Determinants of Smoking and Quitting in HIV-Infected Individuals.
Cigarette smoking is widespread among HIV-infected patients, who confront increased risk of smoking-related co-morbidities. The effects of HIV infection and HIV-related variables on smoking and smoking cessation are incompletely understood. We investigated the correlates of smoking and quitting in an HIV-infected cohort using a validated natural language processor to determine smoking status. We developed and validated an algorithm using natural language processing (NLP) to ascertain smoking status from electronic health record data. The algorithm was applied to records for a cohort of 3487 HIV-infected from a large health care system in Boston, USA, and 9446 uninfected control patients matched 3:1 on age, gender, race and clinical encounters. NLP was used to identify and classify smoking-related portions of free-text notes. These classifications were combined into patient-year smoking status and used to classify patients as ever versus never smokers and current smokers versus non-smokers. Generalized linear models were used to assess associations of HIV with 3 outcomes, ever smoking, current smoking, and current smoking in analyses limited to ever smokers (persistent smoking), while adjusting for demographics, cardiovascular risk factors, and psychiatric illness. Analyses were repeated within the HIV cohort, with the addition of CD4 cell count and HIV viral load to assess associations of these HIV-related factors with the smoking outcomes. Using the natural language processing algorithm to assign annual smoking status yielded sensitivity of 92.4, specificity of 86.2, and AUC of 0.89 (95% confidence interval [CI] 0.88-0.91). Ever and current smoking were more common in HIV-infected patients than controls (54% vs. 44% and 42% vs. 30%, respectively, both P<0.001). In multivariate models HIV was independently associated with ever smoking (adjusted rate ratio [ARR] 1.18, 95% CI 1.13-1.24, P <0.001), current smoking (ARR 1.33, 95% CI 1.25-1.40, P<0.001), and persistent smoking (ARR 1.11, 95% CI 1.07-1.15, P<0.001). Within the HIV cohort, having a detectable HIV RNA was significantly associated with all three smoking outcomes. HIV was independently associated with both smoking and not quitting smoking, using a novel algorithm to ascertain smoking status from electronic health record data and accounting for multiple confounding clinical factors. Further research is needed to identify HIV-related barriers to smoking cessation and develop aggressive interventions specific to HIV-infected patients.


Intensification of oxidative stress and inflammation in type 2 diabetes despite antihyperglycemic treatment.
The metabolic deregulation associated with diabetes mellitus (DM) causes secondary pathophysiologic changes in multiple organ systems. Endothelial injury is induced by oxidative stress (OS) and inflammation. We have previously shown that DM type 2 patients are exposed to increased OS and inflammation contributed in part by primed peripheral polymorphonuclear leukocytes (PMNLs). To characterize the effect of oral medication on PMNL priming, on PMNL-related and on systemic inflammation, in correlation to changed diabetes parameters in patient with newly diagnosed type 2 DM. PMNLs were separated from DM patient's prior and following treatment with either metformin (Glucophage), or Thiazolidinedione (rosiglitazone) and from healthy control subjects (HC). Rate of superoxide release from phorbol ester-stimulated PMNLs and CD11b on PMNLs assessed PMNL priming. White blood cells (WBC) and PMNL counts and apoptosis reflected PMNL-related inflammation. CRP, fibrinogen, transferrin and albumin blood levels reflected systemic inflammation. Both metformin and rosiglitazone treatments reduced significantly the high levels of glucose and HbA1c, and slightly improved lipid profile during 2 months. PMNL priming parameters, higher compared to HC, increased after 2 months of metformin treatment. Rosiglitazone treatment decreased PMNL priming. ALP, higher in DM, significantly decreased following 2 months of both treatments. Systemic inflammation markers (fibrinogen, CRP), higher in DM, decreased following both treatments. Transferrin and albumin were similar to HC. PMNL-related inflammation markers were higher in DM; however, only PMNL apoptosis decreased after both treatments. Monocyte counts, higher in DM compared to HC, decreased following both treatments. Serum insulin levels, higher in DM compared to HC, decreased following both treatments. PMNL-related priming and inflammation parameters positively correlated with HbA1c. The present research adds new facet in evaluating anti-hyperglycemic treatment in type 2 DM patients. Despite sufficient glycemic control using both treatments, some PMNL-related parameters deteriorated. Thus, anti hyperglycemic treatment should be favored due to its combined anti-PMNL priming and anti-inflammatory effect, in addition to its anti-hyperglycemic characteristics, according to the correlation among these parameters. Such combined treatment may reduce morbidity and mortality common in DM patients.


Comparison of Post-Cesarean Section Opioid Analgesic Requirements in Women With Opioid Use Disorder Treated With Methadone or Buprenorphine.
Buprenorphine is a highly effective treatment for opioid use disorders, but its continuation in the perioperative setting remains controversial, unlike the accepted practice of perioperative methadone continuation. We conducted a retrospective cohort study from 2006 to 2014 comparing post-cesarean section opioid analgesic requirements of women with opioid use disorders treated with methadone or buprenorphine. Preoperative, intraoperative, and postoperative opioid requirements (morphine equivalent dose [MED]), postoperative complications, and length of stay were compared between the methadone and buprenorphine groups. During the 9-year study period, there were 185 women treated with methadone (mean dose 93.7 mg, SD 2.6) and 88 women treated with buprenorphine (mean dose 16.1 mg, SD 7.8). There were no statistically significant differences in MED requirements in the methadone versus buprenorphine groups: preoperative MED (11.4 mg [SD 31.5] vs 20.0 mg [SD 15.1]; mean difference [MD] 8.6, 95% confidence interval [CI] -1.9, 19.1), intraoperative MED (3.5 mg [SD 6.6] vs 5.2 mg [SD 13.7]; MD 1.8, 95% CI -1.1, 4.6), and postoperative MED during hospitalization (97.7 mg [SD 65.6] vs 85.1 mg [SD 73.0]; MD -12.6, 95% CI -31.1, 5.8). There were no statistically significant differences in postoperative complications or length of stay. Our study suggests that buprenorphine treatment will not interfere more than methadone with pain management after a cesarean section with no significant differences in opioid analgesic requirements, postoperative complications, or length of hospital stay. Future studies should investigate the generalizability to other surgeries.


Prognostic factors for COVID-19 patients.
Determining prognostic factors in patients with coronavirus disease (COVID-19) can have great impact on treatment planning and follow-up strategies. Herein, we aimed to evaluate prognostic factors and clinical scores for confirmed COVID-19 patients in a tertiary-care hospital in the Bursa region of Turkey. Patients who had been diagnosed with COVID-19 microbiologically and/or radiologically between March and October 2020 in a tertiary-care university hospital were enrolled retrospectively. Adult patients (≥ 18 years) with a clinical spectrum of moderate, severe, or critical illness were included. The dependent variable was 30-day mortality and logistic regression analysis was used to evaluate any variables with a significant p value (< 0.05) in univariate analysis. A total of 257 patients were included in the study. The mortality rate (30-day) was 14.4%. In logistic regression analysis, higher scores on sequential organ failure assessment (SOFA) (p < 0.001, odds ratio (OR) = 1.86, 95% CI = 1.42-2.45) and CURB-65 pneumonia severity criteria (p = 0.001, OR = 2.60, 95% CI = 1.47-4.57) were found to be significant in predicting mortality at admission. In deceased patients, there were also significant differences between the baseline, day-3, day-7, and day-14 results of D-dimer (p = 0.01), ferritin (p = 0.042), leukocyte (p = 0.019), and neutrophil (p = 0.007) counts. In our study of COVID-19 patients, we found that high SOFA and CURB-65 scores on admission were associated with increased mortality. In addition, D-dimer, ferritin, leukocyte and neutrophil counts significantly increased after admission in patients who died.


Preoperative evaluation of cervical radiculopathy and myelopathy by surface-coil MR imaging.
During a 2-year period, 256 patients were screened for cervical radiculopathy and myelopathy with surface-coil MR images and plain films. Selected patients had follow-up examinations including CT, myelography, and CT myelography. Thirty-four of these patients underwent cervical spine surgery after MR imaging, which disclosed a total of 50 abnormalities in three major categories: herniated disks, bony canal stenoses, and intradural lesions. MR correctly predicted 88% of all surgically proved lesions compared with 81% for CT myelography, 58% for myelography, and 50% for CT. Missed herniated disks on either MR or CT myelography usually were the result of technically suboptimal studies caused by motion artifacts on MR and beam-hardening artifacts on CT myelography. Small osteophytes adjoining herniated disks sometimes were not predicted on MR, although such osteophytes invariably were seen on plain films and were palpable during standard anterior cervical diskectomy procedures. Herniated disks in the lateral root canals found in two patients appeared to be detected more readily by CT myelography than by MR. All proved lesions were detected by either screening MR images and plain films or by follow-up CT myelograms. MR replaced invasive evaluations by myelography and CT myelography in 32% of preoperative patients. We conclude that MR images, combined with plain films, offer an accurate, noninvasive test for the preoperative evaluation of cervical radiculopathy and myelopathy, while CT myelography is the preferred follow-up examination.


[Cytogenetic effect of temperature on the sunflower varieties].
The influence of increased temperature on the intensity of fission and level of chromosome aberrations (ChA) in root meristeme cells of two lines of sunflower seedlings was studied. Within the first hour of seed germination, the temperature of 40 degrees C reduced proliferation activity of root meristeme cells line 3629 for almost the next 15 h of growth. Heat stress (HS) blocks the beginning of cell fission in the plastome mutant en-chlorina-5. However, subsequent by mitosis activity was seen to increase. The influence of HS on the ChA level is ambiguous: the effect depends on the duration of warm-up influence and the used sunflower lines. So, ChA level does not change inbred line 3629 even after 6 h HS. In mutant en-chlorina-5 the ChA level increases after 1 h HS and decreases after 3 and 6 h HS. The study of HS modification effect has shown that preliminary warm-up influence (40 degrees C for 1 h) reduces differences in reactions of cells 3629 of line on the action of different nitrosomethylurea (NMU) concentrations. Preliminary warm-up influence does not change sensitivity of en-chlorina-5 cells to NMU. The combined action of the increased temperature and NMU induce a powerful cytostatic effect.


Nucleos(t)ide reverse transcriptase inhibitor-sparing regimens in the era of standard 3-drug combination therapies for HIV-1 infection.
Nucleos(t)ide reverse transcriptase inhibitor (NRTI)-sparing regimens have often been selected as antiretroviral therapy (ART) for HIV-1 infection recently, but data for characteristics have been lacking. This study aimed to document the current status of NRTI-sparing regimens in the era of standard 3-drug combination therapies. We cross-sectionally compared characteristics of patients treated with NRTI-sparing regimens (NRTI-sparing group) with dolutegravir plus tenofovir alafenamide fumarate/emtricitabine as a standard ART group in 2018. The NRTI-sparing and the standard ART groups included 61 and 469 patients, respectively. The mean (± standard deviation) age and serum creatinine of the NRTI-sparing group were significantly higher than those of the standard ART group (57.6 ± 12.8 years vs 42.8 ± 10.4 years (p < 0.05) and 2.09 ± 3.10 mg/dL vs. 0.93 ± 0.19 mg/dL (p < 0.05), respectively. The percentage of patients with NRTI-sparing regimens increased with age; with less than 5% in their 50s or younger, 8.4% in their 60s, and 14.1% aged ≥ 70 years. The primary reason for switching to the NRTI-sparing regimen was due to reduced renal function. According to the limited data, viral suppression was achieved at week 48 in all patients in the NRTI-sparing group. No patient had treatment failure nor developed drug resistance. The use of NRTI-sparing regimens increased with age. They were more frequently used in patients aged ≥ 60 years and those with decreased renal function.


[Soil microbial functional diversity of different altitude Pinus koraiensis forests].
In order to comprehensively understand the soil microbial carbon utilization characteristics of Pinus koraiensis forests, we took the topsoil (0-5 cm and 5-10 cm) along the 700-1100 m altitude in Changbai Mountains and analyzed the vertical distributed characteristics and variation of microbial functional diversity along the elevation gradient by Biolog microplate method. The results showed that there were significant differences in functional diversity of microbial communities at different elevations. AWCD increased with the extension of incubation time and AWCD at the same soil depth gradually decreased along with increasing altitude; Shannon, Simpson and McIntosh diversity index also showed the same trend with AWCD and three different diversity indices were significantly different along the elevation gradient; Species diversity and functional diversity showed the same variation. The utilization intensities of six categories carbon sources had differences while amino acids were constantly the most dominant carbon source. Principal component analysis (PCA) identified that soil microbial carbon utilization at different altitudes had obvious spatial differentiation, as reflected in the use of carbohydrates, amino acids and carboxylic acids. In addition, the cluster of the microbial diversity indexes and AWCD values of different altitudes showed that the composition of vegetation had a significant impact on soil microbial composition and functional activity.


Combination chemotherapy of BCNU and Didox acts synergystically in 9L glioma cells.
Compounds inhibiting DNA repair and synthesis are expected to act synergistically with BCNU, a standard agent in the therapy of glioblastoma multiforme, and improve survival of patients with malignant gliomas. Ribonucleotide reductase (EC220.127.116.11; RR) catalyzes the rate-limiting step in DNA synthesis and plays a critical role in maintaining crucial substrates for DNA repair. We have studied the effects of Didox, an inhibitor of RR on 9L glioma cells in combination with BCNU. We analyzed intracellular dNTP pools and found that Didox significantly depleted the intracellular dNTP concentrations. Experiments using cytotoxicity, growth inhibition and clonogenic assays showed significant synergism of Didox and BCNU. Combination regimens using synchronous administration demonstrated highest cytotoxicity. We have also identified altered gene expression in a number of DNA repair related enzymes after BCNU treatment using large-scale cDNA arrays. The coadministration with Didox could reverse the expression of some of the overexpressed repair gene suggesting possible pathways to circumvent the developing resistance in 9L glioma cells against BCNU. These results introduce the combination of Didox and BCNU as a viable alternative for the treatment of malignant gliomas.


Discovery of ellagic acid as a competitive inhibitor of Src homology phosphotyrosyl phosphatase 2 (SHP2) for cancer treatment: In vitro and in silico study.
Targeting SHP2 has become a potential cancer treatment strategy. In this study, ellagic acid was first reported as a competitive inhibitor of SHP2, with an IC50 value of 0.69 ± 0.07 μM, and its inhibitory potency was 34.86 times higher that of the positive control NSC87877. Ellagic acid also had high inhibitory activity on the SHP2-E76K and SHP2-E76A mutants, with the IC50 values of 1.55 ± 0.17 μM and 0.39 ± 0.05 μM, respectively. Besides, the IC50 values of ellagic acid on homologous proteins SHP1, PTP1B, and TCPTP were 0.93 ± 0.08 μM, 2.04 ± 0.28 μM, and 11.79 ± 0.83 μM, with selectivity of 1.35, 2.96, and 17.09 times, respectively. The CCK8 proliferation experiment exhibited that ellagic acid would inhibit the proliferation of various cancer cells. It was worth noting that the combination of ellagic acid and KRASG12C inhibitor AMG510 would produce a strong synergistic effect in inhibiting NCI-H358 cells. Western blot experiment exhibited that ellagic acid would downregulate the phosphorylation levels of Erk and Akt in NCI-H358 and MDA-MB-468 cells. Molecular docking and molecular dynamics studies revealed the binding information between SHP2 and ellagic acid. In summary, this study provides new ideas for the development of SHP2 inhibitors.


Homozygous sequestosome 1 (SQSTM1) mutation: a rare cause for childhood-onset progressive cerebellar ataxia with vertical gaze palsy.
Mutations in sequestosome 1 (SQSTM1) gene are associated with neurodegenerative diseases, such as frontotemporal dementia and amyotrophic lateral sclerosis. Recently, mutation in SQSTM1 was also found to cause a progressive childhood-onset cerebellar ataxia. We describe here a case of progressive childhood-onset cerebellar ataxia with vertical supra nuclear gaze palsy with no family history and a normal magnetic resonance imaging (MRI) of brain. The clinical exome sequencing in this patient showed a homozygous mutation in SQSTM1. This case highlights the importance of next-generation sequencing in the diagnosis of inherited ataxia syndromes. SQSTM1 mutation should be considered in the differential diagnosis in a patient with both cerebellar ataxia and ophthalmological manifestations.


Probing Spin-Dependent Ballistic Charge Transport at Single-Nanometer Length Scales.
The coherent transport of charge and spin is a key requirement of future devices for quantum computing and communication. Scattering at defects or impurities may significantly reduce the coherence of quantum-mechanical states, thereby affecting the device functionality. While numerous methods exist to experimentally assess charge transport, the real-space detection of a material's ballistic spin transport properties with nanometer resolution remains a challenge. Here we report on a novel approach that utilizes a combination of spin-polarized scanning tunneling microscopy (SP-STM) and the recently introduced molecular nanoprobe (MONA) technique. It relies on the local injection of spin-polarized charge carriers from a magnetic STM tip and their detection by a single surface-deposited phthalocyanine molecule via reversible electron-induced tautomerization events. Based on the particular electronic structure of the Rashba alloy BiAg2, which is governed by a spin-momentum-locked surface state, we prove that the current direction inverses upon tip magnetization reversal.


Serum Exosome MicroRNA as a Minimally-Invasive Early Biomarker of AML.
Relapse remains the major cause of mortality for patients with Acute Myeloid Leukemia (AML). Improved tracking of minimal residual disease (MRD) holds the promise of timely treatment adjustments to preempt relapse. Current surveillance techniques detect circulating blasts that coincide with advanced disease and poorly reflect MRD during early relapse. Here, we investigate exosomes as a minimally invasive platform for a microRNA (miRNA) biomarker. We identify a set of miRNA enriched in AML exosomes and track levels of circulating exosome miRNA that distinguish leukemic xenografts from both non-engrafted and human CD34+ controls. We develop biostatistical models that reveal circulating exosomal miRNA at low marrow tumor burden and before circulating blasts can be detected. Remarkably, both leukemic blasts and marrow stroma contribute to serum exosome miRNA. We propose development of serum exosome miRNA as a platform for a novel, sensitive compartment biomarker for prospective tracking and early detection of AML recurrence.


Auranofin lethality to prostate cancer includes inhibition of proteasomal deubiquitinases and disrupted androgen receptor signaling.
Auranofin (Aur) inhibits thioredoxin reductases and is also an inhibitor of 19S proteasome associated deubiquitinases, targeting USP14 and UCHL5. Androgen receptor is often over-expressed in prostate cancer (PCa) and is strongly linked to PCa growth and progression. Consequently, androgen deprivation therapy (ADT) that reduces androgen has been applied to treat androgen receptor-mediated PCa for decades. Nevertheless, most ADT treated patients experience relapse due to the development of the castration-resistant PCa. Numerous studies have shown that down-regulation of cellular androgen receptor level, including inhibiting its transcription and promoting its protein degradation, is lethal to PCa cells. Here we report that Aur arrested cell cycle progression and induced apoptosis of PCa cells. Co-inhibition of USP14 and UCHL5 with Aur facilitated the ubiquitination and degradation of androgen receptors in LNcap and 22RV1 PCa cells. Our results also show that Aur decreases the mRNA level of androgen receptors. In conclusion, our findings suggest that Aur is a promising agent for clinical translation to treat PCa.


Prolonged atrial natriuretic peptide exposure stimulates guanylyl cyclase-a degradation.
Natriuretic peptide receptor-A (NPR-A), also known as guanylyl cyclase-A, is a transmembrane receptor guanylyl cyclase that is activated by the cardiac hormones atrial natriuretic peptide and B-type natriuretic peptide. Although ligand-dependent NPR-A degradation (also known as down-regulation) is widely acknowledged in human and animal models of volume overload, down-regulation in cultured cells is controversial. Here, we examined the effect of ANP exposure on cellular NPR-A levels as a function of time. Relative receptor concentrations were estimated using guanylyl cyclase and immunoblot assays in a wide variety of cell lines that endogenously or exogenously expressed low or high numbers of receptors. ANP exposures of 1 h markedly reduced hormone-dependent but not detergent-dependent guanylyl cyclase activities in membranes from exposed cells. However, 1-h ANP exposures did not significantly reduce NPR-A concentrations in any cell line. In contrast, exposures of greater than 1 h reduced receptor concentrations in a time-dependent manner. The time required for half of the receptors to be degraded (t(1/2)) in primary bovine aortic endothelial and immortalized HeLa cells was approximately 8 h. In contrast, a 24-h exposure of ANP to 293T cells stably overexpressing NPR-A caused less than half of the receptors to be degraded. To our knowledge, this is the first report to directly measure NPR-A down-regulation in endogenously expressing cells. We conclude that down-regulation is a universal property of NPR-A but is relatively slow and varies with receptor expression levels and cell type.


Anterior cervical graft and plate load sharing.
Anterior discectomy and fusion with an interbody bone graft and anterior plate is a common procedure in cervical spine surgical management. However, the graft may be shielded from some mechanical loading by the plate. Mechanical testing was performed on six cadaveric calf spines that were subjected to a simulated anterior cervical discectomy and fusion with an interbody bone graft alone and with an anterior plate to determine the amount of load sharing between the graft and plate. The load-displacement data were used to compute the amount of load sharing between the graft and the plate as a continuous function of the applied axial compression load. Although the percent load transmitted through the graft decreased (53 to 41%) as the axial load increased (45 to 90 N), the magnitude of load transmitted through the graft increased (24 to 37 N), with corresponding intervertebral strains <6%. In a single-level procedure, an anterior cervical plate serves as a load-sharing device rather than a load-shielding device, enabling graft consolidation as observed in clinical studies.


Nasal allergen provocation induces adhesion molecule expression and tissue eosinophilia in upper and lower airways.
Allergic rhinitis (AR) and asthma are characterized by means of a similar inflammatory process in which eosinophils are important effector cells. The migration of eosinophils from the blood into the tissues is dependent on adhesion molecules. To analyze the aspects of nasobronchial cross-talk, we studied the expression of adhesion molecules in nasal and bronchial mucosa after nasal allergen provocation (NP). Nine nonasthmatic subjects with seasonal AR and 9 healthy control subjects underwent NP out of season. Bronchial and nasal biopsy specimens were taken before (T(0)) and 24 hours after NP (T(24)). Mucosal sections were analyzed for the presence of eosinophils, IL-5, eotaxin, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, and human endothelium (CD31). At T(24), an influx of eosinophils was detected in nasal epithelium (P =.01) and lamina propria (P <.01), as well as in bronchial epithelium (P =.05) and lamina propria (P <.05), of the patients with AR. At T(24), increased expression of ICAM-1, as well as increased percentages of ICAM-1+, VCAM-1+, and E-selectin+ vessels, were seen in nasal and bronchial tissue of patients with AR. The number of mucosal eosinophils correlated with the local expression of ICAM-1, E-selectin, and VCAM-1 in patients with AR. This study shows that NP in patients with AR results in generalized airway inflammation through upregulation of adhesion molecules.


The in vitro antioxidative properties of the essential oils and methanol extracts of Satureja macrosiphonia Bornm.
This study was designed to examine the in vitro antioxidant activities of the essential oil and methanol extracts of Satureja macrosiphonia in pre-flowering and flowering stages. GC and GC-MS analyses of the essential oils resulted in the identification of 35 and 24 compounds, representing the 95.1% and 92.6% of the oils, respectively. Major constituents of the oil of the pre-flowering stage were terpinene-4-ol (20.8%) and α-terpineol (14.7%), while in the oil of the flowering stage α-terpineol (26.7%) and borneol (16.6%) were found to be the main components. The samples were subjected to screening for their possible antioxidant activity by using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and β-carotene-linoleic acid assay. In general, the polar subfraction of methanol extract in the flowering stage exhibited the greatest antioxidant activity in the DPPH test. In the β-carotene-linoleic acid test, the essential oil of the flowering stage had the highest antioxidant activities.


Responses of ACTH, epinephrine, norepinephrine, and cardiovascular system to hemorrhage.
Hemorrhages of various magnitudes were performed on conscious rats, and arterial pressure, heart rate, and plasma levels of adrenocorticotropin hormone (ACTH), epinephrine, and norepinephrine were measured. Eight rats were prepared with chronic femoral arterial cannulas and received a 10, 15, or 20 ml/kg X 3 min hemorrhage in random order on day 4, 7, or 10 after surgery. Mean arterial blood pressure, heart rate, and plasma ACTH, epinephrine, and norepinephrine concentrations were determined before and 20 min after hemorrhage. Arterial blood pressure decreased significantly immediately after each hemorrhage and slowly recovered over the next 20 min. Heart rate did not change during the 10 ml/kg X 3 min hemorrhage but decreased significantly after 15 and 20 ml/kg X 3 min hemorrhages. Plasma ACTH and epinephrine levels increased significantly 20 min after the 15 and 20 ml/kg X 3 min hemorrhages but not after 10 ml/kg X 3 min hemorrhage. Norepinephrine increased significantly 20 min after the 20 ml/kg X 3 min hemorrhage but not after the 10 or 15 ml/kg X 3 min hemorrhage. There was no significant effect of time and repeated hemorrhages on resting levels of plasma ACTH, epinephrine, norepinephrine, osmolality, or proteins. Since hemorrhage leads to a fall in arterial pressure and a subsequent rise in plasma ACTH, the relationship between plasma ACTH and mean arterial blood pressure during hemorrhage was examined in both conscious and acutely prepared pentobarbital sodium-anesthetized rats.(ABSTRACT TRUNCATED AT 250 WORDS)


Plasma membrane expression of G protein-coupled estrogen receptor (GPER)/G protein-coupled receptor 30 (GPR30) is associated with worse outcome in metachronous contralateral breast cancer.
G protein-coupled estrogen receptor (GPER), or G protein-coupled receptor 30 (GPR30), is reported to mediate non-genomic estrogen signaling. GPR30 associates with breast cancer (BC) outcome and may contribute to tamoxifen resistance. We investigated the expression and prognostic significance of GPR30 in metachronous contralateral breast cancer (CBC) as a model of tamoxifen resistance. Total GPR30 expression (GPR30TOT) and plasma membrane-localized GPR30 expression (GPR30PM) were analyzed by immunohistochemistry in primary (BC1; nBC1 = 559) and contralateral BC (BC2; nBC2 = 595), and in lymph node metastases (LGL; nLGL1 = 213; nLGL2 = 196). Death from BC (BCD), including BC death or death after documented distant metastasis, was used as primary end-point. GPR30PM in BC2 and LGL2 were associated with increased risk of BCD (HRBC2 = 1.7, p = 0.03; HRLGL2 = 2.0; p = 0.02). In BC1 and BC2, GPR30PM associated with estrogen receptor (ER)-negativity (pBC1<0.0001; pBC2<0.0001) and progesterone receptor (PR)-negativity (pBC1 = 0.0007; pBC2<0.0001). The highest GPR30TOT and GPR30PM were observed in triple-negative BC. GPR30PM associated with high Ki67 staining in BC1 (p<0.0001) and BC2 (p<0.0001). GPR30TOT in BC2 did not associate with tamoxifen treatment for BC1. However, BC2 that were diagnosed during tamoxifen treatment were more likely to express GPR30PM than BC2 diagnosed after treatment completion (p = 0.01). Furthermore, a trend was observed that patients with GPR30PM in an ER-positive BC2 had greater benefit from tamoxifen treatment. PM-localized GPR30 staining is associated with increased risk of BC death when expressed in BC2 and LGL2. Additionally, PM-localized GPR30 correlates with prognostic markers of worse outcome, such as high Ki67 and a triple-negative subtype. Therefore, PM-localized GPR30 may be an interesting new target for therapeutic exploitation. We found no clear evidence that total GPR30 expression is affected by tamoxifen exposure during development of metachronous CBC, or that GPR30 contributes to tamoxifen resistance.


Phase I Safety and Feasibility Pilot of Hepatic Artery Infusion Chemotherapy in a Rural Catchment Area Using The Codman Vascular Catheter with The Medtronic SynchroMed II Pump for Intrahepatic Cancers.
Discontinuation of the Codman 3000 pump in 2018 left no Food and Drug Administration (FDA)-approved hepatic artery infusion (HAI) device for unresectable colorectal liver metastases (uCLM) and intrahepatic cholangiocarcinoma (uIHC). Historically, HAI has been performed at academic medical centers in large metropolitan areas, which are often inaccessible to rural patients. Consequently, feasibility of dissemination of HAI to rural populations is unknown. Under an FDA investigational device exemption, we opened the only HAI program in Kentucky and enrolled patients with uCLM and uIHC in a phase I clinical trial. The trial examined the safety of the hybrid Codman catheter/Medtronic SynchroMed II pump (hCMP) combination, defined as successful completion of one cycle of HAI chemotherapy. Rural feasibility was assessed by number of missed pump fills appointments. A total of 21 patients (n = 17 uCLM, n = 4 uIHC) underwent hCMP implantation before accrual was stopped early owing to FDA approval of the Intera 3000 pump. 20/21 (95%) patients met the primary safety endpoint. Serious adverse events (AEs) included a grade 5 coronavirus disease 2019 (COVID-19) infection (n = 1) and a grade 3 catheter erosion into the bowel (n = 1). Biliary sclerosis developed in two patients (9.5%). Median distance to infusion center was 47.6 miles (2-138 miles), and 62% were from Appalachia, yet there were no missed pump fill appointments. The 2-year overall survival was 82.4% (uCLM) and 50% (uIHC). The hCMP device had an acceptable safety profile. Despite the complexity of starting a new HAI program, early results showed feasibility for HAI delivery in a rural catchment area and comparable outcomes to larger urban-based HAI centers.


Androgen receptor expression in androgen-independent prostate cancer is associated with increased expression of androgen-regulated genes.
The human prostate cancer (CaP) xenograft, CWR22, mimics human CaP. CWR22 grows in testosterone-stimulated nude mice, regresses after castration, and recurs after 5-6 months in the absence of testicular androgen. Like human CaP that recurs during androgen deprivation therapy, the recurrent CWR22 expresses high levels of androgen receptor (AR). Immunohistochemical, Western, and Northern blot analyses demonstrated that AR expression in the androgen-independent CWR22 is similar to AR expression in the androgen-dependent CWR22 prior to castration. Expression of prostate-specific antigen and human kallikrein-2 mRNAs, two well-characterized androgen-regulated genes in human CaP, was androgen dependent in CWR22. Despite the absence of testicular androgen, prostate-specific antigen and human kallikrein-2 mRNA levels in recurrent CWR22 were higher than the levels in regressing CWR22 tumors from 12-day castrate mice and similar to those in the androgen-stimulated CWR22. Other AR-regulated genes followed a similar pattern of expression. Differential expression screening identified androgen regulation of alpha-enolase and alpha-tubulin as well as other unknown mRNAs. Insulin-like growth factor binding protein-5, the homeobox gene Nkx 3.1, the AR coactivator ARA-70, and cell cycle genes Cdk1 and Cdk2 were androgen regulated in CWR22. In recurrent CWR22, the steady-state levels of all these AR-dependent mRNAs were similar to those in the androgen-stimulated CWR22, despite the absence of testicular androgen. Expression of AR and AR-regulated genes in the androgen-deprived recurrent CWR22 at levels similar to the androgen-stimulated CWR22 suggests that AR is transcriptionally active in recurrent CWR22. Induction of these AR-regulated genes may enhance cellular proliferation in relative androgen absence but through an AR-dependent mechanism. Alternatively, in androgen-independent tumors, induced expression of the AR-regulated gene network might result from a non-AR transcription control mechanism common to these genes.


Smells from the desert: Microbial volatiles that affect plant growth and development of native and non-native plant species.
The plant microbiota can affect host fitness via the emission of microbial volatile organic compounds (mVOCs) that influence growth and development. However, evidence of these molecules and their effects in plants from arid ecosystems is limited. We screened the mVOCs produced by 40 core and representative members of the microbiome of agaves and cacti in their interaction with Arabidopsis thaliana and Nicotiana benthamiana. We used SPME-GC-MS to characterize the chemical diversity of mVOCs and tested the effects of selected compounds on growth and development of model and host plants. Our study revealed that approximately 90% of the bacterial strains promoted plant growth both in A. thaliana and N. benthamiana. Bacterial VOCs were mainly composed of esters, alcohols, and S-containing compounds with 25% of them not previously characterized. Remarkably, ethyl isovalerate, isoamyl acetate, 3-methyl-1-butanol, benzyl alcohol, 2-phenylethyl alcohol, and 3-(methylthio)-1-propanol, and some of their mixtures, displayed beneficial effects in A. thaliana and also improved growth and development of Agave tequilana and Agave salmiana in just 60 days. Volatiles produced by bacteria isolated from agaves and cacti are promising molecules for the sustainable production of crops in arid and semi-arid regions.


Spatial distribution and conservation of speckled hind and warsaw grouper in the Atlantic Ocean off the southeastern U.S.
There is broad interest in the development of efficient marine protected areas (MPAs) to reduce bycatch and end overfishing of speckled hind (Epinephelus drummondhayi) and warsaw grouper (Hyporthodus nigritus) in the Atlantic Ocean off the southeastern U.S. We assimilated decades of data from many fishery-dependent, fishery-independent, and anecdotal sources to describe the spatial distribution of these data limited stocks. A spatial classification model was developed to categorize depth-grids based on the distribution of speckled hind and warsaw grouper point observations and identified benthic habitats. Logistic regression analysis was used to develop a quantitative model to predict the spatial distribution of speckled hind and warsaw grouper as a function of depth, latitude, and habitat. Models, controlling for sampling gear effects, were selected based on AIC and 10-fold cross validation. The best-fitting model for warsaw grouper included latitude and depth to explain 10.8% of the variability in probability of detection, with a false prediction rate of 28-33%. The best-fitting model for speckled hind, per cross-validation, included latitude and depth to explain 36.8% of the variability in probability of detection, with a false prediction rate of 25-27%. The best-fitting speckled hind model, per AIC, also included habitat, but had false prediction rates up to 36%. Speckled hind and warsaw grouper habitats followed a shelf-edge hardbottom ridge from North Carolina to southeast Florida, with speckled hind more common to the north and warsaw grouper more common to the south. The proportion of habitat classifications and model-estimated stock contained within established and proposed MPAs was computed. Existing MPAs covered 10% of probable shelf-edge habitats for speckled hind and warsaw grouper, protecting 3-8% of speckled hind and 8% of warsaw grouper stocks. Proposed MPAs could add 24% more probable shelf-edge habitat, and protect an additional 14-29% of speckled hind and 20% of warsaw grouper stocks.


Modulation by drugs of human hepatic sodium-dependent bile acid transporter (sodium taurocholate cotransporting polypeptide) activity.
Adequate bile flow, maintained in part by the efficient enterohepatic recirculation of bile acids, is critical for normal liver function. One important component of this process is the uptake of bile acids from the portal circulation into hepatocytes by the bile acid uptake transporter sodium taurocholate cotransporting polypeptide (NTCP). Thus, the expression and functional activity of this transporter may affect the rate of bile acid removal from the portal circulation. Accordingly, we assessed NTCP mRNA expression from human livers using a sensitive RNase protection assay. In addition, the ability of various bile acids and drugs to inhibit NTCP activity was determined using a recombinant vaccinia expression system. A 40-fold interindividual variability was found in NTCP mRNA levels determined in eight liver samples of disease-free donors. Expressed NTCP exhibited high-affinity, sodium-dependent uptake of taurocholate, and as expected, this was markedly inhibited by bile acids and organic anions. A number of drugs, including peptidomimetic renin inhibitors, propranolol, cyclosporin, and progesterone, were found to be potent inhibitors, whereas antiarrhythmic agents, including bupivicaine, lidocaine, and quinidine, were found to enhance NTCP activity. Accordingly, these results indicate that large interindividual variability exists in NTCP mRNA level and that a number of drugs currently in clinical use have the potential to interact with and alter NTCP activity, thereby affecting hepatic bile acid uptake.


EXTL3-Associated Immunoskeletal Dysplasia with Neurodevelopmental Abnormalities: A Lethal Phenotype.
Background: Immunoskeletal dysplasia with neurodevelopmental abnormalities (ISDNA) caused by Exostosin-Like Glycosyltransferase 3 (EXTL3) biallelic mutations is a very rare syndrome with only 16 cases reported in the literature. Skeletal dysplasia, neurodevelopmental delay, immunodeficiency, liver, and kidney cysts are the most common findings of this syndrome. Case Presentation: Here, we report on a patient who exhibited a lethal phenotype with clinical characteristics of this syndrome and had a homozygous pathogenic mutation in EXTL3 gene. Conclusions: ISDNA should be kept in mind in the differential diagnosis of patients presenting with neuro-immuno-skeletal dysplasia phenotype.


Impact of residency requirement for dental licensure: an update.
As of 2007, New York State Education Law requires successful completion of dental school training and completion of an approved dental residency program for dental licensure. In a transitional period, from 2003-2006, a dental licensure applicant could select the path of an approved residency program or the New York State-recognized regional standardized clinical examination. By contrast, in 2007, the state of Connecticut adopted and continues to abide by regulations that permit licensure by either completion of an approved residency program or passage of the recognized regional standardized clinical examination. A review of the changing number of dentists licensed in these two adjoining Northeastern states under new licensure guidelines is considered in terms of the possible relationship to the new licensing process.


Use and Efficacy of Analgesic Agents in Sheep (Ovis aries) Used in Biomedical Research.
Sheep (Ovis aries) are widely used as large animal models in biomedical research. However, current literature on the use of analgesics in sheep generally focuses on an industry or farm level of use. This structured review evaluates use and efficacy of analgesics administered to sheep in a biomedical research setting. Electronic databases were searched with terms related to analgesia in research sheep. After application of exclusion criteria, 29 peer-reviewed publications were evaluated from 1995 to 2018. Drugs used for analgesia in sheep include opioids, α₂ agonists, NSAID, local anesthetics, NMDA receptor antagonists, and calcium channel blockers. Opioid agonists have previously been considered short acting and of questionable efficacy in sheep, but newer modalities may provide effective analgesia. NSAID may exhibit an analgesic effect only when inflammatory pain is present and may not be beneficial for use in acute pain models. α₂ agonists provide effective yet short-lived analgesia; however, side effects are of concern. Local anesthetics were previously widely used as stand-alone agents, as alternatives to the use of general anesthetics in sheep. These agents have since fallen out of favor as sole agents. Despite this, they provide a valuable analgesic effect when used as adjuncts to general anesthetic regimes. The NMDA antagonist ketamine provided good analgesia and is likely underutilized as an analgesic agent in sheep. Future controlled studies should further evaluate the analgesic properties of ketamine in sheep.


The effect of intravenous golimumab on health-related quality of life in rheumatoid arthritis: 24-week results of the phase III GO-FURTHER trial.
To evaluate the effects of intravenous (IV) golimumab 2 mg/kg + methotrexate (MTX) on patient-reported measures of health-related quality of life (HRQOL) in patients with active rheumatoid arthritis (RA) despite prior MTX therapy. In this randomized, multicenter, double-blind, placebo-controlled, phase III trial, adults with RA were randomly assigned to receive IV placebo (n = 197) or golimumab 2 mg/kg (n = 395) infusions at Week 0, Week 4, and every 8 weeks thereafter. All patients continued stable oral MTX (15-25 mg/wk). HRQOL assessments included Health Assessment Questionnaire-Disability Index (HAQ-DI; physical function), Medical Outcomes Study Short Form-36 questionnaire physical/mental component summary (SF-36 PCS/MCS) scores, EQ-5D assessment of current health state, Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) questionnaire, and disease effect on productivity [10-cm visual analog scale (VAS)]. Mean HAQ-DI improvements from baseline were significantly greater with golimumab + MTX than placebo + MTX at Week 14 and Week 24 (p < 0.001). Significantly greater improvements in all 8 individual SF-36 subscores and both the SF-36 PCS and MCS scores (p < 0.001) also accompanied golimumab + MTX therapy. Improved EQ-5D and EQ-5D VAS (p < 0.001) and FACIT-Fatigue (p < 0.001) scores were also observed for golimumab + MTX-treated patients at Week 12, Week 16, and Week 24, and greater proportions of golimumab + MTX-treated patients had clinically meaningful improvements in these measures. Greater reductions in disease effect on productivity were observed with golimumab + MTX versus placebo + MTX at Week 24 (p < 0.001). Improvements in physical function, HRQOL, fatigue, and productivity significantly correlated with disease activity improvement. In active RA, IV golimumab + MTX significantly improved physical function, HRQOL, fatigue, and productivity using multiple measurement tools; all correlated with improvements in disease activity (NCT00973479, EudraCT 2008-006064-11).


Primary Topography-Guided LASIK: A Comparative Study Comparing Treating the Manifest versus the Topographic Astigmatism.
To investigate if topography-guided laser in situ keratomileusis (LASIK) depending on the topographic astigmatism which is measured using the Topolyzer leads to a better refractive outcome when compared to treatment of the manifest refractive astigmatism in cases of myopic astigmatism. This was a prospective non-masked, randomized study (block randomization) of postoperative vision and refraction of patients with myopic astigmatism that had LASIK using Contoura vision software. They were divided into three groups according to the treatment strategy, treating the manifest astigmatism in one group, the topographic astigmatism with compensation for the spherical power in the second group and treating the topographic astigmatism without changing the spherical power in the third group. It was conducted at Kasr Alainy Hospital and Dar Eloyon Hospital. The postoperative uncorrected distant visual acuity (UDVA) in each group separately was better than the preoperative corrected distant visual acuity (CDVA) (58% (n=35) had UDVA better than 20/20 and gained 1 line or more); however, eyes treated with the topographic astigmatism without changing the spherical power showed the statistically best results (75% (n=15) had UDVA better than 20/20). The residual anterior corneal astigmatism was lower in this group (the mean 0.47 vs 0.95 and 0.59). No significant difference was noted in the residual refractive astigmatism, but it was also the least in that group. Topography-guided LASIK is a safe and effective ablation profile for treatment of myopic astigmatism. Treating according to the topographic astigmatism shows the best outcome as regards the vision and residual astigmatism.


Suppression of fever and the acute-phase response in a patient with juvenile chronic arthritis treated with monoclonal antibody to tumour necrosis factor-alpha (cA2).
Juvenile chronic arthritis (JCA) is the commonest chronic rheumatic disorder of childhood. Although conventional therapy of JCA continues to improve, many patients experience long-term ill health as a result of their disease or treatment. In adult rheumatoid arthritis (RA), similar concerns have led to the development of therapies designed to interfere in key disease processes. One such therapy is cA2, a chimeric neutralizing monoclonal antibody to the inflammatory cytokine, tumour necrosis factor-alpha (TNF-alpha). The administration of cA2 in adult RA has led to impressive short-term suppression of disease, with a good safety profile. Here, we report the first use of cA2 in childhood arthritis, choosing a patient with severe systemic-onset JCA, resistant to conventional therapies. The patient received two i.v. infusions of cA2, each at a dose of 10 mg/kg, separated by 1 week. The treatment was well tolerated and induced rapid control of fever, anorexia and serositis, together with downregulation of interleukin (IL)-6, soluble TNF receptors (sTNFR) and IL-1ra, and the acute-phase proteins C-reactive protein (CRP) and serum amyloid A (SAA). In contrast, we saw no significant improvement in joint pain or tenderness. Our findings suggest that TNF-alpha is a mediator of fever and other systemic aspects of disease in systemic JCA. TNF-alpha blockade as a treatment modality in JCA deserves further study.


LIME: Low-Light Image Enhancement via Illumination Map Estimation.
When one captures images in low-light conditions, the images often suffer from low visibility. Besides degrading the visual aesthetics of images, this poor quality may also significantly degenerate the performance of many computer vision and multimedia algorithms that are primarily designed for high-quality inputs. In this paper, we propose a simple yet effective low-light image enhancement (LIME) method. More concretely, the illumination of each pixel is first estimated individually by finding the maximum value in R, G, and B channels. Furthermore, we refine the initial illumination map by imposing a structure prior on it, as the final illumination map. Having the well-constructed illumination map, the enhancement can be achieved accordingly. Experiments on a number of challenging low-light images are present to reveal the efficacy of our LIME and show its superiority over several state-of-the-arts in terms of enhancement quality and efficiency.


Energy expenditure associated with the use of neighborhood parks in 2 cities.
Availability of public neighborhood parks is associated with physical activity. Little is known about how parks contribute to population energy balance. This study estimated energy expenditure associated with the use of neighborhood parks and compared energy expenditure by activity areas within parks and by neighborhood race/ethnicity and income. The System for Observing Play and Leisure Activity among Youth (SOPLAY), a direct observation approach, was used to estimate energy expenditure in 10 Tampa (Florida) parks and 19 Chicago (Illinois) parks. Parks were selected from census tracts with a moderate to high representation of white, Latino, and African American populations. A total of 9454 park users were observed. Sedentary, moderate, and vigorous activities were assigned metabolic equivalence intensity (MET) values of 1.5, 3, and 6, respectively. Park use in Tampa generated 15 336 total METs over the study period. Chicago parks generated 7305.6 METs. Mean METs varied by activity areas in parks. For Chicago parks, mean METs were higher for parks in African American and higher-income neighborhoods. Public parks can contribute to population energy balance. Policies to make parks available, promotions to encourage park use, and programs to encourage active use of parks are necessary to achieve this potential.


Measurement of the volume of a leg ulcer using a laser scanner.
Effective management of leg ulcer healing depends on accurate and reliable measurements of wound size. Current techniques usually rely on estimates of surface area or circumference which do not fully describe the healing process. A novel instrument has been developed that is capable of measuring the variations in the surface contours (topography) of a solid object. Its primary application is to measure the size of a leg ulcer by scanning a laser displacement sensor over the affected area. There is no contact with the wound and scanning takes approximately 2 minutes to perform. Volume is calculated by subtracting the measured topography from one calculated using an algorithm to reconstruct a healthy leg surface. A study was carried out where patients had their ulcers scanned during their visits to the leg ulcer clinic. Data are presented from two venous leg ulcers showing the calculated volume reducing over time.


Laser instrumentation and safety.
A review of the operation principles of lasers and the various types used in chest medicine is given. This includes CO2, Nd:YAG, argon, krypton, and dye lasers. Safety considerations in the use of lasers are also outlined.


Abnormal urinary kallikrein in hypertension is not related to aldosterone or plasma renin activity.
The relationships between urinary kallikrein (Ukal), and plasma renin activity (PRA), urinary aldosterone (Ualdo), Na+ balance, SK+, and renal function were studied in essential hypertensives (EHT) and normals. Ukal was measured by a radiochemical esterolytic assay. We studied 18 white patients with EHT (15 men, 3 women) ages 31.6 to +/- 2.1 (SEM) yrs, BP 138 +/- 2/95 +/- 2 mm Hg. and 12 white normals (NLS) (7 men, 5 women) ages 30.2 +/- 2.3 yrs, BP 112 +/- 4/71 +/- 2 mm Hg. All received a 5-day diet of 400 mEq Na+, 80 mEq K+/day, and 5 days of 10 mEq Na+, 80 mEq K+/day. All achieved Na+ balance by Day 5. On Day 5 of the low Na+ diet, 24 hr. Ukal in EHT was 15.8 +/- 2.4 (esterase units/24 hr) vs NLS, 17.0 +/- 2.8 PRA was the same in EHT and NLS, but Ualdo was higher in NLS. (Day 5, low Na+, EHT, Ualdo = 29.4 +/0 3.3 microgram/24h. vs NLS 41.8 +/- 4.7, p less than 0.02). Analysis of individuals showed that all NLS increased Ukal after salt restriction, while 3 EHT decreased Ukal after salt restriction. This abnormal response in EHT was not related to abnormalities in Ualdo, PRA, Na+ balance, SK+, or creatinine clearance. In 3 EHT with low-renin EHT, the Ukal response was normal. In two of four patients with primary aldosteronism, Ukal was normal despite increased Ualdo. The Ukal response to salt restriction is abnormal in some EHT, unrelated to Ualdo or PRA, suggesting either a primary defect in Ukal and/or the presence of other factors modulating Ukal in EHT.


Early Operative Versus Delayed Operative Versus Nonoperative Treatment of Pediatric and Adolescent Anterior Cruciate Ligament Injuries: A Systematic Review and Meta-analysis.
Treatment options for pediatric and adolescent anterior cruciate ligament (ACL) injuries include early operative, delayed operative, and nonoperative management. Currently, there is a lack of consensus regarding the optimal treatment for these injuries. The purpose was to determine the optimal treatment strategy for ACL injuries in pediatric and adolescent patients. We hypothesized that (1) early ACL reconstruction results in fewer meniscal tears than delayed reconstruction but yields no difference in knee stability and (2) when compared with nonoperative management, any operative management results in fewer meniscal tears and cartilage injuries, greater knee stability, and higher return-to-sport rates. Systematic review and meta-analysis; Level of evidence, 4. A systematic search of databases was performed including PubMed, Embase, and Cochrane Library using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Inclusion criteria were a pediatric and adolescent patient population (≤19 years old at surgery), the reporting of clinical outcomes after treatment of primary ACL injury, and original scientific research article. Exclusion criteria were revision ACL reconstruction, tibial spine avulsion fracture, case report or small case series (<5 patients), non-English language manuscripts, multiligamentous injuries, and nonclinical studies. A total of 30 studies containing 50 cohorts and representing 1176 patients met our criteria. With respect to nonoperative treatment, knee instability was observed in 20% to 100%, and return to preinjury level of sports ranged from 6% to 50% at final follow-up. Regarding operative treatment, meta-analysis results favored early ACL reconstruction over delayed reconstruction (>12 weeks) for the presence of any meniscal tear (odds ratio, 0.23; P = .006) and irreparable meniscal tear (odds ratio, 0.31; P = .001). Comparison of any side-to-side differences in KT-1000 arthrometer testing did not favor early or delayed ACL reconstruction in either continuous mean differences (P = .413) or proportion with difference ≥3 mm (P = .181). Return to preinjury level of competition rates for early and delayed ACL reconstruction ranged from 57% to 100%. Delaying ACL reconstruction in pediatric or adolescent patients for >12 weeks significantly increased the risk of meniscal injuries and irreparable meniscal tears; however, early and delayed operative treatment achieved satisfactory knee stability. Nonoperative management resulted in high rates of residual knee instability, increased risk of meniscal tears, and comparatively low rates of return to sports.


Anti-inflammatory effects of water extract from bell pepper (Capsicum annuum L. var. grossum) leaves in vitro.
Fruits and vegetables have been recognized as natural sources of various bioactive compounds. Peppers, one such natural source, are consumed worldwide as spice crops. They additionally have an important role in traditional medicine, as a result of their antioxidant bioactivity via radical scavenging. However, there are no reports regarding the bioactivity of the bell pepper (Capsicum annuum L. var. grossum), a commonly used edible vegetable. The present study aimed to evaluate the anti-inflammatory effect of water extract from bell pepper leaves on mouse spleen cells, and explore the potential mechanism underlying this effect. The extract was prepared through homogenization of bell pepper leaves in deionized water. The sterilized supernatant was added to a mouse spleen cell culture stimulated by concanavalin A. Following 72 h of culture, the levels of inflammatory cytokines in the culture supernatant were measured using a sandwich enzyme-linked immunosorbent assay system, and levels of inflammatory proteins were assessed using western blotting. The bell pepper leaf extract significantly inhibited inflammatory cytokine production, inhibited cell proliferation without producing cytotoxicity, and suppressed the expression of inflammatory proteins. These results suggest that components of the bell pepper leaf extract possess anti-inflammatory activity. The study of the anti-inflammatory mechanism of bell pepper leaf extract has provided useful information on its potential for therapeutic application.


The importance of hemolysis in the lethal effects of equnatoxin II, a protein from the sea anemone Actinia equina (L.).
Equinatoxin II (EqT II) is one of the three isotoxins isolated from the sea anemone Actinia equina (L). The cause of death due to i.v. application of Eq T II was attributed to its hemolytic activity and hiperkaliemia, and the direct cardio-respiratory effects of the toxin. The toxin also binds to plasma lipids and forms toxic conglomerates with them. In our study we tried to evaluate the importance of interaction of the toxin with blood components in the toxin lethality. Anaesthetized male Wistar rats were used. The respiratory activity, ECG and animal serum ionic composition were monitored. To simulate isolated effects of the toxin hemolytic activity, hemolysed erythrocytes, KCl and mixture of rat serum with the toxin were injected i.v.. It was shown that neither the lysed erythrocytes nor the mixture of rat serum with the toxin were lethal for the experimental animals. Even KCl, in concentrations detected in serum of rats killed by the toxin, did not cause the death of experimental animals. Our results indicate that either a combination of the tested effects of the toxin on blood components or more probably the direct effects of the toxin on vital organs are responsible for the toxin lethality.


Effects of interdental osteotomies on the periodontal and osseous supporting tissues.
The effects of 40 interdental osteotomies on surrounding osseous and periodontal structures were evaluated clinically and radiographically. No statistically significant changes were noted in any of the clinical parameters except gingival height, which decreased slightly in the maxilla and increased in the mandible. These changes were found to be statistically significant, but not clinically significant, and are most likely explained by the direction of movement of the bony segment. Radiographic evaluations revealed no statistically significant changes other than an increase in interdental width in both the maxillary and mandibular sites. These measurements were made at the root level, and, although the crowns were moved closer, the roots may actually have flared apart because the anterior segment was tipped to upright the incisors. The lack of change in the other radiographic parameters indicated that there was no loss of alveolar bone support.


The British quasi-market in health care: a balance sheet of the evidence.
To summarise the findings from a comprehensive review of research on the effects of the three main elements of the quasi-market reforms of the UK National Health Service (NHS) introduced in 1991/92: General practices becoming fundholders by volunteering to purchase elective care for their patients; Health authorities becoming purchasers of emergency, unplanned and elective services, together with a range of alternatives to fundholding operating under their auspices; The conversion of providers of hospital and community health services to NHS trusts separate from their local health authorities. Published and unpublished studies which included any data on the impact of the three main planks of the quasi-market changes, produced between 1991 and late 1998, were identified using a combination of electronic databases, library catalogues at the King's Fund, London, bibliographies, reference lists of individual studies, a survey of NHS directors of public health and consultations with subject area experts. Each main element of the quasi-market was assessed in relation to its impact on: efficiency (primarily productivity); equity; quality; choice and responsiveness; and accountability. There was relatively little measurable change that could be related unequivocally to the core mechanisms of the quasi-market. The incentives were generally too weak and the constraints too strong to generate the consequences predicted by either proponents or critics of the quasi-market. On the other hand, the way in which the NHS operates was changed irrevocably by the reforms.


The Holliday junction in an inverted repeat DNA sequence: sequence effects on the structure of four-way junctions.
Holliday junctions are important structural intermediates in recombination, viral integration, and DNA repair. We present here the single-crystal structure of the inverted repeat sequence d(CCGGTACCGG) as a Holliday junction at the nominal resolution of 2. 1 A. Unlike the previous crystal structures, this DNA junction has B-DNA arms with all standard Watson-Crick base pairs; it therefore represents the intermediate proposed by Holliday as being involved in homologous recombination. The junction is in the stacked-X conformation, with two interconnected duplexes formed by coaxially stacked arms, and is crossed at an angle of 41.4 degrees as a right-handed X. A sequence comparison with previous B-DNA and junction crystal structures shows that an ACC trinucleotide forms the core of a stable junction in this system. The 3'-C x G base pair of this ACC core forms direct and water-mediated hydrogen bonds to the phosphates at the crossover strands. Interactions within this core define the conformation of the Holliday junction, including the angle relating the stacked duplexes and how the base pairs are stacked in the stable form of the junction.


Substantial and sustained improvement of serrated polyp detection after a simple educational intervention: results from a prospective controlled trial.
Serrated polyps (SPs) are an important cause of postcolonoscopy colorectal cancers (PCCRCs), which is likely the result of suboptimal SP detection during colonoscopy. We assessed the long-term effect of a simple educational intervention focusing on optimising SP detection. An educational intervention, consisting of two 45 min training sessions (held 3 years apart) on serrated polyp detection, was given to endoscopists from 9 Dutch hospitals. Hundred randomly selected and untrained endoscopists from other hospitals were selected as control group. Our primary outcome measure was the proximal SP detection rate (PSPDR) in trained versus untrained endoscopists who participated in our faecal immunochemical test (FIT)-based population screening programme. Seventeen trained and 100 untrained endoscopists were included, who performed 11 305 and 51 039 colonoscopies, respectively. At baseline, PSPDR was equal between the groups (9.3% vs 9.3%). After training, the PSPDR of trained endoscopists gradually increased to 15.6% in 2018. This was significantly higher than the PSPDR of untrained endoscopists, which remained stable around 10% (p=0.018). All below-average (ie, PSPDR ≤6%) endoscopists at baseline improved their PSPDR after training session 1, as did 57% of endoscopists with average PSPDR (6%-12%) at baseline. The second training session further improved the PSPDR in 44% of endoscopists with average PSPDR after the first training. A simple educational intervention was associated with substantial long-term improvement of PSPDR in a prospective controlled trial within FIT-based population screening. Widespread implementation of such interventions might be an easy way to improve SP detection, which may ultimately result in fewer PCCRCs. NCT03902899.


History of entomopathogenic nematology.
The history of entomopathogenic nematology is briefly reviewed. Topic selections include early descriptions of members of Steinernema and Heterorhabditis, how only morphology was originally used to distinguish between the species; descriptions of the symbiotic bacteria and elucidating their role in the nematode- insect complex, including antibiotic properties, phase variants, and impeding host defense responses. Other topics include early solutions regarding production, storage, field applications and the first commercial sales of entomopathogenic nematodes in North America. Later studies centered on how the nematodes locate insect hosts, their effects on non-target organisms and susceptibility of the infective juveniles to soil microbes. While the goals of early workers was to increase the efficacy of entomopathogenic nematodes for pest control, the increasing use of Heterorhabditis and Photorhabdus as genetic models in molecular biology is noted.


Supply of a nondrug substitute reduces escalated heroin consumption.
Escalation of drug consumption-a hallmark of addiction-has been hypothesized to be associated with a relative devaluation of alternative nondrug rewards and thus with a decrease in their ability to compete with or to substitute for the drug. In a behavioral economic framework, decreased substitutability of nondrug rewards for drug would explain why drug consumption is behaviorally dominant and relatively resistant to change (eg price-inelastic) in drug-addicted individuals. The goal of the present study was to test this hypothesis using a validated rat model of heroin intake escalation. Escalation was precipitated by long (6 h, long access (LgA)), but not short (1 h, short access (ShA)), daily access to i.v. heroin self-administration. After escalation, the effects of price (ie fixed-ratio value) on heroin consumption were assessed under two alternative reward conditions: in the presence or absence of a nondrug substitute for heroin (ie four freely available chow pellets). As expected, escalated heroin consumption by LgA rats was less sensitive to price than heroin consumption by ShA rats, showing that heroin had acquired greater reinforcing strength during escalation. However, supplying a substitute during access to heroin was sufficient to reverse this post-escalation increase in the reinforcing effectiveness of heroin. Thus, escalated heroin consumption is not associated with a decreased sensitivity to competing nondrug rewards. Escalated drug use may therefore persist, not so much because of a relative devaluation of nondrug substitutes, but because of a loss or reduction of their availability.


[Correlation between the nucleic acid homeostasis disorders and location of ischemic insult and its consequences].
The characteristic feature of ischaemic insult was the excess of the majority components of the nucleinic homeostasis (DNA, RNA, DNA-ases) in the blood serum of the patients with unfavourable development of process and the low activity of ribonucleases. This tendency was also observed in patients with insult localization in carotid region concerning the brain infarct in the invertebrobasilar system. At the favourable course of disease the gradual decrease of the nucleinic acids' level and the nucleases activity in the studied fluids were observed.


Dietary natural flavonoids treating cancer by targeting aryl hydrocarbon receptor.
The role of aryl hydrocarbon receptor (AhR) as a ligand-activated transcription factor in the field of cancer has gradually been unveiled. A strong body of evidence indicated that AhR is implicated in cell proliferation and apoptosis, immune metabolism and other processes, which further affected tumor growth, survival, migration, and invasion. Therefore, AhR targeted therapy may become a new method for cancer treatment and provide a new direction for clinical tumor treatment. Astonishingly, the largest source of exposure of animals and humans to AhR ligands (synthetic and natural) comes from the diet. Myriad studies have described that various natural dietary chemicals can directly activate and/or inhibit the AhR signaling pathway. Of note, numerous natural products contribute to AhR active, of which dietary flavonoids are the largest class of natural AhR ligands. As interest in AhR and its ligands increases, it seems sensible to summarize current research on these ligands. In this review, we highlight the role of AhR in tumorigenesis and focus on the double effect of AhR in cancer therapy. We explored the molecular mechanism of AhR ligands on cancer through a few AhR agonists/antagonists currently in clinical practice. Ultimately, we summarize and highlight the latest progression of dietary flavonoids as AhR ligands in cancer inhibition, including the limitations and deficiencies of it in clinical research. This review will offer a comprehensive understanding of AhR and its dietary ligands which may dramatically pave the way for targeted cancer treatment.


Pyruvate kinase M2 (PKM-2) expression and prognostic significance in glioblastoma patients.
Pyruvate kinase M2 (PKM2) is a key enzyme that catalyzes the irreversible and final step of glycolysis. It is closely associated with cancer development and progression. The relationship between PKM2 and prognosis in glioblastoma (GB) patients is unknown. The aim of this study was to measure PKM2 expression and evaluate its effect on prognosis in GB patients. Patients who underwent radiotherapy (RT) for glioblastoma between 2010 and 2021 were evaluated immunohistochemically. A single pathologist evaluated pathology specimens of all patients. The intensity and extent of staining of tumor cells were scored. Patients were categorized as low and high PKM2. A total of 119 patients were evaluated. While 80.7% of the cases had a low score, 19.3% had a high PKM2 score. It was observed that the group with high PKM2 expression had lower performance, received more hypofractionated RT and received adjuvant chemotherapy (CT) less frequently. Median overall survival (OS) was 15.77 months in the low PKM2 expression group and 6.50 months in the high PKM2 group. In univariate analyses, PKM2 expression, age, performance status, type of surgery, RT scheme, and concurrent and adjuvant CT were prognostic factors in predicting OS. In multivariate analyses, PKM2 expression, type of surgery, RT scheme and receiving adjuvant CT were prognostic factors for OS. PKM2 is an independent prognostic factor for survival and is associated with poor prognosis in GBM patients treated with radiotherapy. It may be a potential therapeutic target for anticancer therapy.


Increased Neutrophil Count and Decreased Neutrophil CD15 Expression Correlate With TB Disease Severity and Treatment Response Irrespective of HIV Co-infection.
Tuberculosis remains a leading cause of death globally despite curative treatment, partly due to the difficulty of identifying patients who will not respond to therapy. Simple host biomarkers that correlate with response to drug treatment would facilitate improvement in outcomes and the evaluation of novel therapies. In a prospective longitudinal cohort study, we evaluated neutrophil count and phenotype at baseline, as well as during TB treatment in 79 patients [50 (63%) HIV-positive] with microbiologically confirmed drug susceptible TB undergoing standard treatment. At time of diagnosis, blood neutrophils were highly expanded and surface expression of the neutrophil marker CD15 greatly reduced compared to controls. Both measures changed rapidly with the commencement of drug treatment and returned to levels seen in healthy control by treatment completion. Additionally, at the time of diagnosis, high neutrophil count, and low CD15 expression was associated with higher sputum bacterial load and more severe lung damage on chest x-ray, two clinically relevant markers of disease severity. Furthermore, CD15 expression level at diagnosis was associated with TB culture conversion after 2 months of therapy (OR: 0.14, 95% CI: 0.02, 0.89), a standard measure of early TB treatment success. Importantly, our data was not significantly impacted by HIV co-infection. These data suggest that blood neutrophil metrics could potentially be exploited to develop a simple and rapid test to help determine TB disease severity, monitor drug treatment response, and identify subjects at diagnosis who may respond poorly to treatment.


Protein expression profile and prevalence pattern of the molecular classes of breast cancer--a Saudi population based study.
Breast cancer is not a single entity but a diverse group of entities. Advances in gene expression profiling and immunohistochemistry as its surrogate marker have led to the unmasking of new breast cancer molecular subtypes, resulting in the emergence of more elaborate classification systems that are therapeutically and prognostically more predictive. Molecular class distribution across various ethnic groups may also reveal variations that can lead to different clinical outcomes in different populations. We aimed to analyze the spectrum of molecular subtypes present in the Saudi population. ER, PR, HER2, EGFR and CK5/6 were used as surrogate markers for gene expression profiling to classify 231 breast cancer specimens. Correlation of each molecular class with Ki-67 proliferation index, p53 mutation status, histologic type and grade of the tumor was also carried out. Out of 231 cases 9 (3.9%) were classified as luminal A (strong ER +ve, PR +ve or -ve), 37 (16%) as luminal B (weak to moderate ER +ve, and/or PR +ve), 40 (17.3%) as HER2+ (strong or moderately positive HER 2 with confirmation by silver enhanced in-situ hybridization) and 23 (10%) as basal (CK5/6 or EGFR +ve). Co-positivity of different markers in varied patterns was seen in 23 (10%) of cases which were grouped into a hybrid category comprising luminal B-HER2, HER2-basal and luminal-basal hybrids. Ninety nine (42.8%) of the tumors were negative for all five immunohistochemical markers and were labelled as unclassified (penta negative). A high Ki-67 proliferation index was seen in basal (p=0.007) followed by HER2+ class. Overexpression of p53 was predominantly seen in HER2+(p=0.001) followed by the basal group of tumors. A strong correlation was noted between invasive lobular carcinoma and hormone receptor expression with 8 out of 9 lobular carcinoma cases (88.9%) classifiable as luminal cancers. Otherwise, there was no association between the molecular class and the histologic type or grade of the tumor. Subtyping by use of this immunohistochemical panel revealed a prevalence pattern that is unique to our population; luminal tumors comprised only 19.9%, and the unclassified group (penta negative) 42.8%, a distribution which is distinctive to our population and in contrast with all Western studies. The presence of a predominant unclassified group also suggests that the currently used molecular analytic spectrum may not completely encompass all molecular classes and there is a need to further refine and develop the existing classification systems.


[Allergies in adults].
Only few epidemiological studies have assessed allergic diseases in adults. In a follow-up study of the MONICA survey S3 (1994/95), which was performed 1997-1999, a total of 1,537 persons were interviewed and tested by skin prick and patch test. Furthermore data of the MONICA survey (RAST, cholesterol, food diaries) could be used. Within survey S4 (1999/2001) a total of 4,261 subjects were interviewed concerning their personal history of atopic diseases and the corresponding history of their partners. In survey S3 the prevalence of allergic sensitisation was 20.5 % for persons without formal graduation from school and 48.1 % for those with a university degree. 20.8 % reported a hypersensitivity to food and about one quarter exhibited a positive reaction in skin prick test. Atopic eczema and hay fever increased over quartiles of HDL cholesterol. Similar, allergic sensitisation (RAST) increased over quartiles of uptake of unsaturated fatty acids in men. 40 % of those who were patch tested exhibited a positive reaction, with perfume mix, nickel, thimerosal and balsam of Peru being the most prominent allergens. Inhabitants of the City of Augsburg were sensitised more often (34.0 % overall, 23.9 % pollen) than inhabitants of villages with (29.4 %, 17.0 %). Full time farmers were sensitised less frequently (22.0 %, 8.4 %). In survey S4 the lifetime prevalence of atopic diseases diagnosed by doctors was 5.1 % for atopic eczema, 6.1 % for asthma and 13.7 % for hay fever. Subjects who lived together with a partner who suffered from hay fever were affected in 19.6 % whereas 13.1 % had hay fever when the partner was not affected. Future studies will offer an unique opportunity to analyse the incidence and remission of manifestations of atopy in adults.


HGMB1 and RAGE as Essential Components of Ti Osseointegration Process in Mice.
The release of the prototypic DAMP High Mobility Group Box 1 (HMGB1) into extracellular environment and its binding to the Receptor for Advanced Glycation End Products (RAGE) has been described to trigger sterile inflammation and regulate healing outcome. However, their role on host response to Ti-based biomaterials and in the subsequent osseointegration remains unexplored. In this study, HMGB1 and RAGE inhibition in the Ti-mediated osseointegration were investigated in C57Bl/6 mice. C57Bl/6 mice received a Ti-device implantation (Ti-screw in the edentulous alveolar crest and a Ti-disc in the subcutaneous tissue) and were evaluated by microscopic (microCT [bone] and histology [bone and subcutaneous]) and molecular methods (ELISA, PCR array) during 3, 7, 14, and 21 days. Mice were divided into 4 groups: Control (no treatment); GZA (IP injection of Glycyrrhizic Acid for HMGB1 inhibition, 4 mg/Kg/day); RAP (IP injection of RAGE Antagonistic Peptide, 4 mg/Kg/day), and vehicle controls (1.5% DMSO solution for GZA and 0.9% saline solution for RAP); treatments were given at all experimental time points, starting 1 day before surgeries. HMGB1 was detected in the Ti-implantation sites, adsorbed to the screws/discs. In Control and vehicle groups, osseointegration was characterized by a slight inflammatory response at early time points, followed by a gradual bone apposition and matrix maturation at late time points. The inhibition of HMGB1 or RAGE impaired the osseointegration, affecting the dynamics of mineralized and organic bone matrix, and resulting in a foreign body reaction, with persistence of macrophages, necrotic bone, and foreign body giant cells until later time points. While Control samples were characterized by a balance between M1 and M2-type response in bone and subcutaneous sites of implantation, and also MSC markers, the inhibition of HMGB1 or RAGE caused a higher expression M1 markers and pro-inflammatory cytokines, as well chemokines and receptors for macrophage migration until later time points. In conclusion, HMGB1 and RAGE have a marked role in the osseointegration, evidenced by their influence on host inflammatory immune response, which includes macrophages migration and M1/M2 response, MSC markers expression, which collectively modulate bone matrix deposition and osseointegration outcome.


Magnetically aligned nanodomains: application in high-performance ion conductive membranes.
Polyelectrolyte-coated magnetic nanoparticles were prepared by decorating the surface of superparamagnetic iron oxide nanoparticles (SPIONs) with crosslinked chitosan oligopolysaccharide (CS). These positively charged particles (CS-SPIONs) were then added to a negatively charged polymer (Nafion), and cast into membranes under an applied magnetic field. TEM and SAXS measurements confirmed this process created aligned, cylindrical nanodomains in the membranes. This was also indirectly confirmed by proton conductivity values. The strong electrostatic interaction between chitosan and Nafion prevented oxygen permeability and water evaporation at elevated temperatures through the proton conductive channels. The resultant proton exchange membranes showed lower conduction dependency to relative humidity, which is highly desirable for hydrogen fuel cells. The fuel cell performance tests were performed on the designed polyelectrolyte membrane by hydrogen-oxygen single cells at elevated temperature (120 °C) and low relative humidity.


10.5% efficient polymer and amorphous silicon hybrid tandem photovoltaic cell.
Thin-film solar cells made with amorphous silicon (a-Si:H) or organic semiconductors are considered as promising renewable energy sources due to their low manufacturing cost and light weight. However, the efficiency of single-junction a-Si:H or organic solar cells is typically <10%, insufficient for achieving grid parity. Here we demonstrate an efficient double-junction photovoltaic cell by employing an a-Si:H film as a front sub-cell and a low band gap polymer:fullerene blend film as a back cell on planar glass substrates. Monolithic integration of 6.0% efficienct a-Si:H and 7.5% efficient polymer:fullerene blend solar cells results in a power conversion efficiency of 10.5%. Such high-efficiency thin-film tandem cells can be achieved by optical management and interface engineering of fully optimized high-performance front and back cells without sacrificing photovoltaic performance in both cells.


Sudden fetal death associated with both duodenal atresia and umbilical cord ulcer: a case report and review.
We encountered one case of duodenal atresia complicated by massive intrauterine hemorrhage due to the perforation of an umbilical cord ulceration (UCU). UCU is an extremely rare complication in the perinatal period. Although the prenatal diagnosis of upper intestinal atresia has been established, little is known about the association between UCU and upper intestinal atresia. In this article, we report our case, review past articles, and discuss the underlying pathophysiological mechanisms of the cause of an UCU. Given the characteristic sites of upper intestinal atresia, we speculate that regurgitation of gastric or intestinal juice into the amniotic fluid could be responsible for the development of UCU. We also believe that close observation is required for patients who have upper intestinal atresia.


Flexible migration program regulates gamma delta T-cell involvement in humoral immunity.
gamma delta T cells are inadequately defined both in terms of their migration potential and contribution to antimicrobial immunity. Here, we have examined the migration profile of human blood gamma delta T cells and related cell lines and correlated these findings with their distribution in secondary lymphoid tissues and their function in B-cell cocultures. We find that resting gamma delta T cells are characterized by an inflammatory migration program similar to cells of the innate immune system. However, T-cell receptor (TCR) triggering resulted in the rapid but transient induction of a lymph node (LN)-homing program, as evidenced by functional CCR7 expression and concomitant reduction in expression and function of CCR5 and, to a lesser degree, CCR2. Moreover, the LN-homing program was reflected by the presence of gamma delta T cells in gastrointestinal lymphoid tissues, notably in clusters within germinal centers of B-cell follicles. In line with these findings, V gamma V delta-TCR triggering resulted in prominent expression of essential B-cell costimulatory molecules, including CD40L, OX40, CD70, and ICOS. Furthermore, gamma delta T cells were shown to provide potent B-cell help during in vitro antibody production. Collectively, our findings agree with a role for gamma delta T cells in humoral immunity during the early phase of antimicrobial responses.


Comparison of paravertebral and interpleural block in patients undergoing modified radical mastectomy.
Paravertebral and inter pleural blocks (IPB) reduce post-operative pain and decrease the effect of post-operative pain on lung functions after breast surgery. This study was designed to determine their effect on lung functions and post-operative pain in patients undergoing modified radical mastectomy. A total of 120 American Society of Anesthesiologists physical status 1 and 2 patients scheduled to undergo breast surgery were randomly allocated to receive IPB (Group IPB, n = 60) or paravertebral block (PVB) (Group PVB, n = 60) with 20 ml of 0.5% bupivacaine pre-operatively. A standard protocol was used to provide general anesthesia. Lung function tests, visual analog scale (VAS) for pain at rest and movement, analgesic consumption were recorded everyday post-operatively until discharge. Lung functions decreased on 1(st) post-operative day and returned to baseline value by 4(th) post-operative day in both groups. VAS was similar in both groups. There was no significant difference in the consumption of opioids and diclofenac in both groups. Complete block was achieved in 48 patients (80%) in paravertebral group and 42 patients (70%) in inter pleural group. To conclude, lung functions are well-preserved in patients undergoing modified radical mastectomy under general anesthesia supplemented with paravertebral or IPB. IPB is as effective as PVB for post-operative pain relief. PVB has the added advantage of achieving a more complete block.


Effect of surface elasticity on the rheology of nanometric liquids.
The rheological properties of liquids confined to nanometer scales are important in many physical situations. In this Letter, we demonstrate that the long-range elastic deformation of the confining surfaces must be taken into account when considering the rheology of nanometric liquids. In the case of a squeeze-flow geometry, we show that below a critical distance D(c), the liquid is clamped by its viscosity and its intrinsic properties cannot be disentangled from the global system response. Using nanorheology experiments, we demonstrate that picometer elastic deflections of the rigid confining surfaces dominate the overall mechanical response of nanometric liquids confined between solid walls.


Impact of dyslipidemia in end-stage renal disease.
Heart disease is a major cause of morbidity and mortality among patients with renal failure. Premature atherosclerotic coronary heart disease is driven by multiple risk factors, including dyslipidemia and oxidative stress. In the nondialysis population, there is overwhelming evidence that treatment of dyslipidemia can significantly improve cardiovascular outcomes. Accumulating data indicate that dialysis patients have atherogenic lipid abnormalities. Although LDL cholesterol (LDL-C) levels in patients who undergo hemodialysis are normal or near normal, increased oxidized LDL-C, triglycerides, and lipoprotein (a) [Lp(a)]; decreased HDL cholesterol (HDL-C); and triglyceride-rich VLDL have been noted. Patients who receive peritoneal dialysis have a more atherogenic lipid profile with increased LDL-C, apolipoprotein B, oxidized LDL-C, triglycerides, and Lp(a) and decreased HDL-C. Furthermore, the LDL particles of peritoneal dialysis patients are small and dense. However, there is a dearth of information regarding the goals, efficacy, and safety of dyslipidemia treatment among dialysis patients. Given the strong evidence of risk reduction and the benefits of lipid-lowering treatment in the nondialysis population, the emerging consensus is that dialysis patients should be treated aggressively for dyslipidemia to an LDL-C goal below 100 mg/dl. Although physicians and patients may be reluctant to add medications because of concerns about polypharmacy, potential decreased compliance, and increased cost, the use of agents such as sevelamer that can serve multiple functions, including phosphate control, lipid lowering (decreased LDL-C and total cholesterol), and anti-inflammatory effects (decreased high-sensitivity C-reactive protein), should be explored and considered for patients who would benefit from such treatment.


Geographic variation in vector competence for West Nile virus in the Culex pipiens (Diptera: Culicidae) complex in California.
We evaluated the susceptibility to infection and transmission of West Nile virus (WNV) in seven populations of Culex pipiens pipiens (L.), Cx. p. quinquefasciatus Say, and from populations containing Cx. pipiens/quinquefasciatus hybrids in a north-south transect of California. Samples were identified to species or as hybrid forms based on morphology of male terminalia. After 7 and 14 days of extrinsic incubation, few females were infected and none transmitted WNV from samples of Cx. p. pipiens from northern Shasta County and of Cx. p. quinquefasciatus from southern Los Angeles County. Seven days after infective feeding, 13%-36% of mosquitoes from the counties of Merced, Fresno, Kern, and San Bernardino were infected, and 12%-40% of infected mosquitoes expressed WNV in salivary expectorate. Fourteen days after infective feeding, 18%-43% of mosquitoes from these counties were infected, and 50%-69% of infected mosquitoes transmitted WNV in salivary expectorate. A sample of Cx. p. quinquefasciatus from Riverside County did not transmit WNV after 7 days, but 71% transmitted 14 days after infective feeding. These results reveal extensive geographic variation in vector competence for WNV in the Culex pipiens complex in California.


Application of Biocides and Super-Absorbing Polymers to Enhance the Efficiency of Filtering Materials.
Studies on the functionalization of materials used for the construction of filtering facepiece respirators (FFRs) relate to endowing fibers with biocidal properties. There is also a real need for reducing moisture content accumulating in such materials during FFR use, as it would lead to decreased microorganism survival. Thus, in our study, we propose the use of superabsorbent polymers (SAPs), together with a biocidal agent (biohalloysite), as additives in the manufacturing of polypropylene/polyester (PP/PET) multifunctional filtering material (MFM). The aim of this study was to evaluate the MFM for stability of the modifier's attachment to the polymer matrix, the degree of survival of microorganisms on the nonwoven, and its microorganism filtration efficiency. Scanning electron microscopy (SEM) and Fourier transform infrared (FTIR) spectroscopy were used to test the stability of the modifier's attachment. The filtration efficiency was determined under conditions of dynamic aerosol flow of S. aureus bacteria. The survival rates (N%) of the following microorganisms were assessed: Escherichia coli and Staphylococcus aureus bacteria, Candida albicans yeast, and Aspergillus niger mold using the AATCC 100-2004 method. FTIR spectrum analysis confirmed the pre-established composition of MFM. The loss of the active substance from MFM in simulated conditions of use did not exceed 0.02%, which validated the stability of the modifier's attachment to the PP/PET fiber structure. SEM image analysis verified the uniformity of the MFM structure. Lower microorganism survival rates were detected for S. aureus, C. albicans, and E. coli on the MFM nonwoven compared to control samples that did not contain the modifiers. However, the MFM did not inhibit A. niger growth. The MFM also showed high filtration efficiency (99.86%) against S. aureus bacteria.


Angiotensin-related sodium appetite and thirst in cattle.
Cows depleted of Na by loss of saliva from a parotid fistula for 46 h had an avid appetite for Na solution. They drank 21.0 +/- 1.6 liter of 0.3 M NaHCO3-NaCl solution during 2 h of access but little or no water during that time. Solutions of angiotensin II or captopril were infused for 3 h intravenously or into a lateral ventricle (intracerebroventricular) beginning 1 h before access to Na solution. Intravenous angiotensin II increased Na intake (to 26.8 +/- 2.9 liter, P less than 0.01) but did not alter water intake. Intracerebroventricular angiotensin II increased water intake but did not alter Na intake. Intravenous captopril reduced Na intake (to 11.0 +/- 2.1 liter, P less than 0.001) and concurrent intravenous angiotensin II prevented the reduction but concurrent intracerebroventricular angiotensin II did not. Intracerebroventricular captopril did not alter Na or water intake. Intravenous captopril reduced to zero the water intake during the hour before Na access, and concurrent intravenous angiotensin II prevented that reduction also. The dipsogenic action of intracerebroventricular angiotensin II was potentiated by intravenous captopril. The results of these experiments suggest that if angiotensin II receptors involved in the mechanism regulating Na appetite are in the brain, they are accessible only from the blood, e.g., in circumventricular organs. Thirst was inhibited by reduction of angiotensin II in blood but was stimulated only by angiotensin II acting inside the blood-brain barrier.


Long-term mortality and trajectory of potassium measurements following an episode of acute severe hyperkalaemia.
Hyperkalaemia is a common condition in patients with comorbidities such as chronic kidney disease (CKD) or congestive heart failure (HF). Moreover, severe hyperkalaemia is a potentially life-threatening condition that is associated with a higher risk of adverse clinical events such as ventricular arrhythmias and sudden cardiac death. Currently, data regarding the prognostic implications of chronic hyperkalaemia are available; however, information about the long-term clinical consequences after an episode of severe hyperkalaemia remains scarce. The objective of this study was to evaluate the association between the trajectory of potassium measurements in patients with acute hyperkalaemia and long-term all-cause mortality. This is a retrospective observational study that included patients with acute severe hyperkalaemia [potassium (K) >6 mEq/L] without haemolysis in the emergency room of Dr Peset University Hospital in Valencia, Spain searching the lab database from January 2016 to March 2017. The multivariable-adjusted association of serum potassium with mortality was assessed by using comprehensive state-of-the-art regression methods that can accommodate time-dependent exposure modelling. We found 172 episodes of acute hyperkalaemia in 160 patients in the emergency room. The mean ± standard deviation age of the sample was 77 ± 12 years and 60.5% were males. The most frequent comorbidities were CKD (71.2%), HF (35%) and diabetes mellitus (56.9%). Only 11.9% of the patients were on chronic dialysis. A quarter of the patients did not have previous CKD, making hyperkalaemia an unpredictable life-threatening complication. During the acute episode, mean potassium and estimated glomerular filtration rate (eGFR) were 6.6 ± 0.6 (range 6.1-9.2) mEq/L and 23 ± 16 (range 2-84) mL/min/1.73 m2, respectively. After a median (interquartile range) follow-up of 17.3 (2.2-23.7) months, 68 patients died (42.5%). Recurrences of hyperkalaemia (K >5.5 mEq/L) were detected in 39.5% of the patients who were monitored during follow-up. We found that previous potassium levels during an acute severe hyperkalaemia episode were not predictors of mortality. Conversely, the post-discharge longitudinal trajectories of potassium were able to predict all-cause mortality (overall P = 0.0015). The effect of transitioning from hyperkalaemia to normokalaemia (K >5.5 mEq/L to K ≤5.5 mEq/L) after the acute episode was significant, and inversely associated with the risk of mortality. Potassium levels prior to a severe hyperkalaemic event do not predict mortality. Conversely, following an episode of acute severe hyperkalaemia, serial kinetics of potassium trajectories predict the risk of death. Further evidence is needed to confirm these findings and clarify the optimal long-term management of these patients.


[BCG ostitis in children: the epidemiological parameters of some regions of the Russian Federation].
The incidence of BCG ostitis was studied by the data of questionnaires sent from 36 areas of the Russian Federation (RF). Particular emphasis is laid on 15 northwestern RF regions where an indepth study dealing with the 2000-2004 detection rates of postvaccination osseous complications was conducted. The mean incidence rate was 6.62 per 100,000 vaccinated persons with great data differences between the regions. The reasons for the detected differences and the perspectives of further studies of the epidemiological indices of the incidence of postvaccination osseous complications are analyzed.