Antenatal Corticosteroids for Small for Gestational Age in Late Preterm Newborns.
The administration of antenatal corticosteroids (ACS) is standard practice for management of threatened preterm birth. Its benefit, especially in small for gestational age (SGA) late preterm, is unclear. To evaluate the impact of ACS on perinatal outcome of late preterm SGA neonates. We conducted a retrospective cohort study of all women carrying a singleton gestation who had late preterm delivery (34-36 gestational weeks) of SGA neonates at a single tertiary university-affiliated medical center (July 2012-December 2017). Exclusion criteria included termination of pregnancy, intrauterine fetal death, and birth weight ≥ 10th percentile. Outcomes were compared between ACS and non-ACS treatment prior to delivery. Neonatal composite outcome included neonatal intensive care unit (NICU) admission, respiratory distress syndrome, mechanical ventilation, and transient tachypnea. Overall, 228 women met inclusion criteria; 102 (44.7%) received ACS and 126 did not (55.3%). Median birth weight among the non-ACS group was significantly higher (1896.0 vs. 1755.5 grams P < 0.001). Rates of NICU and jaundice requiring phototherapy were higher among the ACS group (53.92% vs. 31.74%, P = 0.01; 12.74% vs. 5.55%, P = 0.05, respectively). Composite neonatal outcome was significantly higher among the ACS group (53.92% vs. 32.53%, odds ratio [OR] 2.42, 95% confidence interval [95%CI] 1.41-4.15, P = 0.01). After adjustment for potential confounders, this association remained significant (OR 2.15, 95%CI 1.23-3.78, P = 0.007). ACS given during pregnancy did not improve respiratory outcome for SGA late preterm neonates. ACS may be associated with a worse outcome.


Phylogeography of the Cactophilic Drosophila and Other Arthropods Associated with Cactus Necroses in the Sonoran Desert.
Studies on the population genetics, phylogenetic relationships, systematics and evolution of arthropods that inhabit necrotic tissue of cacti in the Sonoran Desert of North America are reviewed. These studies have focused upon several species of insects (orders Diptera and Coleoptera) and arachnids (order Pseudoscorpiones). For most taxa studied, little genetic structure and high dispersal ability are found in populations inhabiting the mainland and Baja California peninsula regions of the Sonoran Desert, consistent with the availability of the rotting cactus microhabitat which is patchily distributed and ephemeral. There is evidence, however, that the Gulf of California, which bisects the Sonoran Desert, has played a role in limiting gene flow and promoting speciation in several taxa, including histerid beetles, whereas other taxa, especially Drosophila nigrospiracula and D. mettleri, apparently are able to freely cross the Gulf, probably by taking advantage of the Midriff Islands in the northern Gulf as dispersal "stepping stones". Genetic evidence has also been found for historical population expansions dating to the Pleistocene and late Pliocene in several taxa. Overall, these studies have provided important insights into how arthropods with different life history traits, but generally restricted to a necrotic cactus microhabitat, have evolved in an environmentally harsh and tectonically active region. In addition, they suggest some taxa for further, and more detailed, hypothesis driven studies of speciation.


Ruptured Internal Carotid Artery Pseudoaneurysm 10 Years after Cervical Spine Surgery.
An iatrogenic internal carotid artery (ICA) pseudoaneurysm is an extremely rare complication of cervical spine surgery. Here we report an extraordinary case of massive hematemesis due to a ruptured ICA pseudoaneurysm caused by the laminoplasty plate 10 years after cervical spine surgery. Computed tomography angiography revealed a ruptured 4×10-mm left extracranial ICA pseudoaneurysm probably connected to the pharynx. Emergent surgery was performed because of the uncontrolled massive bleeding. After complete resection of the injured segment, an interposition graft with a 6-mm polytetrafluoroethylene graft was placed and the fistula tract to the pharynx was repaired.


A comparative analysis of animals' understanding of the human pointing gesture.
We review studies demonstrating the ability of some animals to understand the human pointing gesture. We present a 3-step analysis of the topic. (1) We compare and evaluate current experimental methods (2) We compare available experimental results on performance of different species and investigate the interaction of species differences and other independent variables (3) We evaluate how our present understanding of pointing comprehension answers questions about function, evolution and mechanisms. Recently, a number of different hypotheses have been put forward to account for the presence of this ability in some species and for the lack of such comprehension in others. In our view, there is no convincing evidence for the assumption that the competitive lifestyles of apes would inhibit the utilization of this human gesture. Similarly, domestication as a special evolutionary factor in the case of some species falls short in explaining high levels of pointing comprehension in some non-domestic species. We also disagree with the simplistic view of describing the phenomenon as a simple form of conditioning. We suggest that a more systematic comparative research is needed to understand the emerging communicative representational abilities in animals that provide the background for comprehending the human pointing gesture.


Design of and metrological results from a bent parabolic mirror.
This article describes the successful design and fabrication of, and metrological results from, an elastically bent parabolic mirror. The mirror is equipped with a bending structure that allows the mirror to be bent meridionally to a parabolic shape. This bent parabolic mirror is the key component of the extremely high-quality monochromators designed for the SPring-8 figure-8 soft X-ray undulator and the 2.0 GeV high-brilliance synchrotron radiation source (VSX).


Endovascular and Surgical Treatment of Spinal Dural Arteriovenous Fistulas: Assessment of Post-treatment Clinical Outcome.
Spinal dural arteriovenous fistulas (DAVFs) are the most commonly encountered vascular malformation of the spinal cord and a treatable cause of progressive para- or tetraplegia. It is an elusive pathology that tends to be under-diagnosed, due to lack of awareness among clinicians, and affects males more commonly than females, typically between the fifth and eighth decades. Early diagnosis and treatment may significantly improve outcome and prevent permanent disability and even mortality. The purpose of our retrospective, single-center study was to determine the long-term clinical and radiographic outcome of patients who have received endovascular or surgical treatment of a spinal DAVF. In particular, during a 6-year period (2009-2014) 14 patients with a spinal DAVF were treated at our department either surgically (n = 4) or endovascularly (n = 10) with detachable coils and/or glue. There was no recurrence in the follow-up period (mean: 36 months, range 3-60 months) after complete occlusion with the endovascular treatment (n = 9; 90%), while only one patient (10%) had residual flow both post-treatment and at 3-month follow-up. All four surgically treated patients (100%) had no signs of residual DAVF on follow-up magnetic resonance angiography (MRA) and/or angiography (mean follow-up period of 9 months). Since improvement or stabilization of symptoms may be seen even in patients with delayed diagnosis and substantial neurological deficits, either endovascular or surgical treatment is always justified.


Folic acid ameliorates celecoxib cardiotoxicity in a doxorubicin heart failure rat model.
The cardiotoxic effect of selective cyclo-oxygenase-2 inhibitors is well known. While rofecoxib and valdecoxib have been withdrawn, celecoxib remains on the market. Folic acid, a naturally occurring vitamin, has been shown to reduce myocardial ischemia and post-reperfusion injury in rats. This study examined the cardiac effects of celecoxib and folic acid on doxorubicin-induced cardiomyopathy in rats. Cardiomyopathy was induced in male Wistar rats with six intraperitoneal injections of 2.5 mg/kg doxorubicin over a period of two weeks. The effect of 28 days of celecoxib (100 mg/kg/day) and its combination with folic acid (10 mg/kg/day) was studied on doxorubicin-induced cardiomyopathy according to serum lactate dehydrogenase (LDH), creatine kinase (CK-MB), troponin-T (Tn-T), tumor necrosis factor alpha (TNF-α), cardiac thiobarbituric acid reactive substance (TBARS), and glutathione (GSH) levels as well as systolic blood pressure (SBP), heart rate (HR) and ultrastructural studies. Celecoxib cardiotoxicity was manifested by significant increases in the LDH, Tn-T, TNF-α, CK-MB, SBP, HR (p < 0.001) and TBARS (p < 0.01) levels and a significant decrease in the GSH (p < 0.05) level when used alone or administered with doxorubicin. However, the combination of folic acid with celecoxib caused a significant reversal of these parameters and reduced the cardiotoxicity of celecoxib that was aggravated by doxorubicin. The ultrastructural study also revealed myocardial protection with this combination. Folic acid protects against the cardiotoxic effects of celecoxib, which are aggravated in the presence of doxorubicin. Folic acid may act as a useful adjunct in patients who are taking celecoxib.


[Expert consensus on diagnosis, treatment and prevention of allergic diseases (Part Ⅰ)].
Allergic diseases are mainly type I allergic reactions mediated by IgE, which can involve multiple organs and systems of the whole body, and run through a person's whole life, with genetic susceptibility. Since most hospitals in China do not have independent allergy departments, this consensus established by multidisciplinary experts will provide guidance for the diagnosis, treatment and prevention of allergic diseases. This article is the first part of the consensus, which includes the definition of terms, epidemiology, pathogenesis, diagnosis and concomitant diseases. The prevalence of allergic diseases is increasing rapidly, and the patients are getting younger, which brings serious harm. Innate immunity, hygiene hypothesis, microecological imbalance, flora imbalance, air pollution and so on are involved in the disease. The diagnosis can be made according to typical medical history, family history, symptoms, signs, allergen detection, auxiliary examination, etc. Allergens must be tested. It is often accompanied by chronic sinusitis, secretory otitis media, snoring, chronic obstructive pulmonary disease, etc.


An Institutional Repository Experience at a Large Health Care System.
Institutional repositories (IRs) collect, preserve, and disseminate the scholarly output of an organization. Though common in academic settings, they are less so in hospitals or health care systems. The librarians for Aurora Health Care decided to create a primarily citation-level IR to organize and promote the scholarly output of Aurora faculty, residents, and fellows using the proprietary software Digital Commons, a product of the company bepress. The repository also hosts a newly published peer-reviewed journal and includes digitized historical images and institutional memorabilia. Suggested alternatives are given for hospitals or health care systems that may not currently be able to pursue a full-fledged IR.


Oral Administration of Fermented Papaya (FPP®) Controls the Growth of a Murine Melanoma through the In Vivo Induction of a Natural Antioxidant Response.
Prolonged oxidative stress may play a key role in tumor development. Antioxidant molecules are contained in many foods and seem to have a potential role in future anti-tumor strategies. Among the natural antioxidants the beneficial effect of Fermented Papaya (FPP®) is well known. The aim of this study was to investigate the effects of orally administered FPP® in either the prevention or treatment of a murine model of melanoma. The tumor growth was analyzed together with the blood levels of both oxidants (ROS) and anti-oxidants (SOD-1 and GSH). The results showed that FPP® controlled tumor growth, reducing the tumor mass of about three to seven times vs. untreated mice. The most significant effect was obtained with sublingual administration of FPP® close to the inoculation of melanoma. At the time of the sacrifice none of mice treated with FPP® had metastases and the subcutaneous tumors were significantly smaller and amelanotic, compared to untreated mice. Moreover, the FPP® anti-tumor effect was consistent with the decrease of total ROS levels and the increase in the blood levels of GSH and SOD-1. This study shows that a potent anti-oxidant treatment through FPP® may contribute to both preventing and inhibiting tumors growth.


[Six cases of hydroencephalodysplasia (author's transl)].
Six cases of hydroencephalodysplasia were evaluated from the points of clinical signs and symptoms and neuroradiological procedures and diagnostic problems were discussed. All of our cases were characterized by extensive dysplasia of the brain and increased cerebrospinal fluid pressure. Deformity of the head and developmental arrest of the psychomotor function were observed in five cases. The side of the skull deformity was consisted with that of the brain defect. Pneumoencephalography and cerebral angiography are characteristic in this disease, but these procedures have to be carried out with caution in case of poor general condition. Transillumination and brain scan are also useful procedures and RI-cisternography is important for indication of shunting operation. Early rehabilitation for the motor dys function is main therapeutic trial, though the cases with increased intracranial pressure require cerebrospinal fluid shunt.


Lipid rafts and regulation of the cytoskeleton during T cell activation.
The ability of polarized cells to initiate and sustain directional responses to extracellular signals is critically dependent on direct communication between spatially organized signalling modules in the membrane and the underlying cytoskeleton. Pioneering work in T cells has shown that the assembly of signalling modules critically depends on the functional compartmentalization of membrane lipids into ordered microdomains or lipid rafts. The significance of rafts in T cell activation lies not only in their ability to recruit the signalling partners that eventually assemble into a mature immunological synapse but also in their ability to regulate actin dynamics and recruit cytoskeletal associated proteins, thereby achieving the structural polarization underlying stability of the synapse-a critical prerequisite for activation to be sustained. Lipid rafts vary quite considerably in size and visualizing the smallest of them in vivo has been challenging. Nonetheless it is now been shown quite convincingly that a surprisingly large proportion-in the order of 50%-of external membrane lipids (chiefly cholesterol and glycosphingolipids) can be dynamically localized in these liquid ordered rafts. Complementary inner leaflet rafts are less well characterized, but contain phosphoinositides as an important functional component that is crucial for regulating the behaviour of the actin cytoskeleton. This paper provides an overview of the interdependency between signalling and cytoskeletal polarization, and in particular considers how regulation of the cytoskeleton plays a crucial role in the consolidation of rafts and their stabilization into the immunological synapse.


Invading parasitoids suffer no Allee effect: a manipulative field experiment.
One frequent explanation for the failure of biological invasions is the Allee effect: due to positive density dependence, initially small invading populations may fail to establish and spread. Populations released for biological control are similar to fortuitous invading populations and may therefore suffer from Allee effects. However, unlike fortuitous invasions, biological control allows the experimental manipulation of initial population size and, thus, offers a unique opportunity to test for the occurrence of Allee effects. We manipulated the initial size of 45 populations of a parasitoid wasp introduced for the biological control of a phytophagous insect and followed the population dynamics of both parasitoids and hosts during three years. Our results suggest an absence of Allee effects but clear negative density dependence instead: (1) the probability of establishment after three years was not affected by initial population size; (2) net reproductive rate was highest at low parasitoid density and high host density; (3) the sex ratio, reflecting the proportion of virgin females, did not increase at low density, suggesting that low densities did not impede mate-finding; (4) the depression of host populations did not depend upon the number of parasitoids introduced. This is, to our knowledge, the first experimental test of the Allee effect in an invading parasitoid. It leads us to propose that a number of behavioral and life-history features of many parasitoids could protect them from Allee effects.


Maintenance of sterility in 1-mL polypropylene syringes.
The sterility of syringes filled with a growth-promoting broth when stored under various temperature conditions was studied. Samples of tryptic soy broth (TSB) were injected into 150 1-mL polypropylene syringes and incubated at 33-37 degrees C for 14 days, after which time they were visually inspected for microbial contamination. In addition to visual inspection, the sterility of all syringes was tested by inoculating samples into 10-mL tubes of thioglycollate broth, incubating at 35 degrees C, and observing for growth for 5 days. After the 14-day incubation period, 30 syringes were removed for sterility validation and microbial growth promotion. TSB from 15 syringes was transferred into sterile culture tubes and challenged with Staphylococcus aureus, Escherichia coli, Bacillus cereus, Candida albicans, and Aspergillus niger. The remaining 120 syringes were repackaged and stored at room temperature (22 degrees C), in a refrigerator (5 degrees C), or in a freezer (-20 degrees C). The sterility of the samples was evaluated at 30 days, 45 days, three months, and six months. No microbial growth was detected by visual inspection in any of the 15 syringes examined for turbidity during validation testing. All study syringes (n = 120) remained sterile throughout the respective evaluation periods, regardless of storage condition. Growth-promoting broth stored in 1-mL polypropylene syringes remained sterile when stored at room temperature, in a refrigerator, or in a freezer for six months.


Current perspectives in the USA on the diagnosis and treatment of pelvic inflammatory disease in adolescents.
In this review, the epidemiology, diagnosis, and treatment of pelvic inflammatory disease (PID) are discussed from a USA perspective and the difficulties that USA adolescents face in recognizing and seeking care for PID and other sexually transmitted infections (STIs) are emphasized. Females aged 15-24 years have the highest incidence of cervical infection with Chlamydia trachomatis and Neisseria gonorrheae, the principal causes of PID. PID is common in this age group. However, the incidence of PID in the USA is not known, because it is not a reportable disease, and because clinicians vary in the criteria used for the diagnosis. The Centers for Disease Control and Prevention (CDC) recommended the following diagnostic criteria that include lower abdominal or pelvic pain and at least one of the following: adnexal tenderness or cervical motion tenderness or uterine tenderness. Because PID can have serious sequelae, the criteria emphasize sensitivity (few false-negatives) at the expense of specificity (some false-positives). Patients who have PID are usually treated in the outpatient setting, following the CDC's Guidelines for the Treatment of Sexually Transmitted Diseases 2015. They receive one dose of an intramuscular cephalosporin, together with 2 weeks of oral doxy cycline, and sometimes oral metronidazole. Improvement should usually be evident in 3 days. The USA does not offer comprehensive sex education for adolescents in public or private schools. Adolescents are unlikely to recognize the symptoms of PID and seek medical treatment. Confidentiality is important to adolescents, and low cost or free sources of confidential care are uncommon, making it unlikely that an adolescent would seek care even if she suspected an STI. The CDC has concluded that screening programs for chlamydia and gonorrhea infection help prevent PID; however, the lack of appropriate sources of care makes adolescents' participation in screening programs unlikely.


Reoperative surgery in anorectal malformation patients.
Currently accepted primary repair of congenital anorectal malformations (ARMs) includes a posterior sagittal incision, which allows for optimal visualization and identification of important pelvic structures and anatomical features. Reconstructive surgery involves meticulous dissection and separation of pelvic structures, and careful reconstruction can result in good functional outcomes for many patients, who live without ongoing sequelae from their malformation. However, some patients may require reoperative procedures for anatomic or functional reasons. Males and females present with slightly different symptoms and should be approached differently. Males are most likely to require reoperations for anorectal or urethral pathologies, but the urinary system is often spared in females-they instead must contend with Mullerian duct anomalies, of which there are many varieties. Depending on the original malformation and severity of symptoms, redo surgery may be needed to optimize function and quality of life. Surgical management with reoperative surgery in ARMs ranges from straightforward to complex, depending on the issue. One must weigh the risks of reoperative surgery and potentially creating more scarring against the need for a better anatomical and functional outcome. Current management trends and practice patterns with regards to reoperative surgery in ARM patients are not widely studied or standardized but we provide an overview of the more common pathologies, preoperative evaluation and workup required to identify the issues, and options for reoperative repair in these patients.


Effect of immobilization on collagen synthesis in rat skeletal muscles.
The activities of prolyl 4-hydroxylase (PH) and galactosylhydroxylysyl glucosyltransferase (GGT), both enzymes of collagen biosynthesis, and the concentration of hydroxyproline (Hyp) were measured in the soleus, gastrocnemius, and tibialis anterior muscles of rats after cast immobilization in the middle position for 1 or 3 wk. The specific activity of PH decreased by 54 and 70-75% (P less than 0.001) in the soleus muscle after 1 and 3 wk, respectively, the corresponding decreases in GGT activity were 43 and 47% (P less than 0.001). A less pronounced decrease in the activities of these enzymes was observed in gastrocnemius and tibialis anterior muscles. The Hyp concentration in the soleus increased during the first week of immobilization but began to decrease thereafter, and the total muscular Hyp content was reduced after immobilization for 3 wk. The results suggest a marked inhibition of muscular collagen synthesis during immobilization. Electrical stimulation of the sciatic nerve partially prevented this disuse atrophy and the decreases in PH, GGT, and Hyp in the tibialis anterior muscle but not in the gastrocnemius or soleus muscles.


Surface Roughed and Pt-Rich Bimetallic Electrocatalysts for Hydrogen Evolution Reaction.
Platinum-based alloys with low cost transition metals have been considered as promising electrocatalysts in the field of sustainable energy conversion and storage. Herein, chloroplatinic acid, cobalt chloride, and carbon nanotubes are used as platinum, cobalt precursors, and carriers, respectively, to prepare rich Pt dealloying PtCo nanoparticles (SD-PtCo/CNT) via co-liquid phase reduction and chemical dealloying methods. The characterization and test results confirm that PtCo alloy nanoparticles are evenly dispersed on carbon nanotubes, further dealloying and resulting in the partial dissolving of cobalt, simultaneously generating a rich Pt layer and roughly active surface. Benefiting from the unique structure, the SD-PtCo/CNT catalyst displays obviously enhanced HER activity in both acidic and alkaline conditions. In 1.0 M KOH, SD-PtCo/CNT exhibits a low overpotential of 78 mV at 10 mA/cm2 and a small tafel slope (38.28 mV/dec). In 0.5 M H2SO4, SD-PtCo/CNT still shows the superior performance compared with un-dealloying PtCo/CNT, with an overpotential of 17 mV at 10 mA/cm2 and corresponding tafel slope of 21.35 mV/dec. The high HER activity of SD-PtCo/CNT can be attributed to the formation of a platinum rich layer and the uniformly dispersed PtCo nanoparticles supported on superior conductive carbon nanotubes, suggesting its great potential for hydrogen generation via water splitting.


Studies on the terminal stages of antibody-complement mediated killing of a tumor cell. III. Effect of membrane active agents.
A comparison of the events leading from T to dead cell and E to E ghost and hemoglobin was made. Transformation of T to dead cells was inhibitable by EDTA, NaF, histamine, DMSO, cytochalasin B and 3'5' cAMP. Transformation of E to E ghost and hemoglobin was only inhibited by EDTA.


Network meta-analysis of four kinds of traditional Chinese exercise therapy in the treatment of type 2 diabetes: protocol for a systematic review.
Traditional Chinese exercise therapy, as one of the commonly used exercise interventions for the treatment of type 2 diabetes patients in China, has been proven effective by many clinical practices, but there is still a lack of evidence-based research. This study aims to integrate clinical randomised controlled correlations via network meta-analysis evidence. The comprehensive search included Chinese and other language databases such as the MEDLINE (PubMed), Web of Science, Excerpt Medica Database (EMBASE), The Cochrane Library, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China Scientific Journal Database (VIP), China Biomedical Literature Database (CBM). Clinical randomised controlled trials of four traditional Chinese exercise therapies in the treatment of type 2 diabetes, including Tai Chi, Ba Duan Jin, Yi Jin Jing and Wu Qin Xi were retrieved. The search time was conducted from the establishment of the database to 30 October 2020. Two researchers screened the documents that met the inclusion criteria, extracted data according to the preset table, and evaluated the methodological quality of the included studies according to the quality evaluation tools recommended by the Cochrane System Reviewer Manual V.5.1. The R language and ADDIS statistical software were used to conduct statistics and analysis of intervention measures. CRD42020214786.


Anthropogenic impact on environmental filamentous fungi communities along the Mediterranean littoral.
We hypothesised that anthropogenic influences impact the filamentous fungi community structure and that particular species or species patterns might serve as markers to characterise ecosystems. This study aimed to describe the filamentous fungi community structure in various biotopes along the Mediterranean shore that were exposed to various levels of anthropogenic influence. We sampled filamentous fungi from yellow-legged gull faecal samples at five study sites along the Mediterranean littoral in southern France. The sites were characterised by variable anthropogenic influence, ranging from building rooftops in two cities to a natural reserve. The sites also included two suburban ecoclines, one of which was exposed to sewer pollution. Filamentous fungal colonies were quantified and identified via MALDI-TOF mass spectrometry. Interestingly, we found that both fungal diversity and abundance were low in urban areas compared with suburban ecocline or environments little affected by anthropogenic influence. Furthermore, some fungal species were clearly associated with particular environments. In particular, Mucor circinelloides was associated with a natural environment with little anthropogenic impact and distant from human settlements. Whereas, Scedosporium apiospermum was associated with an ecocline polluted by sewage. Our findings indicate that particular fungal species or species combination might be used as surrogate markers of ecosystems exposed to anthropogenic pollution.


Tinnitus-related distress and pain perceptions in patients with chronic tinnitus - Do psychological factors constitute a link?
To investigate the co-occurrence of tinnitus-related distress and pain experiences alongside psychological factors that may underlie their association. Patients with chronic tinnitus (N = 1238) completed a questionnaire battery examining tinnitus-related distress and affective and sensory pain perceptions. A series of simple, parallel- and serial multiple mediator models examined indirect effects of psychological comorbidities as well as -process variables including depressivity, perceived stress and coping attitudes. Moderator and moderated mediation analyses examined differential relational patterns in patients with decompensated vs. compensated tinnitus. There were significant associations between tinnitus-related distress and pain perceptions. These were partially mediated by most specified variables. Psychological comorbidities appeared to influence tinnitus-pain associations through their impact on depressivity, perceived stress, and coping attitudes. Some specific differences in affective vs. sensory pain perception pathways emerged. Patients with decompensated tinnitus yielded significantly higher symptom burden across all measured indices. Tinnitus decompensation was associated with heightened associations between [1] tinnitus-related distress and pain perceptions, depressivity and negative coping attitudes; and [2] most psychological comorbidities and sensory, but not affective pain perception. Moderated mediation analyses revealed stronger indirect effects of depressivity and anxiety in mediating affective-, and anxiety in mediating sensory pain perception in patients with decompensated tinnitus. Psychological constructs mediate the co-occurrence of tinnitus- and pain-related symptoms across different levels of tinnitus-related distress. Psychological treatment approaches should conceptualize and address individualised interactions of common cognitive-emotional processes in addressing psychosomatic symptom clusters across syndromatic patients with varying distress levels.


Is urodynamic evaluation a must in all operated cases of open neural tube defects.
Spina bifida is a common cause of pediatric neurogenic bladder. It causes renal failure in almost 100% of patients if the associated detrusor sphincter dyssynergia (DSD) is inadequately managed. Detrusor instability and high detrusor pressures (Figure) have been implicated as the major factors predictive of renal damage in these patients. Urodynamic studies provide early identification of "at risk" kidneys so that appropriate intervention can be made. However, the role in post-operative patients of spina bifida who have no clinical manifestations remains unclear. To study the bladder dynamics in asymptomatic post-operative patients of spina bifida and to determine whether routine urodynamic study is justifiable. Urodynamics was performed on 15 operated patients of spina bifida who did not have any neurological deficit and were asymptomatic. The mean age of the patients was 4.97 years. None of the patients had any urological complaints with their ultrasonography being normal. None had scars on nuclear scan. Of the 15 patients, 12 (80%) had abnormal findings on urodynamic assessment. Three patients (20%) had detrusor pressures greater than 40 cm of H2O. One patient had significant residual urine and detrusor instability. The use of urodynamic studies in asymptomatic patients of spina bifida remains controversial, with one school of thought advocating early invasive urodynamic testing. In contrast, some favor noninvasive sonological monitoring, reserving invasive tests only for patients with renal tract dilatation. In our subset of patients none had renal tract dilatation but three patients (20%) had "at risk" bladders. These patients would benefit from early intervention aimed at renal preservation. The study is limited by a small sample size because of the relative rarity of the patient profile included. A further multicenter study with a case-control design could conclusively indicate the role of urodynamic testing in these patients. Patients of spina bifida, even when asymptomatic, have a high incidence of unsafe bladders. Early identification and appropriate measures can protect kidneys from long-term damage, hence urodynamic profiling is mandatory for identification of potentially high-risk bladders.


Negative differential resistance and memory effect in diodes based on 1,4-dibenzyl C60 and zinc phthalocyanine doped polystyrene hybrid material.
Negative differential resistance (NDR) and memory effect were observed in diodes based on 1,4-dibenzyl C60 (DBC) and zinc phthalocyanine doped polystyrene hybrid material. Certain negative starting sweeping voltages led to a reproducible NDR, making the hybrid material a promising candidate in memory devices. It was found that the introduction of DBC enhanced the ON/OFF current ratio and significantly improved the memory stability. The ON/OFF current ratio was up to 2 orders of magnitude. The write-read-erase-reread cycles were more than 106, and the retention time reached 10,000 s without current degradation.


The Effect of Abobotulinum Toxin A on the Symptoms of Raynaud's Phenomenon: A Case Series.
Raynaud's phenomenon (RP) is a relatively common syndrome occurring alone or in combination with autoimmune and inflammatory diseases. It is characterized by pain and ulceration due to vasospasm in response to cold and stress, most often affecting the digits. Although pharmacologic treatment for this condition exists, it is not always efficacious. Our case series demonstrates the use of abobotulinum toxin A in the treatment of RP. We report the cases of four patients who received injections of abobotulinum toxin A to treat their mild to severe RP symptoms. They experienced clinical improvement for up to one year after treatment.


Adjuvant chemotherapy in gastric cancer: a meta-analysis of randomized trials and a comparison with previous meta-analyses.
Up to now adjuvant chemotherapy after curative resection for gastric cancer (GC) has been considered an experimental approach. The results of existing phase III randomized trials comparing chemotherapy with control after surgery are controversial. Three meta-analyses have been published in recent years. It is likely that each of them presents a theoretical bias, mainly as regards the inclusion criteria of the trials. In this article we re-examine this potential bias, highlighting the differences between the present and past meta-analyses on adjuvant chemotherapy for GC. Only randomized controlled clinical trials comparing systemic adjuvant chemotherapy with control after radical resection of GC were eligible. Total mortality was assessed as outcome measure of the treatment effect and a pooled odds ratio was calculated using the Peto-Mantel-Haenszel method. After the selection process 17 papers (18 comparisons) proved eligible for inclusion in the meta-analysis with a total of 3118 patients, of whom 1546 randomized to the treatment arms and 1572 to the control arms; 762 and 871 deaths occurred in the treatment and control arms, respectively. Statistical analysis suggests an absence of significant heterogeneity between the trials and a significant advantage in survival for adjuvant chemotherapy (pooled odds ratio, 0.72, 95% Cl, 0.62-0.84). Our meta-analysis would seem to indicate that adjuvant chemotherapy results in a significant survival advantage in patients with GC. However, this observation undoubtedly requires confirmation in large randomized controlled trials including cisplatin before adjuvant chemotherapy after curative resection for GC can be proposed for use in clinical practice.


Correlation of SOX9 and NM23 genes with the incidence and prognosis of prostate cancer.
Correlation of sex determining region Y-box (SOX)9 and NM23 genes with the incidence and prognosis of prostate cancer (PC) was investigated. SOX9-small interfering ribonucleic acid (siRNA) and NM23-siRNA were constructed and transfected into PC-3 cells. The expression levels of SOX9 and NM23 messenger RNAs (mRNAs) and proteins in PC-3 cells were detected via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. MTT assay was adopted to examine the proliferation ability of the transfected cells, and Transwell assay was applied to detect the migration ability of the transfected cells. Sixty-three patients with PC and 56 patients with benign prostatic hyperplasia who were treated in Huadu District People's Hospital were enrolled. Correlation analyses were conducted for the relative expression levels of SOX9 and NM23 and the Gleason grade; and the survival curves of the patient SOX9/NM23 (S/N) Cq values were plotted. The proliferation and migration abilities of PC-3 cells were remarkably reduced after low expression of SOX9 (P<0.01), while those of PC-3 cells were significantly improved after low expression of NM23 (P<0.01). Compared with that in tissues of PC patients, the relative expression of SOX9 mRNA in patients with benign prostatic hyperplasia was obviously decreased (P<0.01), while that of NM23 mRNA was significantly elevated (P<0.01). The larger the S/N was, the shorter the patient's survival time would be (P<0.05). The low expression of SOX9 gene can significantly reduce the proliferation and migration abilities of PC cells, which is negatively associated with the incidence and prognosis of patients. The low expression of NM23 gene can markedly enhance the proliferation and migration abilities of PC cells, and it is positively related to the incidence and prognosis of patients.


Living with impairment: the effects on children of having an autistic sibling.
Although children of impaired siblings are generally believed to be at risk of suffering from a variety of problems themselves, research studies indicate that living with impairment is not necessarily a harmful experience. This report reviews studies in this area, with particular emphasis on those involving autistic sibships. Although often lacking adequate experimental controls, the current literature suggests various factors that are likely to influence the risks on siblings. Possible ways of minimizing such risk factors are discussed.


Bad weed: synthetic cannabinoid-associated coagulopathy.
Recent multistate outbreaks of coagulopathy caused by brodifacoum-tainted synthetic cannabinoids or "fake weed" highlight the public health impact of long-acting anticoagulant rodenticides (LAARs). Patients presenting with this syndrome have had recent exposure to synthetic cannabinoids, evidence of isolated vitamin K antagonism with or without bleeding, and detectable levels of brodifacoum and other LAARs in circulation. This article will provide information on synthetic cannabinoids, LAARs, and coagulopathic manifestations arising from use of adulterated synthetic cannabinoids and their management.


Dehydroepiandrosterone inhibits events related with the metastatic process in breast tumor cell lines.
Dehydroepiandrosterone (DHEA), an adrenal hormone, has a protective role against cancer. We previously shown that DHEA inhibits the proliferation and migration of cell lines derived from breast cancer; however, the role of DHEA in others events related with these effects are unknown. We hypothesized that DHEA inhibits the expression of proteins and some events related with cell migration and metastasis. We determined the migration in Boyden chambers, the invasion in matrigel, anchorage-independent growth and the formation of spheroids in 3 cell lines (MCF-7, MDA-MB-231, ZR-75-30) derived from breast cancer exposed to DHEA. The secretion of metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and several pro-inflammatory molecules in the secretome of these cells was also evaluated. DHEA inhibited the migration in transwells and the invasion in matrigel of MCF-7 and MDA-MB-231 cells. Besides, DHEA inhibited the anchorage-independent growth on agar and decreased the size of spheroids, and also reduced the secretion of IL-1α, IL-6, IL-8, and TNF-α in all cell lines. Metalloproteinase-1 (MMP-1) secretion was slightly decreased by DHEA treatment in MDA-MB-231 cells. Our results also showed that inhibition of migration and invasion induced by DHEA in breast cancer cells is correlated with the decrease of cytokine/chemokine secretion and the diminution of tumor cells growth. MCF-7 cells were the most responsive to the exposure to DHEA, whereas ZR-75-30 cells responded less to this hormone, suggesting that DHEA could be used in the treatment of breast cancer in early stages.


Transcranial direct current stimulation in treatment-resistant obsessive-compulsive disorder: An open-label pilot study.
Obsessive-compulsive disorder (OCD) is a severe mental illness. OCD symptoms are often resistant to available treatments. Abnormalities within the orbitofronto-striato-pallido-thalamic circuitry, especially orbitofrontal cortex (OFC) hyperactivity and cerebellar hypoactivity have been observed in patients. Non-invasive brain stimulation studies have indicated that transcranial direct current stimulation (tDCS) may be a useful alternative to alleviate treatment-resistant symptoms in various neuropsychiatric conditions. In an open-label pilot study, 8 patients with treatment-resistant OCD received 10 sessions (twice a day) of 2mA tDCS applied with the cathode over the left OFC and the anode over the right cerebellum. OCD (Y-BOCS and OCD-VAS) as well as depressive (MADRS) symptoms were measured 4 times: one time before tDCS and 3 times after (immediately after, 1 and 3months after the 10th tDCS session). We reported a significant 26.4% (±15.8) decrease of Y-BOCS score (p=0.002). The beneficial effect lasted during the 3month follow-up. No effect of tDCS was observed on depressive symptoms. At end point, 5 out of 8 patients had a decrease of ≥25%; and 3 out of 8 patients had a decrease of ≥35% in Y-BOCS score. tDCS was well tolerated. tDCS with the cathode placed over the left OFC combined with the anode placed over the right cerebellum is a suitable and safe approach to decrease OCD symptoms in patients with treatment-resistant OCD. Large scale randomized controlled studies are needed to confirm this promising result.


Phosphatidylinositol 3-kinase could be a promising target in lung cancer therapy.
To investigate the prevalence of phosphatidylinositol 3-kinase (PIK3CA) gene amplification in lung cancer, and to explore its prognostic value. A total of 647 lung tumor samples from 290 patients were included in the study. The ratio of PIK3CA signals/centromere 3 signals in cancer cells was estimated by fluorescence in situ hybridization (FISH7rpar; analysis. Both gains and amplifications were significantly more frequent in squamous cell (gains: 19.4%; amplifications: 34.1%; p<0.0001) and large cell carcinoma (gains: 22.4%; amplifications: 20.4%; p<0.0001) compared with adenocarcinomas (gains 3.0%; amplifications: 4.0%). Conversely, adenocarcinomas displayed significantly more frequent deletions of the PIK3CA locus than the other two histologic types (p<0.0001). No clear correlation between PIK-3CA status and the pT stage, pN stage or the degree of tumor differentiation was found. Ki67 significantly increased with increasing of PIK3CA copy number: 47 tumors with a PIK-3CA deletion had a mean Ki67 of 16, while 103 tumors with PIK3CA amplification showed a mean Ki67 of 28 (p=0.004). Significant association between cell proliferation and PIK-3CA was found (p<0.05). However, no significant correlation was seen between patient survival and PIK3CA amplifications, deletions and gains. PIK3CA amplifications in large cell and squamous cell carcinomas were significantly higher compared with adenocarcinomas. The results suggest that PIK-3CA could be a promising target for selective lung cancer therapy.


Energetics of inclusion-induced bilayer deformations.
The material properties of lipid bilayers can affect membrane protein function whenever conformational changes in the membrane-spanning proteins perturb the structure of the surrounding bilayer. This coupling between the protein and the bilayer arises from hydrophobic interactions between the protein and the bilayer. We analyze the free energy cost associated with a hydrophobic mismatch, i.e., a difference between the length of the protein's hydrophobic exterior surface and the average thickness of the bilayer's hydrophobic core, using a (liquid-crystal) elastic model of bilayer deformations. The free energy of the deformation is described as the sum of three contributions: compression-expansion, splay-distortion, and surface tension. When evaluating the interdependence among the energy components, one modulus renormalizes the other: e.g., a change in the compression-expansion modulus affects not only the compression-expansion energy but also the splay-distortion energy. The surface tension contribution always is negligible in thin solvent-free bilayers. When evaluating the energy per unit distance (away from the inclusion), the splay-distortion component dominates close to the bilayer/inclusion boundary, whereas the compression-expansion component is more prominent further away from the boundary. Despite this complexity, the bilayer deformation energy in many cases can be described by a linear spring formalism. The results show that, for a protein embedded in a membrane with an initial hydrophobic mismatch of only 1 A, an increase in hydrophobic mismatch to 1.3 A can increase the Boltzmann factor (the equilibrium distribution for protein conformation) 10-fold due to the elastic properties of the bilayer.


[Gender differences in the relationship between sleep and depression among elderly people residing at home].
To investigate gender differences in the relationship between sleep and depression in the elderly. Residents of a village in Kumamoto Prefecture, Japan (563 people) aged > or =65 years were given a self-administered questionnaire survey between June and July 2010. To evaluate levels of sleep and depression, the Pittsburgh Sleep Quality Index (PSQI) and the Geriatric Depression Scale-Short Form (GDS-SF) were used. Adjustment factors assessed age, income, residence status, social role, medical history, nursing situation, and cognitive function. As with previous studies, respondents were evaluated as having a disturbed sleep or depression if the sum of their PSQI and GDS-SF scores was 6 or more. We examined the relationship between sleep and depression using multiple logistic regression analysis, with presence of depression in each gender introduced as a dependent variable. Given that some degree of correlation was expected among adjustment factors in the model, we constructed a model that introduced the adjustment factors stepwise to confirm the robustness of the model and any effect of multicollinearity. Overall (n=424), a significant relationship was found between disturbed sleep and depression in all models. The odds ratio was 1.92 (95% confidence interval: 1.11-3.32) in the final model, controlling all adjustment factors. In men (n=198), although the relationship between disturbed sleep and depression was significant before adjustment, no significance was observed after adjustment. In women (n=226), however, a significant relationship was observed between disturbed sleep and depression in both models. After the introduction of all variables as adjustment factors, the odds ratio was 2.28 (95% confidence interval: 1.11-4.69). Our findings suggest a significant relationship between disturbed sleep and depression in elderly women, but not in men. While the reasons for this gender difference are unclear at present, various factors, such as the endocrine system, are likely to be involved. Future studies should take this gender difference into account in order to enact more effective measures for preventing depression in the elderly.


Closure of patent foramen ovale defects using GORE® CARDIOFORM septal occluder: Results from a prospective European multicenter study.
The GORE® CARDIOFORM Septal Occluder (GSO) is a novel device designed for rapid and effective closure of patent foramen ovale (PFO) which has distinctive features making it suitable for a broad spectrum of anatomical variations. We report the procedural and 6 months follow-up results of the first prospective, multicenter study using GSO. This single-arm study included 150 subjects undergoing closure of PFO in 10 European centers. In 149 out of 150 patients implantation of a GSO device was successful. One patient had a different PFO-closure device implanted. Periprocedural complications were few including one patient with suspected transient ischemic attack, two access site bleedings, and one patient with AV-fistula. No device embolization occurred. During the 6-month follow-up period one patient had a transient asymptomatic thrombus on the device and four patients (2.6%) were diagnosed new onset paroxysmal atrial fibrillation, which were successfully treated. No thrombembolic events occurred. Closure was successful in 94.2% of subjects at discharge evaluation and 96.9% at 6 months follow-up. This prospective, multicenter study adds to previous published data and suggests that GSO is a versatile device for PFO closure with high procedural and closure success rates and low complication rates through mid-term follow-up. © 2017 Wiley Periodicals, Inc.


3,4-Methylenedioxymethamphetamine causes cytotoxicity on 661W cells through inducing macrophage polarization.
The abuse of 3,4-methylenedioxymethamphetamine (MDMA), a psychedelic drug, can lead to a variety of disorders in neural system, including the death of retinal neural cells. MDMA at lower doses does not cause obvious cytotoxicity to photoreceptor cells, indicating potential indirect mechanisms which have not yet been elucidated. This study investigated the effect of MDMA at nontoxic concentration on macrophage activation state and its resultant toxicity to photoreceptor cells. Using a co-culture system, cytotoxicity was caused by MDMA on 661W cells after co-culturing with RAW264.7 macrophage. Results showed that MDMA induced the macrophages to M1 polarization, releasing more pro-inflammatory cytokines, upregulating the M1-related gene and protein expression. The phenotype, secretion pattern, and cytotoxicity of the macrophages treated by MDMA are comparable to those of the ones stimulated by IFNγ and LPS. Our study demonstrated that MDMA promoted macrophage polarization to M1 and induced inflammatory response, providing the scientific rationale for the photoreceptor cell damage caused by the MDMA abuse.


Naturally processed non-canonical HLA-A*02:01 presented peptides.
Human leukocyte antigen (HLA) class I molecules generally present peptides (p) of 8 to 11 amino acids (aa) in length. Although an increasing number of examples with lengthy (>11 aa) peptides, presented mostly by HLA-B alleles, have been reported. Here we characterize HLA-A*02:01 restricted, in addition to the HLA-B*0702 and HLA-B*4402 restricted, lengthy peptides (>11 aa) arising from the B-cell ligandome. We analyzed a number of 15-mer peptides presented by HLA-A*02:01, and confirmed pHLA-I formation by HLA folding and thermal stability assays. Surprisingly the binding affinity and stability of the 15-mer epitopes in complex with HLA-A*02:01 were comparable with the values observed for canonical length (8 to 11 aa) HLA-A*02:01-restricted peptides. We solved the structures of two 15-mer epitopes in complex with HLA-A*02:01, within which the peptides adopted distinct super-bulged conformations. Moreover, we demonstrate that T-cells can recognize the 15-mer peptides in the context of HLA-A*02:01, indicating that these 15-mer peptides represent immunogenic ligands. Collectively, our data expand our understanding of longer epitopes in the context of HLA-I, highlighting that they are not limited to the HLA-B family, but can bind the ubiquitous HLA-A*02:01 molecule, and play an important role in T-cell immunity.


Effect of intravenous enkephalin administration on kallikrein-kinin system in experimental hemorrhagic shock. Evidence for activation of kallikrein-kinin system by naloxone.
The effects of enkephalin derivates with different opioid receptor subtype specificity and naloxone on cardiovascular responses and kallikrein-kinin system (KKS) were studied in anesthetized rats exposed to 30% hemorrhage. Administration of a mu-receptor agonist (DAGO) in early hemorrhage improved mean arterial blood pressure (MAP) responses to hemorrhage. This effect could be abolished by naloxone pretreatment. Moreover, a delayed MAP recovery after hemorrhage could be observed. Treatment with a delta-agonist (DADL) resulted in transient depression of MAP and heart rate (HR). Hemorrhage by itself caused only a slight activation of KKS as indicated by decreased plasma kallikreinogen concentration and reduced kallikrein inhibitor capacity after 20% blood loss. Enkephalin administration did not exert significant effects on KKS. Naloxone pretreatment, in contrast, induced prehemorrhagic activation of KKS, which was potentiated by subsequent hemorrhage. Naloxone-induced activation of KKS could be confirmed by an in vitro study. Taken together these results suggest that the KKS is not involved in MAP and HR responses to enkephalin administration during hemorrhage, whereas it might be implicated in naloxone-induced delayed posthemorrhagic MAP recovery.


Buprenorphine and addiction: challenges for the pharmacist.
To present an analysis of the Drug Addiction Treatment Act of 2000 (DATA) and its impact on the practice of pharmacy. Statutes, codes, regulations, newspaper articles, journal articles; search of articles posted on MEDLINE identified using the search terms methadone, buprenorphine, treatment, opioid abuse, and opioid addiction. Not applicable. Not applicable. DATA and Food and Drug Administration approval of sublingual tablets of buprenorphine and buprenorphine with naloxone (Reckitt and Benckiser) will dramatically expand opioid addicts' access to treatment and increase the number of opioid addicts receiving prescriptions for buprenorphine and buprenorphine with naloxone. The availability of buprenorphine will pose unique challenges to pharmacists and suggests the need for education on addiction and greater awareness of the unique needs of patients recovering from addiction. The stage is being set to expand access to treatment and reach more untreated opioid addicts in the United States. Professional organizations such as the American Pharmaceutical Association should work with the U.S. Department of Health and Human Services and its Substance Abuse and Mental Health Services Administration to develop training materials, curricula, and guidelines for pharmacists on substance abuse with a special focus on outpatient opioid treatment. Such materials could be used in continuing education programs and materials and in pharmacy schools.


MiR-148a-3p Regulates Skeletal Muscle Satellite Cell Differentiation and Apoptosis via the PI3K/AKT Signaling Pathway by Targeting Meox2.
As bioinformatic approaches have been developed, it has been demonstrated that microRNAs (miRNAs) are involved in the formation of muscles and play important roles in regulation of muscle cell proliferation and differentiation. Previously, it has been demonstrated that miR-148a-3p is one of the most abundant miRNAs in chicken skeletal muscle. Here, we build on that work and demonstrate that miR-148a-3p is important in the control of differentiation of chicken skeletal muscle satellite cells (SMSCs). Elevated expression of miR-148a-3p significantly promoted differentiation and inhibited apoptosis of SMSCs but did not affect proliferation. Furthermore, it was observed that the mesenchyme homeobox 2 (Meox2) is a target gene of miR-148a-3p and that miR-148a-3p can down-regulate expression of Meox2, which promote differentiation of SMSCs and suppress apoptosis. Furthermore, miR-148a-3p overexpression encouraged activation of the PI3K/AKT signaling pathway, which could be recovered by overexpression of Meox2. Overall, these findings suggest that microRNA-148a-3p is a potent promoter of myogenesis via direct targeting of Meox2 and increase of the PI3K/AKT signaling pathway in chicken SMSCs.


Understanding the Mental Health Impact of the COVID-19 Pandemic Among Individuals With Chronic Illness.
People with chronic illnesses are vulnerable to stress and psychopathology during population-level disasters, as a subset of individuals with disabilities. We aimed to examine the relationships between chronic illness, cumulative and specific stressors, and probable depression, probable anxiety, and post-traumatic stress in an under-resourced urban population in New York City during the COVID-19 pandemic. Using cross-sectional survey data collected in April 2020, we utilized bivariate chi-square analyses and multivariable logistic regression models to estimate differences in and adjusted odds of stressor endorsement and diagnostic prevalence between people with and without chronic illness. We also assessed effect modification of the relationship between stressor exposure and psychopathology by chronic illness status. Compared to people without chronic illness, those who reported having a chronic illness experienced increased odds of probable depression, probable anxiety, and post-traumatic stress. They were also more likely to report high cumulative COVID-19-related stress exposure, death of someone close to them due to coronavirus or COVID-19, family problems, feeling alone, supply shortages, and financial problems. Chronic illness was found to be an effect modifier in the relationship between the death of someone close due to coronavirus or COVID-19 and probable depression and between household job loss and probable anxiety.


Curcumin-loaded chitosan-cholesterol micelles: evaluation in monolayers and 3D cancer spheroid model.
To improve the bioavailability and anticancer potential of curcumin by using a cholesterol-conjugated chitosan micelle. Methods & methods: Cholesterol was conjugated to chitosan (15 kDa) to form self-assembled micelles, which loaded curcumin. Physicochemical characterization and formulation optimization of the drug-loaded micelles (curcumin-loaded chitosan-cholesterol micelles [C-CCM]) were performed. In vitro cellular uptake and viability of C-CCM were investigated in melanoma and breast cancer cell lines. The antitumor efficacy was evaluated in 3D lung cancer spheroid model. The optimized C-CCM had size of approximately 162 nm with loading efficiency of approximately 36%. C-CCM was taken up efficiently by the cells, and it reduced cancer cell viability significantly compared with free curcumin. C-CCM enhanced the antitumor efficacy in spheroids, suggesting that C-CCM could be used as an effective chemotherapy in cancer.


Long-term continuously monocropped peanut significantly changed the abundance and composition of soil bacterial communities.
Soil sickness is the progressive loss of soil quality due to continuous monocropping. The bacterial populations are critical to sustaining agroecosystems, but their responses to long-term peanut monocropping have not been determined. In this study, based on a previously constructed gradient of continuous monocropped plots, we tracked the detailed feedback responses of soil bacteria to short- and long-term continuous monocropping of four different peanut varieties using high-throughput sequencing techniques. The analyses showed that soil samples from 1- and 2-year monocropped plots were grouped into one class, and samples from the 11- and 12-year plots were grouped into another. Long-term consecutive monocropping could lead to a general loss in bacterial diversity and remarkable changes in bacterial abundance and composition. At the genera level, the dominant genus Bacillus changed in average abundance from 1.49% in short-term monocropping libraries to 2.96% in the long-term libraries. The dominant species Bacillus aryabhattai and Bacillus funiculus and the relatively abundant species Bacillus luciferensis and Bacillus decolorationis all showed increased abundance with long-term monocropping. Additionally, several other taxa at the genus and species level also presented increased abundance with long-term peanut monocropping; however, several taxa showed decreased abundance. Comparing analyses of predicted bacterial community functions showed significant changes at different KEGG pathway levels with long-term peanut monocropping. Combined with our previous study, this study indicated that bacterial communities were obviously influenced by the monocropping period, but less influenced by peanut variety and growth stage. Some bacterial taxa with increased abundance have functions of promoting plant growth or degrading potential soil allelochemicals, and should be closely related with soil remediation and may have potential application to relieve peanut soil sickness. A decrease in diversity and abundance of bacterial communities, especially beneficial communities, and simplification of bacterial community function with long-term peanut monocropping could be the main cause of peanut soil sickness.


Effect of preoperative finasteride on perioperative blood loss during transurethral resection of the prostate and on microvessel density in patients with benign prostatic hyperplasia: An open label randomized controlled trial.
Transurethral resection of the prostate (TURP) is a common procedure for the treatment of benign prostatic hyperplasia (BPH). Previous studies on the effect of 5-alpha reductase inhibitors on perioperative blood loss in TURP and microvessel density (MVD) in the prostate are equivocal. We evaluated whether pretreatment with finasteride for 2 weeks before surgery can reduce perioperative blood loss in TURP and MVD in the prostate. Sixty-eight patients of BPH planned for TURP were randomized into two groups. The study group comprising 34 patients was treated with finasteride (5 mg/day) for 2 weeks and the placebo group comprising 34 patients received placebo for 2 weeks, before TURP. Blood loss was measured in terms of a reduction in the blood hemoglobin (Hb) and hematocrit (HCT) levels between preoperative values and 24 h after surgery. MVD was measured in the resected prostate tissue stained with anti-CD31 monoclonal antibody. The reduction of Hb and HCT in the finasteride group was significantly lower than the reduction in the placebo group (P < 0.05). The artery (P = 0.005), vein (P = 0.05), and gland (P = 0.008) densities were significantly less in the finasteride group than in the placebo group. There was no significant correlation between blood loss and MVD. Our study suggests a clear advantage of the preoperative use of finasteride for 2 weeks by reducing the perioperative blood loss in TURP in patients with BPH. While there is a significant reduction in MVD in the prostate on treatment with finasteride, it is not clear that this is the mechanism of reduction in blood loss in TURP.


Passive sampling: partition coefficients for a silicone rubber reference phase.
Silicone rubber sheeting can be used as a passive sampling device for hydrophobic organic contaminants in the environment to determine the available concentrations in water and sediments. Reliable sampler-water partition coefficients are required to determine the sampling rates and the dissolved contaminant concentrations in water and in sediment pore water. Log partition coefficients (logK(sr,w)) for silicone rubber-water have been estimated for 32 polycyclic aromatic hydrocarbons (PAHs), 2 deuterated PAH analogues and 32 chlorobiphenyls (CBs) using the cosolvent method, with methanol as cosolvent. Strong linear relationships were found with literature values for the corresponding log octanol-water partition coefficients (logK(ow)) for both CBs and PAHs, confirming that partitioning into the silicone rubber is strongly determined by the hydrophobicity of the compounds, which suggests logK(ow) is a good predictor of logK(sr,w) and that absorption is the main mechanism for accumulation of analytes into the silicone rubber polymer.


Recent randomized controlled trials in pancreaticoduodenectomy.
To analyze and summarize the recent randomized controlled trials (RCTs) investigating pancreaticoduodenectomy (PD). A MEDLINE search was performed to identify prospective RCTs on PD published during the last decade. Eligible RCTs were analyzed using the following items: publication year, geographical area, study theme, sample size, and multicenter study. Moreover, the quality of each RCT was evaluated. Thirty-four articles were eligible for review. One to 6 RCTs have been carried out annually during the recent 10 years. Geographically, 15 trials were performed in Europe, 10 trials in North America, and 9 in Asia. Studies concerning postoperative complications in the early postoperative period such as pancreatic fistula and delayed gastric emptying have been most frequent. Randomized controlled trials comparing anastomotic procedures for the remnant pancreas, standard PD versus PD with extended lymphadenectomy, and PD versus pylorus-preserving PD follow in descending order. The average sample size has been 117, and 10 RCTs had sample size less than 50. The rate of multicenter studies among all RCTs is 21%, with the rate in the most recent 5 years having increased 2-fold compared with that in the earlier period. Concerning the quality of RCTs, calculation of sample size was described in only 14 RCTs and intention to treat analysis was performed in 26 RCTs. This study reviewed 34 RCTs on PD performed all over the world. Although the quality of every RCT was not satisfactory, high-grade evidence obtained by these RCTs should be applied in clinical settings to improve surgical quality and quality of life for each patient.


Interaction between dopamine D1 and D2 receptors in modulation of the immune response.
The interaction between dopamine D1 and D2 receptors plays a role in immunomodulation. The results of thus interaction depends on the degree of receptor activation with selective agonists in different doses. Combined treatment with agonists of D1 and D2 receptors in high doses had a synergistic effect in the mechanisms of immunomodulation. Receptor agonists in low doses suppressed the immune response. Our results suggest that weak activation of one of these receptors is accompanied by inactivation of the other receptor type.


Cutaneous ulcers in typhoid fever.
Cutaneous lesions in typhoid fever are uncommon. We report cutaneous ulcers in two children (aged 10 years and 3 years) with typhoid fever.


Genetic profile of FOXO3 Single Nucleotide Polymorphism in colorectal cancer patients.
Colorectal cancer (CRC) heritability is determined by the composite relations between inherited variants and environmental factors. In developing countries like India, the incidence rates of CRC are especially increasing. In this study, we have focused on the distribution of the FOXO3 gene polymorphisms among the patients with colorectal cancer in North India. A case-control study was conducted on 487 colorectal cancer patients and 487 age-matched controls. We genotyped SNPs rs2253310 and rs4946936 through PCR-Restriction fragment length polymorphism (RFLP) analysis and PCR-single stranded conformation polymorphism (SSCP) procedure followed by sequence detection. A significantly increased risk of CRC was observed for the CC genotype of the rs4946936 polymorphism compared to the TT genotype (p= 0.02; OR= 1.40 CI=1.05-1.87). GT haplotype appeared to be a "risk" haplotype (OR- 1.71, 95%CI= 0.82~2.19), while as other haplotypes CC (OR- 0.83, 95% CI=0.32~1.54]), CT (OR- 0.75, 95%CI= 0.25~1.01) and GC (OR- 0.98, 95%CI= 0.88~1.14) were found to be "protective" for developing colorectal cancer. This study suggests an association of increased risk of CRC with the rs4946936 polymorphism, but not with the rs2253310 polymorphism.


Non-invasive biomarker sampling and analysis of the exhaled breath proteome.
Exhaled breath condensate (EBC) is a biological fluid that contains trace amounts of secreted pulmonary proteins, and is emerging as a potentially valuable and non-invasively obtained source of disease biomarkers. Proteome analysis of these samples could lead to the identification of prognostic indicators of airway diseases. The objective of this study was to develop a protocol for proteome analysis of EBC samples. In this report, an improved procedure for EBC sample preparation and concentration is presented, together with a method for comparison of the protein profiles between two groups. The presented approach enabled to study the condensed exhaled breath proteome for biomarker analysis, and revealed proteins not previously identified in an EBC proteomics approach. In a comparative pilot study, EBC protein profiles obtained from smokers and non-smokers showed distinct differences and are illustrative for its potential in clinical studies. EBC from smokers contained higher concentrations of the more abundant proteins, such as cytokeratins, compared to non-smokers, and calgranulin B was identified uniquely in EBC samples from smokers.


Activation of hypothalamic neurons by intraovarian pressure signals in a teleost fish, Clarias batrachus: role of mechanosensitive channels.
Application of intraovarian pressure is known to trigger profound cytomorphological changes in the neurosecretory cells of nucleus preopticus in the teleost Clarias batrachus. These findings indicate the presence of stretch receptors in the ovaries, perhaps equipped with mechanosensitive channels that transduce the stretch signals to be transmitted to the brain. To test the occurrence of the mechanosensitive channels in the ovaries, we administered a range of pharmacological agents (lignocaine, quinidine, tetraethylammonium chloride, ethylene-diaminetetraacetic acid and gadolinium) known to block the mechanosensitive ion channels, in the ovarian lumen prior to the administration of the intraovarian pressure. Pretreatment with the above agents inhibited the response by the nucleus preopticus neurosecretory cells to intraovarian pressure. The results suggest the occurrence of the mechanosensitive channels in the ovaries of teleostean fishes. In terms of function we speculate that the stretch sensory system and the ensuing pathway connecting the ovaries with the hypothalamus might play a role in apprising the brain of the status of ovarian maturity and in the initiation of the spawning reflex.


NUSAP1 knockdown inhibits cell growth and metastasis of non-small-cell lung cancer through regulating BTG2/PI3K/Akt signaling.
Non-small-cell lung cancer (NSCLC) is the most common malignancy along with high mortality rate worldwide. Recently, nucleolar and spindle-associated protein 1 (NUSAP1) has been reported to be involved in the malignant progression of several cancers. However, in NSCLC, the biological function of NUSAP1 and its molecular mechanism have not been reported. Here, our findings indicated that the NUSAP1 messenger RNA expression level was remarkably upregulated in NSCLC tissues compared with that of adjacent normal tissues. We also found that NUSAP1 gene expression was notably upregulated in NSCLC cell lines (A549, 95-D, H358, and H1299) compared with that of normal human bronchial epithelial cell line (16HBE). Subsequently, the biological function of NUSAP1 was investigated in A549 and H358 cells transfected with NUSAP1 small interfering RNA (siRNA), respectively. Results showed that NUSAP1 knockdown inhibited NSCLC cell proliferation, and promoted cell apoptosis. Furthermore, the number of cell migration and invasion was significantly suppressed by NUSAP1 knockdown. In addition, our results indicated that NUSAP1 knockdown increased the gene expression of B-cell translocation gene 2 (BTG2), but decreased the expression levels of phosphoinositide 3-kinase (PI3K) and phosphorylated serine/threonine kinase (p-AKT). BTG2 siRNA partly abrogates the effect of NUSAP1 knockdown on BTG2 gene expression. Fumonisin B1 (FB1), a AKT activator, reversed the effect of NUSAP1 knockdown on the biological function in NSCLC. Taken together, NUSAP1 knockdown promotes NSCLC cell apoptosis, and inhibits cell proliferation, cell migration, and invasion, which is associated with regulating BTG2/PI3K/Akt signal pathway. Our findings suggest that NUSAP1 is a promising molecular target for NSCLC treatment.


Assessing potential exposure of birds to pesticide-treated seeds.
Seed treatments are widely used for crop protection and present a particular risk to granivorous birds. UK risk assessment for seed treatments has tended to focus on highly granivorous species; however, under some conditions, non-granivorous birds will take seeds. Better data is needed on which species eat seeds for which pesticide treatments are used. To identify which species will take and eat a range of crop seeds in common usage in the UK, birds visiting bait stations at which untreated seed was presented were video recorded. Information was also obtained on how much seed is taken by individual birds. The seeds tested were wheat, barley, maize, oilseed rape, grass, peas and pelleted sugar beet. For many of the species observed at the bait stations, the amounts of seed consumed during single visits were sufficient to pose a potential risk (toxicity-exposure ratio < 10) if the seed had been treated with one of the more acutely toxic seed treatments. Previous studies have shown that de-husking of seeds can substantially reduce birds' exposure. This paper provides information on which of the species recorded de-husked which seeds, in field conditions. The use of these data in pesticide risk assessment is considered.


In vivo delivery and long-term tissue retention of nano-encapsulated sirolimus using a novel porous balloon angioplasty system.
Among antirestenotic compounds, sirolimus displays a superior safety profile compared to paclitaxel, but its pharmacokinetic properties make it a challenging therapeutic candidate for single-time delivery. Herein we evaluate the feasibility of delivery, long-term retention and vascular effects of sirolimus nanoparticles delivered through a novel porous angioplasty balloon in normal porcine arteries and in a swine model of in-stent restenosis (ISR). Sirolimus nanoparticle formulation was delivered via porous balloon angioplasty to 753 coronary artery segments for pharmacokinetic studies and 26 segments for biological effect of sirolimus delivery in different clinical scenarios (de novo [n=8], ISR [n=6] and following stent implantation [n=12]). Sirolimus coronary artery concentrations were above the target therapeutic level of 1 ng/mg after 26 days, and were >100-fold higher in coronary artery treatment sites than in distal myocardium and remote tissues at all time points. At 28 days, reduction in percent stenosis in formulation-treated sites compared to balloon angioplasty treatment was noted in all three clinical scenarios, with the largest effect seen in the de novo study. Local coronary delivery of sirolimus nanoparticles in the porcine model using a novel porous balloon delivery system achieved therapeutic long-term intra-arterial drug levels without significant systemic residual exposure.


Home food access and children's heart healthy dietary intake at home and child care.
Background: About 12 million children under 5 years of age attend early care and education centers (ECEs). Child intake at home can be impacted by food insecurity, which is higher among low income, rural, and racially diverse families. Aim: Determine whether greater access to fruits, vegetables, and snacks at home was associated with heart-healthy diet score at home and at ECEs in preschool-age children, and to determine whether there is a difference in heart-healthy diet score between home and ECEs. Methods: Cross-sectional study involving children (3-to-5-year-old, n = 88) who attended 16 licensed ECEs across Oklahoma. Caregivers completed the Healthy Home Survey and 3-Dinner Dietary recall to report children's home food access and home dinner dietary intake, respectively. Researchers recorded children's ECE lunch consumption using the Dietary Observation for Child Care. Heart-healthy diet score was derived from composite scores for six variables: consumption of fish, fruits, vegetables, sodium, fiber, and sugary drinks. Results: Home access to total fruits and vegetables (16.2 ± 6.3) outnumbered snacks (5.5 ± 3.0). No difference in composite heart-healthy diet score between ECEs (1.50 ± 0.8) and home (1.27 ± 0.9, P = 0.0851). Children within neither environment met recommendations for most variables (vegetables [18-24%], fruit [6-10%], fish [5-10%], fiber [1%], sodium [22-39%]). No relationship between home food access variables and the heart-healthy diet scores at home or ECEs. Conclusion: Dietary intake of children at home and ECEs does not meet heart-healthy diet score recommendations. Interventions should support preschool aged children from families that are located rurally, low-income, racial minorities, and whose primary caregivers work outside the home.


Enhanced fault-tolerant quantum computing in d-level systems.
Error-correcting codes protect quantum information and form the basis of fault-tolerant quantum computing. Leading proposals for fault-tolerant quantum computation require codes with an exceedingly rare property, a transversal non-Clifford gate. Codes with the desired property are presented for d-level qudit systems with prime d. The codes use n=d-1 qudits and can detect up to ∼d/3 errors. We quantify the performance of these codes for one approach to quantum computation known as magic-state distillation. Unlike prior work, we find performance is always enhanced by increasing d.


[Vitamin D and anti-aging medicine].
Vitamin D has many important roles in calcium and phosphorus metabolisms, the prevention of the cancer, therapeutic effects of autoimmune disease, and the protective effects on the atherosclerotic cardiovascular disease and diabetes. These functions are quite essential factors for the treatment of anti-aging medicine. We had given 1,000 IU/day vitamin D(3) to the patients who had low vitamin D levels in their blood and confirmed the increased vitamin D levels into the optimal range after the treatment. To keep the normal functions of the bone mineral metabolisms and the immune function, it is clinically relevant to detect the vitamin D levels in the blood and support these levels using supplements in the vitamin D deficient patients. Vitamin D is now one of the most essential vitamins in the anti-aging medicine.


A multicenter analysis of the prognostic value of histone H3 K27M mutation in adult high-grade spinal glioma.
High-grade spinal glioma (HGSG) is a rare but aggressive tumor that occurs in both adults and children. Histone H3 K27M mutation correlates with poor prognosis in children with diffuse midline glioma. However, the role of H3 K27M mutation in the prognosis of adults with HGSG remains unclear owing to the rarity of this mutation, conflicting reports, and the absence of multicenter studies on this topic. The authors studied a cohort of 30 adult patients with diffuse HGSG who underwent histological confirmation of diagnosis, surgical intervention, and treatment between January 2000 and July 2020 at six tertiary academic centers. The primary outcome was the effect of H3 K27M mutation status on progression-free survival (PFS) and overall survival (OS). Thirty patients (18 males and 12 females) with a median (range) age of 50.5 (19-76) years were included in the analysis. Eighteen patients had H3 K27M mutation-positive tumors, and 12 had H3 K27M mutation-negative tumors. The median (interquartile range) PFS was 3 (10) months, and the median (interquartile range) OS was 9 (23) months. The factors associated with increased survival were treatment with concurrent chemotherapy/radiation (p = 0.006 for PFS, and p ≤ 0.001 for OS) and American Spinal Injury Association grade C or better at presentation (p = 0.043 for PFS, and p < 0.001 for OS). There were no significant differences in outcomes based on tumor location, extent of resection, sex, or H3 K27M mutation status. Analysis restricted to HGSG containing necrosis and/or microvascular proliferation (WHO grade IV histological features) revealed increased OS for patients with H3 K27M mutation-positive tumors (p = 0.017). Although H3 K27M mutant-positive HGSG was associated with poor outcomes in adult patients, the outcomes of patients with H3 K27M mutant-positive HGSG were somewhat more favorable compared with those of their H3 K27M mutant-negative HGSG counterparts. Further preclinical animal studies and larger clinical studies are needed to further understand the age-dependent effects of H3 K27M mutation.


Clinical implications of the new diagnostic guidelines for dementia.
New criteria have been proposed for diagnosing Alzheimer's disease. These emphasize that this illness exists on a continuum and begins early on. This article reviews the pros and cons of these criteria. It also provides practical guidelines for psychiatrists whose patients may be affected by these new criteria. Particular attention is given to patients who, as opposed to their wanting to know whether they are likely to have AD, want to deny this possibility.


Comparison of coblation annuloplasty and radiofrequency thermocoagulation for treatment of lumbar discogenic pain.
This study aimed to compare the effectiveness and safety of coblation annuloplasty and radiofrequency thermocoagulation for lumbar discogenic pain.Patients who suffered from lumbar discogenic pain and underwent coblation annuloplasty and radiofrequency thermocoagulation surgery were included. A questionnaire, including the visual analo scale (VAS), MacNab criteria, pain relief rate, and any complications due to surgery, was completed by the patients with the help of a trained volunteer who was blinded to the study. Data were collected at 1 week, and 1, 3, 6, and 12 months after surgery. Significant pain relief was defined as postoperative pain relief ≥50% compared with the preoperative state. Any complications during or after surgery were also recorded.A total of 122 patients were included; 37 patients were lost in the follow-up and 85 were evaluated. Among these, 45 patients underwent coblation annuloplasty (CA group, n = 45) and 40 underwent radiofrequency thermocoagulation procedures (RF group, n = 40).VAS pain scores were decreased at 1 week and 1, 3, 6, and 12 months postoperatively compared with preoperation in both groups (P < .05). The CA group had significantly lower VAS scores at 6 and 12 months of follow-up than did the RF group (P < .05). According to the modified MacNab criteria, the proportions of patients with excellent and/or good results at 3, 6, and 12 months of follow-up were significantly higher in the CA group compared with the RF group (P < .05).Only 2 patients reported soreness at the needle insertion site in the CA group. However, 3 patients had soreness at the needle insertion site, 3 had increased intensity of low back pain, 1 had intracranial hypotension, and 2 had new numbness in the leg and foot in the RF group. At the 1-year follow-up, this numbness was present all of the time. No major complications occurred in the CA group.Our study suggests that CA is a more effective and safe minimally invasive procedure than RF for treating lumbar discogenic pain.


Intense Pulsed Plus Low-Level Light Therapy in Meibomian Gland Dysfunction.
To analyse the clinical outcome in patients with meibomian gland dysfunction (MGD) who underwent intense pulsed light (IPL) plus low-level light therapy (LLL). The prospective non-comparative study included identified by MGD patients with altered interferometry and lower loss area of the meibomian glands (LAMG), who underwent IPL plus LLL, between July 2020 and August 2020. A multimodal assessment was performed before, 2-3 weeks, and 6 months after treatment. The main outcome was lipid layer thickness (LLT) and the secondary outcomes were the ocular surface disease index (OSDI) score, presence of corneal fluorescein staining (CFS), blink rate (BR), Schirmer test (ST), tear meniscus height (TMH), tear osmolarity (OSM), non-invasive break-up time (NIBUT) and LAMG. This study included 62 eyes of 31 patients, 61.3% female, with a mean age of 66.94±9.08 years at the time of IPL plus LLL treatment. LLT (<0.001) grades improved 6 months after treatment. The mean OSDI score improved (p<0.001) from 45.02±21.17 (severe symptoms) to 22.35±17.68 (moderate symptoms) at 2-3 weeks and 8.24±17.9.91 (normal) at 6 months after treatment. CFS was identified in 51.6% (32/62) before and in 45.2% (28/62) 6 months (p=0.293) after treatment. ST (p=0.014) grades improved; OSM grades mild worsened (p<0.001); TMH, NIBUT and LAMG grades did not modify 6 months after treatment. No patient suffered any adverse effects. IPL combined with LLL was effective and safe, improving the lipid layer thickness in MGD and decreasing the level of symptoms.


Overexpressed immunoglobulin-like transcript (ILT) 4 in lung adenocarcinoma is correlated with immunosuppressive T cell subset infiltration and poor patient outcomes.
The poor response to current PD-1/PD-L1 inhibitors in lung cancer patients requires development of novel immunotargets. Immunoglobulin-like transcript (ILT)4 is an immunosuppressive molecule mainly expressed in myeloid innate cells. Recent studies showed that ILT4 was highly expressed in multiple malignant cells and regulated tumor biologies including proliferation, invasion and metastasis. However, the immunomodulatory role of tumor cell-derived ILT4 is unclear. Here we aimed to analyze the correlation of tumor cell ILT4 expression with T cell infiltration and subset distribution, illustrate ILT4-regulated immunosuppressive microenvironment, and raise tumor cell-derived ILT4 as a novel immunotherapeutic target and prognostic biomarker for lung adenocarcinoma (LUAD) patients. We collected the tissue samples and corresponding clinicopathological data from 216 primary LUAD patients. Using immunohistochemical staining and public database analyses we investigated the relationship between ILT4 expression and different T cell subset density as well as patient outcomes. Enriched ILT4 expression in tumor cells of LUAD tissues indicated reduced T cell infiltration in the tumor microenvironment (TME), advanced diseases and poor patient overall survival (OS). Further T cell subset analyses revealed that ILT4 expression was correlated with decreased CD8+T cell and increased Treg frequency in both cancer nest and stroma, but not with altered CD4+T cell frequency. High ILT4 level combined with low CD8+T cell/high Treg density predicted markedly poorer clinical outcomes compared with any of these biomarkers alone. Tumor cell-derived ILT4 is correlated with immunosuppressive T cell subset infiltration and poor clinical outcomes, and might be a potential immunotherapeutic target and prognostic biomarker for LUAD patients. Combined ILT4 expression and CD8+ T cell/Treg frequency in tumor infiltrating lymphocytes (TILs) are stronger predictors for patient outcomes.


Contrast-Induced Acute Kidney Injury: Comparison of Preventative Therapies.
Contrast medium is used daily for diagnostic and interventional procdures as a means to visualize blood vessels. The administration of contrast dye, however, can lead to an acute reduction in kidney function. This complication can impact length of hospital stay, risk of dialysis, and increased hospital mortality. Common preventative measures include N-acetylcysteine and intravenous hydration. The evidence reviewed revealed hydration to be the more effective treatment to reduce the risk of acute kidney injury.


Spatially resolved quantification of metal ion concentration in a biofilm-mediated ion exchanger.
A bioremediation process to remove Co(2+) from aqueous solution is investigated in this study using a magnetic resonance imaging (MRI) protocol to rapidly obtain multiple 2D spatially resolved Co(2+) ion concentration maps. The MRI technique is described in detail and its ability to determine the evolution in both axial and radial concentration profiles demonstrated, from which total column capacity can be determined. The final ion exchange column design allows operation in the 'plug flow' regime, hence making use of its full capacity before breakthrough. Conventional techniques for such process optimization are either restricted to the analysis of the exchanger outlet, which provides no information on the spatial heterogeneity of the system, or are invasive and need a variety of sample points to obtain 1D concentration information. To the best of our knowledge, our results represent the first concentration maps describing the bioremediation of metal ion contaminated water.


Computational fluid dynamics analysis and experimental study of a low measurement error temperature sensor used in climate observation.
To improve the air temperature observation accuracy, a low measurement error temperature sensor is proposed. A computational fluid dynamics (CFD) method is implemented to obtain temperature errors under various environmental conditions. Then, a temperature error correction equation is obtained by fitting the CFD results using a genetic algorithm method. The low measurement error temperature sensor, a naturally ventilated radiation shield, a thermometer screen, and an aspirated temperature measurement platform are characterized in the same environment to conduct the intercomparison. The aspirated platform served as an air temperature reference. The mean temperature errors of the naturally ventilated radiation shield and the thermometer screen are 0.74 °C and 0.37 °C, respectively. In contrast, the mean temperature error of the low measurement error temperature sensor is 0.11 °C. The mean absolute error and the root mean square error between the corrected results and the measured results are 0.008 °C and 0.01 °C, respectively. The correction equation allows the temperature error of the low measurement error temperature sensor to be reduced by approximately 93.8%. The low measurement error temperature sensor proposed in this research may be helpful to provide a relatively accurate air temperature result.


Survival rates and periimplant soft tissue evaluation of extraoral implants over a mean follow-up period of three years.
The use of implants with extraoral prostheses provides excellent support, stability, and retention, thereby offering the potential for improving a patient's appearance and quality of life. However, few studies have examined cumulative survival rates of extraoral implants, nor have these reports documented long-term aspects of treatment, such as soft tissue health around abutments. The purpose of this study was to evaluate the survival rates and the periimplant soft tissue responses of extraoral implants used to retain facial prostheses. Thirty-three patients with auricular, nasal, and orbital anatomical compromise were treated with 98 craniofacial and dental implants. Of the 33 patients, 14 had auricular, 9 had nasal, and 10 had orbital defects. After a 3-month osseointegration period, implant-retained prostheses were fabricated. Following completion of treatment, each patient was seen at 6-month intervals. These examinations were recorded for this patient cohort from 25 to 50 months. Data were analyzed using Kaplan-Meier survival analysis. A 5-point scale was used to record the health of periimplant soft tissues. The unit of measure as a visit/site unit was assigned for each instance and implant site. Periimplant soft tissue reactions were assessed for auricular, nasal, and orbital defects, for each implant site used for these patients' treatments. The overall cumulative survival rates were 100% for auricular, 83.3% for nasal, and 77.4% for orbital implants, respectively. The survival rates of the implants were 72.7% for those placed in irradiated sites treated without adjunctive HBO therapy, and 93.4% for implants placed in nonirradiated sites. To evaluate the response of the periimplant soft tissues to the implants, a total of 524 visits/sites were recorded. Absence of inflammation (grade 0) of the periabutment soft tissues was observed in 73.3% of the visits/sites. The anatomical site into which the implant is placed has an effect on success rate. The auricular site is the most predictable implant site. Survival rates of nasal and orbital implants were found to offer promising results in achieving reliable implant prognoses in these regions. Regardless of the implant site, a decreased survival rate was observed in the irradiated sites. Periimplant soft tissue reactions were most commonly associated with lapses in hygiene.


ZIP It: Neural Silencing Is an Additional Effect of the PKM-Zeta Inhibitor Zeta-Inhibitory Peptide.
Protein kinase M ζ (PKMζ), an atypical isoform of protein kinase C, has been suggested to be necessary and sufficient for the maintenance of long-term potentiation (LTP) and long-term memory (LTM). This evidence is heavily based on the use of ζ inhibitory peptide (ZIP), a supposed specific inhibitor of PKMζ that interferes with both LTP and LTM. Problematically, both LTP and LTM are unaffected in both constitutive and conditional PKMζ knock-out mice, yet both are still impaired by ZIP application, suggesting a nonspecific mechanism of action. Because translational interference can disrupt neural activity, we assessed network activity after a unilateral intrahippocampal infusion of ZIP in anesthetized rats. ZIP profoundly reduced spontaneous hippocampal local field potentials, comparable in magnitude to infusions of lidocaine, but with a slower onset and longer duration. Our results highlight a serious confound in interpreting the behavioral effects of ZIP. We suggest that future molecular approaches in neuroscience consider the intervening level of cellular and systems neurophysiology before claiming influences on behavior. Long-term memory in the brain is thought to arise from a sustained molecular process that can maintain changes in synaptic plasticity. A so-called candidate for the title of "the memory molecule" is protein kinase M ζ (PKMζ), mainly because its inhibition by ζ inhibitory peptide (ZIP) interferes with previously established synaptic plasticity and memory. We show that brain applications of ZIP that can impair memory actually profoundly suppress spontaneous brain activity directly or can cause abnormal seizure activity. We suggest that normal brain activity occurring after learning may be a more primary element of memory permanence.


Platelet-activating factor induces the gene expression of TIMP-1, -2, and PAI-1: imbalance between the gene expression of MMP-9 and TIMP-1 and -2.
Previous studies in the laboratory have shown that platelet-activating factor (PAF), a potent inflammatory mediator that accumulates rapidly in the cornea after an injury, stimulates the expression of urokinase (uPA) and matrix metalloproteinase-1 (MMP-1) and -9 (MMP-9). Tissue inhibitors of MMPs (TIMPs) and plasminogen activator inhibitor (PAI-1) are produced in conjunction with these enzymes and are important regulators of their activity. Here, the authors investigated how PAF affects the expression of PAI-1, TIMP-1 and -2 relative to that of uPA, MMP-1, and -9 in rabbit corneal epithelial cells. Rabbit corneas were incubated in MEM medium containing 100 nM cPAF. To block the effects of PAF in some studies, corneas were preincubated for 1 hr in the presence of the PAF antagonist BN50730 (10 microM). At several time intervals, mRNA was extracted from epithelial cells and the levels of gene expression for the enzymes and their inhibitors were determined by real-time PCR. All quantitations were normalized to the 18s rRNA values (endogenous control) and changes in gene expression were reported as fold increase relative to untreated controls. PAF produced a 20-fold increase in the gene expression of PAI-1 at 8 hr, while similar fold increases in uPA mRNA expression occurred at 2 hr. PAF treatment also stimulated the expression of TIMP-1 and -2 genes, with a six-fold increase in TIMP-1 expression occurring at 36 hr and a four-fold increase in TIMP-2 expression at 24 hr. Maximal induction of MMP-1 and -9 mRNA, on the other hand, occurred at 4 and 8 hr, respectively. Induction of MMP-1 gene expression was similar to that of its inhibitors TIMP-1 and -2, while MMP-9 mRNA induction exceeded that of these inhibitors by 100-fold. The PAF-induced expression of PAI-1, TIMP-1 and -2 mRNAs was abolished by pre-treatment with BN50730. These data indicate that PAF activates the gene expression of TIMP-1, -2, and PAI-1 in corneal epithelium by a receptor-mediated mechanism. Furthermore, PAF induced overexpression of MMP-9 mRNA relative to that of TIMP-1 and -2, suggesting an imbalance between the expression of this proteolytic enzyme and its inhibitors, which may contribute to changes in the wound-healing process and ultimately lead to corneal ulcer development.