Characteristics of excitation and inhibition of the receptive fields of the retina and lateral geniculate body.
The process of excitation and inhibition in the receptive fields (RF) of the ganglion cells and lateral geniculate body (LGB) of the cat were examined. The extent of the dependence of the magnitude of excitation and inhibition in RF on stimulus intensity was determined. This dependence is a power function with power indices of 0.15--0.20 (LGB) and 0.3--0.5 (retina) for excitation and 0.2--0.3 (LGB) and 0.5--0.6 (retina) for inhibition.


A review on nanomaterials and nanohybrids based bio-nanocomposites for food packaging.
With an increasing demand for a novel, eco-friendly, high-performance packaging material "bio-nanocomposites" has attracted great attention in recent years. The review article aims at to evaluating recent innovation in bio-nanocomposites for food packaging applications. The current trends and research over the last three years of the various bio-nanocomposites including inorganic, organic nanomaterials, and nanohybrids, which are suitable as food packaging materials due to their advanced properties such as high mechanical, thermal, barrier, antimicrobial, and antioxidant are described in detail. In addition, the legislation, migration studies, and SWOT analysis on bio-nanocomposite film have been discussed. It has been observed that the multifunctional properties of the bio-nanocomposite materials, has the potential to improve the quality and safety of the food together with no /or fewer negative impact on the environment. However, more studies need to be performed on bio-nanocomposite materials to determine the migration levels and formulate relevant legislation.


An insight into the hepatoprotective role of Velpatasvir and Sofosbuvir per se and in combination against carbon tetrachloride-induced hepatic fibrosis in rats.
Hepatitis C is a global health issue. Hepatitis C Virus (HCV) induces fibrosis by redox reactions, which involve the deposition of collagen in extracellular matrix (ECM). This study aimed to examine the antifibrotic effect of direct-acting antivirals; Sofosbuvir and Velpatasvir, per se and in combination against carbon tetrachloride (CCl4)-induced fibrosis in rats. Carbon tetrachloride (intraperitoneal; 0.5 ml/kg) twice weekly for six weeks was used to induce hepatic fibrosis in rats. After two weeks of CCl4, oral administration of Sofosbuvir (20 mg/kg/d) and Velpatasvir (10 mg/kg/d) was administered to rats for the last four weeks. Liver function tests (LFTs), renal function tests (RFTs), oxidative stress markers, and the levels of TNF-a, NF-κB, and IL-6 were measured through ELISA and western blotting at the end of the study. CCl4 significantly ameliorated the values of RFTs, LFTs and lipid profiles in the diseased group, which were normalized by the SOF and VEL both alone and in combination. These drugs produced potent antioxidant effects by significantly increasing antioxidant enzymes. From the histopathology of hepatic tissues of rats treated with drugs, the antifibrotic effect was further manifested, which showed suppression of hepatic stellate cells (HSCs) in treated rats, as compared to the disease control group. The antifibrotic effect was further demonstrated by significantly decreasing the levels of TNF-a, NF-κB and IL-6 in serum and hepatic tissues of treated rats as compared to the disease control group. Sofosbuvir and Velpatasvir alone and in combination showed marked inhibition of fibrosis in the CCl4-induced non-HCV rat model, which was mediated by decreased levels of TNF-a/NF-κB and the IL-6 signaling pathway. Thus, it can be concluded that Sofosbuvir and Velpatasvir might have an antifibrotic effect that appears to be independent of their antiviral activity.


A synthetic hemoregulatory peptide (HP5B) inhibits human myelopoietic colony formation (CFU-GM) but not leukocyte phagocytosis in vitro.
A synthetic analog of a hemoregulatory peptide associated with mature human granulocyte (HP5B) has been investigated for inhibitory effects on human myelopoietic stem cells in vitro. In addition, it has been tested for effects on phagocytosis by human granulocytes and monocytes by use of an automatic flow cytometric method. A dose-dependent inhibition of colony formation was found after preincubation of bone marrow cells for 1 h at 37 degrees C in the range 10(7) -10(-11) mol/l. Above or below these concentrations, no inhibitory effects were seen. The degree of inhibition varied from experiment to experiment, indicating variable responsiveness of the donor cells. Maximal effect was of magnitude 90% inhibition, and the optimal dose was 10(7) mol/l. The peptide had no effect on the kinetics of phagocytosis by measurements of the uptake of fluorescent Zymosan particles or Staphylococcus aureus. This may indicate a selective effect on the precursor cells, with no effect on the functional state of their progeny, the granulocytes and monocytes.


Tramadol versus Celecoxib for reducing pain associated with outpatient hysteroscopy: a randomized double-blind placebo-controlled trial.
Which is better, Tramadol or Celecoxib, in reducing pain associated with outpatient hysteroscopy? Both Tramadol and Celecoxib are effective in reducing pain associated with outpatient hysteroscopy but Celecoxib may be better tolerated. Pain is the most common cause of failure of outpatient hysteroscopy. A systematic review and meta-analysis showed that local anaesthetics were effective in reducing pain associated with hysteroscopy but there was insufficient evidence to support the use of oral analgesics, opioids and non-steroidal anti-inflammatory drugs, to reduce hysteroscopy-associated pain and further studies were recommended. This was a randomized double-blind placebo-controlled trial with balanced randomization (allocation ratio 1:1:1) conducted in a university hospital from May 2014 to November 2014. Two hundred and ten women who had diagnostic outpatient hysteroscopy were randomly divided into three equal groups: Group 1 received oral Tramadol 100 mg, group 2 received Celecoxib 200 mg and group 3 received an oral placebo. All the drugs were given 1 h before the procedure. A patient's perception of pain was assessed during the procedure, immediately afterwards and 30 min after the procedure with the use of a visual analogue scale (VAS). There was a significant difference in the pain scores among the groups during the procedure, immediately afterwards and 30 min after the procedure (P< 0.001, 0.001, <0.001 respectively). Tramadol had significantly lower pain scores when compared with the placebo during the procedure (mean difference = 1.54, 95% confidence interval (CI) (0.86, 2.22), P < 0.001), immediately after the procedure (mean difference = 1.09; 95% CI (0.5, 1.68), P < 0.001) and 30 min later (mean difference = 0.95, 95% CI (0.48, 1.41), P < 0.001). Celecoxib administration also led to significantly lower pain scores than the placebo during the procedure (mean difference = 1.28, 95% CI (0.62, 1.94), P < 0.001), immediately after the procedure (mean difference = 0.72; 95% CI (0.13, 1.32), P = 0.016) and 30 min later (mean difference = 0.77, 95% CI (0.3, 1.24), P = 0.001). There were no significant differences in pain scores between Tramadol and Celecoxib at any time. Time until no pain differed significantly among the groups (P = 0.01); it was shorter with both Tramadol and Celecoxib groups when compared with placebo (P = 0.002 and 0.046, respectively). The procedure failed to be completed in one patient in the placebo group but no failure to complete the procedure occurred in Tramadol and Celecoxib groups. Four women in the Tramadol group reported nausea but no side effects were reported with Celecoxib group and no complications were reported in any group of patients. All results were based on the subjective perception of pain, which varies among individuals and is related to the individuals' previous pain experience and level of anxiety. Tramadol and Celecoxib are effective in reducing pain in outpatient hysteroscopy. Celecoxib may be better tolerated as no side effects were reported in the study, however further research on a larger sample size is required before drawing firm conclusions about lack of side effects. This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector. All authors declare no conflict of interest. www.clinicaltrials.gov - NCT02071303.


Dendrites determine the contribution of after depolarization potentials (ADPs) to generation of repetitive action potentials in hypothalamic gonadotropin releasing-hormone (GnRH) neurons.
The impact of structure in modulating synaptic signals originating in dendrites is widely recognized. In this study, we focused on the impact of dendrite morphology on a local spike generating mechanism which has been implicated in hormone secretion, the after depolarization potential (ADP). Using multi-compartmental models of hypothalamic GnRH neurons, we systematically truncated dendrite length and determined the consequence on ADP amplitude and repetitive firing. Decreasing the length of the dendrite significantly increased the amplitude of the ADP and increased repetitive firing. These effects were observed in dendrites both with and without active conductances suggesting they largely reflect passive characteristics of the dendrite. In order to test the findings of the model, we performed whole-cell recordings in GnRH neurons and elicited ADPs using current injection. During recordings, neurons were filled with biocytin so that we could determine dendritic and total projection (dendrite plus axon) length. Neurons exhibited ADPs and increasing ADP amplitude was associated with decreasing dendrite length, in keeping with the predictions of the models. Thus, despite the relatively simple morphology of the GnRH neuron's dendrite, it can still exert a substantial impact on the final neuronal output.


Progressive hearing loss, hypoplasia of the cochlea and widened vestibular aqueducts are very common features in Pendred's syndrome.
Long-term hearing threshold-on-age follow-up data, including non-linear regression analysis, are given for 12 consecutive Pendred patients. The clinical diagnosis of Pendred's syndrome was confirmed by a mutation analysis of the PDS gene in 11 out of the 11 cases tested. Recent imaging of the temporal bones in seven out of these 12 patients showed widened vestibular aqueducts in each case. The diagnostic perchlorate test was negative in one patient, but this test was positive in her affected sister. Mutation analysis of the PDS gene in these patients confirmed that Pendred's syndrome is a monogenetic disorder. Progressive sensorineural hearing loss and widened vestibular aqueducts are characteristic features of Pendred's syndrome, which provides the opportunity to diagnose Pendred's syndrome clinically in the first few years of life, as has recently been suggested in a case report (Cremers et al., Progressive sensorineural hearing loss and a widend vestibular aqueduct in Pendred syndrome, Arch. Otolaryngol. 124 (1998) 501-505). Mutation analysis of the involved gene can be used to confirm the clinical diagnosis.


Controversies in Maxillofacial Trauma.
Craniomaxillofacial trauma management has continued to improve and evolve as a result of advances in technology and scientific inquiry. Controversies exist where there is little evidence-based literature to guide treatment in frontal sinus management, rigid versus absorbable fixation, open versus closed treatment of mandibular condyle fractures, extraction of teeth in the line of fracture, optimal timing for repair of mandible fractures, antibiotic use for facial wounds and fractures, and reconstructive materials in orbital fracture reconstruction. This article reviews current literature to resolve some of the controversies, to improve patient care by reducing variability and uncertainty in the optimal management of facial trauma patients.


[Bilateral proximal pulmonary embolism without associated hypoxemia. Case report].
Pulmonary embolism is a classic complication in intensive care. It is characterized by hypoxemia secondary to perturbed ventilation/perfusion ratios. We report a case of proximal and bilateral pulmonary embolism that occurred without associated hypoxemia. A spiral computed tomography (CT) scan was performed to explore unexplained fever in a patient with a negative infectious investigation. We discuss the mechanisms underlying the absence of hypoxemia in this patient. A 43-year-old patient with no significant pathological history was admitted to intensive care for the management of multiple injuries following a road accident. During resuscitation, the patient developed a proximal and bilateral pulmonary embolism without signs of hypertension of the pulmonary artery or associated hypoxemia. The patient improved under treatment. This case shows that bilateral proximal pulmonary embolism may be associated with normal gas exchange. The absence of hypoxemia could be explained by the bilateral nature of the pulmonary embolism that led to balanced ventilation/perfusion ratios on both sides. Furthermore, bronchoconstriction was bilateral, explaining the maintenance of a stable ventilation/perfusion ratio on both sides. The presence of unexplained fever in a victim of multiple trauma, despite the absence of hypoxemia, suggests the diagnosis of pulmonary embolism.


Subpopulations of B cells distinguished by cell surface expression of Ia antigens. Correlation of Ia and idiotype during activation by cloned Ia-restricted T cells.
We have investigated in vitro the induction of antibody responses to phosphorylcholine (PC) by cloned T helper (Th) cell lines. The cloned Th cells are antigen specific, in this case ovalbumin (OVA), self-Ia recognizing, and induce antibody secretion only if the hapten, PC, is physically linked to the carrier (OVA) molecule. The plaque-forming cell (PFC) response generated in the presence of cloned Th cells is idiotypically diverse with 5-40% of the secreting B cells bearing the TEPC-15 (T15) idiotype. The interaction of the cloned Th cells and unprimed B cells requires recognition of B cell surface Ia glycoproteins for all B cells activated to secrete anti-PC antibody, whether they be T15-bearing or not. More importantly, however, effective interaction between a cloned Th cell and a B cell is determined by the quantity of B cell surface Ia glycoproteins. Our results indicate that quantitative differences in B cell surface Ia antigens are directly related to B cell activation by the cloned Th cell. The high Ia density B cells are most easily activated by cloned Th cells, and these appear to be mainly non-T15-bearing. These data suggest that the failure of cloned Th cells to effectively activate T15-bearing B cells in vitro may be due to the lower relative Ia density of these B cells and therefore to their inability to interact effectively with cloned Ia-recognizing Th cells. These results imply that monoclonal T cells may distinguish between T15-bearing and non-T15-bearing B cells based on their Ia density.


Fungal Pseudoallescheria boydii lung infiltrates unresponsive to amphotericin B in leukaemic patients.
The management of patients with acute leukaemia is often complicated by serious fungal infections, especially of the lungs. The outcome of therapy has historically depended on the early use, efficacy and toxicity of amphotericin B. Pseudoallescheria boydii is an uncommon cause of such infections but as it is more often resistant to amphotericin B early identification may enable the prompt use of alternative and newer antifungal agents. Here we report our experience and review the literature in three cases of P. boydii infection in patients with leukemia, showing unique features such as childhood and central nervous system disease, positive blood cultures and response to itraconazole.


Vitrectomy in Diabetic Macular Edema:: A Swept-source OCT Angiography Study.
The foveal avascular zone (FAZ) has been reported to decrease after anti-VEGF injections in diabetic macular edema (DME) in the long term. This study aimed to present the changes in swept-source OCT angiography after vitrectomy in patients with DME. Retrospective interventional study. Thirty-five eyes were included (mean age: 62 years). Patients were followed for 12 months after vitrectomy with internal limiting membrane peeling for DME. The following parameters were measured: central retinal thickness (CRT), central choroidal thickness, superficial FAZ, deep FAZ (dFAZ), and vessel density in the superficial and deep retinal layers (dVD). The CRT and superficial FAZ significantly decreased after surgery (401 μm-338 μm; P < 0.00, 401 μm-293 μm; P < 0.001, respectively). Initial visual acuity (VA) improved from 20/160 (0.97 logarithm of the minimum angle of resolution [LogMAR]) to 20/80 (0.62 LogMAR) (P < 0.001). The vessel density in the superficial retinal layers rate was 42.3% and decreased after surgery, reaching 41.6% at the end of the follow-up. The dVD rate 1 week after surgery was 28.9% and remained stable throughout the observation period. The most important prognostic factors for the final VA were preoperative VA and preoperative CRT, while the dFAZ and dVD at the time of edema resolution also correlated with the final VA. The superficial FAZ decreases after vitrectomy, which might indicate that vitrectomy has a protective effect on DME, similar to anti-VEGF injections. Prognostic factors for better final functional results are better initial VA and lower CRT before vitrectomy, in addition to a lower dFAZ diameter and a higher dVD at the moment of edema resolution. The author(s) have no proprietary or commercial interest in any materials discussed in this article.


Higher hamstring-to-quadriceps isokinetic strength ratio during the first post-operative months in patients with quadriceps tendon compared to hamstring tendon graft following ACL reconstruction.
The aim of this study was to compare isokinetic quadriceps and hamstring muscle strength in patients following anterior cruciate ligament (ACL) reconstruction who received either hamstring (HT) or quadriceps (QT) tendon autografts at two time intervals within the first year after surgery. One hundred twenty-four patients, 81 males (age 22.0 ± 6.2 years) and 43 females (age 20.9 ± 8.7 years), participated in this study. ACL reconstruction was performed with either quadriceps tendon autografts (QT; n = 61) or hamstring tendon autografts (HT; n = 63). Two isokinetic muscle strength tests (t1: 5.5 ± 1.2 months; t2: 7.6 ± 1.6 months) were performed at an angular velocity of 60°/s in both the injured and contralateral knees. An independent t test as well as a two-factor analysis of variance with repeated measurements was used. The significance level was set at p < 0.05. A statistically significant lower knee extensor strength was observed in the QT group within one year after surgery (p < 0.001). Additionally, data showed a significant higher H/Q ratio in QT patients compared to the HT group at t1 (p < 0.001) and t2 (p = 0.001) as well as a significant effect over time (p < 0.001) and interaction effect of time and graft (p = 0.007). Side-to-side values for extensor muscle strength were significantly (p < 0.001) greater in HT graft patients, while QT patients showed significantly (p < 0.001) greater values for flexor muscle strength at both time points of isokinetic testing, respectively. The results of this study indicate that graft choice has an impact on extensor strength in the first months after ACL reconstruction; however, there is no impact on flexor strength. The finding of a higher H/Q ratio in patients with QT grafts within the first months following surgery is possibly of clinical relevance. This may potentially be associated with lower stress on the maturing ACL graft. Furthermore, normal thigh strength can be restored over time. III.


Assessing racial residential segregation as a risk factor for severe maternal morbidity.
To measure associations of area-level racial and economic residential segregation with severe maternal morbidity (SMM). We conducted a retrospective cohort study of births at two Philadelphia hospitals between 2018 and 2020 to analyze associations of segregation, quantified using the Index of Concentration at the Extremes (ICE), with SMM. We used stratified multivariable, multilevel, logistic regression models to determine whether associations of ICE with SMM varied by self-identified race or hospital catchment. Of the 25,979 patients (44.1% Black, 35.8% White), 1381 (5.3%) had SMM (Black [6.1%], White [4.4%]). SMM was higher among patients residing outside (6.3%), than inside (5.0%) Philadelphia (P < .001). Overall, ICE was not associated with SMM. However, ICErace (higher proportion of White vs. Black households) was associated with lower odds of SMM among patients residing inside Philadelphia (aOR 0.87, 95% CI: 0.80-0.94) and higher odds outside Philadelphia (aOR 1.12, 95% CI: 0.95-1.31). Moran's I indicated spatial autocorrelation of SMM overall (P < .001); when stratified, autocorrelation was only evident outside Philadelphia. Overall, ICE was not associated with SMM. However, higher ICErace was associated with lower odds of SMM among Philadelphia residents. Findings highlight the importance of hospital catchment area and referral patterns in spatial analyses of hospital datasets.


Integration of CRISPR/Cas9 with artificial intelligence for improved cancer therapeutics.
Gene editing has great potential in treating diseases caused by well-characterized molecular alterations. The introduction of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9)-based gene-editing tools has substantially improved the precision and efficiency of gene editing. The CRISPR/Cas9 system offers several advantages over the existing gene-editing approaches, such as its ability to target practically any genomic sequence, enabling the rapid development and deployment of novel CRISPR-mediated knock-out/knock-in methods. CRISPR/Cas9 has been widely used to develop cancer models, validate essential genes as druggable targets, study drug-resistance mechanisms, explore gene non-coding areas, and develop biomarkers. CRISPR gene editing can create more-effective chimeric antigen receptor (CAR)-T cells that are durable, cost-effective, and more readily available. However, further research is needed to define the CRISPR/Cas9 system's pros and cons, establish best practices, and determine social and ethical implications. This review summarizes recent CRISPR/Cas9 developments, particularly in cancer research and immunotherapy, and the potential of CRISPR/Cas9-based screening in developing cancer precision medicine and engineering models for targeted cancer therapy, highlighting the existing challenges and future directions. Lastly, we highlight the role of artificial intelligence in refining the CRISPR system's on-target and off-target effects, a critical factor for the broader application in cancer therapeutics.


Pelvic floor muscle training for prevention and treatment of urinary and fecal incontinence in antenatal and postnatal women: a short version Cochrane review.
Pelvic floor muscle training (PFMT) is commonly recommended during pregnancy and after birth both for prevention and the treatment of incontinence. Effect of pelvic floor muscle training compared to usual antenatal and postnatal care on incontinence. Cochrane Incontinence Group Specialized Register; handsearching (searched February 7, 2012); the references of relevant articles. Randomized or quasi-randomized controlled trials in pregnant or postnatal women having pelvic floor muscle training (PFMT) versus no PFMT or standard care. Duplicate trial assessment, selection and data abstraction. Twenty-two trials involving 8,485 women. Continent pregnant women (prevention) who had intensive antenatal PFMT were less likely to report urinary incontinence up to 6 months after delivery (risk ratio (RR) 0.71, 95% CI 0.54-0.95). Incontinent postnatal women (treatment) who received PFMT were less likely to report urinary incontinence 12 months after delivery (RR 0.60, 95% CI 0.35-1.03). In a mixed population (women with and without incontinence symptoms in late pregnancy or after delivery), PFMT did not reduce incontinence rates after delivery. For women who are continent during pregnancy, PFMT may prevent urinary incontinence up to 6 months after delivery. The extent to which mixed prevention and treatment approaches to PFMT in the postnatal period are effective is less clear that is, offering advice on PFMT to all pregnant or postpartum women whether they have incontinence symptoms or not. There was little evidence about long-term effects for either urinary or fecal incontinence.


Arteriovenous malformation of the gluteal artery during pregnancy.
We describe a case of a congenital arteriovenous fistula of the gluteal artery, a posterior branch of the left iliac artery, developing during pregnancy without postpartum regression after delivery. Surgical excision without preoperative embolisation was made possible by prior ligation of the gluteal artery.


A Comparative Study of the Effects of Different Decellularization Methods and Genipin-Cross-Linking on the Properties of Tracheal Matrices.
Different decellularization methods can affect the integrity and the biomechanical and biocompatible properties of the tracheal matrix. Natural cross-linking with genipin can be applied to improve those properties. The goals of this study were to evaluate the effects of different decellularization methods on the properties of genipin-cross-linked decellularized tracheal matrices in rabbits. The tracheas of New Zealand rabbits were decellularized by the Triton-X 100-processed method (TPM) and the detergent-enzymatic method (DEM) and were then cross-linked with genipin. Mechanical tests, haematoxylin-eosin staining, Masson trichrome staining, Safranin O staining, DAPI staining, scanning electronic microscopy (SEM), and biocompatibility tests were used to evaluate the treatment. The bioengineered trachea and control trachea were then implanted into allogeneic rabbits for 30 days. The structural and functional analyses were performed after transplantation. The biomechanical tests demonstrated that the biomechanical properties of the decellularized tracheas decreased and that genipin improved them (p < 0.05). The histological staining results revealed that most of the mucosal epithelial cells were removed and that the decellularized trachea had lower immunogenicity than the control group. The analysis of SEM revealed that the decellularized trachea retained the micro- and ultra-structural architectures of the trachea and that the matrices cross-linked with genipin were denser. The biocompatibility evaluation and in vivo implantation experiments showed that the decellularized trachea treated with the DEM had better biocompatibility than that treated with the TPM and that immunogenicity in the cross-linked tissues was lower than that in the uncross-linked tissues (p < 0.05). Compared with the trachea treated with the TPM, the rabbit trachea processed by the DEM had better biocompatibility and lower immunogenicity, and its structural and mechanical characteristics were effectively improved after the genipin treatment, which is suitable for engineering replacement tracheal tissue.


The 1.14 A crystal structure of yeast cytosine deaminase: evolution of nucleotide salvage enzymes and implications for genetic chemotherapy.
Cytosine deaminase (CD) catalyzes the deamination of cytosine and is only present in prokaryotes and fungi, where it is a member of the pyrimidine salvage pathway. The enzyme is of interest both for antimicrobial drug design and gene therapy applications against tumors. The structure of Saccharomyces cerevisiae CD has been determined in the presence and absence of a mechanism-based inhibitor, at 1.14 and 1.43 A resolution, respectively. The enzyme forms an alpha/beta fold similar to bacterial cytidine deaminase, but with no similarity to the alpha/beta barrel fold used by bacterial cytosine deaminase or mammalian adenosine deaminase. The structures observed for bacterial, fungal, and mammalian nucleic acid deaminases represent an example of the parallel evolution of two unique protein folds to carry out the same reaction on a diverse array of substrates.


HIV-1 subtypes in Spain: a retrospective analysis from 1995 to 2003.
To perform a retrospective analysis of all HIV-1 non-B variants circulating in Spain from 1995 to 2003 and extend their virological characterization. Samples from a total of 396 HIV-infected subjects with epidemiological suspicion of being infected with non-B clades were analysed during the study period. Subtyping was carried out on the protease (PR), reverse transcriptase (RT) and envelope (env) genes. PR sequences belonging to non-B subtypes were recognized in 43.2% of cases (23 A, 13C, 6D, 3F, 118 G, 3H, 4 J and 1 U). Subtype G and AG recombinants were the most frequent variants (69%), and were found most often in subjects from West and Central Africa. Up to 70% of pol (PR, RT) sequences belonging to subtype G harboured env sequences belonging to clade A (55%), B (13.8%) or K (3.4%). Nearly half were mosaic GA viruses, and a few were CRF 14 BG viruses. Up to 14 new recombinant viruses, which could not be assigned to previously described circulating recombinant forms (CRFs), were found. There is great diversity in the HIV-1 variants and recombinant viruses circulating in Spain. Non-B sequences may be underestimated if only the env region is examined in phylogenetic analyses. Drug resistance testing provides the advantage of pol subtyping, and its additional use for this purpose should be encouraged.


Salzmann's Nodular Degeneration.
Salzmann's nodular degeneration (SND) is a rare, noninflammatory, slowly progressive degenerative disease of the cornea that is characterized by the appearance of nodular bluish gray opacities that vary in number and size. It is usually bilateral; most commonly occurring in people aged 50-60 years old, with a female preponderance; and often associated with a history of prior corneal inflammation. The clinical features usually depend on the location of the nodules. Generally, the nodules of SND are bluish white to gray in color, 1-2 mm in size, and round, conical or prismatic in shape. The overlying Bowman's layer is usually absent from the nodular areas and is partially replaced by granular Periodic Acid Schiff-positive eosinophilic material resembling the basement membrane. Diagnostic investigations include ultrasonic pachymetry, anterior segment optical coherence tomography, ultrasound biomicroscopy, and confocal microscopy. The majority of patients respond well to conservative management with topical lubricants; severe cases may require surgical intervention. The various surgical modalities described include superficial keratectomy, which may be combined with phototherapeutic keratectomy and keratoplasty. Various modifications of these procedures include the use of alcohol-assisted epithelial delamination, intraoperative mitomycin-C or amniotic membrane transplantation to make the procedure easy, reduce the risk of recurrence and improve postoperative comfort. Recurrences are rarely reported; overall, the visual prognosis following treatment is optimal.


Time-updated resting heart rate predicts mortality in patients with COPD.
High resting heart rate (RHR) is associated with higher mortality in the general population and in cardiovascular disease. Less is known about the association of RHR with outcome in chronic obstructive pulmonary disease (COPD). In particular, the time-updated RHR (most recent value before the event) appears informative. This is the first study to investigate the association of time-updated RHR with mortality in COPD. We compared the baseline and time-updated RHR related to survival in 2218 COPD patients of the German COSYCONET cohort (COPD and Systemic Consequences-Comorbidities Network). Patients with a baseline RHR > 72 beats per minute (bmp) had a significantly (p = 0.049) higher all-cause mortality risk (adjusted hazard ratio (HR) of 1.37 (1.00-1.87) compared to baseline RHR ≤ 72 bpm. The time-updated RHR > 72 bpm was markedly superior (HR 1.79, 1.30-2.46, p = 0.001). Both, increased baseline and time-updated RHR, were independently associated with low FEV1, low TLCO, a history of diabetes, and medication with short-acting beta agonists (SABAs). In conclusion, increased time-updated RHR is associated with higher mortality in COPD independent of other predictors and superior to baseline RHR. Increased RHR is linked to lung function, comorbidities and medication. Whether RHR is an effective treatment target in COPD, needs to be proven in controlled trials.


The effect of lidocaine intraoperative infusion on quality of postoperative sleep in patients undergoing thyroidectomy: a randomized controlled trial.
The incidence of thyroid nodules has increased significantly in recent years, and surgical removal is a common treatment. Postoperative sleep disturbance is still a serious problem in the current surgical environment. In this study, we explored whether intraoperative lidocaine infusion could improve the quality of sleep over 7 days and 30 days after surgery and postoperative recovery for patients undergoing thyroid surgery. Seventy patients who underwent thyroid surgery from October 2020 to June 2021 were randomly assigned to the lidocaine or the normal saline group, 35 cases in each group. Patients enrolled in this study were randomized to receive either system lidocaine (a bolus of 1.5 mg·kg- 1, followed by an infusion of 2 mg·kg- 1·h- 1 until the end of the surgical procedure) or identical volumes and rates of normal saline. The primary endpoint was the Pittsburgh Sleep Quality Index (PSQI) scores. Secondary endpoints included intraoperative remifentanil consumption, whether there was a cough within 5 min after extubation and the cough scores, postoperative pain scores, the incidence of postoperative nausea and vomiting (PONV). Totally seventy cases were enrolled and eventually sixty-eight cases were analyzed. PSQI scores did not change significantly over time (F = 2.799, P = 0.069); also, there was no significant difference in PSQI scores between two groups in the entire 30 days follow-up period (F = 0.174, P = 0.678). Further, there was no interaction between the time points and the intervention (F = 0.649, P = 0.513). Similarly, intraoperative remifentanil consumption, the incidence of cough and postoperative pain scores, were comparable between the two groups (all P > 0.05); while patients in the lidocaine group showed significantly lower cough scores (P = 0.042) and lower incidence of PONV (P = 0.015). Systemic lidocaine infusion might not improve the sleep quality and reduce postoperative pain over 7 days or 30 days after the operation of patients who underwent thyroid surgery, but it can reduce postoperative complications and improve the quality of recovery. Furthermore, sleep quality of patients wasn't impaired significantly in the entire 30 days follow-up period after thyroid surgery compared with baseline values. Registered in the Chinese Clinical Trial Registry ( http://www.chictr.org.cn , identifier: ChiCTR2000039764, date: 08/11/2020).


Maximum Power During Vertical Jump and Isometric Knee Extension Torque Alter Mobility Performance: A Cross-Sectional Study of Healthy Individuals.
To provide reference values of muscle function (MF) and mobility performance (MP) and to clarify the effects of MF on MP. A normative cross-sectional study. An urban area of Niigata, Japan. A total of 401 individuals (210 men and 191 women) with a mean age of 41.8 years (range, 7-79 years) who lived in the community and did not have impairments in activities of daily living. Grip strength, isometric knee extension torque (IKET), and maximum ground reaction force (Fmax) and maximum power (Pmax) during a vertical jump were used as measurements of MF. The chair-rise test (CRT) and the timed "Up and Go" test (TUG) were used to assess MP. Mean values of GS, IKET, CRT, TUG, Fmax, and Pmax were calculated according to age and gender. A stepwise multiple regression analysis was used to identify MF factors with an effect on CRT and TUG in participants ≥20 years of age. Our results showed that all MF parameters were decreased in individuals ≥20 years of age compared to those <20 years old. Moreover, all of the MP parameters increasingly deteriorated with increasing age. CRT and TUG were affected by Pmax and IKET in men and by IKET in women according to logistic regression analysis. The study findings suggest that muscle power affects MP more than the muscle strength in persons aged ≥20 years.


Effects of Ilisha elongata protein, soy protein and whey protein on growth characteristics and adhesion of probiotics.
The effects of different food source proteins on the growth characteristics and intestinal adhesion of Lactobacillus plantarum 45 (LP45) were investigated by adding Ilisha elongata protein, soy protein and whey protein to the probiotic bacteria in vitro and using a probiotic adhesion model based on mouse intestinal tissues. Ilisha elongata protein and soy protein significantly reduced the growth time of LP45 and increased the total number of colonies fermented by LP45; whey protein only reduced the growth time of LP45; the effect of the three food source proteins on the acid production capacity of LP45 was small. These showed that the three food-derived proteins promoted the proliferation and adhesion of probiotics in the intestine, which were beneficial to the active role of intestinal probiotics and improved the intestinal microenvironment.


Effect of vitamin D3 supplementation on cellular immunity and inflammatory markers in COVID-19 patients admitted to the ICU.
Vitamin D as an immunomodulator has not been studied in patients with severe COVID-19. This study aimed to estimate the efficacy of vitamin D3 supplementation on cellular immunity and inflammatory markers in patients with COVID-19 admitted to the intensive care unit (ICU). A single-center, double-blind, randomized, placebo-controlled pilot trial was conducted (N = 110). Patients were randomly assigned to receive a weekly oral dose of 60,000 IU of vitamin D3 followed by daily maintenance doses of 5000 IU (n = 55) or placebo (n = 55). Primary outcomes were lymphocyte counts, natural killer (NK) and natural killer T (NKT) cell counts, neutrophil-to-lymphocyte ratio (NLR), and serum levels of inflammatory markers on 7th day of treatment. On day 7, patients in the vitamin D3 group displayed significantly higher NK and NKT cell counts and NLR than those in the placebo group did. The mortality rate (37% vs 50%, P = 0.16), need for mechanical ventilation (63% vs 69%, P = 0.58), incidence of nosocomial infection (60% vs 41%, P = 0.05) did not significantly differ between groups. Vitamin D3 supplementation, compared with placebo, significantly increased lymphocyte counts, but did not translate into reduced mortality in ICU.Trial Registration: ClinicalTrials.gov Identifier: NCT05092698.


A test of color constancy in 4-month-old human infants.
Forty-five 4-month-old infants were tested for color constancy using a familiarization, paired-comparison paradigm. Infants were familiarized and tested with colored stimuli under two conditions: (1) no change in the illuminant between familiarization and test and (2) a change in the illuminant between familiarization and test. Infants correctly recognized the familiarization color when tested with no change in the illuminant. Infants tested with a change in the illuminant correctly recognized the familiar color under some conditions yet failed to do so under others. Several explanations are considered for these results and it is concluded that color constancy operates immaturely at 4 months of age.


Another advantage of nasal septal suturing: pulmonary function unaffected.
Nasal packing (NP) after septoplasty has some negative aspects. The nasal septal suture (NSS) is therefore becoming increasingly preferred. The aim of this study was to analyze the effects of NSS and NP on pulmonary function tests. Sixty patients who suffered from nasal blockage resulting from nasal septal deviation and who were otherwise healthy were included. Patients were randomized into two groups, NP or NSS. Pre-operative spirometry was performed for all patients. The NP group received a finger glove packing for two days after septoplasty, whereas no additional dressing was used for the NSS group. Narcotic analgesics were not used for pain relief after septoplasty in either group. Spirometry was performed post-operatively on the third day for all patients and before removal of the NP for the NP group. We observed statistically significant differences between pre-operative and post-operative values of forced vital capacity (FVC; p = 0.008), forced expiratory volume in the first second (FEV1; p = 0.006), and forced expiratory flow ((FEF)25-75%; p = 0.011) in the NP group. In comparison, pre-operative and post-operative values did not differ for FVC, FEV1, FEV1/FVC%, and FEF25-75% in the NSS group. NP negatively influenced pulmonary function based on spirometric parameters, while NSS did not.


Symptoms and coping of patients with dysphagia after anterior cervical spine surgery: a qualitative study.
To explore the subjective symptoms, psychological characteristics and coping strategies of patients with dysphagia after anterior cervical spine surgery, so as to provide the basis for formulating strategies to help patients with dysphagia solve clinical practice problems and to improve their quality of life after surgery. Using the phenomenological research method and the purpose sampling method, semi-structured interviews were conducted with 22 participants with dysphagia at 3-time points after anterior cervical spine surgery (7 days, 6 weeks, and 6 months). A total of 22 (10 females and 12 males) patients, with years old ranging between 33 and 78 years were interviewed. When analysing the data, the following 3 categories were extracted from the participant interviews: "Subjective symptoms, Coping style and impact on social life". The 3 categories consist of 10 sub-categories. The results showed that swallowing-related symptoms may occur after anterior cervical spine surgery. Many patients had developed compensatory strategies to manage or reduce the burden of these symptoms, but lacked professional guidance from health care professionals. Moreover, dysphagia after neck surgery has its unique characteristics, involving the interaction of physical, emotional and social factors, which requires early screening.Healthcare professionals should provide better psychological support in the early or late postoperative period to ensure the improvement of health outcomes and patients' quality of life.


Asymmetric dimethylarginine (ADMA) induces chronic kidney disease through a mechanism involving collagen and TGF-β1 synthesis.
Asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase (NOS) inhibitor, is accumulated in plasma during chronic kidney disease (CKD). It is considered an independent mortality and cardiovascular risk factor in CKD patients. To test the involvement of ADMA in CKD progression, we investigated the effects of chronic ADMA administration on renal structure and compared these effects with NG-nitro-L-arginine methyl ester (L-NAME) treatment, a widely used exogenous inhibitor of NOS that induces CKD. Three groups of uninephrectomized mice were studied: ADMA (60 mg/kg per day), L-NAME (60 mg/kg per day), and isotonic saline (control) were infused through osmotic mini-pumps for 8 weeks. ADMA and L-NAME induced hypertension (PAS 167 ± 16 and 168 ± 10 versus 100 ± 4 mmHg, p < 0.01, respectively). High level of ADMA was associated with increased renal oxidative stress. ADMA treatment induced glomerular and vascular fibrosis as evidenced by the elevated deposits of collagen I, III, and fibronectin (p < 0.01). A similar profile was observed in the L-NAME group. Mice treated with ADMA had reduced peritubular capillaries versus controls (p < 0.01). Collagen I mRNA expression and renal TGF-β1 concentrations were higher in the ADMA and L-NAME groups. Increased level of TGF-β1 was associated with a significant rise of HIF-1α and endothelin-1 expression. These results demonstrate for the first time that elevated concentrations of ADMA are associated with the development of renal fibrosis. These data suggest that in pathophysiological conditions of endothelial dysfunction, the exaggerated endogenous synthesis of ADMA could contribute to CKD progression by favouring hypertension, extracellular matrix synthesis, and rarefaction of peritubular capillaries.


Combined immune therapy grade IV dermatitis in metastatic melanoma.
Checkpoint inhibition is the mainstay of treatment in metastatic melanoma. More recently combined cytotoxic T-lymphocyte antigen-4 and programmed-death-1 blockade has resulted in improved response rates and overall survival in treatment naïve patients compared to monotherapy albeit with increased rates of adverse events. Dermatologic toxicities are an emerging consequence of the use of checkpoint inhibitors and have reportedly been more prevalent with the use of combined therapy. However, grade 3 and 4 adverse event rates are still less than 5%. Here, we report a case of a 63-year-old Caucasian male with metastatic melanoma treated with first line combined ipilimumab and nivolumab who then developed a steroid refractory, biopsy confirmed pityriasis lichenoides-like, drug related rash that resolved with cyclosporine. Time of onset was 24 days and presenting symptoms demonstrated a maculopapular rash presenting over the back and chest with pruritus. Unfortunately, the patient subsequently had multi-organ failure with acute kidney injury requiring dialysis, hypotension requiring vasopressor support, hepatic dysfunction, and bilateral lung infiltrates resulting in a fatal outcome. This case report highlights the effective use of cyclosporine as an immunomodulatory agent in the management of severe dermatological toxicity due to combination immunotherapy.


Acretoside, a new sucrose ester from Aristolochia cretica.
A new sucrose ester, acretoside, was isolated from the roots of the Greek endemic species Aristolochia cretica and identified as 6-O-p-coumaroyl-beta-D-fructofuranosyl-(2 --> 1)-alpha-D-glucopyranoside (1). In addition, a known sucrose ester, identified as arillatose B, two phenylpropanoid glucose esters, and five derivatives of aristolochic acid were isolated. Their structures were elucidated on the basis of MS and NMR data.


Sustained Releasable Copper and Zinc Biogenic Ions Co-Assembled in Metal-Organic Frameworks Reinforced Bacterial Eradication and Wound Mitigation in Diabetic Mice.
The employment of metal-organic framework (MOF)-based nanomaterials has been rapidly increasing in bioapplications owing to their biocompatibility, drug degradation, tunable porosity, and intrinsic biodegradability. This evidence suggests that the multifunctional bimetallic ions can behave as remarkable candidates for infection control and wound healing. In this study, bimetallic MOFs (Zn-HKUST-1 and FolA-Zn-HKUST-1) embedded with and without folic acid were synthesized and used for tissue sealing and repairing incisional wound sites in mice models. For comparison, HKUST-1 and FolA-HKUST-1 were also synthesized. The Brunauer-Emmett-Teller (BET) surface area measured for HKUST-1, FolA-HKUST-1, Zn-HKUST-1, and FolA-Zn-HKUST-1 from N2 isotherms was found to be 1868, 1392, 1706, and 1179 m2/g, respectively. The measurements of contact angle values for Zn-HKUST-1, FolA-HKUST-1, and Zn-FolA-HKUST-1 were identified as 4.95 ± 0.8, 43.6 ± 3.4, and 60.62 ± 2.0°, respectively. For topical application in wound healing, they display a wide range of healing characteristics, including antibacterial and enhanced wound healing rates. In addition, in vitro cell migration and tubulogenic potentials were evaluated. The significant reduction in the wound gap and increased expression levels for CD31, eNOS, VEGF-A, and Ki67 were observed from immunohistological analyses to predict the angiogenesis behavior at the incision wound site. The wound healing rate was analyzed in the excisional dermal wounds of diabetic mice model in vivo. On account of antibacterial potentials and tissue-repairing characteristics of Cu2+ and Zn2+ ions, designing an innovative mixed metal ion-based biomaterial has wide applicability and is expected to modulate the growth of various gradient tissues.


T-kininogen is a biomarker of senescence in rats.
We have previously reported on the identification of T-kininogen (T-KG) as a gene whose expression is increased during senescence in male Sprague-Dawley (S-D) rats. Serum T-KG levels increase 2.5-4 months before the time of death for any given animal, irrespective of the actual age of the animal at the time of this event. Furthermore, dietary restriction (DR) delays, but does not prevent, the increase in serum T-KG levels. In the present study, we have assessed whether or not the age-related increase in T-KG is a common feature of senescence in other strains of rat. We have analyzed hepatic T-KG mRNA levels in male Fischer 344 rats (F344), as well as in male and female (Fischer 344 x Brown Norway)F1 rats (F1). In both of these strains, we observed a dramatic increase in hepatic T-KG mRNA levels when male rats approach senescence. The mRNA levels behave similarly in F1 and S-D rats, in that the increase occurs late in life, and it is either repressed or delayed by DR. In contrast, the increase in T-KG mRNA levels in F344 rats occurs earlier in life, and is not significantly affected by DR. Young female F1 rats fed ad libitum (AL) show a statistically significant (P = 0.0009) 2.6-fold higher level of T-KG mRNA, as compared to their male counterparts. Thus, while we still observe an age-related increase in this parameter in both AL and DR female F1 rats, the difference is statistically significant (P = 0.0001) only in DR animals. We conclude that the increase in T-KG gene expression is a common feature of senescence and that, at least in males of these commonly used rat strains, T-KG can be used as a reliable biomarker of aging. Since the increase in T-KG gene expression does not appear to correlate with inflammatory processes, and since different strains of animals succumb to different pathologies, these results further suggest that the increase in T-KG expression might be related to the process of aging per se, rather than to any given age-related pathology.


Mechanism of Co(II) adsorption by zero valent iron/graphene nanocomposite.
Nanoscale zero valent iron (ZVI)/graphene (GF) composite was prepared and characterized by Brunauer-Emmett-Teller (BET) surface area measurement and zeta potential determination. The adsorption isotherm of Co(II) in aqueous solution, as well as the influence of pH values and ionic strengths was studied. The mechanism of Co(II) adsorption by GF was investigated through analyzing the sorption products at initial pH of 3.0, 6.0 and 9.0 using high-resolution transmission electron microscope with energy dispersive X-ray detector (HRTEM-EDX), X-ray diffraction (XRD), vibrating-sample magnetometer (VSM), Raman spectra, X-ray photoelectron spectroscopy (XPS) and X-ray absorption fine structure (XAFS) measurement. The results indicated that Langmuir isotherm model fitted well and the adsorption capacity was 131.58 mg g(-1) at 30°C. Adsorption capacity was not significantly influenced by ionic strength and kept high at pH 4.0∼9.0. The detail information of GF-Co interaction at different initial pH values was obtained using XAFS analysis combined with other characterization methods. Coordination numbers (CN) and interatomic distances (R) of both Fe and Co were given. At pH 3.0 and pH 6.0, the Co-substituted iron oxides transformed to CoFe2O4-like structure, while at pH 9.0 they changed to green rust-like phases. Co occupied preferentially in the octahedral sites in acid solution. The adsorption mechanism of Co(II) was attributed to inner-sphere complexation and dissolution/re-precipitation of the substituted metal oxides.


Deterministic Construction of Plasmonic Heterostructures in Well-Organized Arrays for Nanophotonic Materials.
Plasmonic heterostructures are deterministically constructed in organized arrays through chemical pattern directed assembly, a combination of top-down lithography and bottom-up assembly, and by the sequential immobilization of gold nanoparticles of three different sizes onto chemically patterned surfaces using tailored interaction potentials. These spatially addressable plasmonic chain nanostructures demonstrate localization of linear and nonlinear optical fields as well as nonlinear circular dichroism.


Forehead Contouring.
The upper third of the face has an important effect on gendering patients. Forehead contouring modifying a masculine face to a more feminine form is most likely to affect the gender assessment of an individual's face. Contouring involves techniques such as forehead reduction or augmentation, orbital contouring, and hairline adjustment. Traditionally, surgeons have utilized an open technique, though newer innovations such as endoscopic procedures and custom implants provide an alternative for patients with mild defects. Forehead contouring procedures are well tolerated with minimal side effects reported despite the proximity to the frontal sinus and cranial vault.


Questions about behavioral function (QABF): a behavioral checklist for functional assessment of aberrant behavior.
Functional assessment is a method to identify the relationships between a behavior of interest and an individual's environment. Traditional methods for functional assessment have relied on experimental techniques in which analog sessions are designed to replicate conditions in the individual's environment. However, these techniques can be time-consuming, require advanced training, and rely on the availability of extensive resources in the individual's setting. Development of a brief functional assessment checklist would circumvent these difficulties and meet clinical needs for efficient assessment methods. The current study provides psychometric data for the Questions About Behavioral Function. These data include test-retest, inter-rater, and internal consistency.


Chronic disease and labour force participation among older Australians.
To examine the association between long-term health conditions and being out of the labour force among older Australians. Retrospective analysis of cross-sectional data from the Australian Bureau of Statistics 2003 Survey of Disability, Ageing and Carers for people aged 45-64 years. Rates of premature retirement associated with ill health; odds ratios of being out of the labour force associated with each long-term health condition and number of conditions; weighted population estimates; estimates of gross domestic product lost as a result. 9198 people surveyed were aged 45-64 years, 3010 of whom were not in the labour force. Of these, 1373 (45.6%) had retired because of a chronic health condition, most commonly a back problem (10.4%), or arthritis and related disorders (8.6%). When adjusted for age and sex, all conditions studied except diseases of the ear and mastoid process, other endocrine/nutritional and metabolic disorders, noise-induced deafness or hearing loss, and high cholesterol were significantly associated with being out of the labour force. Extrapolating from these results, an estimated 663 235 older Australians were not working because of ill health, reducing Australia's gross domestic product by around $14.7 billion per annum. Prevention of long-term health conditions may help older Australians remain in the labour force longer, thereby increasing revenue to fund health care for the ageing population.


Reactive blue 2 selectively inhibits P2y-purinoceptor-stimulated surfactant phospholipid secretion from rat isolated alveolar type II cells.
1. The effect of reactive blue 2 on adenosine 5'-triphosphate (ATP), 12-O-tetradecanoylphorbol 13-acetate (TPA) and terbutaline-induced surfactant phospholipid secretion from rat isolated alveolar Type II cells was studied. 2. Reactive blue 2 significantly inhibited ATP-induced surfactant phospholipid secretion, but was without effect on C-kinase agonist (TPA) or beta-adrenoceptor agonist (terbutaline)-stimulated surfactant phospholipid secretion. The IC50 for inhibition of ATP-induced surfactant secretion was 1.5 x 10(-4)M. 3. These data are consistent with a P2y-purinoceptor regulating surfactant phospholipid secretion from isolated Type II cells and support previous work suggesting reactive blue 2 is a specific inhibitor at P2y-purinoceptors.


Genetic mutual relationship between PTEN and p53 in gastric cancer.
Both PTEN (encoding phosphate and tensin homologue) and p53 are known as cancer suppressor genes, and they are assumed that their gene mutations and loss of heterozygosity (LOH) occur frequently in various types of carcinoma. In the present study, we investigated both the p53 mutation and LOH of PTEN in 113 gastric cancer patients. We observed the LOH of PTEN in 11.1% of the patients with normal p53s and 46.2% of the patients with p53 gene mutations. The result that LOH of PTEN was frequently observed in the cases with p53 gene mutations and other data in this study suggested that both PTEN and p53 have complimentary roles in gastric carcinoma development.


Total synthesis of (-)-brevenal: a concise synthetic entry to the pentacyclic polyether core.
Total synthesis of (-)-brevenal, a novel marine polycyclic ether natural product, is described. Highly efficient and scalable entries to the AB-ring exo-olefin and the DE-ring enol phosphate and a rapid construction of the C-ring by means of our Suzuki-Miyaura coupling-based strategy realized a concise synthesis of the pentacyclic skeleton of (-)-brevenal. The present synthesis is considerably more efficient than our previous synthesis (longest linear sequence: 50 steps from 2-deoxy-d-ribose).


Clinical Outline of Oral Diseases.
Oral diseases are pathologic conditions that affect oral and maxillofacial tissues. Dental caries and periodontal diseases are the most common forms of oral diseases, but there are a wide variety of diseases that can occur in oral and maxillofacial tissues. These oral diseases range from metabolic, inflammatory, infectious, neoplastic, autoimmune, developmental, to idiopathic origin. Numerous oral conditions have overlapping clinical signs and symptoms, which make the diagnosis and management challenging for the dentist. However, a comprehensive understanding of clinical behavior will help in differentiating the various oral diseases and will provide a logical pathway to formulating a diagnosis.


Contributions of water-borne corticosterone as one non-invasive biomarker in assessing nitrate pollution stress in tadpoles of Rana temporaria.
Among a multitude of stressors to which wildlife is exposed, environmental pollution is a pervasive one that poses a serious threat. The permeable skin of amphibians is likely to increase direct contact of the body with pollutants, making them a group worth studying to access environmental quality. Consequently, finding reliable and complementary biomarkers that will present detectable and predictable changes in response to pollutants is essential to identify pollution sublethal effects on amphibians and to investigate whether these are in part responsible for population declines. The glucocorticoid hormone corticosterone (CORT), involved in many metabolic functions, is often used to measure the physiological stress response to environmental stressors in amphibians. In this study, we evaluated whether water-borne CORT can serve as a non-invasive biomarker for nitrate pollution stress in the European common frog (Rana temporaria) by comparing the effect of nitrate exposure on hormone release rates and on other physiological downstream biomarkers, i.e., ultimate physiological effects of the stressor. Specifically, we investigated the effect of different nitrate concentrations (0, 10, 50, and 100 mg/L) on water-borne CORT release rates, age, size, and body condition. Exposure to nitrate pollution significantly increased age at metamorphosis and water-borne CORT release rates, and led to reduced mass and body condition, but only at higher nitrate concentrations (i.e., 50 and 100 mg/L). Considering this similar sensitivity to other acknowledged biomarkers, water-borne CORT was a reliable biomarker of physiological stress in R. temporaria exposed to nitrate pollution stress in a controlled single-stressor laboratory approach. Thus, water-borne CORT is a promising method to be included in more holistic approaches. We recommend that such approaches keep testing multiple biomarker combinations, as species are exposed to several stressors likely to interact and produce varied outcomes in different biomarkers in their natural habitats.


Laser-induced breakdown spectroscopy (LIBS) for the detection of exogenous contamination of metal elements in lily bulbs.
Natural products with the underground edible part have the risk of excessive heavy metals due to the influence of the growing environment. In this study, the content of five metal elements in lily bulbs was detected by laser-induced breakdown spectroscopy (LIBS). In view of the mutual interference among elements, multivariable analysis models were established to effectively eliminate the interference. The partial least squares regression (PLSR) multivariate analysis model was evaluated by combining different data preprocessing with variable selection methods to achieve the best fit. The results show that the best regression model for Cu, Pb, Zn, Al, and Mg content achieved the coefficients determination of prediction (Rp2) values of 0.9920, 0.9737, 0.9835, 0.9723 and 0.9939, respectively, and root mean square error of prediction (RMSEP) values of 3.2386 mg/kg, 5.8559 mg/kg, 4.6334 mg/kg, 6.0073 mg/kg and 2.8103 mg/kg, respectively. Comprehensively comparing the accuracy, robustness, and number of variables of each model, it can be found that the PLSR model on the least absolute shrinkage and selection operator (LASSO) achieved good results in the quantitative prediction model of three kinds of metal elements. This indicates the superiority of the LASSO-PLSR algorithm framework and confirms the feasibility of LIBS technology for the detection of various metal elements in natural products.


Adolescent exhibitionists: theory and therapy.
In the absence of an agreed etiology or preferred treatment for exhibitionism the author reviews his clinical experience in working with adolescent boys who have indecently exposed themselves. A retrospective analysis indicates that the implicit theories that informed clinical practice construed exhibitionism as social behaviour rather than psychological symptom and placed it in a clear development context. It is argued that adolescent exhibitionism can be viewed as a "strategic interaction" that is characteristically adolescent. Using the individual adolescent's account of his misconduct it may be possible to determine the particular "game" in which he is engaged. This formulation can lead to clinical interventions which will best foster a future change of strategy and reduce the prospects of re-offending. Three clinical vignettes illustrate this model in action. Finally the theoretical limitations and practical difficulties associated with this way of understanding adolescent exhibitionists are discussed.


Historical contributions of research on birds to behavioral neuroendocrinology.
The contributions from bird research to behavioral neuroendocrinology are enormous and wide ranging. I have selected examples that illustrate how through the twentieth century to the present day, birds as experimental models continue to play a major role. Investigations on birds were pivotal in the beginnings of endocrinology, and have laid the foundations for present day developments in neurobiology, physiological ecology and evolutionary biology of neuroendocrine systems. The extensive literature on avian behavior also provides a unique and broad base for the field in general and future progress on a broad front can be expected. Molecular genetics in avian systems is advanced providing us with phylogenetic perspective allowing the comparisons of different avian populations that provide valuable models for integrative research.


Quinolinic acid but not MK-801 protects the dopaminergic system from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced toxicity in goldfish retina.
The toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, intravitreally injected in goldfish eye, involves interplexiform retinal neurons and depletes tyrosine hydroxylase immunoreactivity and dopamine levels. This induced neurotoxicity was prevented by the concomitant administration in non-toxic doses (10 micrograms) of quinolinic acid, an endogenous structural analogue of N-methyl D-aspartate with excitotoxic properties. Quinolinic acid is ineffective on the retinal degeneration induced by 1-methyl-4-phenylpyridinium ion. This fact suggests that quinolinic acid inhibits the MAO-B oxidation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. MK-801, a noncompetitive antagonist of glutamate NMDA-receptors, exerts partial protective effects on MPTP-induced delayed toxicity in mammals. In the goldfish eye, MK-801, injected in low concentration, and in conjunction with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine or 1-methyl-4-phenylpyridinium ion, did not prevent retinal neurodegeneration. Ten micrograms of MK-801 alone did not affect retinal neurons, while a higher concentration (20 micrograms) causes the chromatolysis of some photoreceptor nuclei.


Risk factors for nosocomial rectal colonisation with carbapenem-resistant Gram-negative bacilli in children with haematological malignancies: a case-control study.
Rectal colonisation with carbapenem-resistant Gram-negative bacilli (CR-GNB) may cause CR-GNB infection in children with haematological malignancies (HMs) haematological. To date, information on its epidemiology is limited. This study aimed to assess the the risk factors for rectal colonisation with CR-GNB in children with HMs. A case-control study in a tertiary children's hospital in Hangzhou City, was conducted between July 2019, and September 2021. Based on the hospitalisation date, children in the CR-GNB colonisation group and control groups were matched at a ratio of 1:2. Conditional logistic regression models were used to compute the adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of the risk factors for CR-GNB rectal colonisation in children with HMs. A total of 85 non-duplicated CR-GNB isolates were collected from rectal swab samples of 69 children with HMs. The 30-day mortality rates were 5.8% in the CR-GNB colonisation group and 0% in the control group (P = 0.020).colonisation In the conditional logistic regression model, the aORs were 6.84 (95% CI 1.86-25.20) for acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL), 4.16 (95% CI 1.17-14.84) for prior concomitant infections within the last 1 month, 2.33 (95% CI 1.16-4.69) for prior carbapenems usage within the last 1 month and 7.46 (95% CI 1.81-30.67) for prior hematopoietic stem-cell transplantation (HSCT). AML/ALL, prior concomitant infections within the last 1 month, prior carbapenems usage within the last 1 month, and prior HSCT are associated with an increased risk of rectal colonisation with CR-GNB in children with HMs.


Data on analysis of MK-801 bioavailability in mouse plasma and brain tissue by ultra-performance liquid chromatography-tandem mass spectrometry.
MK-801, a N-methyl-d-aspartate receptor antagonist, is widely used in animal preclinical experiments to induce memory and learning impairments and schizophrenia-like behavior. In the present study, we compared the plasma and brain tissue concentrations of MK-801 after intraperitoneal (i.p.) or subcutaneous (s.c.) administration at a dose of 0.1 mg/kg in male ICR mice. Moreover, these data present the optimization of ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) for the analysis of MK-801 in biological samples. Procedures for the preparation of brain tissue and plasma samples and instrumental analysis are described. This article is related to a research article entitled "Effects of the N-methyl-d-aspartate receptor antagonist, MK-801, on spatial memory and influence of the route of administration" [1].


Microparticle-associated tissue factor activity in patients with metastatic pancreatic cancer and its effect on fibrin clot formation.
Highly elevated microparticle (MP)-associated tissue factor (TF) activity was found in patients with pancreatic cancer, one of the most prothrombotic malignancies. It remains to be elucidated whether MP-TF activity reflects the prothrombotic state in these patients. MP-TF activity levels and the TF-dependent and -independent effect of MPs on fibrin clot formation were determined in patients with metastatic pancreatic cancer (n = 27), in healthy individuals (n = 10) and in plasma samples from lipopolysaccharide (LPS)-stimulated blood (LPS-plasma), which is rich in monocyte-derived TF-bearing MPs. The median MP-TF activity was 1.06 pg/mL (range, from 0.19 to 10.34 pg/mL) in patients with pancreatic cancer, 0.61 pg/mL (range, from 0.36 to 0.79 pg/mL) in LPS-plasma, and 0.18 pg/mL (range, from 0.04 to 0.39 pg/mL) in healthy individuals. MPs derived from LPS-plasma had the strongest impact on fibrin clot formation time (median, 157.6 seconds; range, from 149.5 to 170.4 seconds). Fibrin clot formation occurred significantly later in MPs derived from patients with pancreatic cancer (median, 273.4 seconds; range, from 146.6 to 354.4 seconds; P < 0.001) and in healthy individuals (median, 299.0 seconds; range, from 261.1 to 417.9 seconds; P < 0.001). Only in MPs derived from LPS-plasma the fibrin clot formation time dependent strongly on TF (median prolongation after TF blockade: 68% in LPS-plasma, 10% in patients with pancreatic cancer, and 4% in healthy individuals). In conclusion, highly elevated MP-TF activity was found in patients with metastatic pancreatic cancer, but TF-bearing MPs had a small effect on fibrin clot formation. TF-bearing MPs might not be the main mediators of the prothrombotic state associated with pancreatic cancer. However, the small but significant increase in coagulation potential by TF-bearing MPs might contribute to the multifactorial pathogenesis of venous thromboembolism in pancreatic cancer.


Auditory agnosia with relative sparing of speech perception.
We report a case of auditory agnosia in which the initial clinical picture began with generalized auditory agnosia for verbal and non verbal sounds, but rapidly changed to a selective auditory agnosia confined to the perception of non verbal sounds. CT scanning and MRI did not demonstrate cortical or subcortical damage, except for bilateral ventricular enlargement. The patient was submitted to audiological investigations including physical and psychoacoustic studies. Deficits were revealed during the decay and loudness discrimination test, but no temporal auditory acuity deficit was observed. The results of these studies are discussed in relation to the clinical picture. Also the dissociation between verbal perception and non verbal perception is discussed.


Trends in glaucoma surgical procedures in Ontario: 1992-2012.
To analyze trends in the surgical management of glaucoma in Ontario over the past 2 decades. Retrospective analysis of health records. Ontario Health Insurance Plan billing service claims between 1992 and 2012 were analyzed for the yearly number of glaucoma laser and incisional surgical procedures. The yearly number of Ontarians with primary open-angle glaucoma (POAG) was estimated by applying composite prevalence curves to published population data and the yearly number of procedures per 1000 Ontarians with POAG was calculated. Per 1000 people with POAG, laser trabeculoplasty (LT) rates increased nearly 2-fold (185%) from 1992 to 2012, with the rates stabilizing between 2008 and 2012, and total glaucoma filtration procedure (GFP) rates (trabeculectomy, aqueous shunts, and combined GFP and cataract extraction) in 2012 were similar to those in 1992, with a peak rate noted in 1996. Shunts represented 0.9% of GFP in 1992 and 33% in 2012. Data for combination codes billed on the same day for the same patient were available from 2000. From 2000 to 2012 the rates of trabeculectomy alone remained unchanged, the number of aqueous shunts alone increased more than 5-fold, combined trabeculectomy and cataract extraction decreased 81%, whereas combined shunts and cataract extraction increased from 6 in 2000 to 420 in 2012. Combined aqueous shunts and cataract extraction represented 0.4% of combined cataract extractions in 2000 and 26.3% in 2012. Over the past 2 decades there was an overall increase in the rate of LT, no change in the rate of trabeculectomies, and a significant increase in aqueous shunt surgery.


[Stereometric characteristics of the ultrastructure of presynaptic terminals in the dorsal horn of the cat spinal cord].
Ultrastructure of 240 axo-dendritic presynaptic terminals (PT) in the dorsal horn of the spinal cord of cat was investigated using the morphometrical statistic method. Parameters describing shape and average spatial radius of the three-dimensional PT (approximated by irregular ellipsoid) were estimated on the basis of the morphometry of random PT sections using ideas of the theory of probabilities. A lack of correlation between the synaptic operative zone localization and features of the terminals' shape was demonstrated. The distribution of the spatial PT radii was obtained. The obtained distribution elicited the relatively small variability of these parameters.


A collaborative approach to expand clinical experiences and cultural awareness among undergraduate nursing students.
Nurse educators are constantly seeking opportunities to expose undergraduate students to different cultures. This requirement is essential to prepare tomorrow's nursing professionals to practice culturally component care in diverse health care environments. This article describes a unique collaborative experience between the University of Pittsburgh School of Nursing and the Miami Children's Hospital that offers senior baccalaureate students the opportunity to complete one term of clinical experience in a culturally diverse health care facility.


The fate of the dropped gallstones during laparoscopic cholecystectomy.
Stones can be spilled from the gallbladder during laparoscopic cholecystectomy. These stones can be left in the peritoneal cavity or trapped at the trocar site. The potential late sequel and associated morbidity are not well documented. We reviewed the records of four patients who underwent laparoscopic cholecystectomy at Mount Sinai Medical Center in New York City who suffered from late complications attributed to gallstones left in the peritoneal cavity or abdominal wall. Four patients presented 1-14 months after laparoscopic cholecystectomy with intraabdominal and abdominal wall abscesses. The spillage of gallstones was noticed during the initial operation only in one of the patients. Three patients required laparotomy and open drainage of intraabdominal abscesses with drainage of pus and gallstones after failed attempts at percutaneous drainage. Two patients underwent local exploration of an abdominal wall abscess containing stones. Stones left in the abdominal cavity or trapped in trocar sites after laparoscopic cholecystectomy can cause serious late complications requiring repeated surgical interventions. Every effort should be made in order to avoid spillage of stones during dissection of the gallbladder and cystic duct and during retrieval of the gallbladder through the abdominal wall.


The diagnostic accuracy of CT and MRI in the staging of pelvic lymph nodes in patients with prostate cancer: a meta-analysis.
To compare the diagnostic accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) in the diagnosis of lymph node metastases in prostate cancer. After a comprehensive literature search, studies were included that allowed construction of contingency tables for detection of lymph node metastases using CT or MRI. In addition, a summary receiver-operating characteristic (ROC) analysis was performed. A total of 24 studies were included. For CT, pooled sensitivity was 0.42 (0.26-0.56 95% CI) and pooled specificity was 0.82 (0.8-0.83 95% CI). For MRI, the pooled sensitivity was 0.39 (0.22-0.56 95% CI) and pooled specificity was 0.82 (0.79-0.83 95% CI). The differences in performance of CT and MRI were not statistically significant. CT and MRI demonstrate an equally poor performance in the detection of lymph node metastases from prostate cancer. Reliance on either CT or MRI will misrepresent the patient's true status regarding nodal metastases, and thus misdirect the therapeutic strategies offered to the patient.


Analysis of the HLA-DRw8 haplotype: recognition by HTC typing of three distinct antigen complexes in Caucasians, Native Americans, and Orientals.
We have used seven HLA-D homozygous typing cells (HTC) in a comparative study of the DRw8 antigen complex in three racial groups. Three distinct HLA-D specificities were recognized, each associated with HLA-DRw8. Four of the HTC defined a DRw8-associated HLA-D specificity designated 8.1, one defined a specificity designated 8.2, and two defined a specificity designated 8.3. Each of the three specificities showed an association with a distinct racial group: Dw"8.1" in Caucasians, Dw"8.2" in Pacific Northwest Indians, and Dw"8.3" in Orientals. An informative primed lymphocyte (PLT) cell generated against a Dw"8.1" haplotype was able to distinguish 8.1 from 8.2 and 8.3. Using selected anti-DRw8 sera, a serologic distinction between 8.1 and 8.3 could also be made. It was thus possible, by using both cellular and serologic techniques in a comparative population study, to recognize at least three HLA-D-defined splits of the DRw8 haplotype.


A genome-wide association study in 574 schizophrenia trios using DNA pooling.
The cost of genome-wide association (GWA) studies can be prohibitively high when large samples are genotyped. We conducted a GWA study on schizophrenia (SZ) and to reduce the cost, we used DNA pooling. We used a parent-offspring trios design to avoid the potential problems of population stratification. We constructed pools from 605 unaffected controls, 574 SZ patients and a third pool from all the parents of the patients. We hybridized each pool eight times on Illumina HumanHap550 arrays. We estimated the allele frequencies of each pool from the averaged intensities of the arrays. The significance level of results in the trios sample was estimated on the basis of the allele frequencies in cases and non-transmitted pseudocontrols, taking into account the technical variability of the data. We selected the highest ranked SNPs for individual genotyping, after excluding poorly performing SNPs and those that showed a trend in the opposite direction in the control pool. We genotyped 63 SNPs in 574 trios and analysed the results with the transmission disequilibrium test. Forty of those were significant at P<0.05, with the best result at P=1.2 x 10(-6) for rs11064768. This SNP is within the gene CCDC60, a coiled-coil domain gene. The third best SNP (P=0.00016) is rs893703, within RBP1, a candidate gene for schizophrenia.


DPSS yellow-green 561-nm lasers for improved fluorochrome detection by flow cytometry.
Blue-green 488-nm laser sources are widespread in flow cytometry but suffer some drawbacks for cell analysis, including their excitation of endogenous proteins (resulting in high cellular autofluorescence) and their less-than-optimal coincidence with the excitation maxima of commonly used fluorochromes, including the phycoerythrins (PE). Longer wavelength lasers such as green helium-neons and, more recently, diode-pumped solid state (DPSS) 532-nm sources have previously been employed to overcome these difficulties and improve overall sensitivity for PE. In this study, we evaluate an even longer wavelength DPSS 561-nm for its ability to improve PE and DsRed fluorescent protein detection sensitivity. A DPSS 561-nm laser emitting at 10 mW was mounted onto a BD LSR II. Mouse thymoma cells labeled with cell surface marker antibodies conjugated to the R- and B-forms of PE were analyzed and compared with conventional 488-nm excitation using the same bandpass filters and signal travel distances. A similar analysis was carried out with cell lines expressing the red fluorescent protein DsRed, several green-yellow excited low molecular weight fluorochromes, and a rhodamine-based caspase substrate. Additionally, cells labeled with PE and co-labeled with fluorescein or simultaneously expressing green fluorescent protein (GFP) were analyzed to determine if PE excitation at 561 nm with simultaneous fluorescein/GFP detection was feasible. The DPSS 561-nm laser gave a several-fold improvement in the fluorochrome to autofluorescence ratios between PE-labeled cells and unlabeled controls. Analysis of cells expressing the fluorescent protein DsRed with the DPSS 561-nm source gave a 6-7-fold improvement in sensitivity over 488-nm excitation, and gave excellent excitation of yellow-green excited fluorochromes and rhodamine-based physiological probes. Yellow-green laser light also caused virtually no impingement on the spatially separated fluorescein/GFP detector, a significant problem with green laser sources, and also allowed simultaneous analysis of GFP and PE with virtually no signal overlap or requirement for color compensation. DPSS 561-nm laser excitation gave significantly improved sensitivity for both PE-labeled and DsRed expressing cells, with little contamination of a typical fluorescein/GFP detector.


A novel role for myeloid cell-specific neuropilin 1 in mitigating sepsis.
Sepsis-typically caused by an uncontrolled and amplified host systemic inflammatory response to microbial infection-is a life-threatening complex clinical disorder and remains a major cause of infection-related deaths in the intensive care unit. Emerging evidence suggests that neuropilin 1 (Nrp1), an originally defined coreceptor for class 3 semaphorins and VEGF, plays important roles in the immune system; however, the function and regulation of macrophage Nrp1 in host immune defense against bacterial infection remain unknown. To address this problem, we generated myeloid cell-specific Nrp1-knockout (Nrp1myel-KO) mice and applied 2 stringent animal models of sepsis: cecal ligation and puncture as well as intraperitoneal injection of LPS. Here, we reported that myeloid cell-specific Nrp1-deficient mice exhibited enhanced susceptibility to cecal ligation and puncture- and LPS-induced sepsis, which correlated with significantly decreased survival rates and heightened levels of proinflammatory cytokines in both peritoneal lavage and serum. Mechanistically, LPS specifically attenuated the expression of Nrp1 in macrophages, which was mediated by TLR4-NF-κB p50 and -65 pathways. By using isolated primary macrophages, loss of Nrp1 consistently resulted in increased production of proinflammatory cytokines, including iNOS, TNF-α, and IL-6. Together, these findings demonstrate a novel role of macrophage Nrp1 in sepsis.-Dai, X. Okon, I., Liu, Z., Wu, Y., Zhu, H., Song, P., Zou, M.-H. A novel role for myeloid cell-specific neuropilin 1 in mitigating sepsis.


Health-related quality of life of Canadian Forces veterans after transition to civilian life.
Describe health-related quality of life (HRQoL) of former Canadian Forces (CF) men and women in uniform (Veterans) after transition to civilian life, and compare to age- and sex-adjusted Canadian norms. The 2010 Survey on Transition to Civilian Life was a national computer-assisted telephone survey of CF Regular Force personnel who released during 1998-2007. HRQoL was assessed using the SF-12 Physical (PCS) and Mental (MCS) Component Summary scores. Descriptive analysis of HRQoL was conducted for socio-demographic, health, disability and determinants of health characteristics. Mean age was 46 years (range 20-67). Compared to age- and sex-adjusted Canadian averages, PCS (47.3) was low and MCS was similar (52.0). PCS and MCS were variably below average for middle age groups and lowest for non-commissioned ranks, widowed/divorced/separated, 10-19 years of service, physical and mental health conditions, disability, dissatisfaction with finances, seeking work/not working, low social support and difficulty adjusting to civilian life. Among Veterans Affairs Canada clients, 83% had below-average physical PCS, 49% had below-average MCS, and mean PCS (38.2) was significantly lower than mean MCS (48.3). HRQoL varied across a range of biopsychosocial factors, suggesting possible protective factors and vulnerable subgroups that may benefit from targeted interventions. These findings will be of interest to agencies supporting Veterans in transition to civilian life and to researchers developing hypotheses to better understand well-being in Canadian Veterans.


Single-walled carbon nanotube induces oxidative stress and activates nuclear transcription factor-kappaB in human keratinocytes.
Carbon nanotubes are now becoming an important material for use in day to day life because of their unique physical properties. The toxicological impact of these materials has not yet been studied in detail, thereby limiting their use. In the present study, the toxicity of single-walled carbon nanotubes (SWCNT) was assessed in human keratinocyte cells. The results show increased oxidative stress and inhibition of cell proliferation in response to treatment of keratinocytes with SWCNT particles. In addition, the signaling mechanism in keratinocytes upon exposure to SWCNT particles was investigated. Results from the study suggest that SWCNT particles activate NF-kappaB in a dose-dependent manner in human keratinocytes. Further, the mechanism of activation of NF-kappaB was due to the activation of stress-related kinases by SWCNT particles in keratinocytes. In conclusion, these studies show the mechanism of toxicity induced by SWCNT particles.


Effectiveness of Glaucoma Screening and Factors Associated with Follow-up Adherence among Glaucoma Suspects in a Safety-Net Teleretinal Screening Program.
To evaluate rates and risk factors associated with follow-up adherence to in-person glaucoma evaluations and confirmed glaucoma diagnosis in glaucoma suspects identified through teleretinal diabetic retinopathy screening (TDRS). Retrospective cohort study SUBJECTS: Patients with diabetes identified through teleretinal screening to have large or asymmetric cup-to-disc ratios in a Los Angeles County safety-net primary care-based TDRS program. Retrospective chart review was performed to obtain demographic and clinical information for patients with cup-to-disc ratios concerning for glaucoma on TDRS. Patients who completed an in-person follow-up appointment within 1 year of teleretinal screening were adherent. Factors associated with follow-up adherence and diagnosis of glaucoma were analyzed with chi-square and independent t tests along with multivariable logistic regressions. The proportion of patients with suspected glaucoma who adhered with in-person follow-up examination, proportion of patients with confirmed glaucoma diagnosis, and factors associated with follow-up adherence and glaucoma diagnosis. Eight-hundred seventeen patients with optic discs suspicious for glaucoma were included. Five-hundred thirty-four (65.4%) patients successfully completed an in-person glaucoma evaluation. Among these patients, 62.9% and 24.5% received a diagnosis of glaucoma suspect and glaucomatous optic neuropathy, respectively. Compared with patients aged < 50 years, patients aged 50 to 64 years had 1.57 times higher odds of being adherent with in-person visits (P = 0.036), whereas no difference was seen in those aged ≥ 65 years. For every $10 000 increase in the zip code median income, patients had 11% lower odds of being adherent (P = 0.031). Compared with Latino patients, Black patients had 3.52 times (P < 0.001) higher odds of having confirmed glaucoma. The majority of patients referred as glaucoma suspects on TDRS completed a follow-up examination, and nearly a quarter of those examined received a confirmed glaucoma diagnosis. Patients aged ≥ 50 and < 65 years along with those from lower-income neighborhoods were more likely to follow up for an in-person evaluation. Compared with Latino patients, Black patients had a higher risk for a confirmed glaucoma diagnosis. This demonstrates the effectiveness of glaucoma detection in a large-scale TDRS program for a safety-net patient population. The authors have no proprietary or commercial interest in any materials discussed in this article.


Prolyl endopeptidase and thrombin inhibitory diterpenoids from the bark of Xylopia aethiopica.
The inhibitory effects of seven diterpenes, belonging to three different structural classes and isolated from the bark of Xylopia aethiopica, were investigated against the enzymes prolyl endopeptidase (PEP) and alpha-thrombin. Five compounds exhibited inhibitory activity against them.


Vascular complications following laparoscopy: two unusual cases.
Vascular complications following laparoscopic techniques may often be attributed to the incomplete control of bleeding sites at laparoscopy. When confronted with post-laparoscopy symptoms of hemodynamic insufficiency, the surgeon may infer the existence of hemorrhagic complications neglected at the laparoscopic session. The author reviewed two otherwise normal cases of laparoscopic procedures that were complicated by bleeding disorders of unknown origin. Diagnosis and treatment of the hematologic complications revealed causes other than operator-inflicted injury. While laparoscopists should remain vigilant concerning the very real threat of overlooked vascular injury following laparoscopy, some patients may exhibit hemorrhagic symptoms unrelated to the laparoscopic procedure.


[DNA Sequence-Specific Ligands. 19. Synthesis, Spectral Properties, Virological and Biochemical Studies of DB3(n) Fluorescent Dimeric Trisbenzimidazoles].
In this work, we synthesized and characterized the properties of a series of new fluorescent DB3(n) narrow-groove ligands. DB3(n) compounds based on dimeric trisbenzimidazoles have the ability to bind to the AT regions of DNA. The synthesis of DB3(n), whose trisbenzimidazole fragments are linked by oligomethylene linkers of different lengths (n = 1, 5, 9), is based on the condensation of the MB3 monomeric trisbenzimidazole with α,ω-alkyldicarboxylic acids. DB3 (n) proved to be effective inhibitors of the catalytic activity of HIV-1 integrase at submicromolar concentrations (0.20-0.30 μM). DB3(n) was found to inhibit the catalytic activity of DNA topoisomerase I at low micromolar concentrations.


(o-Phenylenediamino)borylstannanes: Efficient Reagents for Borylation of Various Alkyl Radical Precursors.
(o-Phenylenediamino)borylstannanes were newly synthesized to achieve radical boryl substitutions of a variety of alkyl radical precursors. Dehalogenative, deaminative, decharcogenative, and decarboxylative borylations proceeded in the presence of a radical initiator to give the corresponding organic boron compounds. Radical clock experiments and computational studies have provided insights into the mechanism of the homolytic substitution (SH 2) of the borylstannanes with alkyl radical intermediates. DFT calculation disclosed that the phenylenediamino structure lowered the LUMO level including the vacant p-orbital on the boron atom to enhance the reactivity to alkyl radicals in SH 2. Moreover, C(sp3 )-H borylation of THF was accomplished using the triplet state of xanthone.


Is hypovitaminosis D associated with abdominal aortic aneurysm, and is there a dose-response relationship?
This study aims to investigate the association between plasma 25-hydroxyvitamin D (25(OH)D) concentrations with the presence of abdominal aortic aneurysm (AAA) and aortic diameter. An observational study of 4233 community-dwelling men aged 70-88 years, who participated in a randomised controlled trial of screening for AAA. Infrarenal aortic diameter measured by ultrasound and 25(OH)D by immunoassay. A total of 311 men (7.4%) with AAA (defined as aortic diameter ≥ 30 mm) comprised the study. Multivariable models were adjusted for age, smoking, cardiovascular disease, hypertension, diabetes, dyslipidaemia, body mass index and serum creatinine concentration. Amongst men with the lowest 25(OH)D quartile of values compared with the highest quartile, the adjusted odds ratio of having an AAA increased in a graded fashion from 1.23 (95% confidence interval (CI) 0.87-1.73) for AAA ≥ 30 mm to 5.42 (95% CI 1.85-15.88) for AAA ≥ 40 mm. Similarly, there was a dose-response relationship between 25(OH)D concentrations and the size of the AAA: every 10-nmol l(-1) decrease in 25(OH)D levels was associated with 0.49 mm (95% CI 0.11-0.87) increase in mean aortic diameter. Low vitamin D status is associated with the presence of larger AAA in older men, and there is a graded inverse relationship between 25(OH)D concentrations and AAA diameter. Further research is needed to clarify the mechanisms underlying these associations.


Molecular docking studies of protein-nucleotide complexes using MOLSDOCK (mutually orthogonal Latin squares DOCK).
Understanding the principles of protein receptor recognition, interaction, and association with molecular substrates and inhibitors is of principal importance in the drug discovery process. MOLSDOCK is a molecular docking method that we have recently developed. It uses mutually orthogonal Latin square sampling (together with a variant of the mean field technique) to identify the optimal docking conformation and pose of a small molecule ligand in the appropriate receptor site. Here we report the application of this method to simultaneously identify both the low energy conformation and the one with the best pose in the case of 62 protein-bound nucleotide ligands. The experimental structures of all these complexes are known. We have compared our results with those obtained from two other well-known molecular docking software, viz. AutoDock 4.2.3 and GOLD 5.1. The results show that the MOLSDOCK method was able to sample a wide range of binding modes for these ligands and also scores them well.


Effects of L-phenylalanine on energy intake in overweight and obese women: interactions with dietary restraint status.
L-Phenylalanine (Phe), is a potent releaser of the satiety hormone, cholecystokinin (CCK) and previous studies, conducted primarily in men, show that ingestion of Phe reduces energy intake. The objective of the current study was to test the effects of Phe on energy intake in overweight and obese women. Subjects (n=32) received three treatments (high-dose (10 g Phe), low-dose (5 g Phe and 5 g glucose) or control (10 g glucose)) 20 min before an ad libitum lunch and dinner meal in a within-subjects', counterbalanced, double-blind study. No effect of Phe was found, however, interactions with dietary restraint status were detected in post-hoc analyses. Energy intake over the day was 11% lower following high-dose Phe versus control for women classified in the lower tertile of rigid restraint, a subscale of the dietary restraint scale, whereas no effects were noted for women in the middle and upper tertiles. High-dose Phe increased ratings of nausea, however, reduced energy intake in the high-dose condition was noted only for subjects with low nausea ratings. These results suggest that the satiety response to Phe is modulated by rigid restraint status and that reductions in food intake occur independently of Phe's effects on nausea.


How to teach and learn endoscopic submucosal dissection for upper gastrointestinal neoplasm in Japan.
Endoscopic submucosal dissection (ESD) is an innovative and promising procedure. However, ESD experience is mostly limited to Japan and a few countries in Asia. An appropriate training system should be proposed from Japan to promote a permeation of ESD technique. We conducted questionnaire survey to representative Japanese experts to reveal their training method of ESD for upper gastrointestinal neoplasm. We sent the questionnaire on gastric and esophageal ESD to 9 Japanese experts in ESD. The questionnaire results were discussed in a session of Endoscopic Forum Japan 2011 held in Tokyo. The inception criteria consisted of two main elements, diagnostic ability and primary endoscopy technique of preceptees. Preceptees should observe and attend as many ESD cases as possible. Most of the experts recommend training with isolated or live animal stomach or esophagus. Lesion in the distal stomach is the most suitable for the first real ESD by a preceptee. Being proficient in a gastric ESD is needed before starting esophageal ESD. Preceptor should have significantly high level of diagnostic ability and proficient ESD techniques in the colorectum as well as the stomach and esophagus. The present questionnaire survey seems to reveal basic elements required for ESD training program. We believe that this is also helpful in other countries where ESD would be initiated and penetrated safely and properly.