphosphates, diadenosine tetraphosphate and diadenosine pentaphosphate (Ap5A), can activate an ionotropic dinucleotide receptor that induces Ca2+ transients into synaptosomes prepared from rat brain. This receptor, also termed the P4 purinoceptor, is sensitive only to adenine dinucleotides and is insensitive to ATP. Studies on the modulatory role of protein kinase A (PKA), protein kinase C (PKC), and protein phosphatases on the response of diadenosine polyphosphate receptors were performed by measuring the changes in the intracellular Ca2+ levels with fura-2. Activation and inhibition of PKA were carried out by means of forskolin and the PKA inhibitory peptide (PKA-IP), respectively. The Ap5A response was inhibited by forksolin to 35% of control values, but PKA-IP induced an increase of 37%. The effect of PKC activation was similar to that observed for PKA. PKC stimulation with phorbol 12,13-dibutyrate produced an inhibition of 67%, whereas the PKC inhibitors staurosporine and PKC inhibitory peptide enhanced the responses elicited by Ap5A to 40% in both cases. Protein phosphatase inhibitors diminished the responses elicited by Ap5A to 17% in the case of okadaic acid, to 50% for microcystin, and to 45% in the case of cyclosporin A. Thus, the activity of dinucleotide receptors in rat brain synaptosomes appears to be modulated by phosphorylation/dephosphorylation. These processes could be of physiological significance in the control of transmitter release from neurons that are postsynaptic to nerves that release diadenosine polyphosphates.


A risk-benefit assessment of carvedilol in the treatment of cardiovascular disorders.
Carvedilol is a nonselective beta-adrenoceptor blocking vasodilator drug that may be a promising new agent in the management of cardiovascular disease. The rationale for the development of agents of this type is that the alpha-blocking component may overcome the direct vasoconstrictor consequence of beta 2-blockade, whilst the beta-blocker component may inhibit the reflex tachycardia that occurs following alpha-blockade. In clinical trials published to date, carvedilol has been demonstrated to be effective as an antihypertensive agent as monotherapy and also as additional therapy in those patients whose blood pressure cannot be controlled on other standard agents. It is also effective in the management of angina. Carvedilol has beneficial haemodynamic effects in patients with congestive heart failure. beta-Blocker vasodilator drugs of this type may be particularly useful in this condition as the vasodilator component of the drug may overcome the initial negative inotropy of the beta-blocker. In addition, carvedilol possess potentially useful pharmacological actions. In particular, the drug has antimitogenic and free radical scavenging effects that may make it a useful therapy in the long term management of atherosclerotic vascular disease. Its metabolic profile is also favourable, presumably on the basis of its alpha-blocking properties. Thus, beta 2-mediated adverse effects on peripheral vascular tone, glycaemic control and lipid status appear to be offset by the alpha-blocking property of the drug. Carvedilol thus far appears to be well tolerated, with postural dizziness the major adverse effect, especially in the elderly. As with nonselective beta-blockers, carvedilol is contraindicated in patients with asthma.


Vasoactive hormones in familial pheochromocytoma with predominant norepinephrine secretion.
A family was investigated with an increased occurrence of pheochromocytoma. Three males out of 7 family members showed biochemical and morphological evidence of catecholamine-secreting tumor. Plasma concentrations of norepinephrine, aldosterone, arginine vasopressin and renin activity, as well as urinary excretion of norepinephrine, were enhanced in all the 3 patients. The plasma level of atrial natriuretic peptide decreased. After surgical removal of the tumor the hormonal alterations tended to be normalized; however, plasma concentration of norepinephrine remained above normal. The elevated plasma norepinephrine was postoperatively accompanied by slightly increased urinary norepinephrine excretion in 1 patient without any detectable tumor. The severity of the disease was most pronounced in the youngest patient, while in the oldest one a 'silent' pheochromocytoma was found. The occurrence of familial pheochromocytoma in successive generations may suggest an autosomal-dominant inheritance.


[Hepatic infarction following prolonged prone position].
A 61-year-old woman with chronic renal failure was scheduled for posterior spinal fusion. The duration of surgery was over ten hours and the patient was placed on prone position almost whole period of surgery. Although the surgery was finished without any obvious complications, laboratory examinations revealed marked liver dysfunction the day after the surgery. On the third postoperative day, computed tomography examination strongly suggested the liver infarction. Liver infarction has been considered as a rare complication because of two kinds of blood streams, the hepatic artery and the portal vein, but we should suspect the liver dysfunction from ischemia after the surgery of prolonged prone position.


Five-day comparison of the doubly labeled water method with respiratory gas exchange.
Previous studies have indicated that the doubly labeled water method can be used to measure energy expenditure in free-living humans. In this study, we compare the doubly labeled water method with nearly continuous respiratory gas exchange in five healthy adults. Total body water and isotope elimination rates were determined by mass spectrometric analysis of urinary water after the administration of 2H2 18O. Respiratory gas exchange was measured 22 to 23 h/day for 5 consecutive days. Energy expenditures from the doubly labeled water method averaged 6% more than those from respiratory gas exchange with an 8% coefficient of variation.


Disturbances in hepatic blood flow during anesthesia and surgery.
A study of 88 patients showed a reduction in the estimated hepatic blood flow (EHBF), as measured by a colloidal gold technique, to 88% and 84% of its initial value during ether and halothane anesthesia, respectively. During the operative procedure itself, there was a further fall in the EHBF. In patients undergoing herniorrhaphy or excision of a breast tumor, the EHBF decreased to 82% and 76%, while in patients undergoing partial gastrectomy or cholecystectomy, the EHBF fell to 48% and 42% of its initial value during operations under ether and halothane anesthesia, respectively. The surgical trauma itself would appear to be the main determinant of the alteration in the liver circulation during the operation.


(E)-6-Bromo-3-{2-[2-(2-chloro-benzyl-idene)hydrazin-yl]thia-zol-5-yl}-2H-chromen-2-one dimethyl sulfoxide monosolvate.
In the title compound C(19)H(11)N(3)O(2)SClBr·C(2)H(6)OS, the mol-ecule adopts an E configuration about the central C=N double bond. The chromene ring system and the thia-zole ring are approximately planar, with maximum deviations of 0.027 (2) and 0.003 (1) Å, respectively. The central thia-zole ring makes dihedral angles of 21.82 (9) and 5.88 (7)° with the chloro-substituted phenyl ring and the chromene ring, respectively. In the crystal, mol-ecules are connected via N-H⋯O, N-H⋯S and C-H⋯O hydrogen bonds, forming supra-molecular chains along the c axis. An intra-molecular C-H⋯O hydrogen bond occurs. π-π inter-actions are observed between the thia-zole and phenyl rings [centroid-centroid distance = 3.6293 (10) Å]. A short Br⋯Cl contact of 3.37 (6) Å also occurs.


Feasibility of early emergency room notification to improve door-to-balloon times for patients with acute ST segment elevation myocardial infarction.
An algorithm to lower time from first contact in the field by EMS personnel to in-hospital mechanical reperfusion is described. ECG tracings were telemetered via cellular phone to an emergency room physician, who then activated the cardiac catheterization call team to bypass usual delays seen during ER triage. Seventy-one ECGs were sent to the ER in the time interval from October 2003 to October 2004. Five ECGs (7.0%) failed to transmit due to failure of the cellular phone to receive an adequate signal. Sixty-six patients (93.0%) had an adequate ECG transmitted to the ER and six patients with ST elevation myocardial infarction were identified. Door-to-balloon times were lowered to 44 +/- 17.4 min, a substantial decrease over historical norms that range from 120 min (25th percentile) to 289 min (75th percentile).


Validation of Spectrophotometric Methods for the Determination of Total Polyphenol and Total Flavonoid Content.
The aim of this study was to validate spectrophotometric methods for the measurement of total polyphenol (TP; via the Folin-Ciocalteu method) and total flavonoid (TF) content [via the aluminum chloride (AlCl3) method]. Validation parameters of these methods were determined, including linearity, sensitivity, precision (intra-assay and intermediate), accuracy, LOD, and LOQ. For the validation process, groups of polyphenol standards were used, including phenolic acids (gallic, p-coumaric, caffeic, and chlorogenic acids), flavan-3-ols [(+)-catechin and procyanidins B1 and B2], flavonols (quercetin and quercetin-3-rutinoside), and dihydrochalcones (phloretin and phloretin-2-glucoside). Obtained validation parameters were within acceptable ranges with high determination coefficients, reasonably low LODs and LOQs, and high slopes in the calibration curves for both methods, except for phloretin and phloretin-2-glucoside, for which there were low slopes in the calibration curves for the AlCl3 method. To evaluate differences in polyphenol content, the validated spectrophotometric methods were used to determine TP and TF content in wines (Plavac, Graševina, and Vranac) and juices (blueberry, strawberry, and blackcurrant juice) according to the polyphenol calibration curves. Polyphenol contents were different for both methods in all wines and juices.


Pharmacologic treatment of erectile dysfunction.
Penile erection occurs in response to cavernous smooth muscle relaxation, increased blood flow to the penis, and restriction of venous outflow. These events are regulated by a spinal reflex relying on visual, imaginative, and olfactory stimuli generated within the central nervous system (CNS) and on tactile stimuli to the penis. Drugs can have a facilitatory or inhibitory effect either on the nerves regulating this reflex or on the cavernous smooth muscle. A balance between contractile and relaxant factors governs flaccidity/rigidity within the penis. Drugs that raise cytosolic calcium either prevent or abort erection. Conversely, drugs that lower cytosolic calcium relax smooth muscle and can initiate penile erection. Efficacy in treating erectile dysfunction (ED) with phosphodiesterase inhibitors, especially type 5; alpha-adrenergic-receptor antagonists; and dopamine agonists exploit these mechanisms within the penis or CNS. Recent advances in our understanding of the pharmacology of penile erection are being translated into effective therapies for ED.


Formation of Quinone Methides by Ultrafast Photodeamination: A Spectroscopic and Computational Study.
Formation of quinone methides (QMs) by photoelimination of an ammonium salt from cresol derivatives was investigated by femtosecond transient absorption spectroscopy (fs-TA) and computationally by time-dependent density functional theory using the PCM(water)/(TD-)B3LYP/6-311++G(d,p) level of theory. The photoelimination takes place in an adiabatic ultrafast reaction on the S1 potential energy surface delivering the corresponding QMs(S1), which were detected by fs-TA. Computations predicted a high-energy cation intermediate in the pathway between the Franck-Condon state of a monoammonium salt and the corresponding QM(S1) that was not detected by fs-TA. On the other hand, elimination from a disalt in H2O takes place in one step, giving directly the QM(S1). The combined experimental and theoretical investigation fully disclosed the formation of QMs by the deamination reaction mechanism, which is important in the application of cresols or similar molecules in biological systems.


Construction and Functional Characterization of a Fully Human Anti-mesothelin Chimeric Antigen Receptor (CAR) Expressing T Cell.
Chimeric antigen receptor (CAR) T cell therapy is considered as an encouraging approach for the treatment of hematological malignancies. However, its efficacy in solid tumors has not been satisfying, mainly in the immunosuppressive network of the tumor microenvironment and paucity of appropriate target antigens. Mesothelin (MSLN) is a tumor-associated antigen (TAA) expressed in numerous types of solid tumors such as gastrointestinal, ovarian, and pancreatic tumors. Owing to high expression in tumor cells and low expression in normal tissues, MSLN-targeted therapies like monoclonal antibodies have been previously developed. In the present study, a CAR T cell harboring the second-generation of a fully human anti-MSLN-CAR construct containing CD3ζ and 4-1BB signaling domains was produced and it was functionally evaluated against an MSLN-expressing cell line. The findings showed potent, specific proliferation, cytotoxic activity, and interleukin (IL)-2, Tumor necrosis factor-(TNF) α, and Interferon-(IFN) γ production in an antigen-dependent manner. Cytotoxic activity was shown in effector-to-target ratio from 1:1 to 20:1, but the most adequate efficacy was observed in the ratio of 10:1. Non-specific activity against MSLN negative cell line was not observed. Our data demonstrated that primary human T cells expressing fully human MSLN-CAR construct are effective against MSLN-expressing cell lines in vitro, suggesting this MSLN-CAR construct as a potential therapeutic tool in a clinical setting.


Domestic violence victims in the emergency department. New findings.
Four hundred ninety-two male and female patients from a general hospital emergency department were surveyed to elicit information on the extent and nature of domestic violence among this population. The patient's emergency department medical records were also reviewed. Twenty-two percent of the patients identified themselves on the survey as domestic violence victims. New findings in the areas of medical classification, nature of the abusive relationship, and patients' perceived treatment needs contribute to refining the battered spouse syndrome and are helpful in planning therapeutic intervention. The authors conclude that domestic violence victims should be identified and offered assistance while in the emergency department and outline a crisis intervention plan.


Remodelling the extracellular matrix in development and disease.
The extracellular matrix (ECM) is a highly dynamic structure that is present in all tissues and continuously undergoes controlled remodelling. This process involves quantitative and qualitative changes in the ECM, mediated by specific enzymes that are responsible for ECM degradation, such as metalloproteinases. The ECM interacts with cells to regulate diverse functions, including proliferation, migration and differentiation. ECM remodelling is crucial for regulating the morphogenesis of the intestine and lungs, as well as of the mammary and submandibular glands. Dysregulation of ECM composition, structure, stiffness and abundance contributes to several pathological conditions, such as fibrosis and invasive cancer. A better understanding of how the ECM regulates organ structure and function and of how ECM remodelling affects disease progression will contribute to the development of new therapeutics.


Cornea and iris changes in congenital ectropion uvea after trabeculotomy.
This article details a previously undescribed complication of trabeculotomy occurring in a patient with congenital ectropion uvea and discusses its possible association with an anterior chamber membrane. A 6-year-old boy with congenital ectropion uvea underwent trabeculotomy. After the trabeculotome was swept into the anterior chamber, multiple ovoid and round endothelial and posterior stromal opacities developed in the cornea, and new areas of iris surface irregularities appeared. This is the first reported case of corneal endothelial and iris changes occurring in a patient with congenital ectropion uvea after trabeculotomy without direct endothelial or iris contact from the trabeculotome. The exact cause of these changes is unknown.


A 10-mm MR-Conditional Unidirectional Pneumatic Stepper Motor.
Magnetic resonance (MR) conditional robotic devices facilitate accurate interventional procedures under MR imaging (MRI) guidance. For this purpose, a compact (10-mm diameter) MR-conditional stepper motor is presented. The device features seven key components, which contribute to a dense and easy to fabricate design. Alternating bursts of pressurized air and vacuum can drive the motor in 60° per step to achieve a maximum torque of 2.4 mNm. The relationship between torque and angular speed was investigated to demonstrate motor performance under different loading conditions. The stepper motor was tested in a GE 3T MRI scanner to verify its MR-compatibility. A maximum artifact width of 3 mm was measured in MRI images and a maximum signal-to-noise ratio reduction of 2.49% was recorded.


Mitochondrial reactive oxygen species generation triggers inflammatory response and tissue injury associated with hepatic ischemia-reperfusion: therapeutic potential of mitochondrially targeted antioxidants.
Mitochondrial reactive oxygen species generation has been implicated in the pathophysiology of ischemia-reperfusion (I/R) injury; however, its exact role and its spatial-temporal relationship with inflammation are elusive. Herein we explore the spatial-temporal relationship of oxidative/nitrative stress and inflammatory response during the course of hepatic I/R and the possible therapeutic potential of mitochondrial-targeted antioxidants, using a mouse model of segmental hepatic ischemia-reperfusion injury. Hepatic I/R was characterized by early (at 2 h of reperfusion) mitochondrial injury, decreased complex I activity, increased oxidant generation in the liver or liver mitochondria, and profound hepatocellular injury/dysfunction with acute proinflammatory response (TNF-α, MIP-1α/CCL3, MIP-2/CXCL2) without inflammatory cell infiltration, followed by marked neutrophil infiltration and a more pronounced secondary wave of oxidative/nitrative stress in the liver (starting from 6 h of reperfusion and peaking at 24 h). Mitochondrially targeted antioxidants, MitoQ or Mito-CP, dose-dependently attenuated I/R-induced liver dysfunction, the early and delayed oxidative and nitrative stress response (HNE/carbonyl adducts, malondialdehyde, 8-OHdG, and 3-nitrotyrosine formation), and mitochondrial and histopathological injury/dysfunction, as well as delayed inflammatory cell infiltration and cell death. Mitochondrially generated oxidants play a central role in triggering the deleterious cascade of events associated with hepatic I/R, which may be targeted by novel antioxidants for therapeutic advantage.


Heparin Monitoring with an Anti-Xa Protocol Compared to Activated Clotting Time in Patients on Temporary Mechanical Circulatory Support.
Temporary mechanical circulatory support (tMCS) devices are used for patients with severe cardiac or respiratory failure; however, these patients are at high risk for clotting and bleeding. The best method to monitor heparin in these patients has not been established. To determine the risks for bleeding and clotting while monitoring heparin with either anti-Xa or activated clotting time (ACT) in tMCS patients. A retrospective cohort study was conducted on tMCS patients who received heparin adjusted according to an anti-Xa or ACT protocol. The primary outcome was incidence of major bleeding. Pertinent secondary outcomes were individual components of the primary outcome, clotting events, and time to therapeutic range. There were 103 patients included in the study: 53 in the ACT group and 50 in the anti-Xa group. Overall, there were 30 (56.6%) patients with major bleeding in the ACT group, compared with 16 (32%) patients in the anti-Xa group (P = 0.017). An anti-Xa-based protocol was associated with a decreased hazard of major bleeding (hazard ratio = 0.388 [0.215-0.701]; P = 0.002) in the univariate analysis. In the multivariable analysis, an anti-Xa protocol remained associated with a significantly lower hazard of bleeding. Findings were similar when broken down into more discrete subgroups of the entire cohort, extracorporeal membrane oxygenation life support (ECMO), and non-ECMO groups. Anti-Xa monitoring was associated with a lower hazard of bleeding during tMCS compared to an ACT-based protocol. Further studies should evaluate if anti-Xa monitoring should be preferentially used in tMCS.


Nocturnal problems in postpolio syndrome: sleep apnea symptoms and nocturia.
Nocturia, generally accepted as an inevitable consequence of aging, is also a symptom of a potentially lethal condition--obstructive sleep apnea (OSA). The descriptive study reported in this article examined nocturia and sleep-related breathing problems in persons with postpolio syndrome (PPS) and tested the Sleep Disordered Breathing--Nocturia Model. This model describes the cascade of events that results in polyuria in persons with sleep-related breathing disorders. Data were analyzed with descriptive and inferential statistics. A 34-item questionnaire was published in the newsletter of a national polio support group, and the 584 respondents constituted a convenience sample. The results showed statistically significant associations between OSA symptoms, nocturia, poor sleep quality, daytime sleepiness, lower urinary tract symptoms, naps, and decreased self-rated health. Study limitations were the use of a convenience sample and possible self-selection of persons with more severe sleep and bladder problems. The results support the model and document how nocturia and sleep disturbances negatively impact persons with PPS.


Toxicity profiles in mice treated with hepatotumorigenic and non-hepatotumorigenic triazole conazole fungicides: Propiconazole, triadimefon, and myclobutanil.
Conazoles comprise a class of fungicides used in agriculture and as pharmaceutical products. The fungicidal properties of conazoles are due to their inhibition of ergosterol biosynthesis. Certain conazoles are tumorigenic in rodents; both propiconazole and triadimefon are hepatotoxic and hepatotumorigenic in mice, while myclobutanil is not a mouse liver tumorigen. As a component of a large-scale study aimed at determining the mode(s) of action for tumorigenic conazoles, we report the results from comparative evaluations of liver and body weights, liver histopathology, cell proliferation, cytochrome P450 (CYP) activity, and serum cholesterol, high-density lipoprotein and triglyceride levels after exposure to propiconazole, triadimefon, and myclobutanil. Male CD-1 mice were treated in the feed for 4, 30, or 90 days with triadimefon (0, 100, 500, or 1800 ppm), propiconazole (0, 100, 500, or 2500 ppm) or myclobutanil (0, 100, 500, or 2000 ppm). Alkoxyresorufin O-dealkylation (AROD) assays indicated that all 3 chemicals induced similar patterns of dose-related increases in metabolizing enzyme activity. PROD activities exceeded those of MROD, and EROD with propiconazole inducing the highest activities of PROD. Mice had similar patterns of dose-dependent increases in hepatocyte hypertrophy after exposure to the 3 conazoles. High-dose exposures to propiconazole and myclobutanil, but not triadimefon, were associated with early (4 days) increases in cell proliferation. All the chemicals at high doses reduced serum cholesterol and high-density lipoprotein (HDL) levels at 30 days of treatment, while only triadimefon had this effect at 4 days of treatment and only myclobutanil and propiconazole at 90 days of treatment. Overall, the tumorigenic and nontumorigenic conazoles induced similar effects on mouse liver CYP enzyme activities and pathology. There was no specific pattern of tissue responses that could consistently be used to differentiate the tumorigenic conazoles, propiconazole, and triadimefon, from the nontumorigenic myclobutanil. These findings serve to anchor other transcriptional profiling studies aimed at probing differences in key events and modes of action for tumorigenic and nontumorigenic conazoles.


Machine Learning with Quantum Seagull Optimization Model for COVID-19 Chest X-Ray Image Classification.
Early and accurate detection of COVID-19 is an essential process to curb the spread of this deadly disease and its mortality rate. Chest radiology scan is a significant tool for early management and diagnosis of COVID-19 since the virus targets the respiratory system. Chest X-ray (CXR) images are highly useful in the effective detection of COVID-19, thanks to its availability, cost-effective means, and rapid outcomes. In addition, Artificial Intelligence (AI) techniques such as deep learning (DL) models play a significant role in designing automated diagnostic processes using CXR images. With this motivation, the current study presents a new Quantum Seagull Optimization Algorithm with DL-based COVID-19 diagnosis model, named QSGOA-DL technique. The proposed QSGOA-DL technique intends to detect and classify COVID-19 with the help of CXR images. In this regard, the QSGOA-DL technique involves the design of EfficientNet-B4 as a feature extractor, whereas hyperparameter optimization is carried out with the help of QSGOA technique. Moreover, the classification process is performed by a multilayer extreme learning machine (MELM) model. The novelty of the study lies in the designing of QSGOA for hyperparameter optimization of the EfficientNet-B4 model. An extensive series of simulations was carried out on the benchmark test CXR dataset, and the results were assessed under different aspects. The simulation results demonstrate the promising performance of the proposed QSGOA-DL technique compared to recent approaches.


The influence of playing surface on injury risk in italian elite rugby players.
There is a growing interest in the use of artificial turf surfaces in rugby. In particular, artificial surfaces may be an useful means of increasing participation in the sport by allowing greater usage of a given pitch, especially in regions where natural turf pitches are difficult to maintain. The incidence of site, nature, cause, and severity of training and match injuries was prospectively recorded in two professional teams (one equipped with World Rugby certified third generation artificial turf and the other with natural grass over the 2014-2015 season). A total of 23,840 minutes of exposure was displayed for the whole sample, 1,440 minutes during matches and 22,400 during training sessions. We recorded 37 (48%) traumatic injuries and 39 (52%) overuse injuries. For traumatic injuries, we did not find significant differences in the overall risk injury between grass and artificial turf considering match exposure and training sessions. For overuse injuries, there were significant differences in the overall risk injury between grass and artificial turf considering match exposure (p=0.03) and training sessions (p=0.02). In elite Italian rugby players, artificial turf seems to be safe in regards to traumatic injury while it seems to be a risk factor for overuse injuries. II.


High-energy phosphate metabolism in a neonatal model of hydrocephalus before and after shunting.
The authors studied the effects of hydrocephalus on the high-energy phosphate metabolism of the brain and the impact of ventriculoperitoneal (VP) shunting on these changes in an experimental model of hydrocephalus. High-energy phosphate metabolism was analyzed using in vivo magnetic resonance (MR) imaging and 31P MR spectroscopy. Hydrocephalus was produced in 34 1-week-old kittens by cisternal injection of 0.05 ml of a 25% kaolin solution. Sixteen litter mates were used as controls. A VP shunt with a distal slit valve was implanted in 17 of the 34 hydrocephalic animals 10 days after induction of hydrocephalus. Both MR imaging and 31P MR spectroscopy were obtained 1 and 3 weeks after either kaolin or distilled water injection. Untreated hydrocephalic animals had marked dilatation of the lateral ventricles and periventricular edema. Magnetic resonance spectroscopy showed a significant decrease in the energy index ratio of phosphocreatine (PCR): inorganic phosphate (PI) and an increase in the PI:adenosine triphosphate (ATP) ratio. There was a direct correlation between the decrease in the energy index and ventricular size. Compared with preoperative scans, shunted animals showed no periventricular edema, and the ventricles decreased in size. Also, PCR:PI and PI:ATP ratios were within the levels of controls. This study suggests that neonatal hydrocephalus results in a mild hypoxic/ischemic insult that is treatable by VP shunting.


Phakomatous choristoma of the eyelid: a report of a case.
Phakomatous choristoma is a rare congenital hamartoma of lens tissue. It presents in newborns or young infants as a subcutaneous mass in the medial lower eyelid. We present a case of phakomatous choristoma recently identified among old consultation files at Children's Hospital in Boston. Our case illustrates unique histological features of this entity which has to be included in differential diagnosis of skin lesions of the inferonasal eyelid.


Yeast flocculation: factors affecting the measurement of flocculence.
The physical meaning of the residual absorbance of a yeast suspension after flocculation and settling has been investigated. Starting with a dispersed suspension, agitation accelerates flocculation by increasing the probability of collision between particles. As flocculation advances, agitation also breaks the flocs. A stationary state is reached when flocculence (tendency to flocculate) is counterpoised by agitation. If the intensity of agitation is maintained constant, the free cell concentration reflects the flocculence, provided the stationary state is reached. The residual absorbance, determined after settling of the flocs, is a measure of the free cell concentration and represents an adequate parameter to characterize yeast flocculence.


[Immunoendocrine interactions and autoimmune diseases].
Communications between the immune and endocrine systems are bidirectional. A number of reports have demonstrated that many hormones have profound effects on the immune system. Cytokines produced by cells of the immune system cause changes in the neuroendocrine function. It is shown in various animal models with experimentally induced and spontaneously occurring autoimmune diseases that alterations of the immunoendocrine interactions are involved in the breakdown of self tolerance. This review discusses the role of disturbances along the hypothalamo-pituitary-adrenal and lactotrophic axes in the development of autoimmune diseases. This finding of the defective immuno-endocrine communications may lead to more specific therapy of autoimmune diseases in man. (Fig. 1, Ref. 51.).


Characteristics of cognitive function in patients with cerebellar infarction and its association with lesion location.
Objective: This study aimed to explore the characteristics of cognitive function in patients with cerebellar infarction and its association with lesion location. Methods: Forty-five patients with isolated cerebellar infarction were collected in the Department of Neurology, Beijing Tiantan Hospital. Thirty healthy controls were recruited matched by age and education. Global cognitive function was evaluated by using Addenbrooke's Cognitive Examination version III (ACE-III). An extensive neuropsychological assessment battery was also tested to evaluate the characteristics of each cognitive domain. 3D slicer software was used to draw the lesion, and evaluate the lesions' volume, side, and location. Group analysis was used to compare the differences in cognitive performance between patients and healthy controls, and patients with left and right cerebellar hemisphere infarction. Spearman analysis was used to explore the correlation between cognitive function and lesion volume. We also subdivided each patient's lesions according to the cerebellar atlas to identify the specific cerebellar location related to cognitive decline. Results: Patients with cerebellar infarction had a lower ACE-III score compared with the healthy group (87.9 ± 6.2 vs. 93.7 ± 2.9, p < 0.001), and 22 (48.9%) patients were diagnosed with cognitive impairment. The z-transformed score of attention and executive function in the patients' group was -0.9 ± 1.4 and -0.8 ± 1.0 respectively, with 19 (43.2%) and 23 (56.4%) patients impaired. Compared with healthy controls, the relative risk ratio with 95% confidence interval (CI) for impairment in attention and executive function were 3.24 (1.22-8.57) and 3.39 (1.45-7.89). However, only 10 (22.1%) patients showed impairment in more than two cognitive domains. Compared with the left lesion group, patients with right cerebellar infarction showed significantly impaired executive function (-1.1 ± 0.3 vs. -0.5 ± 0.2, p = 0.01). And the cerebellar posterior lobe regions, especially lobules VI, VIII, and IX, were explored to have lower cognitive performance. Furthermore, lesion volume was identified to be associated with the ACE-III score (r = -0.37, p = 0.04). Conclusion: We identified that cerebellar involvement in cognition, especially in attention processing and executive function. Cerebellar right-sided lateralization of cognition and functional topography were also revealed in the current study.


A Child Infected with COVID-19 in China-A Case Report.
A 16-month-old boy was admitted with cough for 2 days and fever for 1 day. Chest computed tomography (CT) scan of the child revealed large areas of ground-glass opacities in both lungs. Nucleic acid amplification tests (NAATs) were performed repeatedly to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the results were all negative. On day 13 of hospitalization, no clinical symptoms except diarrhea were present in the patient, and re-examination by chest CT revealed lesion shrinkage, but the NAAT on throat swabs was positive. On day 22 of hospitalization, the NAAT on throat swabs was negative and the fecal samples were positive. Positive fecal samples nucleic acid lasted for 62 days. Suggesting that pediatric patients may be important sources of infection during the recovery phase of clinical symptoms and whether SARS-CoV-2 has fecal-oral transmission needs further study.


Isometric Back Exercise Has Different Effect on Pressure Pain Thresholds in Healthy Men and Women.
Isometric exercises produce an acute decrease in the pain sensitivity, known as exercise-induced hypoalgesia (EIH). Existing EIH paradigms use exercises at the extremities with more pronounced EIH at local compared to remote body sites, indicating local inhibition in addition to central inhibitory mechanisms. So far the results on EIH in patients with low back pain (LBP) are equivocal and no studies have investigated an EIH paradigm targeting the lower back in order to assess EIH in patients with LBP. Thus, the aim of this pilot study was to assess pressure pain sensitivity at local and remote assessment sites, before and after an isometric back exercise in healthy women and men. In a pre-posttest design, pressure pain thresholds (PPT) were assessed at the lower back, biceps femoris muscle, and hand in 29 healthy subjects (17 women) before and after 120 seconds of the isometric Biering-Soerensen back extension test. After exercise, PPT increased significantly at the hand in women, but not in men ( P = 0.027). Moreover, PPT at the leg increased independently of sex ( P < 0.004). The increase in PPT at the lower back after exercise approached significance ( P = 0.07). The results of this pilot study indicate that isometric back exercise produces local and remote hypoalgesia. Remote EIH was only demonstrated in women, supporting the influence of sex in the hypoalgesic response after exercise. The effect of isometric back exercise on pain sensitivity in patients with low back pain should be investigated in future studies.


Geometric conjecture about phase transitions.
As phenomena that necessarily emerge from the collective behavior of interacting particles, phase transitions continue to be difficult to predict using statistical thermodynamics. A recent proposal called the topological hypothesis suggests that the existence of a phase transition could perhaps be inferred from changes to the topology of the accessible part of the configuration space. This paper instead suggests that such a topological change is often associated with a dramatic change in the configuration space geometry, and that the geometric change is the actual driver of the phase transition. More precisely, a geometric change that brings about a discontinuity in the mixing time required for an initial probability distribution on the configuration space to reach the steady state is conjectured to be related to the onset of a phase transition in the thermodynamic limit. This conjecture is tested by evaluating the diffusion diameter and ε-mixing time of the configuration spaces of hard-disk and hard-sphere systems of increasing size. Explicit geometries are constructed for the configuration spaces of these systems and numerical evidence suggests that a discontinuity in the ε-mixing time coincides with the solid-fluid phase transition in the thermodynamic limit.


Mapping the autoepitopes of thyroglobulin.
Chronic thyroiditis is currently the best available model of an organ-restricted autoimmune disease, because the principle antigen Tg is a well-characterized protein and the disease can be reproduced by experimental immunization. The pattern of autoantigenic determinants of Tg that is recognized by sera from subjects without detectable thyroid disease is clearly different from that seen with thyroiditis patients. Both sets of sera react with the evolutionary conserved portions, the hormonogenic regions containing the T3 and T4 moieties. Sera of thyroiditis patients, however, also react with the evolutionary variable, species-specific portions of the Tg molecule. Mice immunized with human Tg respond to the same, immunodominant sites. Mice injected with mouse Tg preferentially recognize the analogous, mouse-specific sites of Tg. Mice are not restricted, however, in their use of V-(D)-J genes for Ig production, even when the same antigenic determinant is involved.


Gallbladder and cystic duct absence. An infrequent malformation in laparoscopic surgery.
Gallbladder absence is an infrequent anomaly normally accompanied by lack of the cystic duct. Of unknown etiology, in general it is accepted to be a congenital malformation. A male patient (age 59) diagnosed with nonfunctional symptomatic scleroatrophic gallbladder by echography and ERCP was operated on using a laparoscopic approach. Gallbladder and cystic absence was diagnosed during the procedure. A new case of gallbladder and cystic duct absence, diagnosed by laparoscopy, is presented. This type of extrahepatic bile duct malformation is quite rare, but it must be taken into account due to the generalization of laparoscopic surgery in biliar pathology because of the high risk of serious lesions to the hepatocholedochal system.


Local co-administration of gene-silencing RNA and drugs in cancer therapy: State-of-the art and therapeutic potential.
Gene-silencing miRNA and siRNA are emerging as attractive therapeutics with potential to suppress any genes, which could be especially useful in combination cancer therapy to overcome multidrug resistant (MDR) cancer. Nanomedicine aims to advance cancer treatment through functional nanocarriers that delivers one or more therapeutics to cancer tissue and cells with minimal off-target effects and suitable release kinetics and dosages. Although much effort has gone into developing circulating nanocarriers with targeting functionality for systemic administration, another alternative and straightforward approach is to utilize formulations to be administered directly to the site of action, such as pulmonary and intratumoral delivery. The combination of gene-silencing RNA with drugs in nanocarriers for localized delivery is emerging with promising results. In this review, the current progress and strategies for local co-administration of RNA and drug for synergistic effects and future potential in cancer treatment are presented and discussed. Key advances in RNA-drug anticancer synergy and localized delivery systems were combined with a review of the available literature on local co-administration of RNA and drug for cancer treatment. It is concluded that advanced delivery systems for local administration of gene-silencing RNA and drug hold potential in treatment of cancer, depending on indication. In particular, there are promising developments using pulmonary delivery and intratumoral delivery in murine models, but further research should be conducted on other local administration strategies, designs that achieve effective intracellular delivery and maximize synergy and feasibility for clinical use.


Lack of influence of c-Ha-ras expression on the drug sensitivity of human bladder cancer histocultured in three-dimensions.
The mechanism of drug resistance in human cancers is complex. In addition to overexpression of a series of multiple-drug-resistance genes, there has been the suggestion that the Ha-ras gene may participate in conferring resistance. In this study, a series of three human-bladder carcinoma cell lines were studied, one parental type, one transfected by wild-type Ha-ras and another transfected by mutant Ha-ras. The ras gene was overexpressed in the latter two cell lines which also were more invasive than the parental when injected as individual cells in the nude-mouse bladder. The results described here have indicated that the ras-gene expression level or mutational status did not affect drug resistance when the tumor lines were histocultured as three-dimensional tissue on collagen-sponge-gels. The drug-response spectrum of the histocultured lines qualitatively reflected a clinical experience although all lines were relatively drug resistant, possibly reflecting their three-dimensional configuration in culture.


Estimation of CA 125 concentration in patients with congestive heart failure.
Tumour marker CA 125 is used in the monitoring results of treatment woman with ovarian cancer. Its diagnostic effectiveness in selected groups of patients is defined by sensitivity estimated at approximately 75% and specifity at 95%. In practice diagnostic specificity of CA 125 concentration is lower as it is limited by the increase of concentration different tumour diseases (bladder cancer) and non-tumour diseases (pericardial inflammation). The aim of the paper was to estimate CA 125 concentration in patients with congestive heart failure as well as to define the range of changes taking place according to the advancement of the disease. The research included 39 patients: 20 women and 19 men aged 45-75 with diagnosed congestive heart failure graded II-IV in the NYHA classification. It has been found that CA 125 concentration in blood serum of the patiens with congestive heart failure was on average approximately 35.4 +/- 24.8 U/ml and was included in the range from 5.6 to 874 U/ml (limit value 21 U/ml). The concentration increase above the limit value was observed in 34% of patients. Significant statistic differences in CA 125 concentration rates were dependent on the disease advancement. The highest concentration rates were observed in patients classified in group IV NYHA. The results that have been obtained allow us to draw a conclusion that right interpretation of CA 125 concentration in clinical practice (screening examinations, establishment of the level of advancement, prognostication as well as monitoring the ovarian cancer treatment) brings the necessity of taking into consideration the degree of congestive heart failure.


The alcelaphine herpesvirus-1 ORF 57 encodes a nuclear shuttling protein.
Alcelaphine herpesvirus-1 (AlHV-1) is a gamma(2) rhadinovirus associated with Malignant Catarrhal Fever (MCF) in cattle. ORF 57 is well conserved among gammaherpesviruses and it has been shown that the ORF 57 gene products of Herpesvirus Saimiri (HVS), Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) play an important role in regulating viral gene expression. The AlHV-1 ORF 57 gene product has not been characterized. In the accompanying paper we have demonstrated that AlHV-1 ORF 57 encodes an immediate early protein that acts as a regulator of gene expression. The ORF 57 gene product has an up-regulatory effect only on another immediate early gene product encoded by ORF 50. Here we show that the ORF 57 gene product is a nuclear protein. When ORF 57 was fused to the gene encoding Enhanced Green Fluorescent Protein (EGFP), the fusion protein exhibited a punctate nuclear distribution that co-localized with the nucleolar phosphoprotein C23. The nuclear localisation signal of ORF 57 gene product was located at the N-terminus. The ORF 57 gene product travels from nucleus to the cytoplasm, where it accumulates during Actinomycin D treatment. The domain involved in nuclear shuttling was also localised at the N-terminal region of the protein. Thus in common with homologues in other herpesviruses the AlHV-1 ORF 57 gene product is a nuclear cytoplasmic shuttling protein which may play a role in export of viral mRNAs from the nucleus of infected cells.


Modeling and optimising lactose fermentation using a fluorosensor.
Lactose has been fermented in a Tokyo Rikakikai Fermentor using two percent seeding at various temperatures. The progress of the reaction was followed by measuring the fluorescent signal due to NADH with a Dr. Ingold (Switzerland) fluorosensor which has an excitation wave length of 360 nm and measurement wavelength of 450 nm. The optimum temperature for this fermentation reaction is 34 degree celsius. At this temperature while biomass growth rate and final biomass concentration are a maximum the time taken to reach the final biomass concentration and lag time are a minimum. The fluorescent voltage vs time data fitted a first order plus dead time model with an error of less than one percent. The present work is in good agreement with earlier work on glucose and lactose fermentation with one percent seeding. The increase in seeding from one to two percent has improved the optimum parameters studied. Further work on higher seeding concentration and higher order models is in progress.


Lipoprotein lipase gene polymorphisms and blood pressure levels in the Northern Chinese Han population.
The lipoprotein lipase (LPL) gene has been investigated extensively in linkage studies and in studies of its association with lipid profiles and coronary artery disease (CAD), and this gene has also been reported to have an association with hypertension. In our previous linkage study on 148 Chinese hypertensive families, the regions at or near the LPL gene were found to be associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP). Thus the LPL gene is a logical candidate gene for involvement in the underlying cause of essential hypertension (EH). In the present study, we identified 22 sequence variants by directly sequencing 10 exons and flanking regions of the LPL gene, and investigated the occurrence of 3 of these variants, IVS4-214C>T, 7754C>A and S447X, in a case-control study including 501 normotensive (NT) subjects and 497 EH subjects. In males, the frequencies of the genotypes of each of the 3 variants did not differ significantly between the NT and EH groups. Among the EH group in females, ANCOVA revealed no significant difference in blood pressure levels according to the 7754C>A genotype. However, in female, the distribution of the 7754C>A genotype and the frequency of the A allele of 7754C>A differed significantly between the NT and EH groups (p=0.032 and p=0.027, respectively) with 0.78 (95% confidence interval (CI): 0.56 to 1.07; p=0.12) of odds ratio for the A allele. Moreover, haplotype analysis revealed that T-A-C and T-C-G haplotypes (in the order of IVS4-214C>T, 7754C>A and S447X) were statistically more frequent in the NT group than in the EH group in females and males, respectively. Our indivisual single nucleotide polymorphism (SNP) analysis did not provide substantial evidence of an association between polymorphisms in the LPL gene and hypertension status and/or blood pressure levels in this cohort, but the more powerful haplotypes analysis suggested an association between the LPL gene and hypertension.


Embryo developmental potential of microsurgically corrected human three-pronuclear zygotes.
We explored the embryo development potential of human three-pronuclear (3PN) zygotes reduced to two-pronuclear (2PN) zygotes (3 → 2PN zygotes) by micropuncture. In this study, there were three groups, the 3 → 2PN group (338 zygotes), the non-corrected 3PN group (381 zygotes), and the normal 2PN group (359 zygotes). The first cleavage mode (2-cell cleavage or 3-cell cleavage), 6-8 cell embryogenesis rate, high-quality embryogenesis rate and Day 5/Day 6 blastulation rate were compared between the three groups. The success rate of enucleation was 92.9%. The 2-cell cleavage rate was significantly higher in the 3 → 2PN group (74.3%) than in the 3PN group (36.4%) (P < 0.05), but had no statistical difference compared with the 2PN group (86.0%) (P > 0.05). The 6-8 cell embryogenesis rate was significantly higher in the 3 → 2PN group (91.1%) as compared to the 2PN group (85.6%) (P < 0.05), but had no statistical difference compared with the 3PN group (95.0%) (P > 0.05). Total blastulation rate was significantly higher in the 2PN group (58.8%) as compared to the 3PN group (21.5%) (P < 0.01), and in the 3 → 2PN group as compared to the 3PN group (5.6%) (P < 0.01). Also D5 blastulation rate was significantly higher in the 2PN group (53.7%) as compared to the 3 → 2PN group (8.9%) (P < 0.01), and in the 3 → 2PN group as compared to the 3PN group (1.9%) (P < 0.01). In 3 → 2PN zygotes, the first cleavage mode is mainly 2 cells which is significantly higher than that in 3PN zygotes. Compared with 3PN zygotes, the embryo developmental potential of 3 → 2PN zygotes is improved, but still is lower than that in 2PN zygotes.


Risk factors and outcomes associated with acquisition of colistin-resistant KPC-producing Klebsiella pneumoniae: a matched case-control study.
A matched 1:3 case-control study investigated factors predicting colistin-resistant versus colistin-susceptible KPC-producing Klebsiella pneumoniae acquisition and its impact on patient outcomes. Case patients were more often admitted from other institutions (P = 0.019) and had longer therapy with beta-lactam/beta-lactamase inhibitors (P = 0.002) and higher overall mortality (P = 0.05). All 52 study isolates were clonally related, suggesting horizontal dissemination. None of these parameters independently predicted colistin resistance, which probably occurred in a susceptible KPC-KP strain that was subsequently disseminated horizontally.


Quantifying brain state transition cost via Schrödinger Bridge.
Quantifying brain state transition cost is a fundamental problem in systems neuroscience. Previous studies utilized network control theory to measure the cost by considering a neural system as a deterministic dynamical system. However, this approach does not capture the stochasticity of neural systems, which is important for accurately quantifying brain state transition cost. Here, we propose a novel framework based on optimal control in stochastic systems. In our framework, we quantify the transition cost as the Kullback-Leibler divergence from an uncontrolled transition path to the optimally controlled path, which is known as Schrödinger Bridge. To test its utility, we applied this framework to functional magnetic resonance imaging data from the Human Connectome Project and computed the brain state transition cost in cognitive tasks. We demonstrate correspondence between brain state transition cost and the difficulty of tasks. The results suggest that our framework provides a general theoretical tool for investigating cognitive functions from the viewpoint of transition cost.


Serine 216 phosphorylation of estrogen receptor α in neutrophils: migration and infiltration into the mouse uterus.
Whereas estrogen receptors are present in immune cells, it is not known if they are phosphorylated to regulate immune cell functions. Here we determined the phosphorylation status of estrogen receptor α (ERα) at residue serine 216 in mouse neutrophils and examined its role in migration and infiltration. Serine 216 is the conserved phosphorylation site within the DNA binding domains found in the majority of nuclear receptors. A phospho-peptide antibody specific to phosphorylated serine 216 and ERα KO mice were utilized in immunohistochemistry, double immuno-staining or Western blot to detect phosphorylation of ERα in peripheral blood as well as infiltrating neutrophils in the mouse uterus. Transwell assays were performed to examine migration of neutrophils. An anti-Ly6G antibody identified neutrophils. About 20% of neutrophils expressed phosphorylated ERα at serine 216 in peripheral white blood cells (WBC) from C3H/HeNCrIBR females. Phosphorylation was additively segregated between C3H/HeNCrIBR and C57BL/6 females. Only neutrophils that expressed phosphorylated ERα migrated in Transwell assays as well as infiltrated the mouse uterus during normal estrous cycles. ERα was phosphorylated at serine 216 in about 20% of mouse peripheral blood neutrophils. Only those that express phosphorylated ERα migrate and infiltrate the mouse uterus. This phosphorylation was the first to be characterized in endogenous ERα found in normal tissues and cells. Phosphorylated ERα may have opened a novel research direction for biological roles of phosphorylation in ERα actions and can be developed as a drug target for treatment of immune-related diseases.


[Adjuvant chemotherapy in cancers of the gastrointestinal tract (GIT)].
A critical review of adjuvant therapies of gastrointestinal tumors shows that this is a field of active clinical investigation. Unfortunately the results that have been achieved until now have not fulfilled the expectations. Neoadjuvant therapies of squamous cell carcinomas of the esophagus and the anus in many cases lead to pathologically documented complete remissions. After a 10 years follow-up, it is evident that for anal carcinoma such pathological complete remissions translate into longterm remissions and eventually cures. The same conclusion, however, can not yet be drawn for esophageal cancer. The role of adjuvant chemotherapy in gastric carcinoma remains unclear. The results of the current FAM-studies are eagerly awaited. In pancreatic cancer the combination of radiotherapy and 5-FU may probably prolong disease-free survival and survival for a limited time period. Many adjuvant studies have been done in colonic cancer, without any conclusive data regarding the role of chemotherapy. Some indications point to biological response modifiers, immuno- and regional therapies to be effective in the adjuvant situation. The results of adjuvant chemotherapy in rectal cancer after radiotherapy or radiochemotherapy are easier to judge. They show that some patients profit from adjuvant therapy. But the most efficient combinations and the role of newer modalities remain to be elucidated (Fig. 8 a-8c).


Rape Kit Notification: Recommendations and Barriers to Reconnecting with Survivors.
In the wake of the discovery of untested rape kits across the country, jurisdictions now face questions about how best to reengage with survivors in a sensitive and empowering way. The current study sought to provide guidance on this question through interviews and surveys about effective victim notification procedures. Using a combination of purposive and snowball sampling, the current study interviewed 76 criminal justice, advocacy, and public policy professionals and 19 rape survivors from across the country about their recommendations for rape kit notification. Inductive thematic analysis was used to derive a set of 51 unique recommendations about how and when notification should occur. These recommendations were then transformed into a survey that was sent back to participants for ratings of importance, feasibility, and acceptability. Results suggested that approaches such as involving advocates, responding in a sensitive and empathetic way, engaging in full and ongoing notification, and providing clear information and referrals to survivors were supported by professionals and survivors alike. Results also suggested that feasibility concerns played little role in determining the acceptability of different notification approaches, calling into question the common assertion that feasibility concerns prevent jurisdictions from utilizing survivor-centric and trauma-informed procedures. Implications of these findings for both researchers and practitioners seeking to address the problem of untested rape kits are discussed.


Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis.
Psoriasis is a chronic inflammatory skin disease characterized by hyperplasia of the epidermis (acanthosis), infiltration of leukocytes into both the dermis and epidermis, and dilation and growth of blood vessels. The underlying cause of the epidermal acanthosis in psoriasis is still largely unknown. Recently, interleukin (IL)-23, a cytokine involved in the development of IL-17-producing T helper cells (T(H)17 cells), was found to have a potential function in the pathogenesis of psoriasis. Here we show that IL-22 is preferentially produced by T(H)17 cells and mediates the acanthosis induced by IL-23. We found that IL-23 or IL-6 can directly induce the production of IL-22 from both murine and human naive T cells. However, the production of IL-22 and IL-17 from T(H)17 cells is differentially regulated. Transforming growth factor-beta, although crucial for IL-17 production, actually inhibits IL-22 production. Furthermore, IL-22 mediates IL-23-induced acanthosis and dermal inflammation through the activation of Stat3 (signal transduction and activators of transcription 3) in vivo. Our results suggest that T(H)17 cells, through the production of both IL-22 and IL-17, might have essential functions in host defence and in the pathogenesis of autoimmune diseases such as psoriasis. IL-22, as an effector cytokine produced by T cells, mediates the crosstalk between the immune system and epithelial cells.


Stratified aspartate aminotransferase-to-platelet ratio index accurately predicts survival in hepatocellular carcinoma patients undergoing curative liver resection.
The aspartate aminotransferase-to-platelet ratio index has been reported to predict prognosis of patients with hepatocellular carcinoma. This study examined the prognostic potential of stratified aspartate aminotransferase-to-platelet ratio index for hepatocellular carcinoma patients undergoing curative liver resection. A total of 661 hepatocellular carcinoma patients were retrieved and the associations between aspartate aminotransferase-to-platelet ratio index and clinicopathological variables and survivals (overall survival and disease-free survival) were analyzed. Higher aspartate aminotransferase-to-platelet ratio index quartiles were significantly associated with poorer overall survival (p = 0.002) and disease-free survival (p = 0.001). Multivariate analysis showed aspartate aminotransferase-to-platelet ratio index to be an independent risk factor for overall survival (p = 0.018) and disease-free survival (p = 0.01). Patients in the highest aspartate aminotransferase-to-platelet ratio index quartile were at 44% greater risk of death than patients in the first quartile (hazard ratio = 1.445, 95% confidence interval = 1.081 - 1.931, p = 0.013), as well as 49% greater risk of recurrence (hazard ratio = 1.49, 95% confidence interval = 1.112-1.998, p = 0.008). Subgroup analysis also showed aspartate aminotransferase-to-platelet ratio index to be an independent predictor of poor overall survival and disease-free survival in patients positive for hepatitis B surface antigen or with cirrhosis (both p < 0.05). Similar results were obtained when aspartate aminotransferase-to-platelet ratio index was analyzed as a dichotomous variable with cutoff values of 0.25 and 0.62. Elevated preoperative aspartate aminotransferase-to-platelet ratio index may be independently associated with poor overall survival and disease-free survival in hepatocellular carcinoma patients following curative resection.


Review of radiofrequency microneedling: history, devices and uses.
Radiofrequency microneedling (RFM) has recently become a popular choice for the treatment of various dermatologic conditions and rejuvenation. Many studies have sought to evaluate the efficacy of RFM. However, its role in the management of these conditions remains unclear. A comprehensive literature search including randomized controlled trials, cohort studies, and case series evaluating the efficacy of RFM in various skin conditions was performed. In this review, we discuss the history and mechanism of RFM, describe various device features, and discuss the use of RFM in various skin conditions and rejuvenation.


High resolution kilometric range optical telemetry in air by radio frequency phase measurement.
We have developed an optical Absolute Distance Meter (ADM) based on the measurement of the phase accumulated by a Radio Frequency wave during its propagation in the air by a laser beam. In this article, the ADM principle will be described and the main results will be presented. In particular, we will emphasize how the choice of an appropriate photodetector can significantly improve the telemeter performances by minimizing the amplitude to phase conversion. Our prototype, tested in the field, has proven its efficiency with a resolution better than 15 μm for a measurement time of 10 ms and distances up to 1.2 km.


[Isolation and Identification of the Plant Endophyte R-13 and Its Effect on Cadmium Accumulation in Solanum nigrum L.]
The combination of endophytes and hyperaccumulator plants can significantly improve the efficiency of heavy metal phytoremediation in contaminated soil. A plant endophyte named Herbaspirillum R-13 was isolated from rice roots in a cadmium (Cd) contaminated paddy field. This strain exhibited a strong tolerance to Cd2+ and could grow on a solid medium with a Cd2+ concentration of 300 mg·kg-1. The R-13 strain was able to produce siderophores and Indole acetic acid (IAA), through color reactions. In addition, Pikovskaya's and Ashby's solid medium tests showed that the R-13 strain had a lower capacity for dissolving phosphorus but a higher capacity for fixing nitrogen. In the pot experiment, high-throughput sequencing technology was used to track the colonization of the R-13 strain in Solanum nigrum L. roots. Three days after inoculation, the relative abundance of Herbaspirillum in the root of Solanum nigrum L. had increased by 201.88% compared to the blank control (CK) and after two inoculations, the relative abundance of Herbaspirillum in the root of Solanum nigrum L. had increased by 1182.44% compared to CK. The relative abundance of Herbaspirillum in the root of Solanum nigrum L. began to decrease significantly from 5 days after inoculation. Inoculation with 20 mL·pot-1 of R-13 fermentation broth resulted in no significant effects on the Cd content of roots, stems, leaves, or fruits of S. nigrum L. With 40 mL·pot-1 of fermentation broth, the Cd content of vegetative organs and fruits was significantly increased. When it reached 200 mL·pot-1, the Cd content of vegetative organs was the highest, with Cd concentrations in the roots, stems, leaves, and fruits increasing by 84.42%, 43.67%, 64.06%, and 20.29%, respectively. In conclusion, root inoculation with endophytic Herbaspirillum R-13 can significantly increase the relative content of Herbaspirillum in the root system and enhance Cd absorption of S. nigrum L. Therefore, this strain has excellent prospects for application in the phytoremediation of soil contaminated with Cd.


Controlled propulsion in viscous fluids of magnetically actuated colloidal doublets.
We study the propulsion of a micron-size paramagnetic colloidal doublet dispersed in water and driven above a surface by an external precessing magnetic field. The applied field forces the doublet to precess around an axis parallel to the plane of motion and the rotation of the colloidal assembly is rectified into translation due to a periodic asymmetry in dissipation close to the bounding plate. These recent experimental findings [P. Tierno, R. Golestanian, I. Pagonabarraga, and F. Sagués, Phys. Rev. Lett. 101, 218304 (2008)] are complemented here with a theoretical analysis of the system and extended to more complex magnetic modulations such as elliptical driving fields. Experimental results show a good agreement with numerical simulations with the aim to find the best conditions toward the optimization of propulsion speed and swimming efficiency.


Lead Pellet Ingestion in 3 Children: Another Source for Lead Toxicity.
Acute ingestions of spherical lead ammunition foreign bodies such as bullets and lead shot can cause acute blood lead level elevations and clinical symptoms necessitating emergency department evaluations and sometimes treatment. This article presents 3 cases of children ingesting lead ammunition, all receiving gastrointestinal (GI) decontamination and chelation therapy for significantly elevated blood lead level. Case-specific exposures and treatments for the lead ammunitions are presented. Radiographs documented lead pellet ingestion in all 3 cases. Pediatric patients absorb lead from the GI tract more quickly than adults and may necessitate more urgent evaluation and treatment than adolescents/adults. More rapid GI absorption has the potential to result in possible irreversible neurotoxicity and neurocognitive deficits as well as behavioral changes. Failure of lead foreign bodies to pass from the GI tract may require more aggressive interventions for their removal to prevent ongoing absorption. Emergency health care providers should be aware of alternative lead sources besides the most common source of paint, as these lead foreign bodies also need urgent evaluation and possibly treatment.


The hemodynamic actions of insulin are blunted in the sublesional microvasculature of healthy persons with spinal cord injury.
The aim of this study was to gain a better understanding of the hemodynamic actions of insulin on cutaneous microcirculation in persons with spinal cord injury (SCI). A prospective, open-label, nonrandomized, placebo-controlled investigation was performed in an otherwise healthy cohort of persons with SCI (n = 10) and in an age- and sex-matched cohort of control subjects whose neurologic function is intact (n = 10). Laser Doppler flowmetry characterized the peak blood perfusion unit (BPU) response (percent change from baseline) to insulin or placebo iontophoresis above and below the neurologic level of injury. Placebo iontophoresis did not result in any statistically significant changes in BPU. In the arm, insulin iontophoresis resulted in a 20% mean increase in BPU (P < 0.05) in the control group and a 9% mean increase in the SCI group (P = 0.14). In the leg, insulin iontophoresis resulted in an 81% (P < 0.01) mean increase in BPU in the control group and a 29% (P < 0.001) mean increase in BPU in the SCI group. The relative effect of insulin on the lower extremity BPU response was significantly greater (P < 0.05) in the control group compared with the SCI group (77% vs. 35%, respectively). The hemodynamic actions of insulin are markedly blunted in the sublesional microvasculature of persons with SCI, most likely as a result of impaired sublesional sympathetic nervous system control.


Activation of gelatinase A (72-kDa type IV collagenase) induced by monensin in normal human fibroblasts.
In monolayer culture, fibroblasts secrete all matrix metalloproteinases, including gelatinase A (72-kDa type IV collagenase), as inactive zymogens. Whereas limited proteolysis by plasmin or other matrix metalloproteinases (MMPs) can accomplish the extracellular activation of other proenzymes in this family, gelatinase A proenzyme is uniquely refractory to cleavage by such proteinases. Previously it has been shown that fibroblasts cultured in the presumably more physiologic culture milieu of a type I collagen lattice can be induced to secrete active gelatinase A. In monolayer culture, however, the plant lectin concanavalin A will induce gelatinase A activation. Here we show that in monolayer culture activation of gelatinase A by normal fibroblasts is also induced by the sodium ionophore monensin. The monensin response is dose-dependent, time-dependent, requires protein synthesis, and is specific to gelatinase A among the secreted matrix metalloproteinases. The activator appears to be associated with cell membranes and may be membrane-type matrix metalloproteinase 1(MT-MMP1). Both mRNA and immunodetectable protein of MT-MMP1 are increased with monensin treatment while message for the protein inhibitor of gelatinase A, TIMP-2, is unchanged. The monensin-induced signal transduction pathway leading to gelatinase activation in monolayer culture appears to be different from the integrin-mediated pathway operative in the collagen lattice system. The tyrosine kinase inhibitor genistein blocks monensin activation of gelatinase A in monolayer culture. In contrast, genistein has no effect on proenzyme activation in the collagen lattice. Likewise, the cyclooxygenase inhibitor indomethacin abrogates the monensin effect in monolayer culture and can be reversed by addition of exogenous prostaglandin E2 (PGE2). Neither indomethacin nor PGE2 affects activation of gelatinase A in the collagen lattice.


Application value of gray-scale ultrasound and shear wave elastography in differential diagnosis of thyroid nodules.
The global prevalence of thyroid cancer has increased significantly in recent years. Ultrasonography is the preferred method for differentiating benign and malignant thyroid nodules preoperatively and is recommended by guidelines. To assess the application value of gray-scale ultrasound and shear wave elastography in distinguishing small thyroid nodules. A retrospective analysis of 228 thyroid nodules, all of which were confirmed by pathology after surgery or FNA from January 2019 to January 2020, was carried out. All nodules were divided into a ⩽ 5 mm group and a > 5 mm group according to their maximum size. We compared the differences in the gray scale and elastography of the nodules between the two groups and the accuracy of different diagnostic methods. The accuracies of gray-scale ultrasound and shear wave elastography in the ⩽ 5 mm group were found to be lower than those in the > 5 mm group, and the gray-scale accuracy was slightly higher than that of shear wave elastography in both groups (p< 0.05). The largest AUC (area under the curve) of elastic parameters in the ⩽ 5 mm and > 5 mm groups was found for Emax and Esd, respectively. Based on a combination of these two parameters, the accuracies of the two groups were significantly higher than those of the parameters or gray scale alone (p< 0.05) and were 84.62% and 85.48%, respectively. Shear wave elastography is valuable in the diagnosis of benign and malignant thyroid nodules using ultrasonography. When combining gray-scale ultrasound and shear wave elastography, the diagnostic accuracy is obviously improved, especially for ⩽ 5 mm small thyroid nodules.


Betamethasone-dixyrazine versus metoclopramide as antiemetic treatment in cancer chemotherapy.
In a prospective randomized and double-blind cross-over study betamethasone-dixyrazine was compared with metoclopramide as antiemetic treatment in cisplatin and doxorubicin chemotherapy. Sixty-two consecutive patients without prior experience of chemotherapy entered the study and were followed during 1-4 courses of treatment. Effect parameters were recorded on questionnaires using the visual analog scale for quantification. The median number of courses per patient was 3.0 (range 1-4). Full protection against nausea and vomiting was achieved in 74% with betamethasone-dixyrazine and in 45% with metoclopramide regardless of the chemotherapy regimen employed. With doxorubicin regimens betamethasone-dixyrazine gave full protection in 94% and metoclopramide in 45%. In cisplatin regimens full emetic protection was achieved in 40% with betamethasone-dixyrazine and in 29% with metoclopramide. Adverse reactions were a significant problem with metoclopramide: restlessness 48%, akathisia 26%, parkinsonism 13%, and acute dystonia 3%. One case (3.2%) of parkinsonism was noted as the only extrapyramidal reaction in the dixyrazine group. Various degrees of sedation were noted in 84% during dixyrazine treatment compared with 71% during metoclopramide therapy. Diarrhea was encountered in 48% after high-dose metoclopramide compared with 6% after antiemetic treatment with betamethasone-dixyrazine. Betamethasone-dixyrazine appears to be a promising antiemetic combination with regard to both efficacy and side effects, but further refinement of the regimen is probably possible through dose adjustments and alternative routes of administration.


Defective Temporal Window of the Foveal Visual Processing in High Myopia.
To investigate the temporal characteristics of visual processing at the fovea and the periphery in high myopia. Eighteen low (LM, ≤ -0.50 and > -6.00 D) and 18 high myopic (HM, ≤ -6.00 D) participants took part in this study. The contrast thresholds in an orientation discrimination task under various stimulus onset asynchrony (SOA) masking conditions were measured at the fovea and a more peripheral area (7°) for the two groups. An elaborated perceptual template model (ePTM) was fit to the behavioral data for each participant. An analysis of variance with three factors (SOA, degree of myopia and eccentricity) was performed on the threshold data. The interaction between SOA and degree of myopia in the fovea was significant (F (4, 128) = 2.66, P = 0.036), suggesting that the masking effect had different temporal patterns between the two groups. The temporal profiles for the two groups were derived based on the ePTM model. The peak and the spread of the temporal window in the fovea were much lower and wider, respectively, in the HM group than that in the LM group (both Ps < 0.05). There was no significant difference in the peripheral temporal window between the two groups. High myopia is associated with defective temporal processing in the fovea, captured by a flattened temporal window.


Molecular structure of taka-amylase A. I. Backbone chain folding at 3 A resolution.
The crystal structure of Taka-amylase A was studied by an X-ray diffraction method at 3 A resolution. A total of 452 amino acid residues were found from the electron density map at the present stage. The four disulfide bonds and the branched carbohydrate were also located on the map. The difference electron density map of the maltotriose-soaked crystal showed that a maltose unit was bound in the active center left. The binding of iodine atoms to the enzyme was also studied.


Quantitative measurements of loss on ignition in iron ore using laser-induced breakdown spectroscopy and partial least squares regression analysis.
Laser-induced breakdown spectroscopy (LIBS) and partial least squares regression (PLSR) have been applied to perform quantitative measurements of a multiple-species parameter known as loss on ignition (LOI), in a combined set of run-of-mine (ROM) iron ore samples originating from five different iron ore deposits. Global calibration models based on 65 samples and their duplicates from all the deposits with LOI ranging from 0.5 to 10 wt% are shown to be successful for prediction of LOI content in pressed pellets as well as bulk ore samples. A global independent dataset comprising a further 60 samples was used to validate the model resulting in the best validation R(2) of 0.87 and root mean square error of prediction (RMSEP) of 1.1 wt% for bulk samples. A validation R(2) of 0.90 and an RMSEP of 1.0 wt% were demonstrated for pressed pellets. Data preprocessing is shown to improve the quality of the analysis. Spectra normalization options, automatic outlier removal and automatic continuum background correction, which were used to improve the performance of the PLSR method, are discussed in detail.


A survey of extant organizational and computational setups for deploying predictive models in health systems.
Artificial intelligence (AI) and machine learning (ML) enabled healthcare is now feasible for many health systems, yet little is known about effective strategies of system architecture and governance mechanisms for implementation. Our objective was to identify the different computational and organizational setups that early-adopter health systems have utilized to integrate AI/ML clinical decision support (AI-CDS) and scrutinize their trade-offs. We conducted structured interviews with health systems with AI deployment experience about their organizational and computational setups for deploying AI-CDS at point of care. We contacted 34 health systems and interviewed 20 healthcare sites (58% response rate). Twelve (60%) sites used the native electronic health record vendor configuration for model development and deployment, making it the most common shared infrastructure. Nine (45%) sites used alternative computational configurations which varied significantly. Organizational configurations for managing AI-CDS were distinguished by how they identified model needs, built and implemented models, and were separable into 3 major types: Decentralized translation (n = 10, 50%), IT Department led (n = 2, 10%), and AI in Healthcare (AIHC) Team (n = 8, 40%). No singular computational configuration enables all current use cases for AI-CDS. Health systems need to consider their desired applications for AI-CDS and whether investment in extending the off-the-shelf infrastructure is needed. Each organizational setup confers trade-offs for health systems planning strategies to implement AI-CDS. Health systems will be able to use this framework to understand strengths and weaknesses of alternative organizational and computational setups when designing their strategy for artificial intelligence.


[Influence of quaternary ammonium salt on liberation of drug with antiseptic effect].
The paper evaluates the influence of three surfactants (carbetopendecinium halogenides) on the liberation of the drug chlorhexidine dihydrochloride (CHX) in 0.1% (w/w) from the dosage form-gel and also the flow properties of gels. The following tensides were evaluated: carbetopendecinium bromide (SB), carbetopendecinium chloride (SC), and carbetopendecinium iodide (SI). The tenside concentration was set under the critical micelle concentration. The biopolymer - chitosan (CHIT) in 2.5% (w/w) concentration was used as a gel creating substance. Based on the flow properties of the studied gels, it was found that the employed tensides exhibited no influence on the character of the system. The gels exhibited the character of plastic systems with time-independent flow. The drug liberation was evaluated at the temperatures of 20, 30 and 40 °C. Between the types of the tensides, the statistically significant differences (P < 0.05) were found as to the amount of the liberated CHX, which was reflected by the increased amount of the liberated drug. Based on the obtained results, it can be concluded that the most suitable was the SI tenside. From the gel with this tenside the greatest amount of CHX was liberated, which had the highest value of the liberation rate constant.


Failure to use an interpreter.
Case studies are based on actual medical negligence claims or medicolegal referrals; however certain facts have been omitted or changed by the author to ensure the anonymity of the parties involved. This article discusses a Medical Board complaint involving an allegation of failure to use an interpreter, resulting in the death of a patient, aged 35 years.


Molecular complexity analysis of de novo designed ligands.
The de novo approach to structure-based rational drug design can provide a powerful tool for suggestion of entirely novel potential leads. However, programs for structure generation typically generate large numbers of putative ligands; therefore, various heuristics (such as estimation of binding affinity and synthetic accessibility) have to be adopted to evaluate and prune large answer sets with the goal of suggesting ligands with high binding affinity but low structural complexity. A novel method for complexity analysis is described. This method provides a rapid and effective ranking technique for elimination of structures with complicated molecular motifs. This complexity analysis technique, implemented within the SPROUT de novo design system, is based on the statistical distribution of various cyclic and acyclic topologies and atom substitution patterns in existing drugs or commercially available starting materials. A novel feature of the technique that distinguishes it from other published methods is that the matching takes place at various levels of abstraction, so that it can evaluate complexity scores, even for structures which contain atoms with unspecified atom type, which is sometimes the case with the initial output of de novo structure generation systems.


The meanings of suffering.
Western thinkers have usually falsified our experience of suffering in trying to make sense of it. In a postmodern age, their accounts seem implausible. We need a way of making sense of suffering while admitting its horror.


Evaluation of the Illumina(®) Beta Version ForenSeq™ DNA Signature Prep Kit for use in genetic profiling.
While capillary electrophoresis-based technologies have been the mainstay for human identity typing applications, there are limitations with this methodology's resolution, scalability, and throughput. Massively parallel sequencing (MPS) offers the capability to multiplex multiple types of forensically-relevant markers and multiple samples together in one run all at an overall lower cost per nucleotide than traditional capillary electrophoresis-based methods; thus, addressing some of these limitations. MPS also is poised to expand forensic typing capabilities by providing new strategies for mixture deconvolution with the identification of intra-STR allele sequence variants and the potential to generate new types of investigative leads with an increase in the overall number and types of genetic markers being analyzed. The beta version of the Illumina ForenSeq DNA Signature Prep Kit is a MPS library preparation method with a streamlined workflow that allows for targeted amplification and sequencing of 63 STRs and 95 identity SNPs, with the option to include an additional 56 ancestry SNPs and 22 phenotypic SNPs depending on the primer mix chosen for amplification, on the MiSeq desktop sequencer (Illumina). This study was divided into a series of experiments that evaluated reliability, sensitivity of detection, mixture analysis, concordance, and the ability to analyze challenged samples. Genotype accuracy, depth of coverage, and allele balance were used as informative metrics for the quality of the data produced. The ForenSeq DNA Signature Prep Kit produced reliable, reproducible results and obtained full profiles with DNA input amounts of 1ng. Data were found to be concordant with current capillary electrophoresis methods, and mixtures at a 1:19 ratio were resolved accurately. Data from the challenged samples showed concordant results with current DNA typing methods with markers in common and minimal allele drop out from the large number of markers typed on these samples. This set of experiments indicates the beta version of the ForenSeq DNA Signature Prep Kit is a valid tool for forensic DNA typing and warrants full validation studies of this MPS technology.


Development of respiration and mitochondria in Mucor genevensis after anaerobic growth: absence of glucose repression.
Respiration and mitochondria in Mucor genevensis, a facultatively anaerobic dimorphic mold, have been studied in aerobically and anaerobically grown cells and in anaerobically grown cells adapting to aerobic conditions. Respiration in hyphae continues at a high level during aerobic growth but drops rapidly on exhaustion of glucose. In anaerobically grown yeastlike cells, containing no recognizable aerobic cytochromes, a small cyanide-insensitive respiration occurs. Mitochondria with well defined cristae are visible in negative contrast after KMnO(4) fixation of stringently anaerobic cells containing low amounts of fatty acid of which 10% or less are unsaturated. On aeration of anaerobically grown cells, respiratory capacity and cytochromes develop rapidly, even in the presence of 10% glucose, indicating that glucose does not repress development of respiration. However, mycelium formation by adapting yeastlike cells is repressed by high glucose concentration. In adapting cells, apparent changes in mitochondrial ultrastructure appear to be more related to changes in fixation properties of cells than to changes in the structure of mitochondria.


Thoracic Extramedullary Hematopoiesis Mimicking Metastatic Cancer.
Thoracic extramedullary hematopoiesis (EMH) is a rare manifestation in patients with myeloproliferative neoplasm. A 76-year-old woman with a long-standing history of polycythemia vera presented with a 2-month history of worsening dyspnea and left-sided wheezing. A chest computed tomography showed an ill-defined soft tissue mass encasing the left mainstem bronchus causing airway obstruction, associated with paratracheal and paraesophageal lymphadenopathy. Endobronchial ultrasound-guided fine needle aspiration of the soft tissue mass and mediastinoscopy with excisional biopsy of a paratracheal lymph node demonstrated EMH with increased myeloid blasts. A bone marrow biopsy confirmed postpolycythemic myelofibrosis consistent with progression of polycythemia vera to myelofibrosis. We describe the bronchoscopic management of a case of EMH presenting as a mediastinal mass, mimicking malignancy.


Graphene Oxide Nanoprisms for Sensitive Detection of Environmentally Important Aromatic Compounds with SERS.
Recent advances in graphene-based sensors have shown that heavily oxidized (GO) and reduced graphene oxide (rGO) are attractive materials for environmental sensing due to their unique chemical and physical properties. We describe here the fabrication of nanostructured GO assemblies with Ag nanoprisms for improved detection with surface enhanced Raman scattering (SERS). Specifically, 100-μm-sized, periodic-nanoprism-array domains were fabricated on top of the GO layers by GO-assisted lithography (GOAL). The atomically thin GO underlayers are shown to attract cyclic aromatic molecules to the surface, likely via π-π stacking interactions. The close proximity of the analyte to GO and nanoprism (NP) tips effectively suppresses fluorescent background and affords a plausible tertiary enhancement of photon emissions via an electron charge transfer (CT) process. The adsorption of analyte to rGO-NP leads to the appearance and/or shift of several Raman bands, which provided a means to gain molecular insights into the graphene-enhanced scattering process. The analytical merits were characterized with model compound Rhodamine 6G, where the detection limit could reach subnanomolar concentrations. The nanoprism GO substrates also prove effective for SERS multiplex measurement of several legacy aromatic pollutants. Three tetrachlorobiphenyl isomers could be identified from a mixture using their autonomous nonoverlapping molecular fingerprints, and the substrate offers remarkable trace detection of 2,2',3,3'-tetrachlorobiphenyl (PCB-77).


Associated diseases.
Yawning is a physiological behavior and, as with all such behaviors, its deregulation is indicative of an underlying disorder. This chapter breaks this topic down into the types of yawning (incomplete, absent or excessive) and the direction of causality (triggering or relieving a disorder).


Plasmonic Measurement of Electron Transfer between a Single Metal Nanoparticle and an Electrode through a Molecular Layer.
We study electron transfer associated with electrocatalytic reduction of hydrogen on single platinum nanoparticles separated from an electrode surface with an alkanethiol monolayer using a plasmonic imaging technique. By varying the monolayer thickness, we show that the reaction rate depends on electron tunneling from the electrode to the nanoparticle. The tunneling decay constant is ∼4.3 nm-1, which is small compared to those in literature for alkanethiols. We attribute it to a reduced tunneling barrier resulting from biasing the electrode potential negatively to the hydrogen reduction regime. In addition to allowing study of electron transfer of single nanoparticles, the work demonstrates an optical method to measure charge transport in molecules electrically wired to two electrodes.