Long-Term Outcome of Fetuses with Soft Marker and Without Genetic or Structural Abnormality.
To determine long-term outcome of infants with isolated or multiple soft markers but no structural or chromosomal abnormalities. A retrospective study of 78 pregnant women who were referred for amniocentesis and found to have soft markers including echogenic intracardiac focus/foci (EIF), echogenic bowel (EB), unilateral or bilateral choroid plexus cysts, (UCPCs or BCPCs) mild pyelectasis and single umbilical artery but no structural anomalies and outcomes of the liveborns with a 4- to 9-year follow-up was conducted. Among 28 fetuses with EIF, allergic asthma and epilepsy were diagnosed in two liveborns. We followed up nine pregnancies with EB, epilepsy was present in one case. Allergic asthma was detected in both UCPCs and BCPCs, whereas epilepsy and attention-deficit/hyperactivity disorder (ADHD) were diagnosed in two liveborns with BCPCs. Twelve liveborns with multiple soft markers were evaluated; no pathology was detected in most of them except one case of allergic asthma, one case of hearing impairment and one case of ADHD. This study shows longer-term favorable outcomes of the liveborns with isolated or multiple soft markers without any aneuploidy and may provide insight into this debated point.


Surgery of metastatic renal cell carcinoma and use of renal infarction.
Surgery can play an important role in selected patients with metastatic renal cell carcinoma although nephrectomy alone neither promotes regression of metastases nor improves survival. However, nephrectomy preceded by renal infarction and followed by medroxyprogesterone acetate produced ten complete responses, nine partial responses, and 22 stabilizations among 145 patients (CR + PR = 13%; overall response rate = 28%). Only patients with parenchymal pulmonary metastases without adenopathy, pleural effusion, or other organ involvement responded consistently (23% objective, 41% overall), and we currently recommend this combination therapy only for this group. However, infarction alone is an easy way to palliate symptoms due to primary or secondary tumors.


Utility of shear wave elastography and high-definition color for diagnosing carpal tunnel syndrome.
The diagnostic values of measuring median nerve (MN) stiffness and vascularity with shear wave elastography (SWE) and high-definition (HD) color were investigated in carpal tunnel syndrome (CTS). Seventy patients (123 wrists) with CTS and thirty-five healthy volunteers (70 wrists) were enrolled. Based on nerve conduction studies (NCS), the patients were subdivided into NCS-negative, mild-to-moderate, and severe CTS groups. MN and abductor pollicis brevis (APB) SWE and MN HD color were performed on a longitudinal plane. The mild-to-moderate and severe CTS groups showed increased MN stiffness at the wrist and MN stiffness ratio (wrist-to forearm) compared with the control (p < 0.001). The NCS-negative CTS group showed increased MN stiffness at the wrist (p = 0.022) and MN stiffness ratio (p = 0.032) compared with the control. The severe CTS group showed increased MN stiffness at the wrist compared with the mild-to-moderate CTS group (p = 0.034). The cutoff-values in diagnosing NCS-confirmed CTS were 50.12 kPa for MN stiffness at the wrist, 1.91 for MN stiffness ratio, and grade 1 for HD color. SWE and HD color are good supportive tools in diagnosing and assessing severity in CTS. SWE and HD color demonstrated that MN in CTS was associated with increased stiffness and hypervascularity.


Environmental enrichment attenuates locomotor sensitization, but not in vitro dopamine release, induced by amphetamine.
Rats were raised from weanling until young adulthood in either an enriched condition (EC) or isolated condition (IC). Following this, the locomotor and rewarding effects of amphetamine were determined using the conditioned place preference (CPP) paradigm. EC rats were more sensitive to the acute locomotor stimulant effect and rewarding effect of amphetamine relative to IC rats. In contrast, EC rats were less sensitive than IC rats to the locomotor sensitization effect obtained across repeated amphetamine injections. To determine the effect of environmental enrichment on alteration of brain dopamine (DA) function induced by amphetamine, the effect of amphetamine on electrically evoked release of DA and dihydroxyphenylacetic acid (DOPAC) was determined in vitro using tissue slices from the nucleus accumbens and striatum of EC and IC rats. No differences between EC and IC rats in release of DA or DOPAC were evident, suggesting that the environmentally induced difference in sensitivity to the behavioral effects of amphetamine involves a neural mechanism extrinsic to the mesolimbic and nigrostriatal terminal field regions.


Grass carp (Ctenopharyngodon idella) Mex3B positively regulates innate immunity by promoting the K63-linked ubiquitination of TLR3.
As a member of Mex3 (muscle excess protein-3) family, Mex3B (Mex-3 RNA binding family member B) is crucial in cell proliferation and migration in mammals. In this study, an ortholog of mammalian Mex3B (denominated CiMex3B, MT276802.1) was cloned and identified in grass carp (Ctenopharyngodon idella). CiMex3B is 1578 bp in length and encodes a polypeptide of 525 amino acids. Consistent with its mammalian counterpart, CiMex3B also contains one C-terminal RING domain and two N-terminal conserved tandem KH domains. CiMex3B up-regulates the expressions of IFN1, ISG15, MX2, as well as the expressions of inflammatory cytokines such as IL6, IL8 and TNFα in response to poly(I:C). A screening test for identifying potential targets indicated that CiMex3B is associated with TLR3 and TRIF. CiMex3B co-localizes with TLR3 in the late endosome, mitochondria and endoplasmic reticulum after poly(I:C) stimulation, whereas they are rarely discovered in the lysosomes. CiMex3B serves as a positive regulator in the phosphorylation of IRF3 and induces IFN1 expression. In addition, two truncation mutants of CiMex3B (1-220 and 221-525) were constructed to better understand the molecular mechanism of CiMex3B-mediated ubiquitination of TLR3. In line with wild-type protein, CiMex3B mutant (1-220) was found mainly in the cytoplasm; however, CiMex3B mutant (221-525) resided in the cytoplasm and the nucleus as well, and it was further confirmed that CiMex3B mutant (221-525) still interacts with TLR3. We also observed that CiMex3B promotes the K63-linked ubiquitination of TLR3, while neither of the truncation mutants (1-220 or 221-525) retains this activity. To sum up, this study revealed that CiMex3B potentiates the K63-linked ubiquitination of TLR3, and then elicits the IRF3-mediated antiviral innate immune responses.


Intrapartum use of zidovudine in a large cohort of pregnant women living with HIV in Italy.
Intravenous administration of zidovudine (ZDV) during labour is a key step for vertical HIV transmission (VT) prevention, but there is no evidence of benefit when maternal HIV-RNA at delivery is <50 copies/mL. The aim of this study is evaluating the appropriateness of intrapartum ZDV use in Italy. Observational study including mother-infant pairs with perinatal HIV exposure during 2002-2019, enrolled in the Italian Register for HIV Infection in Children. Univariable and multivariable logistic regression were used to evaluate factors associated with VT. A total of 3,861 infants, born from 3,791 pregnancies were included. The frequency of ZDV use was 79.9%, 92.1%, 93.7% and 92.8% when HIV-RNA was not available, ≥400 copies, between 50 and 399 copies, and <50 copies/mL. Thirty-three out of 3861 (0.85%) infants were subsequently diagnosed with HIV, 25/3861 (0.6%) of them born to mothers receiving intrapartum ZDV, and 31 (93.9%) to mothers with HIV-RNA ≥50 copies/mL or not available. In women with HIV-RNA < 50 copies/mL, ART discontinuation during pregnancy was the strongest risk factor for VT (odds ratio, OR, 23.1, 95%CI 2.4-219.3), while a higher gestational age (OR 0.6, 95%CI 0.4-0.8) and PEP administration to the newborn (aOR 0.004, 95%CI <0.0001-0.4) were protective factors. Intrapartum ZDV administration did not influence the final outcome in this group. In ART era, more transmission events may occur in utero, limiting value of intrapartum ZDV, particularly for women with suppressed HIV-RNA load. More attention to the HIV-RNA testing of mothers before delivery may avoid unnecessary ZDV use.


Interferon-induced alterations in membrane functions and the growth of Daudi lymphoma and Friend leukemia cells.
The Friend murine erythroleukemia cell system and the Daudi Burkitt's lymphoma cell system were used to study the effect of growth-inhibitory concentrations of interferon on membrane functions. Experiments with Friend-cell clones sensitive and resistant to interferon indicated that a number of changes in membrane transport occur rapidly after the addition of interferon to sensitive cells. While no change was observed in the activity of the (Na+/K+) ATPase in Friend cells sensitive or resistant to interferon, a piretanide-inhibitable Na+,K+, 2Cl- co-transport system was specifically inhibited after interferon treatment of sensitive cells. In contrast, treatment of Daudi cells with purified molecularly cloned or standard preparations of human leukocyte interferon gave rise to no early changes in the transport of amino acids, 32Pi, sugars, or 86Rb+. The major change observed in Daudi cells was a marked reduction in the uptake and incorporation of thymidine, which begins to decrease after 8-10 h of exposure to interferon.


Ability of antibodies specific to the HIV-1 envelope glycoprotein to block the fusion inhibitor T20 in a cell-cell fusion assay.
The anti-HIV peptide T20 is able to inhibit the syncytia formation between CHO-WT and HeLa CD4(+)cells. We found that several sera of HIV-infected patients have the capacity to block the inhibition of fusion by T20. Suggesting that these sera may contain antibody which can block T20 access and prevent membrane fusion, we studied the ability of a panel of antibodies directed to different regions of HIV-1 envelope glycoprotein to block the inhibition of fusion by T20. We found that the C1 and V3 loop regions of gp120 and the heptad repeat 1, the immunodominant C-C region and the Kennedy epitope of gp41 located in the intracytoplasmic tail were the target for antibodies capable to block the inhibition of syncytia formation by T20. We suggest that these antibodies have the capacity to counteract the anti-fusion effect of T20 by preventing its binding to the interaction sites. Further studies are needed to determine if some of them recognize new T20 interaction sites.


Robotic Versus Laparoscopic Minimally Invasive Surgery for Rectal Cancer: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
The aim of this study was to evaluate the safety and efficacy of elective rectal resection for rectal cancer in adults by robotic surgery compared with conventional laparoscopic surgery. Technological advantages of robotic surgery favor precise dissection in narrow spaces. However, the evidence base driving recommendations for the use of robotic surgery in rectal cancer primarily hinges on observational data. We searched MEDLINE, Embase, and CENTRAL for randomized controlled trials (until August 2016) comparing robotic surgery versus conventional laparoscopic surgery. Data on the following endpoints were evaluated: circumferential margin status, mesorectal grade, number of lymph nodes harvested, rate of conversion to open surgery, postoperative complications, and operative time. Data were summarized as relative risks (RR) or weighted mean differences (WMDs) with 95% confidence intervals (95% CIs). Risk of bias of studies was assessed with standard methods. Five trials were eligible, including 334 robotic and 337 laparoscopic surgery cases. Meta-analysis showed that RS was associated with lower conversion rate (7.3%; 4 studies, 544 participants, RR 0.58; 95% CI 0.35-0.97, P = 0.04, I = 0%) and longer operating time (MD 38.43 minutes, 95% CI 31.84-45.01: P < 0.00001) compared with laparoscopic surgery. Perioperative mortality, rate of circumferential margin involvement (2 studies, 489 participants, RR 0.82, 95% CI 0.39-1.73), and lymph nodes collected (mean 17.4 Lymph Nodes; 5 trials, 674 patients, MD -0.35, 95% CI -1.83 to 1.12) were similar. The quality of the evidence was moderate for most outcomes. Evidence of moderate quality supports that robotic surgery for rectal cancer produces similar perioperative outcomes of oncologic procedure adequacy to conventional laparoscopic surgery. Robotic surgery portraits lower rate of conversion to open surgery, while operating time is significantly longer than by laparoscopic approach.


Central pituitary adenylate cyclase 1 receptors modulate nociceptive behaviors in both inflammatory and neuropathic pain states.
The pituitary adenylate cyclase-activating polypeptide type 1 receptor (PAC(1)-R) is a member of the 7-transmembrane domain, group 2 G-protein coupled receptor family. PAC(1)-Rs modulate neurotransmission and neurotrophic actions and have been implicated in both pronociception and antinociception. To better understand the role of PAC(1)-Rs in pain, PACAP 6-38, a PAC(1)-R antagonist, was evaluated in several inflammatory and neuropathic pain models after intrathecal (i.t.) administration. PACAP 6-38 potently reduced mechanical allodynia in a neuropathic spinal nerve ligation model (77% +/- 15% maximal effect at 12 nmol, P < .01) and was also effective in reducing thermal hyperalgesia in the carrageenan model of inflammatory pain (89% +/- 17% maximal effect at 12 nmol, P < .01). Although nociceptive responses were also attenuated with PACAP 6-38 in a dose-dependent manner in models of chronic inflammatory and persistent pain, no effects on motor performance were observed at analgesic doses. Taken together, these data demonstrate that blockade of the PAC(1)-R/PACAP complex by PACAP 6-38 can effectively attenuate thermal hyperalgesia and mechanical allodynia associated with inflammatory and neuropathic pain states. These results further emphasize that at the level of the spinal cord, PAC(1)-R activation is pronociceptive. This article presents the analgesic profile generated by the blockade, at the spinal cord level, of the PAC-1 receptor by a potent peptide antagonist. This comprehensive data set demonstrates that if small molecule PAC-1 receptor antagonists could be identified, they would potentially produce broad-spectrum analgesia in both inflammatory and neuropathic pain states.


Intensive, integrated, in-home psychiatric services. The catalyst to enhancing outpatient intervention.
The authors introduce the Yale Intensive In-Home Child and Adolescent Psychiatric Service, a model of home-based care for children with severe psychiatric disturbances. This model synthesizes the principles and method of the wrap-around paradigm and in-patient child psychiatric practice within the reality of the managed care system. A clinical team, under the direct supervision of a child psychiatrist, works directly within the family to understand and address the multilevel transactions that have affected the child's ability to function in various domains and resulted in recommendations for intensive intervention, including psychiatric hospitalization. This article suggests that if the psychiatrist is to provide the highest level of care, cognizance of and involvement in the child's ecology are as essential for the child and adolescent psychiatrist as other aspects of the child's world and life. In the days of ever shortening patient lengths of stay, this model of care offers promise for both clinical and fiscal effectiveness.


Model of active transport of ions in archaea cells.
A mathematical model of the active transport of main ions in cells of archaebacteria has been constructed. A set of equations has been developed and solved for ion fluxes through the bacterium membrane. The model is based on the principle "one ion-one transport system." Considering experimental data, the major transport mechanism was determined for each ion and the balance equation was written on the basis of this mechanism in the stationary state. This allowed calculating values of the membrane potential and intracellular concentrations of the ions independently. The calculated values of the intracellular concentrations and resting potential are in qualitative agreement with the corresponding experimental values for cells of extremely halophilic archaea.


Interfacial Engineering of W2 N/WC Heterostructures Derived from Solid-State Synthesis: A Highly Efficient Trifunctional Electrocatalyst for ORR, OER, and HER.
To meet the practical demand of overall water splitting and regenerative metal-air batteries, highly efficient, low-cost, and durable electrocatalysts for the oxygen reduction reaction (ORR), oxygen evolution reaction (OER), and hydrogen evolution reaction (HER) are required to displace noble metal catalysts. In this work, a facile solid-state synthesis strategy is developed to construct the interfacial engineering of W2 N/WC heterostructures, in which abundant interfaces are formed. Under high temperature (800 °C), volatile CNx species from dicyanodiamide are trapped by WO3 nanorods, followed by simultaneous nitridation and carbonization, to form W2 N/WC heterostructure catalysts. The resultant W2 N/WC heterostructure catalysts exhibit an efficient and stable electrocatalytic performance toward the ORR, OER, and HER, including a half-wave potential of 0.81 V (ORR) and a low overpotential at 10 mA cm-2 for the OER (320 mV) and HER (148.5 mV). Furthermore, a W2 N/WC-based Zn-air battery shows outstanding high power density (172 mW cm-2 ). Density functional theory and X-ray absorption fine structure analysis computations reveal that W2 N/WC interfaces synergistically facilitate transport and separation of charge, thus accelerating the electrochemical ORR, OER, and HER. This work paves a novel avenue for constructing efficient and low-cost electrocatalysts for electrochemical energy devices.


Timing jitter of high-repetition-rate mode-locked fiber lasers.
We characterize the timing jitter of the pulse trains from 880 MHz Yb-doped nonlinear polarization rotation mode-locked fiber lasers based on a balanced optical cross-correlation method. Jitter spectral density at different net-cavity dispersions has been characterized, and the near-zero dispersion shows the lowest rms timing jitter (10 fs rms, integrated from 30 kHz to 5 MHz). The measurements have been compared with analytical models. The comparison shows that the RIN-coupled timing jitter by nonlinearity is the dominated origin of the measured timing jitter below ∼100 kHz, while amplified spontaneous emission noise makes a major contribution in the high frequency range above hundreds of kilohertz. To the best of our knowledge, this is the first high-precision timing jitter characterization for the ∼gigahertz level repetition rate mode-locked fiber lasers. The results will be of great importance for further improving the laser performance for many applications.


Diabetic striatopathy unusual presentation with ischemic stroke-A case report and literature review.
Diabetic striatopathy (DS) is a rare condition present as a combination of hemichorea or hemiballismus with striatal computed tomography (CT) or magnetic resonance imaging (MRI) changes in the presence of a severely hyperglycemic state. Varying severity and manifestations of DS were reported throughout the literature. However, the exact pathogenesis and mechanism remain unclear. In this case report, we are presenting an unusual case of DS combined with acute ischemic stroke. A 74-year-old male presented with the main complaint of acute left arm and leg weakness, and was found to have significantly high blood sugar and evidence of DS in combination with stroke on CT and MRI. Eventually, he was labeled as a case of combined DS and ischemic stroke.


Host metabolism regulates intracellular growth of Trypanosoma cruzi.
Metabolic coupling of intracellular pathogens with host cells is essential for successful colonization of the host. Establishment of intracellular infection by the protozoan Trypanosoma cruzi leads to the development of human Chagas' disease, yet the functional contributions of the host cell toward the infection process remain poorly characterized. Here, a genome-scale functional screen identified interconnected metabolic networks centered around host energy production, nucleotide metabolism, pteridine biosynthesis, and fatty acid oxidation as key processes that fuel intracellular T. cruzi growth. Additionally, the host kinase Akt, which plays essential roles in various cellular processes, was critical for parasite replication. Targeted perturbations in these host metabolic pathways or Akt-dependent signaling pathways modulated the parasite's replicative capacity, highlighting the adaptability of this intracellular pathogen to changing conditions in the host. These findings identify key cellular process regulating intracellular T. cruzi growth and illuminate the potential to leverage host pathways to limit T. cruzi infection.


Two cases of liver lobe torsion in a white-lipped tamarin (Saguinus labiatus) and an Alaotran gentle lemur (Hapalemur alaotrensis).
This paper describes liver lobe torsion in a white-lipped tamarin (Saguinus labiatus) and an Alaotran gentle lemur (Hapalemur alaotrensis). Both animals had a history of acute collapse, and diagnosis was made post-mortem. To the authors' knowledge, these are the first reported cases of this pathology in non-human primates.


Spawning rings of exceptional points out of Dirac cones.
The Dirac cone underlies many unique electronic properties of graphene and topological insulators, and its band structure--two conical bands touching at a single point--has also been realized for photons in waveguide arrays, atoms in optical lattices, and through accidental degeneracy. Deformation of the Dirac cone often reveals intriguing properties; an example is the quantum Hall effect, where a constant magnetic field breaks the Dirac cone into isolated Landau levels. A seemingly unrelated phenomenon is the exceptional point, also known as the parity-time symmetry breaking point, where two resonances coincide in both their positions and widths. Exceptional points lead to counter-intuitive phenomena such as loss-induced transparency, unidirectional transmission or reflection, and lasers with reversed pump dependence or single-mode operation. Dirac cones and exceptional points are connected: it was theoretically suggested that certain non-Hermitian perturbations can deform a Dirac cone and spawn a ring of exceptional points. Here we experimentally demonstrate such an 'exceptional ring' in a photonic crystal slab. Angle-resolved reflection measurements of the photonic crystal slab reveal that the peaks of reflectivity follow the conical band structure of a Dirac cone resulting from accidental degeneracy, whereas the complex eigenvalues of the system are deformed into a two-dimensional flat band enclosed by an exceptional ring. This deformation arises from the dissimilar radiation rates of dipole and quadrupole resonances, which play a role analogous to the loss and gain in parity-time symmetric systems. Our results indicate that the radiation existing in any open system can fundamentally alter its physical properties in ways previously expected only in the presence of material loss and gain.


Morphology of the male reproductive system and sperm ultrastructure of the green lacewing, Chrysopa pallens (Rambur, 1838) (Neuroptera: Chrysopidae).
Chrysopa pallens is one of the most beneficial and effective natural predators, and is famous for its extensive distribution, wide prey spectrum, and excellent reproductive performance. This study examined the anatomy and fine structure of the C. pallens reproductive system and spermatogenesis. The male reproductive system of C. pallens comprises a pair of testes, a vas deferens, seminal vesicles, accessory glands, and short ejaculatory ducts. The testes were already mature on the day of emergence, but the accessory glands did not mature until 5 days post-emergence. In early spermatids, the flagellum had an axoneme on one side of the two mitochondrial derivatives. The nucleus was surrounded by parallel crystalline and paracrystalline materials. The spermatid envelope extends towards the paracrystalline material in a tail-shaped wing. In mature spermatids, the axoneme is located between the two accessory bodies and mitochondrial derivative sets. The parallel-crystalline and paracrystalline materials disappeared. In the testes, the wall of seminal cysts consists of a layer of epithelium, a muscular-connective sheath, and several vesicles of different sizes. The mature seminal cysts contained 128 spermatozoa. The accessory gland is composed of six parts: ventral papilla-like protuberance, anterior glandular lobe, lateral glandular lobe, seminal cyst, posterior kidney-shaped lobe, and posterior papilla-like protuberance. Muscle fibers and secretory granules are extensive. This study provides information on the reproductive system of C. pallens and offers a resource for taxonomy and reproductive biology.


[Dynamic monitoring of serum soluble HLA class I antigens in renal transplant recipients].
To investigate the relations between serum soluble HLA class I antigens (sHLA-I) and the period of acute rejection and infection in renal transplant recipients. We measured the serum levels of sHLA-I in 36 renal transplant recipients with ELISA dynamically. The serum sHAL-I levels were higher in uremia patients than in normal controls [(2.94 +/- 0.34) microg/L vs. (0.76 +/- 0.33) microg/L, P < 0.05]. After renal transplantation, the serum sHLA-I levels decreased significantly in stable patients [(0.63 +/- 0.33) microg/L], but increased significantly 3 days before acute rejection and 5 or 7 days after infection. The serum sHLA-I levels can be used as a parameter for monitoring acute rejection and infection in renal transplantation.


Effects of acute mental stress and exercise on inflammatory markers in patients with coronary artery disease and healthy controls.
Physical and mental stressors result in increased inflammation markers in populations free of coronary artery disease (CAD). However, inflammatory responses to mental and exercise challenges have not been established in patients with CAD. This study investigated the responses of inflammatory markers, including C-reactive protein (CRP), interleukin-6 (IL-6), and soluble intercellular adhesion molecule-1, in patients with CAD after successful elective percutaneous coronary intervention (n = 36, 59 +/- 8 years of age, 33% women) and healthy controls without a history of CAD (n = 28, 54 +/- 10 years of age, 36% women). Increases in inflammatory markers were examined in response to mental challenge tasks (anger recall and mental arithmetic) and treadmill exercise. Stress echocardiography was used to rule out stress-induced ischemia as a possible confounding factor. Results showed that CRP increased significantly to mental challenge and exercise (p values <0.01), and CRP responses were higher in patients with CAD than in controls (change in mental arithmetic 0.19 +/- 0.11 vs 0.01 +/- 0.03 mg/L, p = 0.003; change in exercise 0.57 +/- 0.11 vs 0.08 +/- 0.0.03 mg/L, p = 0.001). Increased norepinephrine responses were related to larger CRP and IL-6 increases to mental challenge tasks (p values <0.05). Exercise elicited increased CRP, IL-6, and soluble intercellular adhesion molecule-1 levels (p values <0.01), and these responses were larger than with mental challenge tasks (p values <0.05). In conclusion, mental stress and exercise induce increased levels of inflammatory markers in patients with CAD. These stress-induced increases are larger than in healthy subjects, occur in the absence of myocardial ischemia, and are related to the neurohormonal stress response.


A comparative analysis of core needle biopsy and final excision for breast cancer: histology and marker expression.
Core needle biopsy (CNB) is used increasingly not only to diagnose breast cancer, but to determine tumor histology, grade and marker expression, select neoadjuvant therapy, and predict sentinel lymph node status. Thus, we undertook this study to evaluate the accuracy of CNB as a predictor of breast cancer histology and marker expression. We identified 209 Breast Cancer Registry cases with a preoperative CNB and reviewed all clinicopathologic data for accuracy. Statistical analysis was performed with statistical software. CNB unequivocally showed cancer in 93%. Exact tumor histology concordance was 86%. Ductal carcinoma in situ on CNB was upgraded to invasive cancer in 23%. Concordance was substantial for estrogen receptor expression (88%, κ = .71), but kappa values were less than .6 for tumor grade, mitotic rate, progesterone receptor (PR), Ki-67, HER-2/neu, and p53 expression. Reliance on CNB grade and marker expression for critical decision making may be inadvisable. Further study is warranted to optimize breast cancer patient care.


The effect of music therapy during shockwave lithotripsy on patient relaxation, anxiety, and pain perception.
To research the effect of listening to music during shock wave lithotripsy (SWL) on the patient's pain control, anxiety levels, and satisfaction. The study comprised 400 patients from three hospitals. Half of patients listened to music during their first SWL session but not during their second session. The other half had no music for the first session but the second session was accompanied by music. During all sessions, with and without music, pulse rates, blood pressure, State-Trait Anxiety Inventory-State Anxiety scores (STAI-SA), Visual Analog Scale (VAS scores for pain), willingness to repeat procedure (0 = never to 4 happily), and patient satisfaction rates (0 = poor to 4 = excellent) were assessed. There was no statistical difference between the two groups in terms of blood pressure and pulse rates. In both groups, the STAI-SA and VAS pain scores were lower in the session when music was listened to (p < 0.001). The patients requested more SWL treatment be completed while listening to music and their satisfaction was greater. Music lowered the anxiety and pain scores of patients during SWL and provided greater satisfaction with treatment. Completing this procedure while the patient listens to music increases patient compliance greatly and reduces analgesic requirements.


Purification of mouse haptoglobin by antibody affinity chromatography and development of an ELISA to measure serum haptoglobin levels.
Mouse haptoglobin was isolated from acute-phase serum initially by affinity chromatography on haemoglobin-Sepharose. This proved inefficient, but sufficient material was obtained for use as an immunogen. Rabbit anti-haptoglobin antibodies were used as immunoabsorbents to isolate larger quantities of haptoglobin. Subsequently, specific anti-haptoglobin antibodies were prepared by affinity chromatography on haptoglobin-Sepharose. A direct sandwich ELISA for mouse serum haptoglobin was developed, using affinity purified reagents. The working range of the haptoglobin standard curve was 0.02-0.5 microgram/ml. The reagents did not cross-react with albumin or haemoglobin and the antibody also recognised rat haptoglobin.


No news is good news? Three-year postdischarge mortality of octogenarian and nonagenarian patients following emergency general surgery.
Outcome data on the very elderly patients undergoing emergency general surgery (EGS) are sparse. We sought to examine short- and long-term mortality in the 80 plus years population following EGS. Using our institutional 2008-2018 EGS Database, all the 80 plus years patients undergoing EGS were identified. The data were linked to the Social Security Death Index to determine cumulative mortality rates up to 3 years after discharge. Univariate and multivariable logistic regression analyses were used to determine predictors of in-hospital and 1-year cumulative mortality. A total of 385 patients were included with a mean age of 84 years; 54% were female. The two most common comorbidities were hypertension (76.1%) and cardiovascular disease (40.5%). The most common procedures performed were colectomy (20.0%), small bowel resection (18.2%), and exploratory laparotomy for other procedures (15.3%; e.g., internal hernia, perforated peptic ulcer). The overall in-hospital mortality was 18.7%. Cumulative mortality rates at 1, 2, and 3 years after discharge were 34.3%, 40.5%, and 43.4%, respectively. The EGS procedure associated with the highest 1-year mortality was colectomy (49.4%). Although hypertension, renal failure, hypoalbuminemia, hyperbilirubinemia, and elevated liver enzymes predicted in-hospital mortality, the only independent predictors of cumulative 1-year mortality were hypoalbuminemia (odds ratio, 2.17; 95% confidence interval, 1.10-4.27; p = 0.025) and elevated serum glutamic pyruvic transaminase (SGOT) level (odds ratio, 2.56; 95% confidence interval, 1.09-4.70; p = 0.029) at initial presentation. Patients with both factors had a cumulative 1-year mortality rate of 75.0%. More than half of the very elderly patients undergoing major EGS were still alive at 3 years postdischarge. The combination of hypoalbuminemia and elevated liver enzymes predicted the highest 1-year mortality. Such information can prove useful for patient and family counseling preoperatively. Prognostic, Level III.


Eczema: quality of life by body site and the effect of patch testing.
Patients with dermatitis are known to have impaired quality of life. Whether this varies according to body site has not been evaluated. Patch tests have previously been shown to influence quality of life, although no previous studies have shown if this is dependent on the results of the patch tests. To evaluate the impact of patch testing on quality of life according to the outcome of the investigations and to determine how quality of life varies according to eczema body site. One hundred and sixty consecutive adult patients with active eczema were selected from a patch test clinic for inclusion into the study. Quality of life was determined using the Dermatology Life Quality Index (DLQI) and the SF-36, prior to patch testing and 2 months later. Perceived eczema severity at each time point was also noted, along with the outcome of patch testing. Baseline comparison of quality of life was performed between four body site groups (face, hand, generalized, other). Patients confirmed as having relevant positive contact allergens were shown to have a significant improvement in both perceived eczema severity (P = 0.0004) and DLQI score (P = 0.0015) at 2 months after patch testing. No significant changes were noted in the SF-36 score, other than a borderline improvement in the pain score (P = 0.048). The improvement in quality of life and eczema severity was not noted in patients with negative patch tests. Eighty-nine per cent of patients diagnosed as having contact allergy were able to comply with avoidance advice. No significant variation was noted in quality of life according to body site affected by eczema. There was a positive correlation between DLQI score and perceived eczema severity (P < 0.0001). Patients confirmed as having contact allergy show a subsequent improvement in eczema severity and an improvement in quality of life.


A previously unrecognised hydronium di-cation in the crystal structure of a cucurbituril derivative.
Examination of the crystal structure of the adduct of hydronium tetrachloroferrate dichloride with cucurbituril resulted in the discovery that the hydronium cation present therein is not the well known H7O3+ species; rather, it is an unprecedented cyclic species of composition (H14O6)2+, templated by the formation of five hydrogen bonds to cucurbituril.


Drill wear monitoring in cortical bone drilling.
Medical drills are subject to intensive wear due to mechanical factors which occur during the bone drilling process, and potential thermal and chemical factors related to the sterilisation process. Intensive wear increases friction between the drill and the surrounding bone tissue, resulting in higher drilling temperatures and cutting forces. Therefore, the goal of this experimental research was to develop a drill wear classification model based on multi-sensor approach and artificial neural network algorithm. A required set of tool wear features were extracted from the following three types of signals: cutting forces, servomotor drive currents and acoustic emission. Their capacity to classify precisely one of three predefined drill wear levels has been established using a pattern recognition type of the Radial Basis Function Neural Network algorithm. Experiments were performed on a custom-made test bed system using fresh bovine bones and standard medical drills. Results have shown high classification success rate, together with the model robustness and insensitivity to variations of bone mechanical properties. Features extracted from acoustic emission and servomotor drive signals achieved the highest precision in drill wear level classification (92.8%), thus indicating their potential in the design of a new type of medical drilling machine with process monitoring capabilities.


Large abdominoscrotal hydrocele: Uncommon surgical entity.
An abdominoscrotal hydrocele (ASH) consists of a large inguinoscrotal hydrocele which communicates in an hour glass fashion with a large "intraabdominal component". Mostly affects single testis but very rarely can present bilaterally. We are presenting here a young 25 year old patient with large right sided scrotal swelling encroaching over lower abdomen. Clinically it was abdominoscrotal hydrocele which was confirmed with CT abdomen and later on subjected for surgery. Abdominoscrotal hydrocele is rarest type of hydrocele; first described by Dupuytren. The etiology of ASH is unknown; however, different theories have been described in literature to explain the pathogenesis. Diagnosis of ASH is done by clinical examination and is confirmed by radiological examination. Though ultrasonography is the first choice, in few selected cases contrast enhanced computerized tomography or magnetic resonant imaging may be helpful for more anatomical delineation. It may present with various complications secondary to pressure exerted by the components of the ASH. Surgical excision of the sac is the only definitive treatment option. There is no role of conservative treatment. Sometimes, decompression of the cyst needed to ease the dissection of the sac. Abdominoscrotal hydrocele differential should be considered while dealing with large lower abdominal swelling along with scrotal swelling.


Symmetrical "mirror-image" injuries and the "chessboard" pattern: useful markers of self-mutilation.
The evaluation of injuries due to self-mutilation may be complicated by atypical lesions and fabricated histories of the causative events. Four cases are described where one of the most striking findings was the presence of "mirror-image" injuries and/or a "chessboard" pattern of intersecting parallel lines from self-inflicted incised wounds. Case 1: A 32-year-old man was dead in his burnt-out car, with symmetrical, "mirror-image", circular burns from the car cigarette lighter over his forehead, cheeks, ears, upper and lower arms, the dorsal and palmar aspects of the hands, the anterior chest wall including the nipples, the anterior abdomen, thighs, lower legs, and the back of his neck. The deceased had a history of psychotic depression and had died of burns and inhalation of products of combustion. Case 2: A 19-year-old woman who fabricated a history of assault demonstrated multiple, superficial, "mirror-image" injuries of her thighs and forearms. Case 3: A 32-year-old man who exsanguinated from cut wrists showed multiple, superficial, and "mirror-image" incised wounds of the wrists, with a "chessboard" pattern. Case 4: A 26-year-old man died after jumping from a building. He had multiple superficial, "mirror-image" incised wounds of his anterior chest and thighs, with a typical "chessboard" pattern. Given the difficulties that sometimes arise in determining whether injuries have been self-inflicted or not, the finding of symmetrical "mirror-image" injuries, and/or a "chessboard" pattern formed by 2 groups of regular, parallel, superficial incised wounds running at right angles to each other provides compelling evidence of self-mutilation, unless a plausible alternative explanation is available.


Patterns of injury in hospitalized terrorist victims.
Acts of terror increase the demand for acute care. This article describes the pattern of injury of terror victims hospitalized at 9 acute-care hospitals in Israel during a 15-month period of terrorism. To characterize patients hospitalized as a result of terror injuries, we compared terror casualties with other injuries regarding severity, outcome, and service utilization. Using data from the National Trauma Registry, characteristics of casualties are portrayed. During the study period, 23,048 patients were recorded, 561 of them (2.4%) were injured through terrorist acts. Seventy percent were younger than 29 years. Seventy-five percent were males. Thirteen percent of terror victims compared with 3% with other traumatic injuries, arrived by helicopter. Injury mechanism consisted mainly of explosions (n = 269, 48%) and gunshot injuries (n = 266, 47%). One third of the population experienced severe trauma (Injury Severity Score > or = 16). One hundred-forty-two patients (26%) needed to be admitted to the intensive-care unit. Inpatient mortality was 6% (n = 35). Fifty-five percent of the injuries (n = 306) included open wounds and 31% (n = 172) involved internal injuries; 39% (n = 221) sustained fractures. Half of the patients had a procedure in the operating room (n = 298). Duration of hospitalization was longer than 2 weeks for nearly 20% of the population. Injuries from terrorist acts are severe and impose a burden on the healthcare system. Further studies of the special injury pattern associated with terror are necessary to enhance secondary management and tertiary prevention when occurring.


Water Mobility in the Interfacial Liquid Layer of Ice/Clay Nanocomposites.
At solid/ice interfaces, a premelting layer is formed at temperatures below the melting point of bulk water. However, the structural and dynamic properties within the premelting layer have been a topic of intense debate. Herein, we determined the translational diffusion coefficient Dt of water in ice/clay nanocomposites serving as model systems for permafrost by quasi-elastic neutron scattering. Below the bulk melting point, a rapid decrease of Dt is found for charged hydrophilic vermiculite, uncharged hydrophilic kaolin, and more hydrophobic talc, reaching plateau values below -4 °C. At this temperature, Dt in the premelting layer is reduced up to a factor of two compared to supercooled bulk water. Adjacent to charged vermiculite the lowest water mobility was observed, followed by kaolin and the more hydrophobic talc. Results are explained by the intermolecular water interactions with different clay surfaces and interfacial segregation of the low-density liquid water (LDL) component.


Comparative transcriptomics of cyprinid minnows and carp in a common wild setting: a resource for ecological genomics in freshwater communities.
Comparative transcriptomics can now be conducted on organisms in natural settings, which has greatly enhanced understanding of genome-environment interactions. Here, we demonstrate the utility and potential pitfalls of comparative transcriptomics of wild organisms, with an example from three cyprinid fish species (Teleostei:Cypriniformes). We present extensively filtered and annotated transcriptome assemblies that provide a valuable resource for studies of genome evolution (e.g. polyploidy), ecological and morphological diversification, speciation, and shared and unique responses to environmental variation in cyprinid fishes. Our results and analyses address the following points: (i) 'essential developmental genes' are shown to be ubiquitously expressed in a diverse suite of tissues across later ontogenetic stages (i.e. juveniles and adults), making these genes are useful for assessing the quality of transcriptome assemblies, (ii) the influence of microbiomes and other exogenous DNA, (iii) potentially novel, species-specific genes, and (iv) genomic rearrangements (e.g. whole genome duplication). The data we present provide a resource for future comparative work in cypriniform fishes and other taxa across a variety of sub-disciplines, including stress response, morphological diversification, community ecology, ecotoxicology, and climate change.


Just noticeable inhomogeneity criterion for determining wavelength discrimination functions.
The visual criterion of just noticeable inhomogeneity is described for determining wavelength discrimination functions. It involved determining the wavelength differences between reference and test fields required to produce a just noticeable inhomogeneity which cannot be eliminated by a brightness adjustment. The fields formed a checkerboard pattern the element size of which variable. Tritanopic delta lambda functions were obtained by using the small field insensitivity of the fovea. Just noticeable border, data obtained from bipartite field studies, were replicated with this checkerboard field.


Submental lymph node metastasis from invasive ductal breast carcinoma.
This case report presents a 52-year-old woman with a submental swelling which arose 3 years after wide local excision and axillary lymphadenectomy for breast carcinoma. Histopathological examination after excision biopsy of this lesion confirmed the presence of invasive breast carcinoma in a submental lymph node. Computed tomography of the head, neck, thorax, abdomen and pelvis demonstrated multiple brain and pulmonary metastases. Further management was palliative and the patient died 5 months later. This is the first description of a breast carcinoma metastasising to the submental region. Metastatic breast carcinoma should be considered in the differential diagnosis of head and neck lymphadenopathy in patients with previously diagnosed breast carcinoma.


Effect of specific chemotherapy on the immune response and resistance to reinfection in experimental Schistosomiasis mansoni.
Mice infected for 45 days with 120 Schistosoma mansoni cercariae and treated with praziquantel in a dose of 500 mg/kg for two consecutive days had a significant lower resistance to reinfection when challenged two weeks after treatment (45% compared to 88% in infected challenged untreated mice). In praziquantel-treated mice, the reduction in the per cent resistance was accompanied by a diminution in the size of hepatic granulomata and its in vivo correlate the delayed foot pad swelling. Moreover, the granuloma proportionate T-cell subset enumeration revealed a significant reduction in the number of T-helper cells. The humoral immune response as measured by the immediate foot pad swelling was not affected by praziquantel. Results reveal besides the diminution of the state in resistance to reinfection after praziquantel, possible involvement of egg-related pathology as a T-cell mediated reaction and as a mechanical obstacle in maintenance of this resistance.


Cognitive treatment of post-traumatic stress disorder in the elderly. A longitudinal study.
This article aims to verify whether a cognitive treatment of post-traumatic stress disorder (PTSD) by cognitive behavioural therapy (CBT) adapted to elderly subjects can lead to long-term improvement in symptomatology and quality of life. We present a longitudinal study of 32 subjects over the age of 65 years, with no cognitive impairment or mild impairment, residing in two nursing homes. We compare a target group (n=16) with PTSD treated with 20 CBT sessions and a control group (n=16) with PTSD without symptom treatment. The two groups are compared in four stages: (T1) before treatment of the target group's PTSD, (T2) after treatment of PTSD, (T3) after six months of follow-up and (T4) after 18 months of follow-up. The absence of cognitive impairment is verified with the MMSE. The evolution of PTSD is monitored with the CAPS. The evolution of the quality of life of the subjects in the target group is verified with the ADRQL. If both groups show elevated PTSD symptoms at the beginning of the study (T1), the signs of PTSD disappear for the target group at the end of treatment (T2) at the same time as quality of life improves (scores more than doubled). These improvements continue for more than 18 months (T4). Conversely, the control group retains high PTSD symptoms, without significant decrease over time. The treatment of PTSD by cognitive-behavioural therapy adapted to elderly people without cognitive impairment, or with mild cognitive or memory disorders, allows for a lasting disappearance of symptoms and an improvement in quality of life.


The Swr1 chromatin-remodeling complex prevents genome instability induced by replication fork progression defects.
Genome instability is associated with tumorigenesis. Here, we identify a role for the histone Htz1, which is deposited by the Swr1 chromatin-remodeling complex (SWR-C), in preventing genome instability in the absence of the replication fork/replication checkpoint proteins Mrc1, Csm3, or Tof1. When combined with deletion of SWR1 or HTZ1, deletion of MRC1, CSM3, or TOF1 or a replication-defective mrc1 mutation causes synergistic increases in gross chromosomal rearrangement (GCR) rates, accumulation of a broad spectrum of GCRs, and hypersensitivity to replication stress. The double mutants have severe replication defects and accumulate aberrant replication intermediates. None of the individual mutations cause large increases in GCR rates; however, defects in MRC1, CSM3 or TOF1 cause activation of the DNA damage checkpoint and replication defects. We propose a model in which Htz1 deposition and retention in chromatin prevents transiently stalled replication forks that occur in mrc1, tof1, or csm3 mutants from being converted to DNA double-strand breaks that trigger genome instability.


On Estimation of Optimal Treatment Regimes For Maximizing t-Year Survival Probability.
A treatment regime is a deterministic function that dictates personalized treatment based on patients' individual prognostic information. There is increasing interest in finding optimal treatment regimes, which determine treatment at one or more treatment decision points so as to maximize expected long-term clinical outcome, where larger outcomes are preferred. For chronic diseases such as cancer or HIV infection, survival time is often the outcome of interest, and the goal is to select treatment to maximize survival probability. We propose two nonparametric estimators for the survival function of patients following a given treatment regime involving one or more decisions, i.e., the so-called value. Based on data from a clinical or observational study, we estimate an optimal regime by maximizing these estimators for the value over a prespecified class of regimes. Because the value function is very jagged, we introduce kernel smoothing within the estimator to improve performance. Asymptotic properties of the proposed estimators of value functions are established under suitable regularity conditions, and simulations studies evaluate the finite-sample performance of the proposed regime estimators. The methods are illustrated by application to data from an AIDS clinical trial.


Perkinsus olseni and P. chesapeaki detected in a survey of perkinsosis of various clam species in Galicia (NW Spain) using PCR-DGGE as a screening tool.
A survey on perkinsosis was performed involving 15 locations scattered along the Galician coast (NW Spain) and four clam species with high market value (Ruditapes decussatus, Ruditapes philippinarum, Venerupis corrugata and Polititapes rhomboides). The prevalence of Perkinsus parasites was estimated by PCR using genus-specific primers. The highest percentage of PCR-positive cases for perkinsosis corresponded to clams R. decussatus and V. corrugata, while lower values were detected in R. philippinarum and no case was found in P. rhomboides. The discrimination of Perkinsus species was performed by PCR-RFLP and by a new PCR-DGGE method developed in this study. Perkinsus olseni was identified in every clam species, except in P. rhomboides, using both PCR-DGGE and PCR-RFLP. Additionally, Perkinsus chesapeaki was only detected by PCR-DGGE infecting two Manila clams R. philippinarum from the same location, reporting the first case in Galicia. P. chesapeaki identification was further confirmed by in situ hybridisation assay and phylogenetic analysis of ITS region and LSU rDNA.


Relationship between cutaneous allergen response and airway allergen-induced eosinophilia.
Determinants of changes in airway caliber after allergen challenge include nonallergic airway responsiveness, immune response and dose of allergen given. However, determinants of the airway inflammatory response to allergens remain to be determined. To assess the relationship between skin reactivity to airborne allergens and lower airway eosinophilic response to allergen exposure in asthma and allergic rhinitis. Forty-two subjects with mild allergic asthma (mean age 24 years) and 14 nonasthmatic subjects with allergic rhinitis (mean age 25 years) had allergen skin prick tests and titration with the allergen chosen for subsequent challenge. On a second visit, 31 asthmatic subjects had a conventional challenge while 11 asthmatic subjects and all rhinitic subjects had a low-dose allergen challenge over four subsequent days. Induced sputum samples were obtained at 6 and 24 h after the conventional challenge and at days 2 and 4 of the low-dose challenge. In the asthmatic group, there was a weak correlation between wheal diameter induced by the concentration used for challenge and increase in eosinophils 6 h postconventional challenge (r = 0.372, P = 0.05), but no correlation was observed following the low-dose challenge. Rhinitic subjects showed a correlation between wheal diameter with the allergen dose used for bronchoprovocation and increase in eosinophils at day 2 of low dose (r = 0.608, P = 0.02). This study suggests that immediate immune responsiveness to allergen, assessed by the magnitude of the skin response, is a significant determinant of allergen-induced airway eosinophilia and can help to predict the airway inflammatory response.


Malignant risk stratification of thyroid FNA specimens with indeterminate cytology based on molecular testing.
Fine-needle aspiration (FNA) has been employed for many years for examining thyroid nodules, and the cytology of aspirates is the primary determinant for whether thyroidectomy is indicated. Fifteen to thirty percent of thyroid nodules, not being clearly benign or malignant, fall into an indeterminate category. The main goals of molecular diagnostics for thyroid nodules are to prevent unnecessary surgery in patients with benign nodules and to stop patients with malignant nodules from being subjected to repeated operations. This study was designed to evaluate the diagnostic utility of 4 markers in thyroid FNA cytology via testing for the BRAF V600E mutation and the expression of microRNA-221, microRNA-222, and galectin-3 protein in FNA samples with indeterminate cytology. A predictor model distinguishing benign samples from malignant samples on the basis of the 4 aforementioned markers was formulated. This decision model provided a sensitivity of 73.5%, a specificity of 89.8%, and a diagnostic accuracy of 75.7%. The positive predictive value was 80.6%, and the negative predictive value was 85.5%; this suggested that the prediction had good reliability. One hundred twenty FNA samples were examined, and 62 nodules were classified as benign with the proposed diagnostic algorithm. This resulted in a reduction of the initial 120 patients to 58 and thus decreased by half the number of persons undergoing surgery.


Press perturbations of microplastics and antibiotics on freshwater micro-ecosystem: Case study for the ecological restoration of submerged plants.
Microplastics (MPs) can adsorb antibiotics to form complex pollutants, which seriously threatens the health of freshwater ecosystems. Few studies have examined the combined pollution characteristics of microplastics (MPs) and antibiotics in restored freshwater ecosystems and their effects on the growth traits of the aquatic primary producers. We studied both the ecotoxicological effects of polyethylene (PE) MPs and the antibiotics sulfanilamide (sulfa, SA) on the structural (diversity etc.,) and functional (nutrient cycling etc.,) properties of water-plant-sediment ecosystems. The synergistic toxic effects of PE and SA resulted in a reduction in the chlorophyll content and chloroplast fluorescence. Meanwhile, PE and SA single/combined pollution stress inhibits the radial oxygen loss in roots, and activates the antioxidant defense system in leaves. The change in the growth response characteristics of Vallisneria natans (V. natans) under oxidative stress induced by single/combined pollution showed a dosage effect. The microbial compositions of the overlying water and sediment were significantly changed by the pollution exposure, as evidenced by the increased microbial diversity and altered microbial taxa distribution. An increase in the total concentrations of sulfa in the overlying water was accompanied by an increase in the relative abundances of resistance genes. PE-MPs significantly affected the removal of total nitrogen and antibiotics from the overlying water. The interaction between PE and SA affects ammonia and nitrite nitrogen exchange in water-sediment systems. Thus, this study investigated the effects of combined MP and antibiotics pollution on the growth state, metabolic function, microbial community structure and microbial diversity of the freshwater ecosystems. The mechanism underlying of the combined polyethylene-sulfanilamide (PE-SA) effect on the V. natans was revealed. In addition, the correlation between different environmental factors was analyzed, and a structural equation model was constructed. This study provides primary data for evaluating the ecological and environmental effects of combined PE-SA pollution and its possible risks. Moreover, it provides a reference index for the study of ecological wetland environments and phytoremediation.


Silsesquioxane organofunctionalized with 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole: Preparation and subsequent reaction with silver and potassium hexacyanoferrate(III) for detection of L-cysteine.
The octakis(3-chloropropyl)octasilsesquioxane (SS) was organofunctionalized with 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole (Purpald). The functionalized silsesquioxane with Purpald (SP) was characterized by Fourier transform infrared spectroscopy (FT-IR), and nuclear magnetic resonance (NMR). After functionalized, silsesquioxane can interact with silver nitrate and subsequently with potassium hexacyanoferrate (III) (AgHSP). The novel hybrid composite formed (AgHSP) was characterized by Fourier transform infrared spectra, scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDX). AgHSP was electrochemically characterized by cyclic voltammetry (CV) using graphite paste electrode. The AgHSP incorporated into a graphite paste electrode (20% w/w) was tested for detection of l-cysteine. The modified electrode showed a linear response from 9.0 × 10(-5) to 5.0 × 10(-3)mol L(-1) with the corresponding equation Y(A)=0.01315+1.865 [l-cysteine], and a correlation coefficient of r(2)=0.9995. The method showed a detection limit of 1.76×10(-4)mol L(-1) with a relative standard deviation of ± 2% (n=3) and amperometric sensitivity of 1.865 A/mol L(-1).


Use of the Menstrual Cycle to Enhance Female Sports Performance and Decrease Sports-Related Injury.
The impact of the menstrual cycle on female sports performance is a growing interest area in sports and athletics. In March 2017, the British Journal of Sports Medicine, published the article, "Sport, Exercise and the Menstrual Cycle: Where is the Research?", highlighting the significant under-representation of women included in sport and exercise medicine research studies. Dr. Georgie Bruinvels, a research scientist, is focused primarily on menstruation in female athletes and use of the menstrual cycle to optimize training and performance, while decreasing injury. Bruinvels, states, "There is a body of research emerging that highlights that strength training is more advantageous in the first half of the menstrual cycle because the body adapts and recovers better. Pediatric and Adolescent Gynecology has a place in this emerging interest area, given our level of expertise in menstruation, female physiology and the often-avoided female pubertal physiology.


The accuracy of virtual setup in simulating treatment outcomes in orthodontic practice: a systematic review.
To evaluate the accuracy of virtual orthodontic setup in simulating treatment outcomes and to determine whether virtual setup should be used in orthodontic practice and education. A systematic search was performed in five electronic databases: PubMed, Scopus, Embase, ProQuest Dissertations & Theses Global, and Google Scholar from January 2000 to November 2022 to identify all potentially relevant evidence. The reference lists of identified articles were also screened for relevant literature. The last search was conducted on 30 November 2022. This systematic review included twenty-one articles, where all of them were assessed as moderate risk of bias. The extracted data were categorized into three groups, which were: (1) Virtual setup and manual setup; (2) Virtual setup and actual outcomes in clear aligner treatment; (3) Virtual setup and actual outcomes in fixed appliance treatment. There appeared to be statistically significant differences between virtual setups and actual treatment outcomes, however the discrepancies were clinically acceptable. This systematic review supports the use of orthodontic virtual setups, and therefore they should be implemented in orthodontic practice and education with clinically acceptable accuracy. However, high-quality research should be required to confirm the accuracy of virtual setups in simulating treatment outcomes.


Involvement of IL-10 in peroxisome proliferator-activated receptor gamma-mediated anti-inflammatory response in asthma.
Peroxisome proliferator-activated receptor gamma (PPARgamma) plays an important role in controlling immune and inflammatory responses. Recent studies have demonstrated that activation of PPARgamma reduces airway hyper-responsiveness and activation of eosinophils that are increased by induction of asthma. We have used a mouse model of asthma to determine the role of PPARgamma in the regulation of the pulmonary immune response, more specifically in the involvement of immunoregulatory cytokine interleukin (IL)-10. Administration of PPARgamma agonists or adenovirus carrying PPARgamma cDNA (AdPPARgamma) reduced eosinophilic airway inflammation and airway hyper-responsiveness. Expression of PPARgamma was increased by ovalbumin inhalation, and the increase was further enhanced by the administration of PPARgamma agonists or AdPPARgamma. The increased IL-10 levels in lung tissues after ovalbumin inhalation were further increased by the administration of rosiglitazone, pioglitazone, or AdPPARgamma. Levels of IL-4, IL-5, and ovalbumin-specific IgE were also increased after ovalbumin inhalation, and the increased levels were significantly reduced by the administration of the PPARgamma agonists or AdPPARgamma. The results also showed that inhibition of IL-10 activity with anti-IL-10 receptor antibody partially restored the inflammation. These findings suggest that a protective role of PPARgamma in the pathogenesis of the asthma is partly mediated through an IL-10-dependent mechanism.


Fear Over Facts: When Fellow Clinicians Become a Barrier to Dissemination of Exposure and Response Prevention for Obsessive-Compulsive Disorder-A Clinical Response to Licensing Board Investigation of Exposure and Response Prevention.
In 2018, a graduate level student filed a complaint regarding the use of exposure-based therapy for persons with obsessive-compulsive disorder (OCD) experiencing violent obsessions. In the investigation, the licensing board expressed concern about safety of us of exposure and response prevention (ERP) with children and in public venues. The licensing board also struggled with accurate assessment of a clinician's efficacy in following the gold-standard treatment for OCD. Despite extensive research demonstrating ERP is a safe, effective treatment for OCD, stigma against exposure based treatments remain strong, even among clinicians. This commentary article discusses the specific licensing investigation and implications for change throughout the field of psychotherapy.


Discursive junctions in flood risk governance - A comparative understanding in six European countries.
Flood risks are managed differently across Europe. While a number of research studies aim to understand these differences, they tend to pay little attention to the social constructionist aspects of flood risk governance, i.e. the meaning that societies give to flood risk and governance. This paper aims to address this gap by understanding differences in flood risk management approaches (FRMA) from a discursive-institutional perspective. Based on this perspective, an analytical framework was developed to systematically analyse and compare discourses pertaining to flood risk and its governance in six European member states (England (the United Kingdom), Flanders (Belgium), France, the Netherlands, Poland and Sweden). Correspondingly, this paper demonstrates how the hegemonic discursive-institutional patterns of flood risk governance differ between the six European countries. These differences may influence the capability of countries to learn from each other, adopt new FRMAs or cooperate with each other. Moreover, the paper argues that differences in discourses partially account for the differences in FRMAs between countries, combined with other factors. Additionally, broader implications are discussed. For example, the research findings imply that some discourses tend to favour or disfavour other discourses, and that they additionally also tend to favour particular FRMAs; e.g. the flood risk discourse pertaining to high manageability of risks seems to favour a governance discourse of collectivity and central governance. The different insights imply that further research is necessary to understand the complex interaction of discourses and institutional arrangements.


Treatment Differences for Adrenocortical Carcinoma by Race and Insurance Status.
To determine if treatment and clinical outcomes of adrenocortical carcinoma (ACC) vary by race and insurance status. ACC patients from the National Cancer Database (2004-2017) were reviewed. Race was defined as White versus minority (Black and Hispanic). Insurance types were private (PI) versus other (Medicaid/uninsured/unknown). Metastatic ACC (M-ACC) was defined as distant metastases at the time of diagnosis; nonmetastatic ACC (NM-ACC) patient had no distant disease. Of 2351 NM-ACC patients, 83.6% were White and 16.4% minority. There were 1216 M-ACC patients, with 80.3% White and 19.8% minority. Both White NM-ACC and M-ACC patients had more PI (each P < 0.001). PI NM-ACC was associated with a shorter duration from diagnosis to first treatment (14 versus 18 d, P = 0.005). Both NM-ACC and M-ACC with PI were more likely to receive surgery (92.6% versus 86.9%, P = 0.001 and 35.4% versus 27%, P = 0.02) and to receive surgery sooner (13 versus 16 d, P = 0.03). M-ACC with PI were more likely to receive chemotherapy (63.6% versus 54.3%, P = 0.01) and to have lymph nodes examined (14.8% versus 8.6%, P = 0.02). Length of stay postoperatively was shorter for White NM-ACC (6 versus 7 d, P = 0.04) and M-ACC (8 versus 17 d, P = 0.02). For NM-ACC and M-ACC, the 30-d readmission, 90-d mortality, and overall survival were similar by race. A multivariable analysis showed minorities (OR 0.69, 95% confidence interval 0.54-0.88, P = 0.003) and patients without PI (OR 0.75, 95% confidence interval 0.58-0.97, P = 0.03) were less likely to have surgery. However, a multivariable analysis showed survival was similar for White versus minority patients and PI versus other. White NM-ACC or M-ACC and PI were more likely to receive surgery and timely multimodality care. These disparities were not associated with differences in 90-d mortality or overall survival.


Insulin-dependent diabetes mellitus associated with Graves' disease and idiopathic hypoparathyroidism.
We report a case of 26-year-old woman with Graves' disease and idiopathic hypoparathyroidism diagnosed at 11 years of age, who subsequently developed insulin-dependent diabetes mellitus (IDDM) at 17 years of age. Treatment with antithyroid agents had failed to control her Graves' disease and her IDDM was unmanageable despite insulin therapy. Surgical intervention was carried out, resulting in an improvement of both her hyperthyroidism and IDDM. This case is the first report of polyglandular autoimmune (PGA) syndrome, presenting the association of IDDM, Graves' disease and idiopathic hypoparathyroidism.


A Coupled SD and CLUE-S Model for Exploring the Impact of Land Use Change on Ecosystem Service Value: A Case Study in Baoshan District, Shanghai, China.
Most of the cities in developing countries are experiencing rapid urbanization. Land use change driven by urban sprawl, population growth, and intensified socio-economic activities have led to a steep decline of ecosystem service value (ESV) in rapid urbanization areas, and decision-makers often ignore some valuable ecosystem service functions and values in land use planning. In this paper, we attempt to build a modeling framework which integrated System Dynamics model with Conversion of Land Use and its Effects at Small Extent model to simulate the dynamics of ESV of landscape and explore the potential impacts of land use change on ESV. We take Baoshan district of Shanghai as an example which is a fast urbanization area of metropolitan in China. The results of the study indicate that: (1) The integrated methodology can improve the characterization and presentation of the dynamics of ESV, which may give insight into understanding the possible impacts of land use change on ESV and provide information for land use planning. (2) Land use polices can affect the magnitude and location of ESV both directly and indirectly. Land use changes tend to weaken and simplify ecosystem service functions and values of landscape at urban rural fringe where land use change is more intensive. (3) The application of the methodology has proved that the integration of currently existing models within a single modeling framework could be a beneficial exploration, and should be encouraged and enhanced in the future research on the changing dynamics of ESV due to the complexity of ecosystem services and land use system.


A clinicians' review of the respiratory microbiome.
The respiratory microbiome and its impact in health and disease is now well characterised. With the development of next-generation sequencing and the use of other techniques such as metabolomics, the functional impact of microorganisms in different host environments can be elucidated. It is now clear that the respiratory microbiome plays an important role in respiratory disease. In some diseases, such as bronchiectasis, examination of the microbiome can even be used to identify patients at higher risk of poor outcomes. Furthermore, the microbiome can aid in phenotyping. Finally, development of multi-omic analysis has revealed interactions between the host and microbiome in some conditions. This review, although not exhaustive, aims to outline how the microbiome is investigated, the healthy respiratory microbiome and its role in respiratory disease. To define the respiratory microbiome and describe its analysis.To outline the respiratory microbiome in health and disease.To describe future directions for microbiome research.


Contemporary epidemiological data of Rift Valley fever virus in humans, mosquitoes and other animal species in Africa: A systematic review and meta-analysis.
Rift Valley fever (RVF) is a severe zoonotic mosquito-borne disease that represents an important threat to human and animal health, with major public health and socioeconomic impacts. This disease is endemic throughout many African countries and the Arabian Peninsula. This systematic review with meta-analysis was conducted to determine the RVF prevalence in humans, mosquitoes and other animal species in Africa. The review also provides contemporary data on RVF case fatality rate (CFR) in humans. In this systematic review with meta-analysis, a comprehensive literature search was conducted on the PubMed, Embase, Web of Science and Global Index Medicus databases from January 2000 to June 2022 to identify relevant studies. Pooled CFR and prevalence estimates were calculated using the random-effects model. Subgroup analysis and sensitivity analysis were performed, and the I2 -statistic was used to investigate a potential source of heterogeneity. A total of 205 articles were included in the final analysis. The overall RVF CFR in humans was found to be 27.5% [95% CI = 8.0-52.5]. The overall pooled prevalence was 7.8% [95% CI = 6.2-9.6] in humans and 9.3% [95% CI = 8.1-10.6] in animals, respectively. The RVF prevalence in individual mosquitoes ranged from 0.0% to 25%. Subgroup analysis showed substantial heterogeneity with respect to geographical regions and human categories. The study shows that there is a correspondingly similar prevalence of RVF in human and animals; however, human CFR is much higher than the observed prevalence. The lack of a surveillance programme and the fact that this virus has subclinical circulation in animals and humans could explain these observations. The implementation of a One Health approach for RVF surveillance and control would be of great interest for human and animal health.


T Helper 17 Cells as Pathogenic Drivers of Periodontitis.
T helper 17 (Th17) cells were first described as a T helper subset involved in the pathogenesis of experimental autoimmune inflammation. Since then, these cells have been described as orchestrators of immunopathology in several human inflammatory conditions including psoriasis, rheumatoid arthritis, and inflammatory bowel disease. More recently, the crucial role of Th17 cells in the regulation of immunity and protection of barrier sites has been unveiled. In the present work, we review the available evidence regarding Th17 cells in health and disease with a focus on the oral mucosa and their role in periodontitis pathogenesis. Recent mechanistic studies in animal models have demonstrated that interleukin-17A (IL-17A) and Th17 cells are critical mediators for alveolar bone destruction during periodontal inflammation. Observations in a cohort of patients with naturally occurring impaired Th17 cell differentiation supported these findings. However, interventional studies are needed to conclusively implicate Th17 cells in the immunopathogenesis of human alveolar bone and tissue destruction that characterize periodontitis.


Evaluation of the use of LC-MS in supporting stability studies for preclinical study formulations.
Assessing the short-term stability of drug development candidates in one or more formulations to be used during their preclinical evaluation is a routine, but important, task. Typically, this is based on data generated by HPLC with ultraviolet detection of the species of interest and using methodology specifically developed and validated for the purpose. This work describes a feasibility study conducted into the use of HPLC with mass spectroscopic detection for work of this type. Experimental details and the results of trials with three different drugs, each in a different vehicle, are given. It was concluded that, by using mass spectroscopic detection, a well-defined strategy could be used to generate stability data, which offered advantages in terms of specificity, speed and sensitivity over that typically used.


Molecular imaging of fibroblast activation in multiple non-ischemic cardiomyopathies.
This pilot study is aimed to perform a pilot visualization study to investigate in vivo fibroblast activation in non-ischemic cardiomyopathies by 68Ga-FAPI-04 PET/CT. Twenty-nine consecutive patients with symptomatic non-ischemic cardiomyopathies who underwent 68Ga-FAPI-04 PET/CT were prospectively recruited. Clinical characteristics and echocardiographic parameters were recorded. Cardiac uptake was quantified by standardized uptake values (SUVmax, SUVmean, SUVR) and left ventricular metabolism volume. The relationship between 68Ga-FAPI-04 uptake with clinical and echocardiography parameters was investigated. Heterogeneous 68Ga-FAPI-04 uptake was observed in different subtypes of non-ischemic cardiomyopathies. Twenty-two (75.9%) patients showed elevated 68Ga-FAPI-04 uptake in the left ventricle, and 10 (34.5%) patients also showed slightly diffuse elevated uptake in the right ventricle. Cardiac uptake values were significantly correlated with enlarged ventricular volume evaluated by echocardiography. FAPI PET/CT presents a potential value for in vivo visualization and quantification of fibroblast activation on the molecular level. Further study is warranted for investigating the theranostic and prognostic value of elevated FAP signal.


Outcomes among 3.5 million newly diagnosed hypertensive Canadians.
This population-based study assessed rates of all-cause mortality, myocardial infarction, heart failure, and stroke for up to 12 years of follow-up in 3.5 million Canadian adults newly diagnosed with hypertension. Hypertension cohort, outcomes, and covariates were defined using validated case definitions applied to inpatient and outpatient administrative health databases. Factors associated with each outcome were identified using Cox proportional hazards models. Of 3,531,089 adults newly diagnosed with hypertension and without a previous history of cardiovascular disease, 29.4% were younger than 50 years of age; 48.2% were male, and 17.2% resided in a rural area. Over a median follow-up length of 6.1 years, the crude all-cause mortality rate was 22.4 per 1000 person-years. The incidence of hospitalized myocardial infarction (8.4 per 1000 person-years) and hospitalized heart failure (8.5 per 1000 person-years) was higher than stroke (6.9 per 1000 person-years). The incidence rate for any cardiovascular hospitalization was 19.3 per 1000 person-years. Older age, male sex, lower income, rural residence, and a higher number of Charlson comorbidities were each independently associated with a higher risk of mortality and incident cardiovascular disease hospitalizations. In a nationally-representative incident cohort of hypertensive adults we have demonstrated higher mortality rates and poorer outcomes for the elderly, males, and those living in rural or low income locations. Innovative approaches to the provision of care for these high-risk individuals will lead to improved patient outcomes.


Aberrant expression of HLA-DR antigens on bileduct epithelium in primary biliary cirrhosis: relevance to pathogenesis.
Direct immunofluorescence with an avidinbiotin system was used to investigate the expression of MHC molecules HLA-DR and HLA-A,B,C on bileducts in cryostat sections from 10 primary biliary cirrhosis (PBC) patients. Needle biopsy specimens from 55 patients with various chronic liver disorders, surgical biopsy specimens from 2 patients with recurrent secondary cholangitis, and 4 normal livers were used as controls. Normal bileducts did not express DR whereas in 8/10 PBC biopsy specimens there were varying degrees of cytoplasmic DR staining in septal or interlobular bileduct epithelium. In the early histological stages of PBC the aberrant DR expression was multifocal, but in late-stage specimens whatever ducts remained were all positive. This pattern resembles that in focal thyroiditis and suggests that DR expression is an early manifestation of autoimmune cholangitis. In 6/61 control biopsies only weak staining was detected in occasional small interlobular ducts. The class I HLA-A,B,C expression normally seen on biliary epithelium was increased in 8/10 PBC cases and in 19/61 non-PBC biopsies. Perhaps the aberrant expression of HLA-DR antigens on bileduct epithelium in PBC enables these cells to present "self antigens" to sensitised T-lymphocytes and to promote autorecognition, possibly in response to several environmental triggers; the increased HLA-A,B,C, expression may be a means of amplifying T-cell cytotoxic responses.


Lack of effect by substance P at sites in the substantia gelatinosa where Met-enkephalin reduces the transmission of nociceptive impulses.
In alpha-chloralose anaesthetized spinal cats, Met-enkephalin amide (M-ENKA) and substance P were administered electrophoretically in the substantia gelatinosa while studying the excitation of deeper spinal neurones by noxious and non-noxious cutaneous stimuli. At sites where Met-enkephalin selectively reduced excitation by noxious skin stimuli, substance P was without effect. This result does not support the hypothesis that enkephalins are released at axo-axonic synapses on the terminals of substance P releasing primary afferent fibres.


Enhancement of human lymphocyte responses to phytomitogens in vitro by incubation at elevated temperatures.
Incubation of human lymphocytes with PHA or Con A at 39 degrees C for 3 days caused a consistent, statistically significant, increase in [3H]thymidine uptake, compared with cultures incubated at 37 degrees C. The responses were also significantly increased after 2 days of incubation, suggesting that hyperthermia not only enhanced, but also caused an earlier onset of the mitogen response.


Fingolimod downregulates brain sphingosine-1-phosphate receptor 1 levels but does not promote remyelination or neuroprotection in the cuprizone model.
Fingolimod is used to treat patients with relapsing-remitting multiple sclerosis; it crosses the blood-brain barrier and modulates sphingosine-1-phosphate receptors (S1PRs). Oligodendrocytes, astrocytes, microglia, and neuronal cells express S1PRs, and fingolimod could potentially improve remyelination and be neuroprotective. We used the cuprizone animal model, histo-, immunohistochemistry, and quantitative proteomics to study the effect of fingolimod on remyelination and axonal damage. Fingolimod was functionally active during remyelination by downregulating S1PR1 brain levels, and fingolimod-treated mice had more oligodendrocytes in the secondary motor cortex after three weeks of remyelination. However, there were no differences in remyelination or axonal damage compared to placebo. Thus, fingolimod does not seem to directly promote remyelination or protect against axonal injury or loss when given after cuprizone-induced demyelination.


Emerging array-based technologies in proteomics.
Microarray format is the method of choice for high-throughput hybridization of nucleic acids. Lately, microarray strategy has been applied to broad studies of interactions of proteins with other molecules. The diversity of these interactions and variations of the properties of proteins present new challenges to microchip technology. Significant achievements have been reported. In particular, three-dimensional (gel-based) chips can be manufactured with limited resources and offer flexibility, capacity, homogeneous solvent environment and the ability to record processes in real time and in variable conditions.


Noncardiogenic pulmonary edema and venous air embolus as complications of operative hysteroscopy.
A 37-year-old patient undergoing operative hysteroscopy developed noncardiogenic pulmonary edema after fluid absorption of 6 L of Ringer's lactate distension solution. No electrolyte or neurologic sequelae were associated with this fluid absorption. A subsequent 35-year-old patient having similar surgery in which a device was used to control intrauterine pressure and fluid absorption, developed a venous air embolus. The use of Ringer's lactate solution reduces the consequences associated with fluid absorption but it is not without risks. A device to limit intrauterine pressure and fluid absorption does not eliminate other risks.


A Comprehensive Optogenetic Pharmacology Toolkit for In Vivo Control of GABA(A) Receptors and Synaptic Inhibition.
Exogenously expressed opsins are valuable tools for optogenetic control of neurons in circuits. A deeper understanding of neural function can be gained by bringing control to endogenous neurotransmitter receptors that mediate synaptic transmission. Here we introduce a comprehensive optogenetic toolkit for controlling GABA(A) receptor-mediated inhibition in the brain. We developed a series of photoswitch ligands and the complementary genetically modified GABA(A) receptor subunits. By conjugating the two components, we generated light-sensitive versions of the entire GABA(A) receptor family. We validated these light-sensitive receptors for applications across a broad range of spatial scales, from subcellular receptor mapping to in vivo photo-control of visual responses in the cerebral cortex. Finally, we generated a knockin mouse in which the "photoswitch-ready" version of a GABA(A) receptor subunit genomically replaces its wild-type counterpart, ensuring normal receptor expression. This optogenetic pharmacology toolkit allows scalable interrogation of endogenous GABA(A) receptor function with high spatial, temporal, and biochemical precision.


Purification of a glycosyl-phosphatidylinositol-specific phospholipase D from human plasma.
Mammalian plasma contains a phospholipase D, which is specific for the glycosyl-phosphatidylinositol anchor found on many eukaryotic cell surface proteins (Davitz, M. A., Hereld, D., Shak, S., Krakow, J., Englund, P. T., and Nussenzweig, V. (1987) Science 238, 81-84; Low, M. G., and Prasad, A. R. S. (1988) Proc. Natl. Acad. Sci. U. S. A. 85, 980-984; Cardoso de Almeida, M. L., Turner, M. J., Stambuk, B. V., and Schenkman, S. (1988) Biochem. Biophys. Res. Commun. 150, 476-482). We have purified this phospholipase D to homogeneity by a four-step procedure involving a Mono Q and phenyl-5PW columns, followed by wheat germ lectin affinity chromatography and finally another Mono Q column. A 4,500-fold purification was achieved with a 5% yield. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the homogeneous enzyme has a Mr of 110,000 and appears to consist of a single polypeptide chain. It exhibits identical substrate specificity as compared with the crude preparation, is active over a broad pH range (4.0-8.5), inhibited by the thiol-blocking agent p-chloromercuriphenylsulfonic acid and by 1,10-phenanthroline, and is partially heat-labile.


Differential effects of LY294002 and wortmannin on inducible nitric oxide synthase expression in glomerular mesangial cells.
Nitric oxide (NO) that is produced by inducible nitric oxide synthase (iNOS) is associated with the pathophysiology of glomerulonephritis. Numerous studies have focused on the regulation of NO production by iNOS to reduce NO-mediated cytotoxicity. In the present study, we demonstrated the differential effects of two phosphatidylinositol 3-kinase (PI3K) inhibitors, LY294002 and wortmannin, on lipopolysaccharide- (LPS) and interferon (IFN)-γ-induced NO production in a glomerular mesangial cell line, MES-13 cells. At dosages without affecting cell viability of MES-13 cells, 5μM LY294002 showed a more-significant inhibitory effect on LPS/IFN-γ-induced NO production, and iNOS protein and gene expressions than did 1μM wortmannin. Akt phosphorylation in MES-13 cells declined upon the addition of wortmannin, but not upon treatment with LY294002. Suppression of PI3K expression by small interfering (si)RNA exhibited no effect on LPS/IFN-γ-stimulated NO production or iNOS protein expression in MES-13 cells. Neither LY294002 nor wortmannin reduced IFN-γ-induced STAT-1α phosphorylation. LY294002 exhibited a more-significant inhibitory effect on NF-κB luciferase activities than wortmannin in LPS/IFN-γ-stimulated MES-13 cells. Moreover, LY294002, but not wortmannin, accelerated iNOS protein degradation and reduced the iNOS dimer/monomer ratio in MES-13 cells. Although both LY294002 and wortmannin are known as PI3K inhibitors, their differential effects on iNOS expression in MES-13 cells indicate that the effects of LY294002 on inhibiting NF-κB activation and accelerating iNOS protein degradation are through a mechanism independent of PI3K.


Vaccine-Associated Neurological Adverse Events: A Case Report and Literature Review.
Vaccination is an effective strategy to reduce the burden of preventable illness. However, many clinical reports revealed that various vaccinations may associate with neurological disorders, mainly including autoimmune disease, febrile seizure, and vaccine-associated paralytic poliomyelitis (VAPP). Although more and more reports revealed that part of the above post-vaccine neurological disorders is not directly related to vaccination, it may be merely a coincidence. However, these reports may increase the hesitancy on vaccination for the public population and influence the coverage of vaccination. In this report, we described a child with acute flaccid paralysis possibly caused by a poliovirus vaccine. To provide feasible ways to realize or reduce the risk of neurological adverse events caused by vaccines, we further provide a mini-review of the literature of vaccination associated with neurological adverse events. This revealed that oral poliomyelitis vaccine use exclusively and type 2 serotype poliomyelitis vaccine virus were the risk factors for VAPP. The combination vaccine was associated with an increased risk of ADEM and FS following immunization when compared with the administration of vaccines separately. Even though cases have been reported that vaccination may be a trigger of anti-NMDARe and GBS, there is no direct evidence to prove that vaccination increased the risk of GBS and anti-NMDARe.


[Variability of the mtDNA Control Region in Goose Anser albifrons Scopoli, 1769].
Sequence variation of the mtDNA (D loop) control region was examined in greater white-fronted goose Anser albifrons Scopoli, 1769 individuals (n = 71). The obtained sequences were compared with those from the NCBI GenBank database. The high level of similarity of the sample from Primorye (A. albifrons) with the sample from Japan (A. a. frontalis) at the level of molecular variation, genetic distance, phylogenetic reconstruction, and haplotype network was demonstrated. A hypothesis on the ways of spring goose migration in the Far East was made. It was confirmed that white-fronted geese wintering in Japan fly to their breeding grounds through Kamchatka.


An autolytic substance in a freshwater cyanobacterium Phormidium tenue.
An autolytic substance in an axenic cyanobacterium, Phormidium tenue, was identified as a mixture of fatty acids, by use of cultured cells in the laboratory. Among them, linoleic acid and linolenic acid were potent growth inhibitors.


Prevalence and associated factors influencing depression in older adults living in rural Thailand: A cross-sectional study.
Depression is a major disease burden in Thailand. In rural areas, young adults will leave home to work in cities, and older adults are left behind. Loneliness and comorbidities can lead to depression in older adults. The present study aimed to evaluate the prevalence and associated factors for geriatric depression. A cross-sectional study was carried out. Questionnaires including the Thai Geriatric Depression Scale and family relationship were obtained by healthcare professions by face-to-face interviews of 584 older people aged ≥60 years in Ban Nayao community, Chachoengsao Province, Thailand. Geriatric depression can be defined as depressive syndromes that arise in adults aged ≥60 years. We excluded those who had visual or auditory disabilities or did not pass the Thai Mini-Mental Status Examination. The prevalence and associated factors for geriatric depression were obtained. Associated factors were analyzed by multivariate logistic regression. A total of 433 older people were eligible. The prevalence of geriatric depression was 18.5%. Of the participants, 54.1% lived in an imbalanced family type. Multivariate analysis showed the significance for female sex (adjusted OR 2.78, 95% CI 1.54-7.49, P = 0.01), illiteracy (adjusted OR 2.86, 95% CI 1.19-6.17, P-value 0.04), current smoker (adjusted OR 4.25, 95% CI 2.12-10.18, P = 0.009) and imbalanced family type (low attachment, low cooperation and poor alignment between each member; adjusted OR 4.52, 95% CI 2.14-7.86, P < 0.001) as risk factors for depression. The prevalence of geriatric depression in rural Thailand is high. Imbalanced family type is an important risk factor for geriatric depression in the rural community. Geriatr Gerontol Int 2019; 19: 1248-1253.


Neurosurgical Treatment of Acromegaly.
Surgical removal of as much tumor mass as possible is usually considered the first step of treatment in acromegaly, unless the patients are unfit for surgery or refuse an operation. To date, in almost all cases, minimally invasive, transsphenoidal microscopic or endoscopic approaches are used. Whether a curative approach is feasible or a debulking procedure is planned, can be anticipated on the basis of preoperative magnetic resonance imaging. It mostly depends on localization, size, and the invasive character of the lesion. The surgical results depend on tumor-related factors such as size, extension, the presence or absence of invasion, and the magnitude of IGF-1 and growth hormone oversecretion, respectively. However, even surgeon-related factors such as experience and case load of the centers have been shown to strongly affect surgical results and complication rates. A reoperation can be considered at various stages in the treatment algorithm. There are several new technical gadgets which might aid in the surgical procedure: navigation, the Doppler probe, and variants of intraoperative imaging.


Randomized clinical trial comparing endoscopic treatment with dextranomer hyaluronic acid copolymer and Cohen's ureteral reimplantation for vesicoureteral reflux: long-term results.
To compare efficacy of Cohen's ureteral reimplantation and endoscopic treatment with Dx/HA in patients with primary VUR grades II, III and IV. From April 2002 to June 2004, patients over 1 year old with VUR grade I, II, III or IV were included. Patients were randomized into two groups: endoscopic treatment (ET) or ureteral reimplantation (UR). In the ET group, an ultrasonography study was performed 24 h and 1 month after surgery, and two voiding cystourethrographies at 3 and 6 months post treatment. In the UR group, an ultrasonography study was done 7 days and 1 month after surgery and a micturial cystography 6 months post surgery. A postoperative nuclear direct cystogram was performed 5 years later in both groups. A total of 41 patients were included in this study: in ET 22 patients with 35 refluxing ureters and in UR 19 patients with 32 refluxing ureters. The VUR grades in ET were: 16 grade II, 16 grade III and 3 grade IV; and in UR: 15 grade II, 12 grade III and 5 grade IV. VUR was resolved in 91% (32/35) of ET (28% of ureters needed a second injection), and in 100% of UR group. Five years after the procedure, VUR was still resolved in 30/32 of ET and 32/32 of UR. Short- and long-term follow up shows that multiple endoscopic treatment of VUR grades II, III and IV with Dx/HA is as effective as ureteral reimplantation.


Abnormal axoglial junctions in the myelin-deficient rat mutant.
Although the myelin-deficient rat displays a gross deficiency of myelin in the CNS, occasional myelin segments of moderate thickness can be found. The typical lamellar pattern, consisting of alternating major dense and intermediate lines, is present in some regions of such segments, but the pattern is abnormal elsewhere. Redundant folds are common, and astrocyte processes occur frequently between the myelin sheath and axolemma or within the sheath. In the paranodal region, myelin lamellae occasionally form a palisade of 'terminal loops' against the axolemma, but discrete transverse bands occur only rarely and regular arrays of transverse bands over an extended length have not been seen. 'Reversed' paranodal junctions occur more often. Here the outermost layer of myelin, instead of being closest to the node, is furthest from it, and successive layers form terminal loops that approach the node progressively. These loops face away from the axon and do not contact it. At paranodal junctions of this kind only the innermost loop, or a small number of inner loops, adjoins the axolemma and, as a result, the size of the paranodal axoglial junction is markedly restricted. These defects in the paranodal junction may underlie the intrusion of astrocyte processes from either end of a myelin segment into the internodal periaxonal space and between myelin lamellae. Thus, one of the normal functions of the paranodal junction may be to restrict extension of astrocyte processes into and beneath myelin segments. The myelin-deficient rat also exhibits node-like specializations of the axolemma in association with glial cell processes.


Oral lichen planus identification by mid-infrared spectroscopy of oral biofluids: A case-control study.
This study aims to access the effectiveness of mid-infrared (MIR) spectroscopy on the identification of the reticular form of OLP, following the assessment of gingival crevicular fluid (GCF) and oral mucosa transudate (OMT). The trial follows a case-control design. Samples were characterized through MIR spectroscopy and chemometric tools were applied to distinguish between case and control participants, further identifying the spectral regions with the highest contribution to the developed models. MIR spectroscopy was capable to discriminate between OLP patients and controls with 95.1% and 85.4% of correct predictions, regarding GCF and OMT samples, respectively. Additionally, the spectral regions mostly contributing to the successful prediction were identified, and possibly related with the distinctive presence of amino acids/proteins and oxidative stress mediators in oral biofluids, supporting the role of the immune-inflammatory activation on OLP etiology and disease course. MIR spectroscopy analysis of GCF and OMT may be regarded as an innovative, non-invasive, low cost and sensitive technique, contributing to the identification of the reticular from of OLP.