[One stage reconstruction of the trachea with an island flap (author's transl)].
After treatment of the tracheal or laryngo-tracheal stenosis and forming a groove or using Rethi's operation, putting a full thickness skin graft or mucosa into the posterior wall, we use a silicone rubber tube for dilatation. An island flap, pedicled upon the long muscles of the larynx is used for closing the defect in the anterior wall of the trachea. We treated four patients with this method, three left hospital with normal diameter of trachea and resistance between 17 and 20 mm H2O/1/s.


Lu 25-109, a combined m1 agonist and m2 antagonist, modulates regulated processing of the amyloid precursor protein of Alzheimer's disease.
To examine the effects of the combined muscarinic ml-agonist/m2-antagonist Lu 25-109 on regulated processing of the amyloid protein precursor (APP), we used both transfected cells expressing human muscarinic m1 or m2 acetylcholine receptors, and fresh rat hippocampal slices. Lu 25-109 readily stimulated APPs secretion from HEK 293 cells overexpressing m1, but not m2, receptors, as well as from the hippocampal brain slices. Time-course analyses revealed a rapid (5-35 minutes), and a delayed (55-75 minutes) secretory response to Lu 25-109 with distinct concentration profiles suggesting two distinct cell biological mechanisms. Both responses appeared to reflect post-translational mechanisms because levels of APP message were unchanged after 60 minutes of stimulation with Lu 25-109. In comparison to carbachol, Lu 25-109 had a significantly lower intrinsic activity at muscarinic m1 receptors, compatible with a pharmacological profile as a partial agonist at recombinantly expressed m1 receptors. In as much as stimulation of APPs secretion is associated with reduced formation of A beta peptides, Lu 25-109 may be useful to reduce A beta generation, and thus, slow amyloid plaque formation. Moreover, Lu 25-109 may be useful in promoting the known neurotrophic and neuroprotective biological functions of secreted APPs.


A cybernetic eye for rare disease.
Deep learning implemented in a collaborative cloud-based platform empowers ophthalmologists in the diagnosis of congenital cataracts.


Attentional demands for static and dynamic equilibrium.
Upright standing and walking tasks require the integration of several sources of sensory information. In a normal and highly predictable environment, locomotor synergies involving several muscles may take place at lower spinal levels with neural circuitry tuned by local loops of assistance or self-organizing processes generated in coordinative networks. When ongoing regulation of gait is necessary (obstacles, changes in direction) supraspinal involvement is necessary to perform movements adapted to the environment. Using a classical information processing framework and a dual-task methodology, it is possible to evaluate the attentional demands for performing static and dynamic equilibrium tasks. The present experiment evaluates whether the attentional requirements for a control sitting condition and for standing and walking conditions vary with the intrinsic balance demands of the tasks. The results show that standing and walking conditions required more attention than sitting in a chair. The attentional cost for walking was also significantly greater than for standing. For the walking task, reaction times when subjects were in single-support phase (small base of support) were significantly longer than those in double-support phase, suggesting that the attentional demands increased with an increase in the balance requirements of the task. Balance control requires a continuous regulation and integration of sensory inputs; increasing balance demands loads the higher level cognitive system.


"I Wasn't a Priority, I Wasn't a Victim": Challenges in Help Seeking for Transgender Survivors of Intimate Partner Violence.
Among the crucial advancements in the study of intimate partner violence (IPV) is an understanding of the distinct help-seeking barriers that gay and lesbian victims face. Despite these additions to the literature, transgender IPV victimization remains under-researched. The current study utilized semi-structured interviews and open-ended questionnaires of 18 trans-identified survivors of IPV. Working through a modified grounded analytic approach, two major themes emerged in the help-seeking process: "walking the gender tightrope" in which participants first struggled with gendered notions of victimization that made it difficult to identify abuse, and second, the challenges of "navigating genderist resources."


Adaptation of renal function to hypotonic medium in the winter flounder (Pseudopleuronectes americanus).
The kidneys of winter flounders transferred to hypotonic medium were investigated for glomerular and tubular handling of fluid and electrolytes and for the urinary excretion of proteins. Media were sea water (925 mosm X kg-1) and brackish water (70 mosm X kg-1). In sea water, the urine was hypertonic to the plasma in 7 fish of this study. Urine flow rate was correlated with the GFR. After adaptation to brackish water a delay of 1 to 3 days was observed until the kidneys switched from fluid retention to the excretion of large amounts of dilute urine. GFR and urine flow rate were increased from 0.61 +/- 0.08 to 1.58 +/- 0.29 ml X h-1 X kg-1 and from 0.14 +/- 0.02 to 0.68 +/- 0.08 ml X h-1 X kg-1, respectively (mean +/- SEM). With increased filtered load the tubular reabsorption of fluid decreased from 74 +/- 2.4% to 45 +/- 11.2%. The excretion rates of sodium and potassium were increased due to decreased fractional sodium and potassium reabsorption. The urinary excretion of divalent cations, however, was reduced because the net tubular reabsorption of calcium was increased and the net secretion of magnesium was diminished. Both the urinary total protein concentration and the protein pattern showed no significant change, but the rate of protein excretion was increased from 0.21 +/- 0.04 to 0.60 +/- 0.05 mg X h-1 X kg-1. The comparison of protein patterns obtained from urine and serum samples revealed that high molecular weight (HMW) proteins prevail in the serum whereas low molecular weight (LMW) proteins dominate in the urine. The diminished quantity of the HMW-protein fraction in the urine thus may reflect size selectivity of the glomerular filtration barrier for serum proteins also in the winter flounder.


Coronavirus Disease 2019 Vaccine-Breakthrough Infections Requiring Hospitalization in Mayo Clinic Florida Through August 2021.
We characterized coronavirus disease 2019 (COVID-19) breakthrough cases admitted to a single center in Florida. With the emergence of delta variant, an increased number of hospitalizations was seen due to breakthrough infections. These patients were older and more likely to have comorbidities. Preventive measures should be maintained even after vaccination.


Watering regime influences Cd concentrations in cultivated spinach.
In washed spinach, a maximum Cd concentration of 0.20 mg/kg fresh weight (FW) is allowed according to European regulations. Producers experience that this concentration can sometimes be exceeded even on soils with baseline Cd concentrations. There is a growing need to quantify the factors determining Cd uptake in the crop in order to anticipate the risk of exceedance when selecting a field for cultivation. Interseasonal variation in precipitation may be one of the factors influencing Cd uptake by crops. A pot experiment was set up where spinach plants were subject to different watering regimes. Treatment with more limited water supply during periods of high demand resulted in significantly higher accumulated Cd concentrations (0.25-0.31 versus 0.17-0.23 mg/kg FW). Concentrations at or above the maximum allowed limit were of concern, considering that the soil used in the experiment originated from a typical field in an agricultural region without any specific contamination. Probabilities to exceed maximum concentrations in the different watering regimes were estimated using Monte Carlo simulation. Results suggested that the watering regimes significantly determine the effective risk of exceeding the maximum concentrations. Their effects may be of high practical importance in the field.


Self-assembled nanoparticles based on hydrophobically modified chitosan as carriers for doxorubicin.
In this study self-assembled nanoparticles based on oleoyl-chitosan (OCH) were prepared with a mean diameter of 255.3 nm and an almost spherical shape. The toxicity profile of OCH nanoparticles was evaluated in vitro via hemolysis test and MTT assay. The hemolysis rates of OCH nanoparticles tested in different conditions came well within permissible limits (5%). The OCH nanoparticles showed no cytotoxicity to mouse embryo fibroblasts. Doxorubicin (DOX) was efficiently loaded into OCH nanoparticles with an encapsulation efficiency of 52.6%. The drug was rapidly and completely released from the nanoparticles (DOX-OCH nanoparticles) at pH 3.8, whereas at pH 7.4 there was a sustained release after a burst release. The inhibitory rates of DOX-OCH nanoparticle suspension to different human cancer cells (A549, Bel-7402, HeLa, and SGC-7901) significantly outperformed that of DOX solution. These results revealed the potential of OCH nanoparticles as carriers for hydrophobic antitumor agents.


Establishment of animal models to analyze the kinetics and distribution of human tumor antigen-specific CD8⁺ T cells.
Many patients develop tumor antigen-specific T cell responses detectable in peripheral blood mononuclear cells (PBMCs) following cancer vaccine. However, measurable tumor regression is observed in a limited number of patients receiving cancer vaccines. There is a need to re-evaluate systemically the immune responses induced by cancer vaccines. Here, we established animal models targeting two human cancer/testis antigens, NY-ESO-1 and MAGE-A4. Cytotoxic T lymphocyte (CTL) epitopes of these antigens were investigated by immunizing BALB/c mice with plasmids encoding the entire sequences of NY-ESO-1 or MAGE-A4. CD8(+) T cells specific for NY-ESO-1 or MAGE-A4 were able to be detected by ELISPOT assays using antigen presenting cells pulsed with overlapping peptides covering the whole protein, indicating the high immunogenicity of these antigens in mice. Truncation of these peptides revealed that NY-ESO-1-specific CD8(+) T cells recognized D(d)-restricted 8mer peptides, NY-ESO-181-88. MAGE-A4-specific CD8(+) T cells recognized D(d)-restricted 9mer peptides, MAGE-A4265-273. MHC/peptide tetramers allowed us to analyze the kinetics and distribution of the antigen-specific immune responses, and we found that stronger antigen-specific CD8(+) T cell responses were required for more effective anti-tumor activity. Taken together, these animal models are valuable for evaluation of immune responses and optimization of the efficacy of cancer vaccines.


Posterior to the ridge laser treatment for severe stage 3 retinopathy of prematurity.
Current methods of treating the avascular retina with laser photocoagulation for severe retinopathy of prematurity (ROP) are not completely effective in the reduction of visual morbidity. We report a case series in which additional laser treatment, called 'posterior laser', was delivered posterior to the neovascular ridge, for eyes with severe stage 3 ROP in zone II with avascular retina posterior to the ridge. Retrospective chart review. Infants who underwent laser treatment, posterior to the neovascular ridge for severe ROP at the Alberta Children's Hospital, between January 2005 and October 2008. Charts were reviewed for 18 eyes of 11 patients and collected information included demographic data, clinical examination results, and digital retinal images. Structural and functional outcomes of treatment. Four (22%) of 18 eyes received 'posterior laser' as primary treatment and the remainder of eyes (78%) received 'posterior laser' following previous laser photocoagulation anterior to the neovascular ridge. Mean birthweight was 688 g (552-930) and mean gestational age was 24 weeks (23-28). There were no complications because of the posterior laser treatment. In all, 16 of 18 eyes experienced rapid regression of the ridge and subsequent decrease in vascular dilation and tortuosity within 1 week. Two eyes required vitrectomy for 4A retinal detachment; however, no eyes developed stage 4B ROP. Posterior to the ridge laser in the setting of the morphological criteria described had no increased safety concerns and resulted in rapid regression of ROP with good outcomes.


Design, synthesis and molecular docking studies of some novel spiro[indoline-3, 4'-piperidine]-2-ones as potential c-Met inhibitors.
Deregulation of receptor tyrosine kinase c-Met has been reported in human cancers and is considered as an attractive target for small molecule drug discovery. In this study, a series of spiro[indoline-3, 4'-piperidine]-2-ones were designed, synthesized and evaluated as novel c-Met inhibitors. The results showed that the majority of the compounds exhibited significant inhibitory effect on c-Met with IC(50) values of 0.0147-17 μM in TR-FRET-based assay and IC(50) values of 1.56-1400 μM in cell-based assay. Furthermore, our docking experiments verified the results and explained the molecular mechanism of eminent activities to c-Met.


In-Hospital Haloperidol Use and Perioperative Changes in QTc-Duration.
Haloperidol may prolong ECG QTc-duration but is often prescribed perioperatively to hip-fracture patients. We aimed to determine (1) how QTc-duration changes perioperatively, (2) whether low-dose haloperidol-use influences these changes, and (3) which clinical variables are associated with potentially dangerous perioperative QTc-prolongation (PD-QTc; increase >50 ms or to >500 ms). Prospective cohort study. Tertiary university teaching-hospital. Patients enrolled in a randomized controlled clinical trial of melatonin versus placebo on occurrence of delirium in hip-fracture patients. Data from ECGs made before and after hip surgery (1-3 days and/or 4-6 days post-surgery) were analyzed. QTc-duration was measured by hand, blinded for haloperidol and pre/post-surgery status. Clinical variables were measured at baseline. Mixed model analysis was used to estimate changes in QTc-duration. Risk-factors for PD-QTc were estimated by logistic regression analysis. We included 89 patients (mean age 84 years, 24% male); 39 were treated with haloperidol. Patients with normal pre-surgery QTc-duration (male ≤430 ms, female ≤450 ms) had a significant increase (mean 12 ms, SD 28) in QTc-duration. A significant decrease (mean 19 ms, SD 34) occurred in patients with prolonged pre-surgery QTc-duration (male >450ms, female >470 ms). Haloperidol-use did not influence the perioperative course of the QTc-interval (p=0.351). PD-QTc (n=8) was not associated with any of the measured risk-factors. QTc-duration changed differentially, increasing in patients with normal, but decreasing in patients with abnormal baseline QTc-duration. PD-QTc was not associated with haloperidol-use or other risk-factors. Low-dose oral haloperidol did not affect perioperative QTc-interval.


mTOR-autophagy promotes pulmonary senescence through IMP1 in chronic toxicity of methamphetamine.
It is growingly concerned about methamphetamine (MA)-induced lung toxicity. IMP1 is identified as a key molecule for cell life processes, but the role of IMP1 in MA-induced senescence remains unclear. The purpose of this study was to investigate whether chronic exposure to MA can cause autophagy and senescence of the lungs, whether there are interactions between Mammalian target of rapamycin (mTOR) and IMP1 and whether IMP1 is involved in pulmonary senescence promoted by mTOR-autophagy. The rats were randomly divided into control group and MA group, following by H&E staining, immunohistochemistry staining and Western blot. The alveolar epithelial cells were proceeded by ß-galactosidase staining, cell cycle detection, transfection and co-immunoprecipitation. Long-term exposure to MA led to the thickening of alveolar septum and more compact lungs. MA promoted the conversion of LC3-I to LC3-II and inhibited the activation of mTOR to induce autophagy. Bioinformatics and co-immunoprecipitation results presented the interactions between IMP1 and mTOR. MA induced cell senescence by decreasing IMP1, up-regulating p21 and p53, arresting cell cycle and increasing SA-β-gal. Overexpression of IMP1 reduced p21 and SA-β-gal to inhibit the senescence of alveolar epithelial cells. These results demonstrated that mTOR-autophagy promotes pulmonary senescence through IMP1 in chronic toxicity of methamphetamine.


History and development of ophthalmology in Taiwan.
Western medicine was first introduced to Taiwan by medical missionaries in the mid-19th century. Modernization of medicine was systematically transplanted to Taiwan in the Japanese colonial period, and ophthalmology was established third among hospital departments, following internal medicine and surgery. Dr Hidetaka Yamaguchi, an ophthalmologist, was the first head of the Taihoku Hospital, later known as National Taiwan University Hospital (NTUH; Taipei, Taiwan). Ophthalmologists during the colonial period conducted studies on tropical and infectious eye diseases. After World War II, ophthalmologists at NTUH played an important role in medical education, residency training, studies, and teaching. Dr Yan-Fei Yang established the Taiwan Ophthalmological Society in 1960 and instituted its official journal in 1962. Dr Ho-Ming Lin established the Department of Ophthalmology at the Tri-Service General Hospital in the 1950s and the Veterans General Hospital in the 1960s. Taiwan ophthalmologists eradicated trachoma by 1971. Cataract surgery and penetrating keratoplasty were initially performed in the 1960s. Currently, there are about 1600 ophthalmologists in Taiwan conducting an estimated 120,000 cataract surgeries and 600 corneal transplantations annually. Many subspecialty societies have been established recently that serve to educate Taiwanese ophthalmologists and to connect with international ophthalmic societies. Taiwan ophthalmologists continue to contribute to the advancement of ophthalmic knowledge globally.


Use of a latissimus dorsi myocutaneous flap for closure of an orocutaneous fistula of the cheek.
The latissimus dorsi myocutaneous flap can be used successfully for external cover in the cheek region when the nature of the defect precludes the use of other local or regional flaps. It is exceedingly useful when a large amount of well-vascularized tissue is needed. The flap is extremely reliable and versatile as a one-stage reconstruction. Its major drawbacks are its bulkiness and the necessity to reposition the patient intraoperatively.


Development of formaldehyde dehydrogenase-coupled assay and antibody-based assays for ALKBH5 activity evaluation.
N6-methyladenosine (m6A) is the most prevalent internal modification of eukaryotic messenger RNA (mRNA). Until now, two RNA demethylases have been identified, including FTO (fat mass and obesity-associated protein) and ALKBH5 (α-ketoglutarate-dependent dioxygenase alkB homologue 5). As a mammalian m6A demethylase, ALKBH5 significantly affects mRNA export and RNA metabolism as well as the assembly of mRNA processing factors in nuclear speckles, and ALKBH5 may play a significant role in these biological processes. Nevertheless, no modulator of ALKBH5 has been reported. The reason for that may be the lack of in vitro assays for ALKBH5 inhibitor screening. Herein, we describe the development of two homogeneous assays for ALKBH5 using N6-methyladenosine as substrate with different principles. Using ALKBH5 recombinant, we developed a formaldehyde dehydrogenase coupled fluorescence based assay and an antibody based assay for the activity evaluation of ALKBH5. These robust coupled assays are suitable for screening ALKBH5 inhibitors in 384-well format (Z' factors of 0.74), facilitating the discovery of modulators in the quest for the regulation of biological processes.


The evolution of quality management in state Medicaid agencies: a national survey of states with comprehensive managed care programs.
Concern has been expressed about whether managed care health plans can successfully meet the special needs of Medicaid beneficiaries. A 1996 survey indicated that state Medicaid agencies had just begun conducting quality oversight and management. Since then the federal government has released guidelines under the Quality improvement System for Managed Care (QISMC) program to assist states with quality management of managed care programs. In 1999 a follow-up telephone survey was conducted with representatives from 45 states to describe the current state of and changes in quality management activities by state Medicaid agencies for Medicaid beneficiaries enrolled in managed care. The 45 states represented a 50% increase between 1995 and 1999. The number of states enrolling the disabled had doubled (from 15 to 30). Most states collecting data on satisfaction and childhood immunizations fed it back to health plans, although feedback of other measures of access and quality occurred less frequently and fewer states provided information to beneficiaries choosing health plans. Fewer than 25% of states reported having even one health plan demonstrate improvement in individual measures of access and quality except for prenatal care (28%) and childhood immunizations (33%). Fewer than half of the states included contractual penalties in their contracts with health plans, and very few (three or fewer per penalty) had over invoked such penalties. State Medicaid agencies continue to adapt to their new roles as value-based purchasers of health care. Although increasing numbers of states collect data on satisfaction, access, and quality of care, few states have been able to document improved performance in the health plans they oversee.


Anatomical risk factors for spermatic cord torsion and their involvement in the choice of orchidopexy technique.
We aim by this article to present a literature review on the anatomical risk factors for spermatic cord torsion and their involvement the different techniques of orchidopexy. The literature review was conducted following PRISMA check-list, using PubMed database and the Mesh terms: testis, torsion, anomaly, orchidopexy. Techniques of surgical management provided by the EMC (French medico-surgical encyclopedia) were also used. Database research identified 500 articles, and 16 mores articles were added from the review of the references lists of relevant articles. At the end, 42 articles were useful for our review including 6 reviews, 5 cross-sectional studies, 14 cohorts, 10 case reports, 1 meta-analysis, 1 letter, and 5 experimental studies. High insertion of the tunica vaginalis, a long mesorchium, deficient attachment of the epididymis to the testis, and anomalies of the gubernaculum testis are the anatomical predispositions for spermatic cord torsion. After reduction of torsion, many surgical techniques for the fixation of the testis have been suggested including: conventional technique by triangulation with or without fasciotomy, window orchidopexy, scrotal pouch, and vaginal eversion with or without dartos fixation. The most common anatomical factor associated with spermatic cord torsion is the high insertion of the tunica vaginalis. Vaginal eversion with fixation to the dartos might be superior to other known techniques and seems promising to become standard.


Nutrients and bioactive compounds of Thai indigenous fruits.
This study determined the nutritional potential of Thai indigenous fruits in terms of nutrients, bioactive compounds, and antioxidant activities. Three indigenous fruits were collected at two conservation areas in Kanchanaburi province, Thailand. The results showed that Phyllanthus emblica L. exhibited the highest levels of vitamin C (575±452mg/100g), total phenolics (TP) (3703±1244mGAE/100g), and antioxidant activities, as measured by DPPH, FRAP and ORAC assays. Compared to the other two fruits, Antidesma velutinosum Blume contained higher levels of most nutrients and dietary fibre (15.6±5.9g/100g), as well as carotenoids (335±98μg/100g) and phytosterols (22.1±3.9mg/100g). Spondias pinnata (L.f.) Kurz was high in total phenolics (3178±887mGAE/100g) and antioxidant activity. Moreover, high correlations were found between TP and antioxidant activities (r>0.9). These Thai indigenous fruits are potentially good sources of nutrients, bioactive compounds, and antioxidant activities. Conservation and utilisation should be promoted for food security and consumption as part of a healthy diet.


Water/silica nanoparticle interfacial kinetics of sulfate, hydrogen phosphate, and dithiocyanate radicals.
The values of the rate constants for the reactions of the sulfate (2.5 x 10(9) M(-1) s(-1)) and hydrogen phosphate (2.2 x 10(8) M(-1) s(-1)) radicals with silica nanoparticles are obtained by flash photolysis experiments with silica suspensions containing S(2)O(8)(2-) or P(2)O(8)(4-), respectively. The interaction of these radicals with the silica nanoparticles leads to formation of transients, probably adsorbed sulfate and hydrogen phosphate radicals, with absorption maxima at around 320 and 350 nm, respectively. A different mechanism takes place for the interaction of the less oxidizing dithiocyanate radicals with the silica nanoparticles. These radicals selectively react with the dissociated silanol groups of the nanoparticles with a rate constant at 298.2K of 7 x 10(7) M(-1) s(-1) (per mol of SiO(-) groups), and there is no evidence for their adsorption at the surface. All the results are discussed in terms of the Smoluchowski equation and redox potential of the inorganic radicals.


Overexpression of theca-cell messenger RNA in polycystic ovary syndrome does not correlate with polymorphisms in the cholesterol side-chain cleavage and 17alpha-hydroxylase/C(17-20) lyase promoters.
To determine whether overexpression of CYP17 or CYP11A messenger (m)RNA in theca cells from polycystic ovaries is related to polymorphic regions in the gene promoters that may increase transcription. Case-control study. Research institute. Fifty-one women with PCOS and 280 regularly cycling controls underwent genotyping. Thecal cells were obtained from 23 women with PCOS and 51 controls. Ovarian tissue was obtained from women with PCOS undergoing wedge resection for treatment of their infertility and from controls undergoing ovariectomy for indications unrelated to the study. Expression of mRNA in theca cells was measured by using competitive reverse transcriptase polymerase chain reaction. Genotype analysis for polymorphisms in the CYP11A and CYP17 promoters was performed by using polymerase chain reaction. Although expression of CYP11A and CYP17 mRNA was higher in women with PCOS, no significant dose effects of CYP11A or CYP17 alleles were observed with respect to serum testosterone; follicular fluid androstenedione, estradiol, and androstenedione-to-estradiol ratio; or CYP11A or CYP17 mRNA expression. Overexpression of CYP17 and CYP11A mRNA in theca cells from polycystic ovaries is explained by polymorphic differences in the gene promoters.


Activation of human alloreactive cytotoxic precursor T lymphocytes.
The requirements for allogeneic T-cell activation have been studied in experiments with T and/or B cells as stimulator. Although target determinants (TDs, defined by CTL effectors in CML) are present on B and T cells used as target cells, this study indicates that TDs are functionally different when expressed on B and T cells used as stimulator cells, as only B cells can activate CTL precursors. Further, the study confirms that inducing TDs and strong lymphocyte-activating determinants (LADs, defined by proliferation in MLC) can be distinct structures found on two different stimulator B cells. The study suggests that binding of cytotoxic precursor T cells to TDs per se does not allow any detectable activation or start of proliferation and differentiation but requires another function of the stimulator cells in the non-T-cell compartment. The nature of this function is unknown, but it is the background for the first signal received by the TD-specific clones of CTL precursors, resulting in the expression of growth receptors for T-cell growth factor or interleukin 2 which is the second signal necessary for clonal expansion and differentiation.


Randomized study with mitomycin C + 5-fluorouracil+cytosine arabinoside (MFC)+5-fluorouracil, MFC+tegafur and uracil (UFT), and MF+UFT in advanced gastric cancer: interinstitutional differences in a multicenter study in Japan.
In a phase III randomized trial of adjuvant chemotherapy for gastric cancer, interinstitutional differences were analyzed. A trial of three regimens: mitomycin C, 5-fluorouracil(5-FU) and CA (MFC) + continuous oral 5-FU (Group C); MFC + continuous oral UFT(tegafur and uracil) (Group B); and MF + UFT (Group C) after operation was conducted in 466 patients with gastric cancer (stage II and III) at four hospitals in Japan (CIH, CAD, ACC and NCC). Patients were stratified by the institution, stage, and tumor size (8 cm ><). The 5-year survival rates were in the order of Group A (79.0%) > B (70.0%) > C (61.0%) (P = 0.1228) in total, A (95.0%) > B (80.0%) > C (58.0%) (P < 0.05) at CAD (82 patients), A > C > B at CIH (215), C > A > B at ACC (95), and B > A > C at NCC (78). The survival rate of patients with S2(serosal exposure), 8 cm < and N0-1 cancer was higher at CIH than at the other institutions. The interinstitutional differences in patient characteristics and surgical technique were more powerful than the differences among the three groups.


A prospective randomised trial comparing intra-articular Hyalgan injection and arthroscopic washout for knee osteoarthritis.
Thirty-eight patients with symptomatic knee osteoarthritis without mechanical symptoms were randomised after informed consent to receive either a course of intra-articular Hyalgan injections or an arthroscopic washout. The patients were prospectively assessed pre-intervention, 6 weeks, 3 months, 6 months and 1 year using a 10 cm visual analogue pain score, the Knee Society function score and the Lequesne index. There was no significant difference between the two groups at 6 weeks, 3 months, 6 months or 1 year. The use of intra-articular Hyalgan injections in patients with knee osteoarthritis without mechanical symptoms gives results comparable with arthroscopic washout. Hyalgan is an alternative to arthroscopy in this patient group. Further study is needed to confirm these findings and improve patient selection.


Construction of plasmids which lead to overproduction of yeast PHR1 photolyase in Saccharomyces cerevisiae and Escherichia coli.
The PHR1 gene of Saccharomyces cerevisiae encodes a DNA photolyase which is normally present in fewer than 300 copies per cell. We have constructed plasmids in which PHR1 expression in yeast and Escherichia coli is under the control of strong, inducible promoters thereby leading to the regulated overproduction of biologically active photolyase. Under inducing conditions, E. coli cells carrying the tac-PHR1 plasmid pCB1241 accumulate up to 8% of total cellular protein as yeast photolyase; similarly, the GAL10-PHR1 fusion plasmid pGBS107 directs the synthesis of at least 1800-2400 molecules of photolyase per log-phase yeast cell. In both plasmids translation begins at the first ATG in the PHR1 open reading frame (ORF). Constructs in which translation initiates at the second or third ATG fail to complement yeast and E. coli phr1 mutations, indicating that the first ATG in the PHR1 ORF is the translational start site in vivo and that all or part of the N-terminal 78 amino acids are required for activity.


Spondylo-epi-metaphyseal dysplasia.
The spondylo-epi-metaphyseal dysplasias (SEMD) are a heterogeneous group of disorders comprising more than 20 distinct entities with differing modes of inheritance, all defined by the combination of vertebral, epiphyseal and metaphyseal abnormalities. The presenting symptom of SEMD patients is usually disproportionate short stature. The diagnosis is either based on the specificity of the skeletal manifestations or on the presence of characteristic extraskeletal features which may appear during the course of the disease, highlighting the importance of follow-up of SEMD patients. The complications are variable but epiphyseal dysplasia is often a predominant feature, and the course of the disease is marked by premature osteoarthritis. A systematic survey of odontoid hypoplasia responsible for atlantoaxial instability with a risk of spinal cord is also required.


Health professionals' knowledge about ethical criteria in the allocation of resources in the COVID-19 pandemic.
Due to the rapid advance of the pandemic caused by COVID-19, several countries perceived that human and material resources would be insufficient to meet the demand of infected patients. The aim of this study is to analyze the knowledge of health professionals working in the pandemic about the application of ethical criteria in decision-making in situations of resource scarcity. This is a cross-sectional, descriptive, and quantitative survey study, conducted from June to December 2020, with health professionals working in the COVID-19 pandemic in Brazil. We applied a questionnaire to assess the professionals' knowledge about ethical criteria in decision-making in the allocation of scarce resources during the pandemic, containing 14 questions and possible score from 0 to 70, which was developed by researchers from documents and protocols validated by organizations from various countries, available in the first months of the pandemic, a sociodemographic characterization questionnaire and a self-assessment questionnaire regarding knowledge about bioethics. A total of 197 health professionals participated in the study, 37.6% of whom were nurses and 22.8% of whom were physicians, working in the Family Health Unit (28.4%) with a degree at the level of specialization (46.2%). Moreover, (9.5%) of nurses, (18.2%) of dental surgeons and (24.4%) of physicians reported that they have no prior knowledge about bioethics. Physicians and hospital workers scored higher on the knowledge assessment questionnaire. The mean score of the participants was 45.4 (SD = 7.2). Investments in training and professional education in the field of health focused on Bioethics are necessary, considering models and ethical theories that help professionals, managers and society to better position themselves in the face of pandemic contexts.


Caloric Intake on the Sabbath: A Pilot Study of Contributing Factors to Obesity in the Orthodox Jewish Community.
The American Orthodox Jewish community has specific cultural factors that may contribute to overweight and obesity. This study aimed to look at caloric intake on the Sabbath and its contribution to overweight and obesity. Twelve married or previously married women who identify themselves as Orthodox Jews were recruited to do 24-h food recalls over the phone. The participants were divided into three weight groups (normal, overweight, and obese) based on their BMI. The overweight and obese participants' data were combined into one group for the purposes of statistical testing. Paired t tests looking at the data for all participants showed significantly great caloric intake during an average Sabbath day than an average weekday [t(4) = 7.58, p < 0.001]. A repeated-measures ANOVA showed significantly greater energy intake on the Sabbath for the overweight-obese women compared to the normal weight women [F(1) = 7.83, p = 0.02]. No statistical difference was seen between the weekday energy intake of the normal weight women as compared to the combined group of overweight-obese women [F(1) = 0.501, p = 0.499]. These results support the hypotheses that all groups eat significantly more on the Sabbath than on weekdays, and overweight and obese individuals eat significantly more on the Sabbath than normal weight individuals. This supports the theory that caloric intake on the Sabbath is a contributing factor to overweight and obesity within the American Orthodox Jewish community.


Social and economic determinants of pediatric health inequalities: the model of chronic kidney disease.
Purpose of this review is to deal with priorities and strategies to significantly tackle inequalities in the management of pediatric diseases in low-middle-income countries. This issue has become a focal point of epidemiological and public health, with special reference to chronic nontransmissible diseases. We will provide our readership with an essential overview of the cultural, institutional, and political events, which have occurred over the last 20 y and which have produced the current general framework for epidemiology and public health. Then the most recent epidemiological data will be evaluated, in order to quantify the interaction between the medical components of the disease profiles and their socioeconomic determinants. Finally, a focus will be added on models of pediatric chronic kidney diseases, which are in our opinion amongst the most sensitive markers of the interplay between health and society. Collaborative, pediatrician-initiated, multicentre projects in these fields should be given priority in calls for grants supported by public agencies. The involvement of a critical mass of those working in the "fringes" of pediatric care is a final, essential mean by which significant results can be produced under the sole responsibility and research interest of centers of excellence.


Localised pigmented villonodular synovitis: an uncommon cause of knee pain mimicking a meniscal tear.
A previously well 30 year old man presented with a short history of intra-articular mechanical locking, swelling, and anteromedial joint line pain. There was localised tenderness, and McMurray's test was positive. Arthroscopy revealed a 3.6 x 2.6 x 1.5 cm firm pedicular localised pigmented villonodular synovitis originating from the insertion of the anterior horn of the medial meniscus. Owing to its size and consistency, mini-arthrotomy was required. This allowed a return to sporting activities. Localised pigmented villonodular synovitis can mimic symptoms of a meniscal tear.


Twenty-four-hour intragastric acidity: 300 mg ranitidine b.d., 20 mg omeprazole o.m., 40 mg omeprazole o.m. vs. placebo.
There is considerable controversy about the degree of acid suppression that is optimal for the treatment of peptic disorders. To compare the effects of three different regimens that are reported to strongly inhibit acid secretion. Intragastric 24-hour pH monitoring was performed in 11 healthy subjects in a randomized, multiple, cross-over, double-blind study. Each subject received four dose regimens, each for 2 weeks, in a random order. The regimens were: 300 mg ranitidine b.d., 20 mg omeprazole o.m., 40 mg omeprazole o.m., and placebo. The decrease in gastric acidity during the daytime and during the total 24-hour period by all three treatments was significantly greater than after placebo; a significant difference in acid inhibition was found between ranitidine and 40 mg omeprazole, but not between ranitidine and 20 mg omeprazole, nor between the two doses of omeprazole. During the night-time the decrease in gastric acidity by all three treatments was significantly greater than after placebo; no difference was seen between the two doses of omeprazole and ranitidine. For the time of pH greater than 3 we found no statistical difference between the various acid decreasing regimens. The pH remained significantly longer above 4 after ranitidine and the two doses of omeprazole compared with placebo, and also longer above 4 after 40 mg omeprazole compared with ranitidine, but not after 20 mg omeprazole compared with ranitidine, nor after the two different doses of omeprazole. Dosing with 300 mg ranitidine b.d., 20 mg omeprazole or 40 mg omeprazole is superior in gastric acid inhibition compared with placebo, when measured using 24-hour pH monitoring.


High-cited favorable studies for COVID-19 treatments ineffective in large trials.
To evaluate for coronavirus disease 2019 treatments without benefits in subsequent large randomized controlled trials (RCTs) how many of their most-cited clinical studies had declared favorable results. Scopus searches (December 23, 2021) identified articles on lopinavir-ritonavir, hydroxychloroquine, azithromycin, remdesivir, convalescent plasma, colchicine, or interferon (index interventions) that represented clinical trials and had >150 citations. Their conclusions were correlated with study design features. The 10 most recent citations for the most-cited article on each index intervention were examined on whether they were critical to the highly cited study. Altmetric scores were also obtained. Forty eligible articles of clinical studies had received >150 citations. Twenty of forty (50%) had favorable conclusions and four were equivocal. Highly cited articles with favorable conclusions were rarely RCTs (3/20), although those without favorable conclusions were mostly RCTs (15/20, P = 0.0003). Only one RCT with favorable conclusions had >160 patients. Citation counts correlated strongly with Altmetric scores, especially news items. Only nine (15%) of 60 recent citations to the most highly cited studies with favorable or equivocal conclusions were critical. Many clinical studies with favorable conclusions for largely ineffective coronavirus disease 2019 treatments are uncritically heavily cited and disseminated. Early observational studies and small randomized trials may cause spurious claims of effectiveness that get perpetuated.


Growth morphologies and optical properties of LTA single crystal.
Atomic force microscopy (AFM) has been used to study the growth morphologies of l-threonine acetate (abbreviated as LTA) crystal. Spiral growth hillocks and typical step patterns are described and discussed. Nuclei with various shapes often distribute at the larger step terraces. Eventually, in order to investigate microscopic second order nonlinear optical properties of LTA crystals, the molecular dipole moment (μ), polarizability (α), and first hyperpolarizability (β) were computed using a series of basis sets including polarized and diffuse functions at the framework of Hartree-Fock and density functional theory methods. The study is helpful to the further development of l-threonine analogs with improved nonlinear optical properties.


Schnurri-3: a key regulator of postnatal skeletal remodeling.
Schnurri-3, a large zinc finger protein distantly related to Drosophila Shn, is a potent and essential regulator of adult bone formation. Mice lacking Shn3 display an osteosclerotic phenotype with profoundly increased bone mass due to augmented osteoblast activity. Shn3 controls protein levels of Runx2, the principal regulator of osteoblast differentiation, by promoting its degradation. In osteoblasts, Shn3 functions as a component of a trimeric complex between Runx2 and the E3 ubiquitin ligase WWP1. This complex inhibits Runx2 function and expression of genes involved in extracellular matrix mineralization due to the ability of WWP1 to promote Runx2 polyubiquitination and proteasome-dependent degradation. Our study reveals an essential role for Shn3 as a regulator of postnatal bone mass. Compounds designed to block Shn3/WWP1 function may be possible therapeutic agents for the treatment of osteoporosis.


The role of intra-abdominal pressure on splanchnic and pulmonary hemodynamic and metabolic changes during carbon dioxide pneumoperitoneum.
To find an intra-abdominal pressure (IAP) range for laparoscopic procedures that elicits only moderate splanchnic and pulmonary hemodynamic and metabolic changes, including hepatic and intestinal tissue pH and superficial hepatic blood flow, we installed an IAP of 7 and 14 mm Hg each for 30 minutes in 10 healthy pigs (30 +/- 4 kg). In parallel with the increase of IAP, the mean transmural pulmonary artery pressure increased (from 25 +/- 3 to 27 +/- 4 at 7 mm Hg IAP and 30 +/- 6 mm Hg at 14 mm Hg IAP, p < 0.05); the pulmonary artery-to-pulmonary capillary wedge pressure gradient also increased (from 17 +/- 2.7 to 21 +/- 3 mm Hg at 7 mm Hg IAP and 24 +/- 4.2 mm Hg at 14 mm Hg IAP, p < 0.01), and the arterial oxygenation decreased (p < 0.005). Relevant changes at an IAP of 14 mm Hg were observed in right atrial pressure during inspiration (from 7 +/- 2 to 12 +/- 3 mm Hg, p < 0. 0001) and in abdominal aortic flow (from 1.43 +/- 0.4 to 1.19 +/- 0. 3 L/min, p < 0.01). However, transmural right atrial pressure and cardiac output remained essentially unchanged. Portal and hepatic venous pressure increased in parallel with the IAP (portal: from 12 +/- 3 to 17 +/- 3 at 7 mm Hg IAP and 22 +/- 3 mm Hg at 14 mm Hg IAP, p < 0.01; hepatic venous: from 8 +/- 3 to 14 +/- 6 at 7 mm Hg IAP and 19 +/- 6 mm Hg at 14 mm Hg IAP, p < 0.005), but the transmural portal and hepatic venous pressures decreased (p < 0.01), indicating decreased venous filling. Portal flow was maintained at 7 mm Hg but decreased at 14 mm Hg from 474 +/- 199 to 395 +/- 175 mL/min (p < 0. 01), whereas hepatic arterial flow remained stable. Hepatic superficial blood flow decreased during insufflation and increased after desufflation. Tissue pH fell together with portal and hepatic venous pH (intestinal: from 7.323 +/- 0.05 to 7.217 +/- 0.04; hepatic: from 7.259 +/- 0.04 to 7.125 +/- 0.06, both p < 0.01) at 14 mm Hg. The hemodynamic and metabolic derangement in the pulmonary and splanchnic compartments are dependent on the extent of carbon dioxide pneumoperitoneum. The effect of low IAP (7 mm Hg) on splanchnic perfusion is minimal. However, higher IAPs (14 mm Hg) decrease portal and superficial hepatic blood flow and hepatic and intestinal tissue pH.


Doxorubicin conjugates for selective delivery to tumors.
With the aim of improving the therapeutic utility of doxorubicin, numerous conjugates or prodrugshave been prepared to be selectively activated at the tumor site while releasing the cytotoxic drug.Among immuno-conjugates representing a widely studied class of doxorubicin derivatives,the clinical development of cBR96-Dox, undoubtedly the most quintessential derivative, was discontinueddue to severe secondary effects. More potent cBR-96 analogues and IMMU-110, another doxorubicin immunoconjugate,are still under study.Antibody-directed prodrug therapy has been designed to overcome some of the problems associatedwith the treatment of solid tumors. Concerning the anthracycline-based prodrugs, two glucuronideconjugates have reached the preclinical level, HMR 1826 and DOX-GA3. Both conjugates were subsequentlyevaluated against several human cancer xenografts without preliminary administration of fusion protein.Among the novelty in ADEPT approaches, one of the most relevant was based on the design of multiplespacer systems.Closely related to ADEPT, new approaches to selectively deliver prodrug-releasing enzymes intumor cells have been still studied or proposed by means of gene (GDEPT), polymer (PDEPT), bacteria(BDEPT), or exploiting endogenous carbohydrate-lectin binding (LEAPT).Activation of conjugates by tumor-associated endogenous enzymes such as prostate specific antigen,plasmin, matrix metalloproteinase, and various extra and intracellular peptidases has also been reported,some of these conjugates like L377,202, a PSA substrate, having reached the clinical level. Doxorubicinpeptide conjugates were also designed to be activated by endopeptidase legumain, and extracellularthimet oligopeptidase to deliver Leu-Dox, known to be cleaved intracellularly by peptidase.A third class of conjugates has been designed for receptor-mediated targeted delivery,including folate, somatostatin, bombesin, LHRH receptors or integrin and lectin.Transportation of doxorubicin with peptide vectors has been simultaneously investigated to overcomethe problem of penetration in the brain or the problem of multidrug resistance.


Reduced Neural Recruitment for Bayesian Adjustment of Inhibitory Control in Methamphetamine Dependence.
Delineating the processes that contribute to the progression and maintenance of substance dependence is critical to understanding and preventing addiction. Several previous studies have shown inhibitory control deficits in individuals with stimulant use disorder. We used a Bayesian computational approach to examine potential neural deficiencies in the dynamic predictive processing underlying inhibitory function among recently abstinent methamphetamine-dependent individuals (MDIs), a population at high risk of relapse. Sixty-two MDIs were recruited from a 28-day inpatient treatment program at the San Diego Veterans Affairs Medical Center and compared with 34 healthy control subjects. They completed a stop-signal task during functional magnetic resonance imaging. A Bayesian ideal observer model was used to predict individuals' trial-to-trial probabilistic expectations of inhibitory response, P(stop), to identify group differences specific to Bayesian expectation and prediction error computation. Relative to control subjects, MDIs were more likely to make stop errors on difficult trials and had attenuated slowing following stop errors. MDIs further exhibited reduced sensitivity as measured by the neural tracking of a Bayesian measure of surprise (unsigned prediction error), which was evident across all trials in the left posterior caudate and orbitofrontal cortex (Brodmann area 11), and selectively on stop error trials in the right thalamus and inferior parietal lobule. MDIs are less sensitive to surprising task events, both across trials and upon making commission errors, which may help explain why these individuals may not engage in switching strategy when the environment changes, leading to adverse consequences.


Inhibition of opioid systems in the hypothalamus as well as the mesolimbic area suppresses feeding behavior of mice.
Opioid receptors, especially μ-opioid receptors, in the ventral tegmental area (VTA) and nucleus accumbens (NAcc) are reported to regulate food motivation. However, the roles of μ-, δ- and κ-opioid receptors are not fully understood. Moreover, since μ-, δ- and κ-opioid receptors are reported to distribute in the hypothalamus, these receptors in the hypothalamus might regulate feeding behavior. Thus, the present study investigated the role of μ-, δ- and κ-opioid receptors in the VTA, the NAcc and the hypothalamus in the regulation of feeding behavior. Male ICR mice were subjected to a feeding test after food deprivation for 16h. The mRNA levels of proopiomelanocortin (POMC), preproenkephalin (PENK) and prodynorphin (PDYN), the precursors of endogenous opioid peptides, were measured by reverse transcription-polymerase chain reaction (RT-PCR). The systemic injection of non-selective (naloxone) and selective μ (β-funaltrexamine; β-FNA), δ (naltrindole) and κ (norbinaltorphimine; norBNI) opioid receptor antagonists markedly reduced food intake. In contrast, the systemic injection of preferential μ (morphine), selective δ (KNT-127) and κ (U-50,488) opioid receptor agonists did not change food intake. The mRNA levels of POMC, PENK and PDYN were decreased in the hypothalamus and the midbrain after food deprivation, whereas the mRNA levels of PENK and PDYN, but not POMC, were decreased in the ventral striatum. The injection of naloxone into the NAcc, VTA and lateral hypothalamus (LH), but not the ventromedial nucleus of the hypothalamus, significantly decreased food intake. The injection of β-FNA and naltrindole into the LH, but not the VTA or NAcc, decreased food intake. The injection of norBNI into the LH and VTA, but not the NAcc, decreased food intake. These results indicate that μ-, δ- and κ-opioid receptors in the LH play a more important role in the regulation of feeding behavior than those receptors in the VTA and the NAcc.


The diverse bacterial origins of the Arabidopsis polyamine biosynthetic pathway.
We functionally identified the last remaining step in the plant polyamine biosynthetic pathway by expressing an Arabidopsis thaliana agmatine iminohydrolase cDNA in yeast. Inspection of the whole pathway suggests that the arginine decarboxylase, agmatine iminohydrolase, N-carbamoylputrescine amidohydrolase route to putrescine in plants was inherited from the cyanobacterial ancestor of the chloroplast. However, the rest of the pathway including ornithine decarboxylase and spermidine synthase was probably inherited from bacterial genes present in the original host cell, common ancestor of plants and animals, that acquired the cyanobacterial endosymbiont. An exception is S-adenosylmethionine decarboxylase, which may represent a eukaryote-specific enzyme form.


Treatment of chronic obstruction as late complication of adjustable gastric band.
Laparoscopic adjustable gastric banding is growing in popularity in the United States. A rare late complication is obstruction at the level of the band, with concentric gastric pouch dilation. In our patient, endoscopy showed gastric pouch dilation with food impaction and a restricted outlet. We describe the combined endoscopic and laparoscopic approach for alleviation of chronic obstruction as a late complication of an adjustable gastric band. This combined approach included laparoscopic band removal and scar excision with intraoperative endoscopic dilation.


Small-molecule inhibition of proteasome and silencing by vascular endothelial cell growth factor-specific siRNA induce additive antitumor activity in multiple myeloma.
Angiogenesis plays an important role in the pathogenesis and progression in multiple myeloma (MM), and MM cells secrete vascular endothelial growth factor (VEGF), which further promotes proliferation of the tumor cells. Therefore, we evaluated the anti-myeloma effect of VEGF small interfering RNA (siRNA) silencing in MM cells and whether it can be augmented by the additional application of bortezomib directed against the 26S proteasome. After transfection with VEGF siRNA, we observed a reduction of VEGF expression in all studied cell lines: OPM-2, RPMI-8226, INA-6, Jurkat, Raji, and Karpas-299, as well as in cells of MM and lymphoma patients. VEGF siRNA significantly induced apoptosis and inhibited proliferation in OPM-2 cells (P<0.0001), RPMI-8226 (P<0.0001), and INA-6 (P<0.01) versus controls. Cotreatment with VEGF siRNA and bortezomib in MM cells resulted in an exaggerated inhibition of proliferation and induction of apoptosis compared with VEGF siRNA or bortezomib alone (P<0.001). In addition, the combination of VEGF siRNA and bortezomib significantly (P<0.01) reversed multidrug resistance gene 1-dependent resistance of MM cells. Our data suggest that small-molecule inhibition of proteasome and silencing by VEGF-specific siRNA may be associated with an additive antitumor activity and might be a suitable target for new, therapeutic strategies using RNA interference in MM.


Asymptomatic bacteriuria in schoolgirls. VII. A follow-up study of the urinary tract in treated and untreated schoolgirls with asymptomatic bacteriuria.
The urinary tracts of 116 schoolgirls with asymptomatic bacteriuria detected at screening were investigated by excretory urography and micturition cystourethrography. Three years later the studies were repeated in 11 patients with scarred kidneys, 11 patients with unscarred kidneys plus reflux, and 14 untreated patients with radiologically normal urinary tracts. Exceptionally small scarred kidneys showed little growth. Unscarred kidneys with vesico-ureteral reflux exhibited normal growth, as did unscarred kidneys in untreated patients. The risk of kidney damage developing as a result of asymptomatic bacteriuria in a schoolgirl with a radiologically normal urinary tract seems to be small.


[The effect of beta-ionine on biosynthesis of carotenes by Actinomyces chrysomallus var. carotenoides].
Biosynthesis of carotenoids by a growing culture of Actinomyces chrysomallus var. carotenoides is totally inhibited by beta-ionone added at different concentrations, at various time of the cultural growth, and in various combinations with oil. The inhibition of carotenoid synthesis by beta-ionone is of a specific character since the biomass growth under the same conditions does not increase.


Keys to the successful implementation of an ICU patient data management system.
Implementation of an ICU data management system requires consideration of many factors, including site preparation for equipment, system backup, ICU & medical staff training and evaluation. This paper describes the strategy for implementing a patient data management system at Cedars-Sinai Medical Center and details our steps for planning, training, configuration and problem resolution.


Osteoblast response to zirconia surfaces with different topographies.
Zirconia-3 mol% yttria ceramics were prepared with as-sintered, abraded, polished, and porous surfaces in order to explore the attachment, proliferation and differentiation of osteoblast-like cells. After modification, all surfaces were heated to 600°C to extinguish traces of organic contamination. All surfaces supported cell attachment, proliferation and differentiation but the surfaces with grain boundary grooves or abraded grooves provided conditions for enhanced initial cell attachment. Nevertheless, overall cell proliferation and total DNA were highest on the polished surface. Zirconia sintered at a lower temperature (1300°C vs. 1450°C) had open porosity and presented reduced proliferation as assessed by alamarBlue™ assay, possibly because the openness of the pores prevented cells developing a local microenvironment. All cells retained the typical polygonal morphology of osteoblast-like cells with variations attributable to the underlying surface notably alignment along the grooves of the abraded surface.


Rapid isolation of any known genes from whole cells of yeast by PCR.
A short protocol was developed that allows the rapid isolation of any known Saccharomyces cerevisiae gene. Two known genes, APN1 and IMP2, were isolated directly from whole cells of yeast using polymerase chain reaction, without the need for purified template genomic DNA.


Rosiglitazone, a PPAR gamma agonist, attenuates inflammation after surgical brain injury in rodents.
Surgical brain injury (SBI) is unavoidable during many neurosurgical procedures. This inevitable brain injury can result in post-operative complications including brain edema, blood-brain barrier disruption (BBB) and cell death in susceptible areas. Rosiglitazone (RSG), a PPAR-gamma agonist, has been shown to reduce inflammation and provide neuroprotection in experimental models of ischemia and intracerebral hemorrhage. This study was designed to evaluate the neuroprotective effects of RSG in a rodent model of SBI. 65 adult male Sprague-Dawley rats were randomly divided into sham, vehicle and treatment groups. RSG was administered intraperitoneally in two dosages (1 mg/kg/dose, 6 mg/kg/dose) 30 min before surgery, and 30 min and 4 h after surgery. Animals were euthanized 24 h following neurological evaluation to assess brain edema and BBB permeability by IgG staining. Inflammation was examined using myeloperoxidase (MPO) assay and double-labeling fluorescent immunohistochemical analysis of IL-1beta and TNF-alpha. Localized brain edema was observed in tissue surrounding the surgical injury. This brain edema was significantly higher in rats subjected to SBI than sham animals. Increased IgG staining was present in affected brain tissue; however, RSG reduced neither IgG staining nor brain edema. RSG also did not improve neurological status observed after SBI. RSG, however, significantly attenuated MPO activity and qualitatively decreased IL-1beta and TNF-alpha expression compared to vehicle-treated group. SBI causes increased brain edema, BBB disruption and inflammation localized along the periphery of the site of surgical resection. RSG attenuated inflammatory changes, however, did not improve brain edema, BBB disruption and neurological outcomes after SBI.


Safety of adjunctive intracoronary thrombolytic therapy during complex percutaneous coronary intervention: initial experience with intracoronary tenecteplase.
Intracoronary thrombus is associated with increased risk of in-laboratory vessel closure, recurrent myocardial infarction (MI), urgent vessel revascularization, and death. There is a lack of consensus on what represents the ideal treatment for patients with thrombotic complications during percutaneous coronary intervention (PCI), but the development of newer thrombolytic agents with increased fibrin specificity and longer half-life provides a potentially useful treatment option. In this study, the safety and efficacy of intracoronary tenecteplase (TNK) was evaluated in 34 patients (22 with acute ST elevation MI, 4 with rescue PCI, 6 with non-ST elevation MI, and 2 during elective PCI) who developed no-reflow, distal embolization, or visible intracoronary thrombus during PCI. The mean age was 57 years, 76% were Caucasian, and there were 14 women and 20 men. Cardiogenic shock was present in seven (21%) patients at baseline. All patients were being treated with aspirin and either unfractionated heparin (33 patients) or bivalrudin. Glycoprotein IIb/IIIa inhibitors were used in 76% of patients. Intracoronary TNK was used at a mean dose of 10.2 +/- 5.2 mg (median, 10 mg; range, 5-25 mg). There was one TIMI major bleeding event and three TIMI minor bleeding events. The mean hematocrit measured the morning following PCI was 35.5% +/- 4.9% in patients receiving TNK and 36.5% +/- 4.4% in a randomly selected sample of 150 consecutive patients undergoing PCI (P = 0.25). In conjunction with mechanical intervention, TNK was successful at dissolving angiographic thrombus and/or improving flow in 91% of patients. In conclusion, intracoronary TNK is safe and well tolerated in patients who develop thrombotic complications during complex PCI.


Type I Interferon Induction by Neisseria gonorrhoeae: Dual Requirement of Cyclic GMP-AMP Synthase and Toll-like Receptor 4.
The innate immune system is the first line of defense against Neisseria gonorrhoeae (GC). Exposure of cells to GC lipooligosaccharides induces a strong immune response, leading to type I interferon (IFN) production via TLR4/MD-2. In addition to living freely in the extracellular space, GC can invade the cytoplasm to evade detection and elimination. Double-stranded DNA introduced into the cytosol binds and activates the enzyme cyclic-GMP-AMP synthase (cGAS), which produces 2'3'-cGAMP and triggers STING/TBK-1/IRF3 activation, resulting in type I IFN expression. Here, we reveal a cytosolic response to GC DNA that also contributes to type I IFN induction. We demonstrate that complete IFN-β induction by live GC depends on both cGAS and TLR4. Type I IFN is detrimental to the host, and dysregulation of iron homeostasis genes may explain lower bacteria survival in cGAS(-/-) and TLR4(-/-) cells. Collectively, these observations reveal cooperation between TLRs and cGAS in immunity to GC infection.


An experimental model to quantify horizontal transmission of Mycoplasma gallisepticum.
Before interventions to control horizontal transmission of Mycoplasma gallisepticum can be tested, a suitable experimental model should be available. Transmission dynamics in a flock can be quantified by two parameters: the average number of secondary cases infected by one typical infectious case (R0) and the number of new infections that occur due to one infectious animal per unit of time (beta). The transmission dynamics of M. gallisepticum have not been studied experimentally, so the aim of this study was to examine the horizontal transmission of M. gallisepticum. The study was carried out using a pairwise design with three different inoculation doses. Every pair consisted of an inoculated chicken and a susceptible in-contact chicken. Five susceptible individually housed chickens were placed in between pairs in order to measure airborne transmission. Infection was detected by serology, quantitative polymerase chain reaction and culture. The inoculated and in-contact chickens were equally infectious and the pairs could be regarded as independent. The R0 was estimated to be greater than 1 (infinity; 95% confidence interval, 4.5 to infinity), the estimated beta was 0.22 per day and there was no significant difference between the different inoculation doses. It was concluded that the animal model as described in this study meets the conditions for the establishment of transmission dynamics of M. gallisepticum and therefore can be used to establish the quantitative effect of intervention measures on horizontal transmission.


Measuring the cost of caring for a foster child.
The problem of determining this cost is complex. Total costs include the direct or out-of-pocket costs and indirect costs, or the value of time devoted to rearing foster children. The use of secondary data for estimating coses in local areas is recommended.


The metabolism of acetone in the pregnant rat.
The administration of a single dose of acetone (100 mg/kg bw) to virgin and 21-day pregnant rats resulted in the appearance of relatively high concentrations of 1,2-propanediol, acetol and methylglyoxal in plasma and liver. In the fetuses no methylglyoxal was detectable. The acetone metabolism curves tend to indicate that the capacity for acetone disposal may be enhanced in the 48 hr-fasted pregnant rat, thus enabling the animal to re-use acetone metabolically, possibly for accelerated gluconeogenesis.


Survival analysis in a sample of oral cancer patients at a reference hospital in Rio de Janeiro, Brazil.
This article gives the results of a 5-year survival analysis of 371 oral cancer patients who received medical care at a cancer reference hospital in Rio de Janeiro between 1986 and 1987. Patient profiles based on selected risk factors for oral cancer and 5-year survival based on prognostically relevant variables are described.


A novel HLA class II allele, HLA-DRB1*04:01:17, identified in a Chinese volunteer donor for China Marrow Donor Program.
One nucleotide replacement at nucleotide 144 of HLA-DRB1*04:01:01 results in a new allele, HLA-DRB1*04:01:17.


Comparison of health of occupants and characteristics of houses among control homes and homes insulated with urea formaldehyde foam. III. Health and house variables following remedial work.
This report describes the second survey of a group of 762 control and urea formaldehyde foam insulated (UFFI) houses performed following an interval of 1 year, after about two-thirds of the UFFI households either had their UFFI removed or performed other UFFI-related remedial work. The UFFI subjects who lived in remedial houses showed a decline in indicators of impaired health status, to roughly equalize with those whose houses were not altered; they continued to show a small excess of adverse health indicators relative to the controls, but at a somewhat lower level than seen in the first survey. This improvement was not associated with changes in indoor levels of formaldehyde. Weak exposure-response relationships were observed between formaldehyde and upper and lower respiratory symptoms, but mainly in the combined UFFI and control populations; these are interpreted as representing the contribution of background levels of formaldehyde to the prevalence of respiratory complaints in the general population. The principal findings of this study were primarily based on subjective variables, but most could be directly validated by objective measurements in the UFFI and control subjects. The support for a causal relationship between impaired health and living in a UFFI house is considered to be moderately strong. However the demonstrated adverse effects are generally minor in nature.


Ultra-low-temperature non-aqueous capillary electrophoretic separation--77 K fluorescence spectroscopic detection for the on-line identification of photo-converted analytes of trans-resveratrol.
We demonstrate here, for the first time, that non-aqueous capillary electrophoresis (NACE) can be interfaced with any ultra-low-temperature (ULT) separation method and 77 K fluorescence spectroscopy (FS). This novel ULT-NACE-FS system consists of a modular CE system, a dry ice bath, and instrumentation for 77 K fluorescence detection. The ULT-NACE method serves to separate structurally similar molecules by a combination of a low electrophoresis current and a high voltage at approximately -70 degrees C. When the ULT-NACE-separated analytes move into the quartz Dewar flask and traverse into the capillary detection window, liquid nitrogen was added, thus freezing the separating analyte zones, allowing the collection of 77 K fluorescence spectra for on-line spectral fingerprint identification. The first application of the ULT-NACE-FS system is described for the analysis of photo-converted analytes of trans-resveratrol; prospects and future applications of ULT-NACE-FS are also briefly addressed.


L-Shape Superior Capsular Augmentation Technique Using Biceps Tendon: The Biceps L-Shape Shifting Technique.
Many therapies have been developed for patients with mass rotator cuff tears. Partial repair is often performed in patients with partially repairable massive rotator cuff tears because it is simpler to perform than superior capsule reconstruction. It may, however, result in rotator cuff retears frequently. This article presents our modified technique of arthroscopic partial reconstruction of the superior capsule using the long head of the biceps tendon with a biceps interposition.


Genetics of cystinuria in an inbred population.
After the identification of 2 cystinurics in a large eastern Virginia isolate a population study was undertaken to identify carriers of the gene and others who could be affected by it. Of 102 individuals 3 additional homozygous cystinurics and 27 possible carriers were found. The cystinuria gene shows a highly variable expression, although all those affected and carriers could be traced to 1 couple who married about 1890. These studies demonstrate that there is considerable variation in urinary concentrations of cystine even in an affected population. No form of therapy should be based on random or isolated samples.


Intraoperative serum lactate levels as a prognostic predictor of outcome for emergency abdominal surgery: a retrospective study.
The relationship between intraoperative lactate levels and prognosis after emergency gastrointestinal surgery remains unclear. The purpose of this study was to investigate the prognostic value of intraoperative lactate levels for predicting in-hospital mortality, and to examine intraoperative hemodynamic managements. We conducted a retrospective observational study of emergency GI surgeries performed at our institution between 2011 and 2020. The study group comprised patients admitted to intensive care units postoperatively, and whose intraoperative and postoperative lactate levels were available. Intraoperative peak lactate levels (intra-LACs) were selected for analysis, and in-hospital mortality was set as the primary outcome. The prognostic value of intra-LAC was assessed using logistic regression and receiver operating characteristic (ROC) curve analysis. Of the 551 patients included in the study, 120 died postoperatively. Intra-LAC in the group who survived and the group that died was 1.80 [interquartile range [IQR], 1.19-3.01] mmol/L and 4.22 [IQR, 2.15-7.13] mmol/L (P < 0.001), respectively. Patients who died had larger volumes of red blood cell (RBC) transfusions and fluid administration, and were administered higher doses of vasoactive drugs. Logistic regression analysis showed that intra-LAC was an independent predictor of postoperative mortality (odds ratio [OR] 1.210, 95% CI 1.070 -1.360, P = 0.002). The volume of RBCs, fluids transfused, and the amount of vasoactive agents administered were not independent predictors. The area under the curve (AUC) of the ROC curve for intra-LAC for in-hospital mortality was 0.762 (95% confidence interval [CI], 0.711-0.812), with a cutoff value of 3.68 mmol/L by Youden index. Intraoperative lactate levels, but not hemodynamic management, were independently associated with increased in-hospital mortality after emergency GI surgery.


Nomogram for predicting the risk of preterm birth in women undergoing in vitro fertilization cycles.
The aim of this study was to develop a nomogram for predicting the risk of preterm birth in women undergoing in vitro fertilization (IVF) cycles. A retrospective study of 4266 live birth cycles collected from January 2016 to October 2021 at the Center for Reproductive Medicine, First Hospital of Jilin University was performed. The sample size was sufficient based on the minimal ten events per variable (EPV) rule. The primary outcome of this study was preterm birth. The cycles were divided into the preterm birth group (n = 827) and the full-term delivery group (n = 3439). A nomogram was established based on the multivariate logistic regression analysis results. The area under the curve (AUC) was calculated to assess the prediction accuracy of the nomogram model. The calibration curve was used to measure the calibration of the nomogram. Multivariate logistic regression analyses showed that female obesity or overweight (OR = 1.366, 95% CI: 1.111-1.679; OR = 1.537, 95% CI: 1.030-2.292), antral follicle count (AFC) of more than 24 (OR = 1.378, 95% CI: 1.035-1.836), multiple pregnancies (OR = 6.748, 95% CI: 5.559-8.190), gestational hypertension (OR = 9.662, 95% CI: 6.632-14.078) and gestational diabetes (OR = 4.650, 95% CI: 2.289-9.445) were the independent risk factors for preterm birth in IVF patients. The area under curve (AUC) under the receiver operating characteristic (ROC) curve in the prediction model was 0.781(95%CI: 0.763-0.799). The calibration curve of the nomogram showed that the prediction model had a good calibration. We used five risk factors to conduct a nomogram to predict preterm birth rates for patients undergoing IVF cycles. This nomogram can provide a visual assessment of the risk of preterm birth for clinical consultation.


Hyperhomocysteinaemia in treated patients with Huntington's disease homocysteine in HD.
Significantly increased plasma total homocysteine levels (t-Hcys) appeared in treated Huntington disease (HD) patients compared to controls and untreated HD subjects. Because the protein Huntingtin interacts with the homocysteine metabolism modulating enzyme cystathionine beta-synthase, we hypothesize that homocysteine promotes neurodegeneration in HD.


One-port retroperitoneoscopic assisted pyeloplasty versus open dismembered pyeloplasty in young children: preliminary experience.
We propose 1-port retroperitoneoscopic assisted pyeloplasty as a minimally invasive approach and compare the results to open dismembered pyeloplasty. All patients 6 months to 5 years old presenting with ureteropelvic junction obstruction between January 2008 and June 2009 were offered 1-port retroperitoneoscopic assisted pyeloplasty. Age matched patients who underwent open dismembered pyeloplasty during 2007 served as controls. The ureteropelvic junction was isolated retroperitoneoscopically and exteriorized through a single operative trocar. Pyeloplasty was performed in an open fashion with Double-J® stenting. Operative time, postoperative pain, surgical complications, hospital stay, ultrasound and mercaptoacetyltriglycine nuclear scan results at 6-month followup were evaluated and compared. Chi-square test and Student's t test were adopted for statistical analysis, with p <0.05 considered statistically significant. A total of 28 children (17 males) with a mean age of 18 months were treated with 1-port retroperitoneoscopic assisted pyeloplasty (18 left side). The control group consisted of 25 patients (11 males) with a mean age of 19 months who underwent open dismembered pyeloplasty (10 left side). Median operative time was 95 minutes (range 70 to 130) in 1-port retroperitoneoscopic assisted pyeloplasty and 72 minutes (58 to 102) in open dismembered pyeloplasty (p <0.05). Median postoperative hospital stay was 2.4 days with the 1-port approach and 6.1 days with the open procedure (p <0.05). Postoperative pain was significantly less in the 1-port group. Skin scar length was 1.4 to 2.9 cm (median 1.7) with 1-port retroperitoneoscopic assisted pyeloplasty and 3.5 to 6.0 cm (4.3) in the open group (p <0.05). The 1-port retroperitoneoscopic assisted pyeloplasty represents a safe and effective minimally invasive technique to treat hydronephrosis and could be the treatment of choice in young children. The procedure does not require laparoscopic suturing skills, and combines the advantages of open and laparoscopic pyeloplasty.


A small nonhuman primate model for filovirus-induced disease.
Ebolavirus and Marburgvirus are members of the filovirus family and induce a fatal hemorrhagic disease in humans and nonhuman primates with 90% case fatality. To develop a small nonhuman primate model for filovirus disease, common marmosets (Callithrix jacchus) were intramuscularly inoculated with wild type Marburgvirus Musoke or Ebolavirus Zaire. The infection resulted in a systemic fatal disease with clinical and morphological features closely resembling human infection. Animals experienced weight loss, fever, high virus titers in tissue, thrombocytopenia, neutrophilia, high liver transaminases and phosphatases and disseminated intravascular coagulation. Evidence of a severe disseminated viral infection characterized principally by multifocal to coalescing hepatic necrosis was seen in EBOV animals. MARV-infected animals displayed only moderate fibrin deposition in the spleen. Lymphoid necrosis and lymphocytic depletion observed in spleen. These findings provide support for the use of the common marmoset as a small nonhuman primate model for filovirus induced hemorrhagic fever.


Cyclotides: Disulfide-rich peptide toxins in plants.
Cyclotides are a plant-derived family of peptides that comprise approximately 30 amino acid residues, a cyclic backbone and a cystine knot. Due to their unique structure, cyclotides are exceptionally stable to heat or proteolytic degradation and are tolerant to amino acid substitutions in their backbone loops between conserved cysteine residues. Their toxicity to insect pests and their make-up of natural amino acids has led to their applications in eco-friendly crop protection. Furthermore, their stability and cell penetrating properties make cyclotides ideal scaffolds for bioactive epitope grafting. This article gives a brief overview of cyclotide discovery, characterization, distribution, synthesis and mode of action mechanisms. We focus on their toxicities to insect pests and their medical and agricultural applications.


Efficacy of Fludora® Fusion (a mixture of deltamethrin and clothianidin) for indoor residual spraying against pyrethroid-resistant malaria vectors: laboratory and experimental hut evaluation.
A new generation of IRS insecticides which can provide improved and prolonged control of pyrethroid-resistant malaria vector populations are being developed. Fludora® Fusion is a new IRS insecticide containing a mixture of deltamethrin and clothianidin, a neonicotinoid. The efficacy of Fludora® Fusion IRS was evaluated over 11-12 months on concrete and mud substrates in laboratory bioassays and experimental huts against wild free-flying pyrethroid-resistant Anopheles gambiae (sensu lato) in Cové, Benin. A comparison was made with the two active ingredients of the mixture; clothianidin and deltamethrin, applied alone. CDC bottle bioassays were also performed to investigate resistance to clothianidin in the wild vector population. Fludora® Fusion induced > 80% laboratory cone bioassay mortality with both susceptible and pyrethroid-resistant An. gambiae (s.l.) for 7-9 months on concrete block substrates and 12 months on mud block substrates. The vector population at the experimental hut site was fully susceptible to clothianidin in CDC bottle bioassays. Overall mortality rates of wild free-flying pyrethroid-resistant An. gambiae (s.l.) entering the experimental huts during the 11-month trial were < 15% with deltamethrin and significantly higher with Fludora® Fusion (69-71%) and clothianidin alone (72-78%). Initial high experimental hut mortality rates with Fludora® Fusion (> 80%) only declined by 50% after 8 months. Monthly in situ wall cone bioassay mortality of susceptible mosquitoes was > 80% for 9-12 months with Fludora® Fusion and clothianidin alone. Fludora® Fusion induced significantly higher levels of early exiting of mosquitoes compared to clothianidin alone (55-60% vs 37-38%, P < 0.05). Indoor residual spraying with Fludora® Fusion induced high and prolonged mortality of wild pyrethroid-resistant malaria vectors for 7-10 months mostly due to the clothianidin component and substantial early exiting of mosquitoes from treated huts due to the pyrethroid component. Fludora® Fusion is an important addition to the current portfolio of IRS insecticides with the potential to significantly reduce transmission of malaria by pyrethroid-resistant mosquito vectors.


Fixation of CO2 into Cyclic Carbonates by Halogen-Bonding Catalysis.
Halogen bonding, parallel to hydrogen bonding, was introduced into the catalytic cycloaddition of carbon dioxide into epoxide (CCE) reactions. A series of halogen-bond donor (XBD) catalysts of N-iodopyridinium halide featured with N-I bond were synthesized and evaluated in CCE reactions. The optimal XBD catalyst, 4-(dimethylamino)-N-iodopyridinium bromide ([DMAPI]Br), under screened conditions at 100 °C, ambient pressure, and 1 mol % catalyst loading, realized 93 % conversion of styrene oxide into cyclic carbonate in 6 h. The substrate scope was successfully extended with excellent yields (mostly ≥93 %) and quantitative selectivity (more than 99 %). 1 H NMR spectroscopy of the catalyst [DMAPI]Br on substrate epoxide certified that the N-I bond directly coordinated with the epoxide oxygen. A plausible mechanism of halogen-bonding catalysis was proposed, in which the DMAPI cation functioned as halogen-bond donor to activate the epoxide, and the counter anion bromide attacked the methylene carbon to initiate the ring-opening of the epoxide. CCE reactions promoted by N-iodopyridinium halide, exemplify a first case of halogen-bonding catalysis in epoxide activation and CO2 transformation.


Electroconductive PEDOT:PSS-based hydrogel prepared by freezing-thawing method.
Biopolymer-based composition with adding of conductive polymer poly-(3,4-ethylenedioxythiophene) polystyrenesulfonate (PEDOT PSS) was made by mixing of iota-carrageenan (CRG), polyvinyl alcohol (PVA) and PEDOT PSS followed by freezing/thawing cycles. The method is environmentally friendly and based on the formation of polymer matrix upon of mixing CRG, PVA and PEDOT PSS and formation of porous physical gel due to freezing/thawing cycles. It is necessary to mention that all components are well-known as biocompatible materials. The resulting material is stable in water and also has swelling capability both in distilled water and physiological solutions. Structure of material was characterized by means of X-ray diffraction, optical and electron microscopy. Electrophysical investigations also were performed. The conductivity of the gel immersed in distilled water is comparable with the dry gel value and close to 0.01 [S/cm].


Recent progress in separation prediction of counter-current chromatography.
As a liquid-liquid partition chromatography, counter-current chromatography has advantages in large sample loading capacity without irreversible adsorption, which has been widely applied in separation and purification fields. The main factors, including partition coefficient, two-phase solvent systems, apparatus, and operating parameters greatly affect the separation process of counter-current chromatography. To promote the applications of counter-current chromatography, it is essential to develop theoretical research to master the principles of counter-current chromatographic separations so as to achieve predictions before laborious trials. In this article, recent progress about separation prediction methods are reviewed from a point of the steady and unsteady state of the mass transfer process of counter-current chromatography and its mass transfer characteristics, and then it is divided into three aspects: prediction of partition coefficient, modeling the thermodynamic process of counter-current chromatography, and modeling the dynamic process of counter-current chromatography.


Pits and fissure sealant guidelines. Summary guideline.
The guideline aims to address four clinical questions relating to the use of pit and fissure sealants:Under what circumstances should sealants be placed to prevent caries?Does placing sealants over early (noncavitated) lesions prevent progression of the lesions?Are there conditions that favour the placement of resin-based versus glass ionomer cement sealants in terms of retention or caries prevention?Are there any techniques that could improve sealants' retention and effectiveness in caries prevention? Medline was searched for all systematic reviews on pit and fissure sealants, and the reference lists of identified reviews were searched for additional references. A second search was carried out to identify clinical studies published after the systematic review were completed. Publications were included that addressed one or more of the identified clinical questions, had a documented search strategy, and were written in English. An expert panel was convened to evaluate the evidence and develop recommendations. The draft recommendations were submitted to a wide range of scientific experts and organisations for review, following which appropriate changes were made. The evidence was classified and clinical recommendations made using a system modified from the approach taken by Shekell et al.(1) The final clinical recommendations were approved by the American Dental Association Council on Scientific Affairs. Plans were not specified for future review and updating of this guideline. Using the evidence grading and recommendation systems described by Shekelle(1) (Table 1 and 2) a number of clinical recommendations were made (see summary in Table 3). A number of topics for additional research to improve the evidence base regarding the use of fissure sealants were identified by the expert panels. These are shown in Table 2.


A Strain-Specific Inhibitor of Receptor-Bound HIV-1 Targets a Pocket near the Fusion Peptide.
Disruption of viral fusion represents a viable, albeit under-explored, target for HIV therapeutics. Here, while studying the receptor-bound envelope glycoprotein conformation by cryoelectron microscopy (cryo-EM), we identify a pocket near the base of the trimer containing a bound detergent molecule and perform in silico drug screening by using a library of drug-like and commercially available molecules. After down-selection, we solve cryo-EM structures that validate the binding of two small molecule hits in very similar manners to the predicted binding poses, including interactions with aromatic residues within the fusion peptide. One of the molecules demonstrates low micromolar inhibition of the autologous virus by using a very rare phenylalanine in the fusion peptide and stabilizing the surrounding region. This work demonstrates that small molecules can target the fusion process, providing an additional target for anti-HIV therapeutics, and highlights the need to explore how fusion peptide sequence variations affect receptor-mediated conformational states across diverse HIV strains.


Building machine-learning-based models for retention time and resolution predictions in ion pair chromatography of oligonucleotides.
Support vector regression models are created and used to predict the retention times of oligonucleotides separated using gradient ion-pair chromatography with high accuracy. The experimental dataset consisted of fully phosphorothioated oligonucleotides. Two models were trained and validated using two pseudo-orthogonal gradient modes and three gradient slopes. The results show that the spread in retention time differs between the two gradient modes, which indicated varying degree of sequence dependent separation. Peak widths from the experimental dataset were calculated and correlated with the guanine-cytosine content and retention time of the sequence for each gradient slope. This data was used to predict the resolution of the n - 1 impurity among 250 000 random 12- and 16-mer sequences; showing one of the investigated gradient modes has a much higher probability of exceeding a resolution of 1.5, particularly for the 16-mer sequences. Sequences having a high guanine-cytosine content and a terminal C are more likely to not reach critical resolution. The trained SVR models can both be used to identify characteristics of different separation methods and to assist in the choice of method conditions, i.e. to optimize resolution for arbitrary sequences. The methodology presented in this study can be expected to be applicable to predict retention times of other oligonucleotide synthesis and degradation impurities if provided enough training data.


Novel chitin/chitosan-glucan wound dressing: Isolation, characterization, antibacterial activity and wound healing properties.
Chitin/chitosan-glucan complex (ChCsGC) was isolated from Schizophyllum commune (S. commune) and dissolved for the first time in precooled (-15°C) 8wt.% urea/6wt.% NaOH aqueous solution. Novel nonwoven microfiber mats were fabricated by wet-dry-spinning technique and evaluated the mechanical of fabrics mats and surface morphology. Isolated and nonwoven mat were characterized employing FTIR-ATR, Optical microscope, TGA, DSC, H/C NMR, SEM and XRD techniques. According to the physical/chemical characterization measurements we can assumed that, the net and the novel dressing mats have the same chemical structure with slightly changes in the thermal stability for the dressing mats.The biological activity of the nonwoven ChCsGC fabric was tested against different types of bacteria exhibiting excellent antibacterial activity. Cell viability of the plain complex and nonwovens mats were evaluated utilizing mouse fibroblast cell line varying concentrations and treatment time. ChCsGC did not show any cytotoxicity against mouse fibroblast cells and the cell-fabrics interaction was also investigated using fluorescence microscope. The novel ChCsGC nonwovens exhibited excellent surgical wound healing ability when tested using rat models.


Modulation of mediator release from human basophils and pulmonary mast cells and macrophages by auranofin.
Auranofin, a new orally absorbable gold compound, inhibits IgE-(anti-IgE) and non-IgE-mediated (f-met-peptide and the Ca2+ ionophore A23187) histamine release from human basophils. Auranofin inhibits the release of histamine induced by phorbol myristate (TPA) and bryostatin 1 both in the presence and absence of extracellular Ca2+. Increasing the Ca2+ concentrations in the extracellular medium does not reduce the inhibitory effect of auranofin on anti-IgE- or A23187-induced secretion. Auranofin inhibits the de novo synthesis of sulfidopeptide leukotriene C4 (LTC4) induced by anti-IgE from basophils and mast cells purified from human lung. However, in both systems auranofin has a significantly greater inhibitory effect on LTC4 release than on histamine secretion. Finally, auranofin induces a concentration-dependent inhibition of A23187-induced leukotrine B4 (LTB4) release from purified human lung macrophages. These data suggest that auranofin modulates the release of preformed (histamine) and de novo synthesized (LTC4 and LTB4) chemical mediators from human inflammatory cells isolated from peripheral blood and human lung tissues.


Feasibility and criterion validity of the GLIM criteria in the critically ill: A prospective cohort study.
This study aimed to evaluate the feasibility and validity of the Global Leadership Initiative on Malnutrition (GLIM) criteria in the intensive care unit (ICU). This was a cohort study involving critically ill patients. Diagnoses of malnutrition by the Subjective Global Assessment (SGA) and GLIM criteria within 24 h after ICU admission were prospectively performed. Patients were followed up until hospital discharge to assess the hospital/ICU length of stay (LOS), mechanical ventilation duration, ICU readmission, and hospital/ICU mortality. Three months after discharge, the patients were contacted to record outcomes (readmission and death). Agreement and accuracy tests and regression analyses were performed. GLIM criteria could be applied to 377 (83.7%) of 450 patients (64 [54-71] years old, 52.2% men). Malnutrition prevalence was 47.8% (n = 180) by SGA and 65.5% (n = 247) by GLIM criteria, presenting an area under the curve equal to 0.835 (95% confidence interval [CI], 0.790-0.880), sensitivity of 96.6%, and specificity of 70.3%. Malnutrition by GLIM criteria increased the odds of prolonged ICU LOS by 1.75 times (95% CI, 1.08-2.82) and ICU readmission by 2.66 times (95% CI, 1.15-6.14). Malnutrition by SGA also increased the odds of ICU readmission and the risk of ICU and hospital death more than twice. The GLIM criteria were highly feasible and presented high sensitivity, moderate specificity, and substantial agreement with the SGA in critically ill patients. It was an independent predictor of prolonged ICU LOS and ICU readmission, but it was not associated with death such as malnutrition diagnosed by SGA.


Paternal Contributions to Offspring Health: Role of Sperm Small RNAs in Intergenerational Transmission of Epigenetic Information.
The most fundamental process for the perpetuation of a species is the transfer of information from parent to offspring. Although genomic DNA contributes to the majority of the inheritance, it is now clear that epigenetic information -information beyond the underlying DNA sequence - is also passed on to future generations. However, the mechanism and extent of such inheritance are not well-understood. Here, I review some of the concepts, evidence, and mechanisms of intergenerational epigenetic inheritance via sperm small RNAs. Recent studies provide evidence that mature sperm are highly abundant in small non-coding RNAs. These RNAs are modulated by paternal environmental conditions and potentially delivered to the zygote at fertilization, where they can regulate early embryonic development. Intriguingly, sperm small RNA payload undergoes dramatic changes during testicular and post-testicular maturation, making the mature sperm epigenome highly unique and distinct from testicular germ cells. I explore the mechanism of sperm small RNA remodeling during post-testicular maturation in the epididymis, and the potential role of this reprograming in intergenerational epigenetic inheritance.


Interhemispheric transfer in normals and acallosals: latency adjusted evoked potential averaging.
Interhemispheric transfer time (IHTT) can be estimated from visual evoked potentials (EPs). Latency adjusted averaging (LAA) produces EPs which have enhanced components. LAA also provides estimates of EP latency variance and signal-to-noise ratio (S/N). LAA was tested in analysis of EP-IHTT in normal and acallosal subjects. It was hypothesized that in normals S/N and latency variance would reveal signal degradation resulting from interhemispheric transfer. LAA in normals replicated IHTT findings for both P1 and N1 latency. Latency variance did not increase for cross-callosal measures, whereas the S/N measure showed significant EP degradation due to callosal transfer. EPs from five subjects with callosal absence (two commissurotomy; two complete and one partial callosal agenesis) showed significantly larger than normal latency variability, as well as decreased S/N ratios, for cross-hemisphere visual EPs. Results support the value of LAA in EP research on adequacy of hemispheric interactions in clinical populations.


A combined pain consultation and pain education program decreases average and current pain and decreases interference in daily life by pain in oncology outpatients: a randomized controlled trial.
Pain education programs (PEP) and pain consultations (PC) have been studied to overcome patient-related and professional-related barriers in cancer pain management. These interventions were studied separately, not in combination, and half of the studies reported a significant improvement in pain. Moreover, most PEP studies did not mention the adequacy of pain treatment. We studied the effect of PC combined with PEP on pain and interference by pain with daily functioning in comparison to standard care (SC). Patients were randomly assigned to SC (n=37) or PC-PEP (n=35). PEP consisted of patient-tailored pain education and weekly monitoring of pain and side effects. We measured overall reduction in pain intensity and daily interference over an 8-week period as well as adequacy of pain treatment and adherence. The overall reduction in pain intensity and daily interference was significantly greater after randomization to PC-PEP than to SC (average pain 31% vs 20%, P=.03; current pain 30% vs 16%, P=.016; interference 20% vs 2.5%, P=.01). Adequacy of pain management did not differ between the groups. Patients were more adherent to analgesics after randomization to PC-PEP than to SC (P=.03). In conclusion, PC-PEP improves pain, daily interference, and patient adherence in oncology outpatients.