Adding a Physical Therapist to the Health Care Team in an HIV Clinic Increases Physical Therapy Referrals and Reduces Opioid Prescriptions Provided for Chronic Musculoskeletal Pain in Patients Living With HIV.
Musculoskeletal (MSK) pain is common in people living with HIV (PLWH). Health care providers sometimes prescribe opioids to control pain, which may lead to opioid misuse. An interdisciplinary approach that includes physical therapy has been successful in managing MSK pain in various health care settings. Therefore, we sought to find the impact of recruiting a physical therapist (PT) on the number of opioid prescriptions and physical therapy referrals made by physicians in training to manage MSK pain in PLWH. We performed a retrospective chart review of patients seen by Internal Medicine physicians in training in an HIV clinic in Detroit before (2017) and after (2018) recruiting a PT to the health care team and collected demographic and clinical data. We also surveyed the trainees to assess how the PT addition influenced their learning. Institutional review board waiver was obtained. Results showed that of all PLWH seen at the clinic, 28/249 (11%) and 37/178 (21%) had chronic MSK pain in the 2017 and 2018 data sets, respectively. In 2017, all 28 patients with MSK pain were prescribed opioids. This decreased in 2018 after the PT addition (10/37 patients; P < .0001). The number of physical therapy referrals significantly increased after the PT addition (2017: 5/28 patients; 2018: 17/37 patients; P = .03). Trainees felt that the PT helped improve their examination skills and develop a treatment plan for patients. The addition of a PT encouraged physicians in training to utilize nonopioid management of MSK pain in PLWH and enhanced their learning experience, as perceived by the trainees.


Far-field auditory evoked potentials in near-miss sudden infant death syndrome.
Auditory evoked potentials (AEPs) were determined in 16 patients with near-miss sudden infant death syndrome. The AEPs were normal in all patients except one with prolonged 1 to V interpeak latency (bilaterally) and another with an asymmetry of interear 1 to V interpeak latency difference. These results indicate that AEPs do not permit detection of infants at high risk for crib death.


[Clinicopathologic and biological correlations (PSA-PAP) in pathology of the prostate. Apropos of 150 cases].
On the basis of 150 patients (16 controls with no disease of the prostate, 96 cases of benign prostatic hypertrophy (BPH) and 38 cases of carcinoma of the prostate (CP)), the authors intended to answer 3 questions: How can the borderline values of PSA in BPH be interpreted? Is there a correlation between the Gleason and PSA values in carcinomas? Should the simultaneous measurements of PSA and PAP be continued? All patients were examined with a rectal touch, transrectal echography (TRE) and PAS and PAP assays. All CP were examined with bone radionuclide scanning (BR). The correlation coefficient being 0.391 (p 0.001), the PSA value and prostatic weight can be regarded as linearly correlated in BPH (5 g BPH = 1 ng/ml PSA). This lower value of PSA is linked with the increase produced by TRE in the assessment of prostatic weight. On the other hand, the authors did no observe a correlation between the PSA and the Glisson grade in carcinomas with negative BR. Lastly, the sensitivity of PSA is noticeably higher than that of PAP (75% vs. 50%), and no false negative finding with PSA was corrected by PAP measurements.


Network formation and gelation in telechelic star polymers.
We investigate the efficiency of gelation and network formation in telechelic star polymer melt, where the tips of polymer arms are dipoles while the rest of the monomers are uncharged. Our work is motivated by the experimental observations [A. Kulkarni et al., Macromolecules 48, 6580 (2015)] in which rheological studies of telechelic star polymers of poly-(L-lactide), a bio-degradable polymer, showed a drastic increase in elastic properties (up to 2000 times) compared to corresponding star polymers without the telechelic arm ends. In contrast to previous studies, we avoid using effective attractive Lennard-Jones potentials or dipolar potentials to model telechelic interactions. Instead we use explicit Coulomb positive and negative charges at the tip of polymer-arms of our bead-spring model of star polymers. By our simulations we show that the dipoles at the tip of star arms aggregate together to form clusters of dipoles. Each cluster has contributions from several stars, and in turn each star contributes to several clusters. Thus the entire polymer melt forms a connected network. Network forming tendencies decrease with a decrease of the value of the effective charge constituting the dipole: this can be experimentally realized by choosing a different ionomer for the star tip. We systematically varied the value of dipole charges, the fraction of star-arms with dipoles at the tip, and the length of the arms. The choice of explicit charges in our calculations enables us to make better quantitative predictions about the onset of gelation; moreover we get qualitatively distinct results about structural organization of dipoles within a dipole-cluster.


Factors Associated With Oral Cancer Adverse Outcome at the Rwanda Military Hospital, a Retrospective Cross-Sectional Study.
Oral cancer (OC) is one of the most common cancers that remain global public health concerns in low- and middle-income countries. The epidemiology of OC in Africa endures uncertain. Earlier reports suggested a relatively low incidence of OC among Africans. Acting on behavioral factors and setting early diagnosis and treatments of OC can tremendously reduce morbidity and mortality related to it. This study determined factors associated with the OC adverse outcome and death in the Rwanda Military Hospital. A cross-sectional study was conducted among 311 medical records of patients who consulted in the Oral and Maxilla Facial Department between January 1, 2007 and December 31, 2019. Associated factors were estimated by use of odds ratios (OR) with their 95% confidence intervals (CI) in bivariate and multivariate logistic regression analyses to estimate predictors of an OC adverse outcome and death. Almost three quarters of the participants were from rural areas (n = 229, 73.6%) and alcohol users (n = 247, 79.1%). Concerning primary site infection, 54.02% of the participants had the intra-oral cavity within the past 5 years. Muslims had greater odds to experience an OC adverse outcome and death [aOR = 6.7; 95% CI (3.8-11.9), p < 0.001] than the Catholics. Those with no formal education significantly had greater likelihoods to have an OC adverse outcome and death [aOR = 2.6; 95% CI (1.3-5.3), p = 0.005] than those with higher education or university. Those with primary education had greater likelihoods [aOR = 1.8; 95% CI (1.1-3.1), p = 0.03] to have an OC adverse outcome than those with higher or university education. Those with oral hygiene had less risk to have an OC adverse outcome and death [aOR = 0.2; 95% CI (0.0-0.9), p = 0.039] than their counterparts. Using multi-sectorial approaches, including policy makers, clinicians, and researchers from public and private institutions, may be of an added value to promote clinical research on OC for earning knowledge, contributing to combat risk behaviors and improve the population's information and education on OC prevention.


[A case of hepatocellular carcinoma implantation to chest wall by percutaneous ethanol injection therapy].
A 62-year-old male patient with hepatocellular carcinoma (HCC) received percutaneous ethanol injection therapy (PEIT) four times following fine needle biopsy (FNB). Six months later, he underwent partial hepatic resection because of the insufficient anti-cancer effect of PEIT. One year and five months after PEIT, a subcutaneous tumor, which appeared to be a needle tract seeding by PEIT, was recognized in the 9th intercostal space of the right chest wall. A curative resection of the partial chest wall, including IXth and Xth ribs, was carried out with reconstruction using dexon mesh five months later. The tumor was 3.5 cm in size, and the histology was moderately-differentiated HCC. PEIT is a useful treatment for small HCCs. When PEIT is carried out, due care should be taken for neoplastic needle-tract seedings as one of the possible complications.


Acute rheumatic fever in north Florida.
Because of the declining incidence and severity of acute rheumatic fever reported in the United States and Europe, we reviewed our clinical experiences with 128 cases of acute rheumatic fever. No decline in the rate of admissions for patients with rheumatic fever was found in our hospital. The most common major manifestation of rheumatic fever in our patients was carditis, followed by arthritis. Chorea, erythema marginatum, and subcutaneous nodules were rare. Carditis was severe in 26% of the patients, moderate in 27%, and mild in 47%. A high percentage of our patients had residual cardiac lesions, and the mortality was higher than what has been reported in the rest of the country. We conclude that primary prevention of rheumatic fever in areas like ours should be continued.


Fatal meningitis by Cryptococcus laurentii in a post-partum woman: A manifestation of immune reconstitution inflammatory syndrome.
Cryptococcal meningitis in immunocompetent post-partum women has been rarely reported. Immune restoration during post-partum period leads to unmasking of many opportunistic infections that may have been acquired during pregnancy but manifest itself in the post-partum period due to immune reconstitution inflammatory syndrome. This case highlights the importance of considering opportunistic pathogens in immunocompetent patients who may be undergoing immune restoration. We report here a fatal case of post-partum immunocompetent women who presented with clinical features of meningitis. Prognosis of the cryptococcal meningitis not only depends on the immune status of the patient but also on how early the disease is diagnosed in the course of illness.


[Cutaneous cicatrizing agents].
Cutaneous healing is an important field of dermatology for it concerns superficial wound, as well as little surgery action, leg ulcer, eschar or burn. In spite of the claiming of their healing properties and their profusion, only a few have been tested and have proved their efficiency. Use precautions must be complied with paying the highest attention among others to the condition of the wound before product applying, the sensitization risk and the systemic risk particularly for young child. After topics, colloids appeared about ten years ago. New technics in development are reflecting, the research perseverance in dermatology.


Ionogel-Based Membranes for Safe Lithium/Sodium Batteries.
Alkali (lithium, sodium)-based second batteries are considered one of the brightest candidates for energy-storage applications in order to utilize the random and intermittent renewable energy to achieve carbon neutrality. Conventional lithium/sodium batteries containing liquid organic electrolytes are vulnerable to electrolytes leakage and even combustion, which hinders their large-scale and reliable application. All-solid-state electrolytes which are considered to have better safety have been developed in recent years. However, most of them suffer from low ionic conductivity and large interfacial resistance with the electrode. Ionogel-electrolyte membranes composed of ionic liquids and solid matrices, have attracted much attention because of their nonvolatility, nonflammability, and superior chemical and electrochemical properties. This review focuses on the most recent advances of ionogel electrolytes that sprang up with the emerging demand and progress of safe lithium/sodium batteries. The ionogel-electrolyte membranes are discussed based on the framework components and preparation methods. Their structure and properties, including ionic conductivity, mechanical strength, electrochemical stabilities, and so on, are demonstrated in combination with their applications. The current challenges and insights on the future development of ionogel electrolytes for advanced safe lithium/sodium batteries are also proposed.


[Effect of superparamagnetic iron oxide on differentiation of rat bone marrow stem cells into chondrocytes in vitro].
To observe the effect of superparamagnetic iron oxide (SPIO) on the differentiation of rat bone marrow stem cells (BMSCs) into chondrocytes in vitro and explore the possible mechanism. CCK8 assay was performed to examine the cytotoxicity of SPIO (1 and 5 µg/mL) on cultured SD rat BMSCs. Prussian blue staining and fluorescence excitation assay were used to assess the binding of the SPIO to BMSCs after the cells had been cultured in chondrocytes-induced medium in the presence of SPIO (1 and 5 µg/mL) for 9 days. The mRNA levels of COL2 α2, aggrecan and MMP13 in the cell culture were examined using Q-PCR, and the chondrogenic differentiation of the BMSCs was analyzed using alcian blue staining and immunofluorescence staining for COL2 α2. The protein levels of COL2 α2, aggrecan, MMP13, Ihh and PTHrP in the cells were examined using Western blotting. CCK8 assay showed no significant toxicity of SPIO on BMSCs. Compared with the control cells, the cells cultured in the presence of SPIO showed increased expressions of COL2 α2 and aggrecan and decreased expression of MMP13 at both mRNA and protein levels with also significantly increased expressions of Ihh and PTHrP proteins. SPIO can promote the differentiation of rat BMSCs into chondrocytes and up-regulate the Ihh/PTHrP signal pathway, suggesting the potential of SPIO as a new therapeutic agent for chondrocyte-related diseases.


Suprarenal vena caval occlusion. Principles of operative management.
Retrohepatic occlusion of the inferior vena cava caused by tumor complicates complete resection and not infrequently is associated with life-threatening symptoms that accelerate the lethality of the underlying malignant process. This report summarizes our experience with caval thrombectomy and reconstruction that allowed complete removal of all gross tumor in seven patients with malignant occlusion of the retrohepatic inferior vena cava. Included in this group are five patients with renal cell carcinoma and extension of tumor into the retrohepatic vena cava. Three of these patients had extension of tumor thrombus into the right atrium. A sixth patient had recurrent right adrenal cortical carcinoma with tumor invasion of the vena cava and occlusion to the right atrium. Associated hepatic vein occlusion and secondary Budd-Chiari syndrome also was successfully managed in this patient. The final patient with occlusion of the entire suprarenal vena cava required caval reconstruction after resection of a primary leiomyosarcoma of the retrohepatic portion of the vena cava. Careful planning of the operative procedure, adequate exposure, complete mobilization of the retrohepatic vena cava, and control of the hepatic venous effluent will allow patients with retrohepatic vena caval occlusions to be managed with safety and success.


[Rehabilitation for Pain Relief: Preface and Comments].
Chronic intractable pain is difficult to manage as the mechanisms of chronic pain are complicated. Recently rehabilitation is used in patients with chronic pain not responding to NSAIDs, non-opioids, anti-depressants and so on. Rehabilitation includes acute, recovery and maintained modes of rehabilitation. This review is focused on the concept of rehabilitation, rehabilitation therapy, rehabilitation during recovery period, nerve rehabilitation, music-trampoline therapy and so on.


1-Methyl-1,2,3,4-tetrahydroisoquinoline enhances the anticonvulsant action of carbamazepine and valproate in the mouse maximal electroshock seizure model.
1-Methyl-1,2,3,4-tetrahydroisoquinoline (1-MeTHIQ - an endogenous parkinsonism-preventing substance) administered intraperitoneally at a dose of 20 mg/kg considerably elevated the threshold for electroconvulsions in mice from 6.4 to 8.4 mA (P < 0.05). In contrast, the agent administered at 5 and 10 mg/kg had no significant impact on the electroconvulsive threshold in mice. Moreover, 1-MeTHIQ (at a subthreshold dose of 10 mg/kg) potentiated the anticonvulsant action of valproate (VPA) against maximal electroshock (MES)-induced seizures in mice, reducing its median effective dose (ED50) from 232 to 170 mg/kg (P < 0.001). Similarly, 1-MeTHIQ (at 10 mg/kg) enhanced the antielectroshock activity of carbamazepine (CBZ) in mice, decreasing its ED50 from 10.8 to 7.8 mg/kg (P < 0.05). In contrast, 1-MeTHIQ (at 10 mg/kg) did not affect the anticonvulsant action of phenytoin and phenobarbital against MES-induced seizures in mice. The evaluation of acute neurotoxic effects of the studied antiepileptic drugs (AEDs) in combination with 1-MeTHIQ, as regards motor coordination impairment in the chimney test, revealed no significant changes in median toxic doses (TD50) of conventional AEDs after systemic administration of 1-MeTHIQ (up to 10 mg/kg). Pharmacokinetic characterization of interactions between 1-MeTHIQ (10 mg/kg) and VPA (170 mg/kg) or CBZ (7.8 mg/kg) revealed no significant changes in total brain concentrations of CBZ and VPA, indicating that the observed enhancement of antiseizure effects of CBZ and VPA by 1-MeTHIQ was pharmacodynamic in nature. Based on our preclinical study, it may be concluded that 1-MeTHIQ exerts the anticonvulsant effects increasing the threshold for electroconvulsions and potentiating the antiseizure action of CBZ and VPA against maximal electroshock. The antiseizure properties of 1-MeTHIQ (an endogenous parkinsonism-preventing substance) and its exact physiological role in the brain need extensive examination in further neuropharmacological studies.


Diabetes resistance/susceptibility in T cells of nonobese diabetic mice conferred by MHC and MHC-linked genes.
Polymorphism of MHC and MHC-linked genes is tightly associated with susceptibility to type 1 diabetes (T1D) in human and animal models. Despite the extensive studies, however, the role of MHC and MHC-linked genes expressed by T cells on T1D susceptibility remains unclear. Because T cells develop from TCR(-) thymic precursor (pre-T) cells that undergo MHC restriction mediated by thymic stroma cells, we reconstituted the T cell compartment of NOD.scid-RIP-B7.1 mice using pre-T cells isolated from NOD, NOR, AKR, and C57BL/6 (B6) mice. T1D developed rapidly in the mice reconstituted with pre-T cells derived from NOD or NOR donors. In contrast, most of the NOD.scid-RIP-B7.1 mice reconstituted with pre-T cells from AKR or B6 donors were free of T1D. Further analysis revealed that genes within MHC locus of AKR or B6 origin reduced incidence of T1D in the reconstituted NOD.scid-RIP-B7.1 mice. The expression of MHC class I genes of k, but not b haplotype, in T cells conferred T1D resistance. Replacement of an interval near the distal end of the D region in T cells of B6 origin with an identical allele of 129.S6 origin resulted in T1D development in the reconstituted mice. These results provide evidence that the expression of MHC class I and MHC-linked genes in T cells of NOD mice indeed contributes to T1D susceptibility, while expression of specific resistance alleles of MHC or MHC-linked genes in T cells alone would effectively reduce or even prevent T1D.


Thrombomodulin Binding Selects the Catalytically Active Form of Thrombin.
Human α-thrombin is a serine protease with dual functions. Thrombin acts as a procoagulant, cleaving fibrinogen to make the fibrin clot, but when bound to thrombomodulin (TM), it acts as an anticoagulant, cleaving protein C. A minimal TM fragment consisting of the fourth, fifth, and most of the sixth EGF-like domain (TM456m) that has been prepared has much improved solubility, thrombin binding capacity, and anticoagulant activity versus those of previous TM456 constructs. In this work, we compare backbone amide exchange of human α-thrombin in three states: apo, D-Phe-Pro-Arg-chloromethylketone (PPACK)-bound, and TM456m-bound. Beyond causing a decreased level of amide exchange at their binding sites, TM and PPACK both cause a decreased level of amide exchange in other regions including the γ-loop and the adjacent N-terminus of the heavy chain. The decreased level of amide exchange in the N-terminus of the heavy chain is consistent with the historic model of activation of serine proteases, which involves insertion of this region into the β-barrel promoting the correct conformation of the catalytic residues. Contrary to crystal structures of thrombin, hydrogen-deuterium exchange mass spectrometry results suggest that the conformation of apo-thrombin does not yet have the N-terminus of the heavy chain properly inserted for optimal catalytic activity, and that binding of TM allosterically promotes the catalytically active conformation.


Top-Down Fabricated microPlates for Prolonged, Intra-articular Matrix Metalloproteinase 13 siRNA Nanocarrier Delivery to Reduce Post-traumatic Osteoarthritis.
Post-traumatic osteoarthritis (PTOA) associated with joint injury triggers a degenerative cycle of matrix destruction and inflammatory signaling, leading to pain and loss of function. Here, prolonged RNA interference (RNAi) of matrix metalloproteinase 13 (MMP13) is tested as a PTOA disease modifying therapy. MMP13 is upregulated in PTOA and degrades the key cartilage structural protein type II collagen. Short interfering RNA (siRNA) loaded nanoparticles (siNPs) were encapsulated in shape-defined poly(lactic-co-glycolic acid) (PLGA) based microPlates (μPLs) to formulate siNP-μPLs that maintained siNPs in the joint significantly longer than delivery of free siNPs. Treatment with siNP-μPLs against MMP13 (siMMP13-μPLs) in a mechanical load-induced mouse model of PTOA maintained potent (65-75%) MMP13 gene expression knockdown and reduced MMP13 protein production in joint tissues throughout a 28-day study. MMP13 silencing reduced PTOA articular cartilage degradation/fibrillation, meniscal deterioration, synovial hyperplasia, osteophytes, and pro-inflammatory gene expression, supporting the therapeutic potential of long-lasting siMMP13-μPL therapy for PTOA.


Cryogenics and its application with reference to spice grinding: a review.
Cryogenics is the study of very low temperature and its application on different materials including biological products. Cryogenics has numerous applications in space science, electronics, automobiles, the manufacturing industry, sports and musical instruments, biological science and agriculture, etc. Cryogenic freezing finds pivotal application in food, that is, spices and condiments. Although there is a wide range of cryogens to produce the desired low temperature, generally liquid nitrogen (LN₂) is used in food grinding. The application of low temperature shows a promising pathway to produce higher quality end product with higher flavor and volatile oil retention. Cryogenic grinders generally consist of precoolers and grinder with the cryogen distribution system. In such grinding systems, cryogens subject the raw material up to or lower than glass transition temperature before it is ground, thus eliminating much of the material and quality hassles of traditional grinding. At present, the capital investment including cryogen and handling costs escalate the final cost of the product. Thus, for large-scale production, a proper design to optimize and make it feasible is the need of the hour and understanding the behavior of different food materials at these low temperature conditions. This article reviews the scenario and application of cryogenics in different sectors, especially to spice grinding.


Hot-water treatments for control of Planococcus ficus (Homoptera: Pseudococcidae) on dormant grape cuttings.
Hot-water immersions were tested for control of mealybug Planococcus ficus (Signoret), on dormant grape cuttings used for nursery stock. A range of hot-water temperatures (47-58 degrees C) were evaluated at immersion periods of 2, 5, 10, or 20 min, by using a total of 353,720 mealybugs across all treatments. A 5-min immersion at 51 degrees C is effective in killing > 99% of P. ficus. At or above this immersion period and temperature, there was no difference in mealybug stage mortality. We evaluated a commercial operation, which used a 5-min immersion in each of three water tanks: preheating (30.0 +/- 3 degrees C), hot-water (52.8 +/- 0.3 degrees C), and cooling (23 +/- 3 degrees C). The commercial procedure provided 99.8-100% mealybug control in each of three separate trials.


A model of caring mentorship for nursing.
Mentoring is a multidimensional relationship that energizes personal and professional growth. This article explores the concept of mentoring in nursing and presents a mentorship model based on a caring philosophy. The RN-student nurse mentoring program cited is the result of a collaborative commitment between a community hospital and two colleges. Discussed are the experience, process, insights, and impact of the program as a retention and professional development tool.


Lower genital tract infections in preterm premature rupture of membranes and preterm labor: a case-control study from Vietnam.
This study aimed to determine the incidence of lower genital infections and related factors in preterm premature rupture of membranes (PPROM) and preterm labor. A case-control study was conducted on pregnant women who were admitted to the Hospital of Hue University of Medicine and Pharmacy, Vietnam between November 2017 and May 2019. Cases from 22 to 36 gestational weeks were included as group 1 (patients with preterm labor and intact membranes) or as group 2 (those with PPROM). The control group included women with singleton pregnancies who were matched on gestational age and recruited concurrently with the study cases. Gram stain was perfomed to identify Lactobacillus, Gardnerella, mobiluncus, Candida, and leucocytes. Trichomonas vaginalis was detected by wet mount. Cultures of vaginal secretions and aminotic fluid were performed to identify aerobic bacteria. Bacterial vaginosis was higher in group 1 (28.9%) compared to control (11.4%). The incidence of isolated aerobic bacteria was 44.1% in group 2, 11.1% in group 1, and 12.7% in the control group (p < 0.001). Fungal infection was not shown to be a risk factor for preterm labor (p = 0.990), whereas, bacterial vaginosis was (OR = 3.16; 95%CI = 1.23-8.15; p = 0.016). Isolated aerobic bacteria were associated with premature rupture of membranes (OR = 5.45; 95%CI = 2.11-14.05; p < 0.001). Bacteria vaginosis increased the risk of preterm labor and preterm premature rupture of membranes. Isolated aerobic bacteria were related to PPROM, while fungal infection was not associated with preterm labor.


The evolution of young people's mental health during COVID-19 and the role of food insecurity: Evidence from a four low-and-middle-income-country cohort study.
Provide evidence on how young people's mental health has evolved in Low-and-Middle-Income-Countries (LMICs) during the progression of the COVID-19 pandemic. Identify particularly vulnerable groups who report high and/or continuously high rates of mental health issues. Longitudinal, observational. Two consecutive phone-surveys (August-October and November-December 2020) in Ethiopia, India, Peru and Vietnam interviewed around 9000 participants of a 20-year cohort study who grew up in poverty, now aged 19 and 26. Rates of at least mild anxiety/depression measured by GAD-7/PHQ-8 were each compared across countries; between males/females, and food secure/food insecure households. Overall, rates of at least mild anxiety and mild depression significantly decreased between mid and end-2020 in all countries but Ethiopia as COVID-19 infection rates fell. Females report higher rates of anxiety and depression in all countries but Ethiopia, however the gender gap is closing. Young people in food insecure households have not shown consistent improvements in their rates of anxiety and depression. Food insecure households are poorer, and have significantly more children (p < 0.05) except in Ethiopia. Food insecurity is negatively associated with young people's mental health and urgent support targeted towards the most vulnerable should be a priority. Further research into increasing rates of mental health issues in Ethiopia is needed.


Trigeminal-mediated headshaking in horses: prevalence, impact, and management strategies.
Trigeminal-mediated headshaking is a little-understood neuropathic facial pain condition of the horse. The condition may affect around 1% of the equine population to a degree of severity sufficient to require veterinary attention. As a pain condition, this represents a significant welfare issue. Horses are usually more severely affected at exercise which can leave them unable to perform, or even dangerous to ride and handle. With little known about the condition and variable response to treatments, severely affected horses are often euthanized. This review article considers the literature on trigeminal-mediated headshaking, focusing on what is known, and indeed not known, about the prevalence of the condition and its impact. The current published management options are considered, along with their challenges and limitations.


CD147 confers temozolomide resistance of glioma cells via the regulation of β-TrCP/Nrf2 pathway.
Background: Drug resistance is one of the biggest challenges in cancer therapy. temozolomide (TMZ) represents the most important chemotherapeutic option for glioma treatment. However, the therapeutic efficacy of TMZ remains very limited due to its frequent resistance in glioma, and the underlying mechanisms were not fully addressed. Herein, we demonstrate that the elevated expression of CD147 contributes to TMZ resistance in glioma cells, potentially through the post-translational regulation of Nrf2 expression. Methods: Cell-based assays of CD147 triggered drug resistance were performed through Edu-incorporation assay, CCK8 assay, TUNEL staining assay and flow cytometric assay. Luciferase reporter assay, protein stability related assays, co-immunoprecipitation assay were used to determine CD147 induction of Nrf2 expression through β-TrCP dependent ubiquitin system. Finally, the effect of the CD147/Nrf2 signaling on glioma progression and TMZ resistance were evaluated by functional experiments and clinical samples. Results: Based on the analysis of clinical glioma tissues, CD147 is highly expressed in glioma tissues and positively associated with tumor malignancy. Suppression of CD147 expression increased the inhibitory effect of TMZ on cell survival in both U251 and T98G cells, whereas the gain of CD147 function blocked TMZ-induced ROS production and cell death. Mechanistic study indicates that CD147 inhibited GSK3β/β-TrCP-dependent Nrf2 degradation by promoting Akt activation, and subsequently increased Nrf2-mediated anti-oxidant gene expressions. Supporting the biological significance, the reciprocal relationship between CD147 and Nrf2 was observed in glioma tissues, and associated with patient outcome. Conclusions: Our data provide the first evidence that glioma resistance to TMZ is potentially due to the activation of CD147/Nrf2 axis. CD147 promotes Nrf2 stability through the suppression of GSK3β/β-TrCP dependent Nrf2 protein degradation, which results in the ablation of TMZ induced ROS production. As such, we point out that targeting CD147/Nrf2 axis may provide a new strategy for the treatment of TMZ resistant gliomas.


Flow distribution in closed networks: minimal sets of measuring sites.
In microvascular research it is of great importance to know how the flow of blood is distributed to all the vessels in a capillary network. However, it is generally impossible to obtain simultaneous measurements of the flow values in all branches of a network. A method of selecting minimal subsets of branches is presented, by which the flow measurements in these branches can be used to compute the flow values in all other branches. It is sufficient to measure between half and one-third of the branch flows. The experimenter can also specify a subset of the branches as inaccessible to measurement; nevertheless the method allows him to decide whether determination of all flows is possible from the remaining branches, and in which branches the measuring devices should then be optimally placed.


The TEFRA medicaid eligibility option for children with severe disabilities: a national study.
The Tax Equity and Fiscal Responsibility Act (TEFRA) Medicaid Eligibility Option, also known as the Katie Beckett Option, was developed to allow children with disabilities from near-poor and middle-income families to qualify for Medicaid. TEFRA has been available since 1982; however, little is known about the number of children served and their qualifying disability. This first national study found that 20 states enrolled nearly 25,000 children in 2001. Only 10 of these states allowed children to qualify because of a mental health disability. Additional research is needed to understand the role of TEFRA in providing insurance to children with disabilities.


Ergonomic Risk Factors for Low Back Pain among Three-Wheel Drivers in Ethiopia: A Community-Based Cross-Sectional Study.
Driving a three-wheel car is an emerging job opportunity in most parts of developing countries. Drivers are at risk for developing low back pain (LBP). However, very little is known about the association between ergonomics factors and LBP among three-wheel drivers. This study was aimed to identify ergonomic risk factors of LBP among three-wheel drivers. A community-based cross-sectional study on 396 participants was conducted in the Jimma city on all selected public three-wheel drivers in March, 2020. The data were collected using a standard questionnaire adapted from the Nordic Musculoskeletal questionnaire, anthropometric measurements, and observation checklist. The collected data were entered into Epi Data and exported to SPSS version 21.0. Logistic regression analysis was used for analysis based on the p value less than 0.05, 95% C.I. Results. Among 422 planned respondents, 396 (93.8%) have given the complete response. The mean age of the study population was 27.94 (±5.45). One hundred four (26.26%) out of 396 participants had experienced low back pain in the last 12 months. Driving in sitting upright position OR = 0.32 (95% CI = 0.12-0.86), steer wheel handling OR = 3.02 (95% CI = 1.58-5.77), not holding extra passengers OR = 0.35 (95% CI = 0.21, 0.60), rest breaks, and brand of the three-wheel vehicles were significantly associated with LBP. Nearly more than one-fourth of three-wheel drivers in our study had LBP. The finding implies a significant number of three-wheel drivers are at risk of developing reduced well-being. An appropriate health visit, lifestyle modification, and adequate policy should be established in the study area.


High density linkage disequilibrium mapping using models of haplotype block variation.
The presence of millions of single nucleotide polymorphisms (SNPs) in the human genome has spurred interest in genetic mapping methods based on linkage disequilibrium. The recently discovered haplotype block structure of human variation promises to improve the effectiveness of these methods. A key difficulty for mapping techniques is the cost involved in separately identifying the haplotypes on each of an individual's chromosomes. We present a new approach for performing linkage disequilibrium mapping using high density haplotype or genotype data. Our method is based on a statistical model of haplotype block variation, which takes account of recombination hotspots, bottlenecks, genetic drift and mutation. We test our technique on two empirically determined high density datasets, attempting to recover the location of an SNP which was hidden and converted into phenotype information. We compare the results against a mapping method based on individual SNPs as well as a competing haplotype-based approach. We show that our strategy significantly outperforms these other approaches when used as a guide for resequencing and that it can also deal with both unphased genotype data and low penetrance diseases. HaploBlock executables for Linux, Mac OS X and Sun OS, as well as user documentation, are available online at http://bioinfo.cs.technion.ac.il/haploblock/


A porphyrin fused to four anthracenes.
We have synthesized a fused tetraanthracenylporphyrin by oxidation of a meso-anthracenyl nickel(II) porphyrin with FeCl(3). This compound exhibits an intense red-shifted absorption spectrum (λ(max) = 1417 nm; ε = 1.2 × 10(5) M(-1) cm(-1)) and a small electrochemical HOMO-LUMO gap (0.61 eV). The crystal structure shows that it forms π-stacked dimers with a short Ni···Ni distance (3.32 Å).


Fragile X-linked mental retardation and the difficulties of reverse genetics.
Fragile X-linked mental retardation is an enigmatic inheritable syndrome in which severe mental retardation, a cytogenetically detectable fragile site at Xq27.3 (FraX) and a number of dysmorphic features are associated. Genetic analysis shows that the mode of inheritance is more complex than a straightforward X-linked recessive trait and probably involves a two-step process for which several models have been proposed. Early attempts at 'cloning the fragile site' provided several DNA segments lying in its general vicinity, and large scale DNA mapping methods were extensively applied in an effort to generate maps including this region. These efforts were complemented by more focussed methods such as microdissection; together these approaches have now provided a number of DNA segments within a 5 cM interval around FraX, and with the help of these new probes the site is indeed being cloned. Unravelling the nature of the sequence(s) responsible for the mental retardation syndrome will probably take some time, however.


EmojiNet: Building a Machine Readable Sense Inventory for Emoji.
Emoji are a contemporary and extremely popular way to enhance electronic communication. Without rigid semantics attached to them, emoji symbols take on different meanings based on the context of a message. Thus, like the word sense disambiguation task in natural language processing, machines also need to disambiguate the meaning or 'sense' of an emoji. In a first step toward achieving this goal, this paper presents EmojiNet, the first machine readable sense inventory for emoji. EmojiNet is a resource enabling systems to link emoji with their context-specific meaning. It is automatically constructed by integrating multiple emoji resources with BabelNet, which is the most comprehensive multilingual sense inventory available to date. The paper discusses its construction, evaluates the automatic resource creation process, and presents a use case where EmojiNet disambiguates emoji usage in tweets. EmojiNet is available online for use at http://emojinet.knoesis.org.


[Ovarian pregnancy: a case report].
We here report a case of left ovarian pregnancy passively detected in the General Reference Hospital outpatient clinic in Dilolo, Democratic Republic of Congo. The diagnosis was confirmed by ultrasound; the patient underwent surgery with uneventful postoperative course. Pregnant women and healthcare personnel should be aware of the importance of proper clinical and echographic monitoring in pregnancy for early diagnosis of abnormal implantations.


Myricitrin Alleviates Oxidative Stress-induced Inflammation and Apoptosis and Protects Mice against Diabetic Cardiomyopathy.
Diabetic cardiomyopathy (DCM) has been increasingly considered as a main cause of heart failure and death in diabetic patients. At present, no effective treatment exists to prevent its development. In the present study, we describe the potential protective effects and mechanisms of myricitrin (Myr) on the cardiac function of streptozotosin-induced diabetic mice and on advanced glycation end products (AGEs)-induced H9c2 cardiomyocytes. In vitro experiments revealed that pretreatment with Myr significantly decreased AGEs-induced inflammatory cytokine expression, limited an increase in ROS levels, and reduced cell apoptosis, fibrosis, and hypertrophy in H9c2 cells. These effects are correlated with Nrf2 activation and NF-κB inhibition. In vivo investigation demonstrated that oral administration of Myr at 300 mg/kg/day for 8 weeks remarkably decreased the expression of enzymes associated with cardiomyopathy, as well as the expression of inflammatory cytokines and apoptotic proteins. Finally, Myr improved diastolic dysfunction and attenuated histological abnormalities. Mechanistically, Myr attenuated diabetes-induced Nrf2 inhibition via the regulation of Akt and ERK phosphorylation in the diabetic heart. Collectively, these results strongly indicate that Myr exerts cardioprotective effects against DCM through the blockage of inflammation, oxidative stress, and apoptosis. This suggests that Myr might be a potential therapeutic agent for the treatment of DCM.


Gastric acid responses to graded i.v. infusion of pentagastrin and histalog in peptic ulcer patients before and after antrum-bulb resection.
Gastric acid responses to graded i.v. infusion of pentagastrin and Histalog were determined in peptic ulcer patients. Single-day multiple-dose tests were performed. The sensitivity to the humoral stimuli as determined by the calculated ED50's was not significantly different for duodenal ulcer patients with moderate (DUmod) or massive (DUmass) observed hypersecretion or for gastric ulcer (GU) patients: median ED50's of pentagastrin were 6.2, 6.6, and 13.1 mug/h in 18 DUmod, 22 DUmass and 7 GU patients respectively, and median ED50's of Histalog were 16.6, 25.3, and 17.1 mg/h in 14 DUmod, 10 DUmass and 6 GU patients respectively. Antrum-bulb resection significantly reduced basal acid secretion and maximal acid responses to the humoral stimuli (about 45% reduction) but did not significantly change the loss of gastric contents to the intestine or the sensitivity to the humoral stimuli (median ED50 of pentagastrin increased from 5.2 to 6.7 mug/h in 14 patients, and median ED50 of Histalog increased from 16.0 to 20.8 mg/h in 12 patients), suggesting that the intact antrum-bulb region of the ulcer patient is controlling the capacity to secrete acid, and indicating that antrum-bulb gastrin is an important trophic factor for the parietal cells in man.


Mycobacterium tuberculosis nucleoside diphosphate kinase inactivates small GTPases leading to evasion of innate immunity.
Defining the mechanisms of Mycobacterium tuberculosis (Mtb) persistence in the host macrophage and identifying mycobacterial factors responsible for it are keys to better understand tuberculosis pathogenesis. The emerging picture from ongoing studies of macrophage deactivation by Mtb suggests that ingested bacilli secrete various virulence determinants that alter phagosome biogenesis, leading to arrest of Mtb vacuole interaction with late endosomes and lysosomes. While most studies focused on Mtb interference with various regulators of the endosomal compartment, little attention was paid to mechanisms by which Mtb neutralizes early macrophage responses such as the NADPH oxidase (NOX2) dependent oxidative burst. Here we applied an antisense strategy to knock down Mtb nucleoside diphosphate kinase (Ndk) and obtained a stable mutant (Mtb Ndk-AS) that displayed attenuated intracellular survival along with reduced persistence in the lungs of infected mice. At the molecular level, pull-down experiments showed that Ndk binds to and inactivates the small GTPase Rac1 in the macrophage. This resulted in the exclusion of the Rac1 binding partner p67(phox) from phagosomes containing Mtb or Ndk-coated latex beads. Exclusion of p67(phox) was associated with a defect of both NOX2 assembly and production of reactive oxygen species (ROS) in response to wild type Mtb. In contrast, Mtb Ndk-AS, which lost the capacity to disrupt Rac1-p67(phox) interaction, induced a strong ROS production. Given the established link between NOX2 activation and apoptosis, the proportion of Annexin V positive cells and levels of intracellular active caspase 3 were significantly higher in cells infected with Mtb Ndk-AS compared to wild type Mtb. Thus, knock down of Ndk converted Mtb into a pro-apoptotic mutant strain that has a phenotype of increased susceptibility to intracellular killing and reduced virulence in vivo. Taken together, our in vitro and in vivo data revealed that Ndk contributes significantly to Mtb virulence via attenuation of NADPH oxidase-mediated host innate immunity.


Embolization in the external carotid artery.
The technical skill set of peripheral interventional radiologists is well-suited to the performance of most transcatheter embolization procedures in the external carotid artery (ECA). These procedures center in large part on hypervascular tumors, epistaxis, and trauma. ECA embolization in the trauma patient is well-defined, albeit in small patient series. The transcatheter treatment of epistaxis is still mostly reserved for cases that are intractable to conservative therapy. Preoperative embolotherapy for vascular tumors remains popular, although it is somewhat controversial in terms of its risk-benefit ratio. The purpose of this review is to highlight pertinent anatomy, selected technical procedural aspects, and the available literature to better characterize the role of ECA embolization in the hands of the practicing peripheral interventionist.


Determination of spatial distributions of thickness and optical constants of thin films by a new optical technique.
A new optical technique for the determination of spatial distributions of the thickness and the optical constants of thin films is proposed. This technique is simple and nondestructive involving mainly an ellipsometer and a coherent light source, and no contact to the thin-film samples is required. A theoretical estimation indicates that this technique may provide a spatial resolution close to the diffraction-limited resolution under certain conditions. Possible applications of this technique are also discussed.


Correlation analysis of the rates of solvolysis of 4-bromopiperidine: a reaction following a Grob fragmentation pathway.
A Grunwald-Winstein treatment of the specific rates of solvolysis of 4-bromopiperidine gives for aqueous ethanol, methanol, acetone, and dioxane a very good logarithmic correlation against the YBr solvent ionizing power values with a slope (m value) of 0.46±0.02, consistent with the operation of a synchronous Grob fragmentation mechanism. When the organic component of the solvent is 2,2,2-trifluoroethanol (TFE), the data points show a negative deviation, consistent with an appreciable deactivating interaction of the acidic TFE component of the solvent with the lone-pair of electrons present on the nitrogen.


Influence of temperature and concentration of VectoBac on control of the salt-marsh mosquito, Ochlerotatus squamiger, in Monterey County, California.
Laboratory susceptibility bioassays were conducted to determine the efficacy of VectoBac TP (Bacillus thuringiensis var. israelensis [Bti]) at different concentrations and temperatures against the salt-marsh mosquito Ochlerotatus squamiger. Bioassays on late 3rd- and early 4th-stage larvae, read at 72 h and 14 degrees C produced an LD90 of 0.223 mg/liter, whereas more than double this dose was required to produce similar mortality at 6 degrees C. A field trial in the winter of 2001-02 of an aerially applied VectoBac TP formulation in Salinas, CA, corroborated laboratory bioassay observations by producing 97-100% control of Oc. squamiger at 72 h postapplication. Inconsistencies in mortality with field applications of VectoBac TP previously observed by North Salinas Valley Mosquito Abatement personnel were most likely caused by uneven application rates and varying temperatures and water volumes.


[Changes in the corpora cavernosa penis in patients with a traumatic lesion of the urethral canal].
Contrast investigations of corpus cavernosum penis (CCP) have been performed in 42 patients with urethral traumas. A hip-bone fracture and urethral injury were associated with CCP rupture in 76% of the cases. Sexual dysfunction was registered in all the patients, a complete erectile failure occurred in 57.2% of them. Indications to and an original technique of cavernosography are described. 32 patients developed venous blood CCP outflow 8 ones fibrous replacement of the cavernous tissue staged by x-ray examination as stage I and II. Static cavernosography is able to effectively determine changes in the cavernous tissue resultant from urethral trauma, disorders in the CCP venous outflow, a degree of morphological abnormalities in the cavernous tissue and, consequently, should become a mandatory examination for such patients, especially before endophalloplasty.


Educational Pathways and Change in Crime Between Adolescence and Early Adulthood.
This article examines the relationship between intergenerational educational pathways and change in crime. Moreover, it examines the potential mediating roles of family and employment transitions, economic stressors, and social psychological factors. Data from the National Longitudinal Study of Adolescent to Adult Health (N = 14,742) and negative binomial models are used to assess associations between educational pathways (i.e., upward, downward, and stable) and change in crime between adolescence and early adulthood. Selection effects are assessed with lagged dependent variables and controls for self-control, grades, and the Add Health Picture Vocabulary Test. Intergenerational educational pathways are significantly associated with changes in crime. Downward educational pathways were predictive of increases in crime, whereas upward pathways were associated with decreases in crime. These associations were partly mediated by family transitions, and more strongly by economic stressors. These results were robust to controls for selection related variables. This study is among the first to examine the relationship between intergenerational educational pathways and crime in the United States. Both upward and downward changes in educational attainments were found to be significant for crime. These findings are notable given the continuing expansion of higher education as well as concerns regarding increasing stratification and downward mobility in the United States.


Pretreatment with IFN-gamma decreases infectious complications after partial hepatectomy in the rat.
Infectious postoperative complications occur commonly after hepatectomy and may lead to a long hospital stay or death. The potential beneficial effects of interferon-gamma (IFN-gamma) in this setting were evaluated in a model of hepatectomy and sepsis in rodents. Incidence of bacterial translocation was measured in animals on days 1, 2, and 5 after partial hepatectomy. Macrophage function was quantified by in vitro tumoricidal activity and superoxide anion (O2-) production. Survival after partial hepatectomy and cecal ligation and puncture (CLP) was recorded. After partial hepatectomy, bacterial translocation was decreased on days 1 and 2 in animals pretreated with IFN-gamma (p < 0.05). Macrophages from animals treated with IFN-gamma had higher in vitro tumoricidal activity and production of O2- (p < 0.05). Hepatectomized animals pretreated with IFN-gamma had an increased survival after CLP (p < 0.05). IFN-gamma may be useful in decreasing the incidence of infectious complications after partial hepatectomy.


Erythrocyte protoporphyrin levels in Aotus trivirgatus.
High levels of the heme precursor, protoporphyrin, were found in a sample of 36 Aotus trivirgatus. The owl monkeys were of five different karyotypes and from three separate colonies. In many animals, a significant proportion of the protoporphyrin was not bound to zinc, as is normal, but existed as the free base protoporphyrin IX. The protoporphyrinemia may be related to major pathologies of captive Aotus.


Intermediate Product Regulation in Tandem Solid Catalysts with Multimodal Porosity for High-Yield Synthetic Fuel Production.
Tandem catalysis is an attractive strategy to intensify chemical technologies. However, simultaneous control over the individual and concerted catalyst performances poses a challenge. We demonstrate that enhanced pore transport within a Co/Al2 O3 Fischer-Tropsch (FT) catalyst with hierarchical porosity enables its tandem integration with a Pt/ZSM-5 zeolitic hydrotreating catalyst in a spatially distant fashion that allows for catalyst-specific temperature adjustment. Nevertheless, this system resembles the case of close active-site proximity by mitigating secondary reactions of primary FT α-olefin products. This approach enables the combination of in situ dewaxing with a minimum production of gaseous hydrocarbons (18 wt %) and an up to twofold higher (50 wt %) selectivity to middle distillates compared to tandem pairs based on benchmark mesoporous FT catalysts. An overall 80 % selectivity to liquid hydrocarbons from syngas is attained in one step, attesting to the potential of this strategy for increasing the carbon efficiency in intensified gas-to-liquid technologies.


Evidence for the involvement of PECAM-1 in a receptor mediated signal-transduction pathway regulating capacitation-associated tyrosine phosphorylation in human spermatozoa.
Mammalian spermatozoa must become ;capacitated' in the female reproductive tract before they gain the ability to fertilize the oocyte. The attainment of a capacitated state has been correlated with a number of biochemical changes, the most notable of which is a dramatic increase in the tyrosine phosphorylation status of these cells. Despite its biological importance, the mechanisms responsible for initiating this tyrosine phosphorylation cascade in vivo are unknown. Here, we report that this signalling pathway can be elicited in a rapid, dose-dependent and lectin-specific manner by wheat germ agglutinin (WGA), but none of 18 other lectins assessed. This response was abrogated by prior enzymatic cleavage of either sialic acid or GlcNAc residues from the sperm surface and by treatment with a range of pharmacological inhibitors directed against protein kinase A, protein tyrosine kinases and intermediates including Src. Proteomic analysis of the WGA-binding sites on the sperm surface identified the putative cognate receptor as platelet cell adhesion molecule 1 (PECAM-1/CD31). This conclusion was supported by the following evidence: (i) anti-PECAM-1 antibodies identified a molecule of the correct molecular mass in human spermatozoa, (ii) PECAM-1 could be isolated from a pool of sperm surface proteins using WGA immobilized on a solid phase support, (iii) PECAM-1 and WGA co-localized to the sperm surface and (iv) anti-PECAM-1 antibodies could completely block the ability of WGA to stimulate tyrosine phosphorylation in these cells. Collectively, these data provide the first evidence that a receptor-mediated signal transduction pathway triggers human sperm capacitation and identifies PECAM-1 as the probable initiator of this second messenger cascade.


Positive and negative syndromes in chronic schizophrenic inpatients.
This study considered whether chronic schizophrenics with positive and negative syndromes represent distinct subtypes. From a survey of 47 schizophrenic inpatients, 18 showed preponderance of productive or deficit features, and four were mixed. The discrete groups were compared on clinical symptoms, cognitive tests, demographic and historical data, and drug side effects. They were significantly distinguished on most criterion symptoms and affect scales but, otherwise, essentially comparable in psychopathology and extrapyramidal symptoms. The tests revealed similar levels of intellectual impairment and visual-motor deficit, yet the negative patients displayed more primitive cognitive mode and greater psychomotor retardation. They also proved older, less educated, more often born in winter-time, hospitalized later in life, and less heavily medicated. The results supported the validity of the positive-negative dimension for identifying schizophrenic subtypes and suggested etiological implications regarding developmental deficiency.


In vitro studies on the mechanism of action of a new antiallergic, Ro 21-7634.
The effects of Ro 21-7634 and disodium cromoglycate (cromoglycate) on the in vitro release of mediators of anaphylaxis from rat peritoneal cells and guinea pig lung tissue were compared. Ro 21-7634 was 25 fold more potent than cromoglycate as an inhibitor of antigen-induced histamine release from passively sensitized (IgE) rat peritoneal cells. Ro 21-7634 was also the more potent inhibitor of both compound 48/80- and concanavalin A-induced histamine release from rat peritoneal cells. The two drugs shared the common properties of producing the same maximal level of inhibition in each of the above releasing systems and exhibiting a time and concentration dependent loss of inhibitory activity when added to the cells prior to the releasing agent. Neither drug inhibited ionophore A23187-or ionophore X537A-induced histamine release from these cells. Ro 21-7634 inhibited antigen-induced (IgG1) histamine and SRS-A release from actively sensitized guinea pig lung fragments, whereas cromoglycate did not. The results indicate that Ro 21-7634 and cromoglycate act through a common mechanism to inhibit allergic mediator release and that Ro 21-7634 is the more potent inhibitor.


Experimental Determination of High-Order Bending Elastic Constants of Lipid Bilayers.
We present a method to describe the formation of small lipid vesicles in terms of three bending elastic constants that can be experimentally measured. Our method combines a general expression of the elastic free energy of the bilayer and the thermodynamic description of molecular aggregation. The resulting model requires the size distribution of liposomes, which is determined from the X-ray scattered intensity spectra of vesicular dispersions. By using two different preparation methods, we studied a series of vesicular solutions made of distinct lipids and we obtained their corresponding bending elastic constants that are consistent with known bending rigidities.


Accurate predictions of crystal densities using quantum mechanical molecular volumes.
A quantum mechanically based procedure for estimation of crystal densities of neutral and ionic crystals is presented. In this method, volumes within 0.001 electrons/bohr3 isosurfaces of electron density for the constituent isolated neutral and ionic molecules are calculated to define the molecular volume or formula unit volumes used in predicting the crystal density. The B3LYP density functional theory in conjunction with the 6-31G** basis set were employed to generate the electron densities. The suitability of this method of crystal density prediction was assessed by subjecting a large number (289) of molecular and ionic crystals to the procedure and comparing results with experimental information. The results indicate that, for neutral molecular crystals, the root-mean-square (rms) deviation from experiment is within 4%, whereas the rms deviation is somewhat larger for the 71 ionic crystals evaluated (within 5%).


[Chronic bronchitis. Development, prevention].
The adoption of an arbitrary epidemiological definition for chronic bronchitis has enabled some progress to be made in the understanding of the frequency and natural course of this disease. It is important to distinguish between chronic airflow obstruction and chronic hypersecretion of bronchial mucus. The prevalence of the disease can only be assessed in selective groups of the population and varies according to the characteristics of these groups, but is approximately 15% of men and 8% of women. There is relatively low mortality in France: 6/100,000 in 1985 and varies according to the departments, up to 38/100,000 inhabitants. These data ought to be interpreted with care and it is also important to take account of factors linked to their evolution. Longitudinal studies undertaken 20 years ago have allowed two hypotheses to be formulated to aid in a more precise understanding of the natural history of the disease: the first of these was the Dutch hypothesis which is currently undergoing a renewal of interest linked to epidemiological studies on HRB, and the English hypothesis which has the merit of emphasizing the principal risk factor in chronic bronchitis. Certain smokers are sensitive to tobacco, even though some others are not. Does the explanation of this lie in the relationship between obstructive ventilatory problems and bronchial hyper-reactivity? This association is discussed in the light of recent work as well as the relationship between bronchial hyperactivity, smoking and chronic bronchitis. Other risk factors have been studied: occupational hazards, air pollution and acute respiratory infections in childhood. But, in spite of all the work carried out to better define the risk factors and prognosis of the disease, this makes up a complex overall picture which is poorly understood and which should stimulate us to further research. The prevention of the disorder should be aimed at three levels; at the primary level (to prevent the appearance of the disorder) the only objective which may lead to a satisfactory solution in public health terms, a secondary level would be to identify those people or groups at special risk, but it is not recommended to undertake systematic examination of large populations in view of the fact that the early diagnosis of non-specific chronic pulmonary disease as well as special studies have not been shown to demonstrate the value of these procedures. The objective of prevention is to eliminate or neutralise factors linked to the disease.(ABSTRACT TRUNCATED AT 400 WORDS)


Myrosin cell development is regulated by endocytosis machinery and PIN1 polarity in leaf primordia of Arabidopsis thaliana.
Myrosin cells, which accumulate myrosinase to produce toxic compounds when they are ruptured by herbivores, form specifically along leaf veins in Arabidopsis thaliana. However, the mechanism underlying this pattern formation is unknown. Here, we show that myrosin cell development requires the endocytosis-mediated polar localization of the auxin-efflux carrier PIN1 in leaf primordia. Defects in the endocytic/vacuolar SNAREs (syp22 and syp22 vti11) enhanced myrosin cell development. The syp22 phenotype was rescued by expressing SYP22 under the control of the PIN1 promoter. Additionally, myrosin cell development was enhanced either by lacking the activator of endocytic/vacuolar RAB5 GTPase (VPS9A) or by PIN1 promoter-driven expression of a dominant-negative form of RAB5 GTPase (ARA7). By contrast, myrosin cell development was not affected by deficiencies of vacuolar trafficking factors, including the vacuolar sorting receptor VSR1 and the retromer components VPS29 and VPS35, suggesting that endocytic pathway rather than vacuolar trafficking pathway is important for myrosin cell development. The phosphomimic PIN1 variant (PIN1-Asp), which is unable to be polarized, caused myrosin cells to form not only along leaf vein but also in the intervein leaf area. We propose that Brassicales plants might arrange myrosin cells near vascular cells in order to protect the flux of nutrients and water via polar PIN1 localization.


The clinical spectrum of blunt cerebrovascular injury.
Incidence, prevalence, and clinical impact of blunt cerebrovascular injury (BCVI) are unknown. There are no standardized recommendations for screening. A databank of 306 patients with a history of trauma was searched for all subjects with a proven or suspected concomitant BCVI. All patients had undergone MRI for the evaluation of traumatic and vascular cerebral lesions. The diagnosis of BCVI relies on angiographic and/or ultrasound findings. By way of illustration, the case histories of the patients are reported. Eleven subjects (3.6%) were identified. In 8 patients (2.6%), the diagnosis of BCVI can be regarded as proven; in 3 patients (0.98%), a diagnosis of BCVI is probable. The patients could be sorted into the following categories: (i) patients with BCVI and early strokes, (ii) patients with BCVI and late strokes, (iii) patients with early strokes and no detectable BCVI/vessel abnormality, (iv) patients with occult BCVI. Evidence of cerebral ischemia/stroke was present in 9 patients (82%, or 2.9% of all patients). In all patients with stroke, it was the major or sole cause of disability. BCVI and BCVI-related strokes are not rare. The time window for the development of ischemic complications is highly variable and may be longer than is currently assumed. Even if clinically silent, a diagnosis of BCVI has medicolegal implications and may influence therapy and prognosis in later life. Because of the association of BCVI and motor vehicle accidents, screening is suggested in these patients, and ultrasound could be a practical tool. Although there is substantial suspicion for BCVI in individual trauma patients suffering from stroke, the diagnosis cannot always been proven.


Exfoliative erythema of malnutrition with zinc and essential amino acid deficiency.
We present a patient with a desquamating predominantly flexural erythema and glossitis due to a combination of alcoholism, zinc deficiency and amino acid deficiency. A similar clinical picture to necrolytic migratory erythema can be seen with zinc deficiency or protein malnutrition, often in patients with alcoholic liver disease, in the absence of glucagonoma. The speed of clinical improvement following zinc replacement therapy, usually within days to weeks, is striking, confirming the clinical diagnosis.


Silencing of LncRNA TCONS_00088786 reduces renal fibrosis through miR-132.
To examine the role of long non-coding ribonucleic acid (LncRNA) TCONS_00088786 in the development of renal interstitial fibrosis and its potential mechanism in this process. Unilateral ureteral obstruction (UUO) was used to induce tubulointerstitial fibrosis. Masson staining showed the degree of renal fibrosis in UUO mice. Immunohistochemistry and immunofluorescence were performed to detect the fibrosis-related proteins, the 24-h urine volume and protein content. The renal functions were reflected via serum creatinine (Scr) and blood urea nitrogen (BUN). Changes in lncRNATCONS_00088786, miR-132 and collagen I and III in the development process of renal fibrosis were detected through reverse transcription-polymerase chain reaction (RT-PCR). Small interfering RNA (siRNA) was transfected into NRK52E cells to mimic the knockdown. Western blot was adopted to detect the changes in miR-132, collagen I and III after the siRNA was transfected by transforming growth factor-β (TGF-β) for 24 h. With the development of renal fibrosis, lncRNA TCONS_00088786 and miR-132 were increased gradually. After the knockdown of lncRNA TCONS_00088786, miR-132 was decreased and fibrosis-related protein was also decreased. Decreased lncRNA TCONS _00088786 inhibits renal interstitial fibrosis by reducing miR-132 and it may be a potential novel molecular target for the treatment of renal interstitial fibrosis.


The Effect of Bipolar Pulsed Radiofrequency Treatment on Chronic Lumbosacral Radicular Pain Refractory to Monopolar Pulsed Radiofrequency Treatment.
Patients with lumbosacral radicular pain may complain of persisting pain after monopolar pulsed radiofrequency (PRF) treatment. We evaluated the effect of bipolar PRF stimulation of the dorsal root ganglion (DRG) in patients with chronic lumbosacral radicular pain who were unresponsive to both monopolar PRF stimulation of the DRG and transforaminal epidural steroid injection (TFESI). This is a prospective observational study. The outpatient clinic of a single academic medical center in Korea. We retrospectively reviewed data from 102 patients who had received monopolar PRF to the DRG for management of lumbosacral radiculopathy. Of these, 32 patients had persistent radicular pain that was scored at least 5 on a numeric rating scale (NRS). Twenty-three of them were included in this study and underwent bipolar PRF of the DRG. The outcomes after the procedure were evaluated using the NRS for radicular pain before treatment and 1, 2, and 3 months after treatment. Successful pain relief was defined as >/= 50% reduction in the NRS score compared with the score prior to treatment. Furthermore, at 3 months after treatment, patient satisfaction levels were examined. Patients reporting very good (score = 7) or good results (score = 6) were considered to be satisfied with the procedure. The NRS scores changed significantly over time. At 1, 2, and 3 months after bipolar PRF, the NRS scores were significantly reduced compared with the scores before the treatment. Twelve (52.2%) of the 23 patients reported successful pain relief and were satisfied with treatment results 3 months after bipolar PRF. No serious adverse effects were recorded. A small number of patients were recruited and we did not perform long-term follow-up. We believe the use of bipolar PRF of the DRG can be an effective and safe interventional technique for chronic refractory lumbosacral radiculopathy. It appears to be a potential option that can be tried before proceeding to spinal surgery. Bipolar, pulsed radiofrequency, lumbosacral radicular pain, chronic pain, dorsal root ganglion, spinal stenosis, herniated disc.


Anxiety sensitivity and its impact on pain experiences and conditions: a state of the art.
This paper serves as an introduction to the special issue of Cognitive Behaviour Therapy devoted to the topic of anxiety sensitivity (AS) and its impact on pain experiences and conditions. We provide a historical overview of relevant cognitive behavioural models of chronic pain, summarize recent models incorporating the AS construct, and introduce the papers in the special issue. These papers are organized into two sets--basic laboratory-based investigations and relatively more applied studies. We attempt to highlight some of the most important findings from each of these investigations and studies, in turn. Then, we consider several important conclusions derived from the set of special issue papers and the implications of these for the practice of cognitive-behavioural interventions with pain populations. Finally, we make several suggestions for directions for future investigations in this burgeoning area of cognitive behavioural research and practice.


[Echography in comparing the fetal growth of infants of African and European mothers].
Ethnic differences after delivery between babies of black or white origin are well know. However, until now, fetal growth during pregnancy has not been studied in relation to ethnic factors. In this study, two groups of 201 women, one of african origin, the other of european origin, were compared for their ultrasonic measurements of fetal abdominal transverse diameter (ATD), biparietal diameter (BPD) and femoral length. The two groups were matched by hospital, date of delivery, parity and socio-economic status. Multiple pregnancies were excluded. ATD was not different between the two groups, whereas BPD was significantly smaller among african fetuses mainly during late pregnancy and femur was greater during the entire pregnancy. Ethnic factor remained significant when taking into account confounding factors. Observed differences appeared to be more probably related to a racial factor than to hypotrophy. These findings have to be considered in order to appreciate fetal growth among african fetuses during pregnancy.


Poly(D,L-lactic acid-co-glycolic acid)-b-poly(ethylene glycol)-b-poly (D,L-lactic acid-co-glycolic acid) triblock copolymer and thermoreversible phase transition in water.
Novel thermoreversible gelation behavior of aqueous solutions of ABA-type triblock copolymers composed of the central polyethylene oxide (PEG) block and two poly(D,L-lactic acid-co-glycolic acid) side blocks was found. Phase transition characteristics, such as critical gel concentration (CGC) and lower and upper critical gel temperature (CGT), are closely related to the molecular structure of the triblock copolymers. The CGC and the lower CGT both increases with increasing PEG/PLGA molecular weight ratio. Increasing the GA content in PLGA block induces a somewhat higher CGC. The copolymer forms micelles with a PLGA loop core and a PEG shell in water. Also grouped micelles are identified seemingly due to the bridging of two micelles sharing two PLGA blocks of a block copolymer chain. As the temperature increases the association of micelles increases, which results in gelation. The ABA-type copolymers exhibit a relatively low CGC (<10%) and low sol-gel transition temperatures compared to BAB-type copolymers. As the temperature increases further gel-sol transition is observed, which would result from the shrinkage of micelles with temperature increase. The hydrodynamic size of the micelles is monitored by dynamic laser scattering, and a possible gelation mechanism was suggested.


Thymocyte subpopulations: an experimental review, including flow cytometric cross-correlations between the major murine thymocyte markers.
Many markers have been used to define thymocyte subpopulations. The literature gives discordant values on their relative proportions, and suggests that many thymocytes must have phenotypes intermediate between those of the dominant subsets. To clarify these issues, a reassessment of murine thymus subpopulations has been made, using internally consistent, quantitative correlations of most of the established markers. Peanut agglutinin (PNA) receptor, Thy 1, H-2, TL, Ly 1 and Ly 2, have been examined and correlated with each other, and with cell size, physical parameters, cortisone sensitivity and anatomical location. The analysis utilised mainly monoclonal antibodies and flow cytometry but also included differential complement-mediated cytotoxicity. The results show that there are two clearly defined major subpopulations, medullary cells (15% of the total) and cortical cells (85% of the total). These are most clearly distinguished by the combined use of PNA and Thy 1 markers, medullary cells (like peripheral T cells) being low for both, cortical cells being high for both. Cortisone-resistant cells represent about 25% of all medullary cells, which indicates that most medullary cells, as well as all cortical cells, are cortisone sensitive. Amongst the non-dividing thymocytes there are few cells that can be considered of intermediate phenotype when a multiparameter approach is used. The situation for the dividing blast cells is more complex, with some displaying apparent 'intermediate' marker combinations. However, three major subdivisions of blasts stand out, namely medullary blasts, cortical Ly 1+2+ blasts and cortical Ly 1-2- blasts. The cortical population in general contains only Ly 1+2+ and Ly 1-2- cells, but no (or few) Ly 1+2- cells. In contrast, the medullary population contains both Ly 1+2- and Ly 1+2+ cells, in similar proportions to peripheral T cells. An important conclusion of the study is that although no single marker can give an adequate definition and clean separation of subpopulations, quantitative multiparameter analysis can achieve these objectives.


Photodissociation of ClN(3) at 157 nm: Theory suggests a pathway leading to cyclic N(3).
The photodissociation dynamics of chlorine azide (ClN(3)) at the 157 nm region was studied theoretically using the multireference configuration interaction method and the complete active space self-consistent field direct dynamics method. The excitation at the 157 nm region was assigned to the 4 (1)A(')(S(7))<--X (1)A(')(S(0)) transition. A likely pathway for the formation of cyclic N(3) after this transition was identified by direct dynamics as follows: ClN(3) excited to 4 (1)A(')(S(7)) dissociates after about 40 fs to excited N(3)(2 (2)A('), with about 44 kcal/mol internal energy) +Cl((2)P). This vibrationally hot N(3)(2 (2)A(')) goes diabatically through a conical intersection with N(3)(1 (2)A(')) at 44 fs onto 1 (2)A('). At 19 fs later and repeatedly after every 55 fs, N(3)(1 (2)A(')) crosses and trickles down via Coriolis coupling to N(3)(2 (2)A(")/ (2)B(1)) state, which has a potential minimum at the cyclic-N(3) structure. Some fraction of N(3)(2 (2)A(")/ (2)B(1)) produced will survive dissociation and will be found as the cyclic N(3), and some other fraction will eventually dissociate to N((2)D)+N(2) over a high barrier found previously.


Investigating relations among stress, sleep and nail cortisol and DHEA.
In the current study, we present data investigating the relationships among stress, sleep disturbance, self-control, and levels of cortisol (CORT) and dehydroepiandrosterone (DHEA) in fingernail clippings. Currently, hair CORT is the only routinely used noninvasive, validated, biomarker of chronic exposure to stress-related hormones. Nail clippings represent an important potential alternative sample matrix for assessing chronic hormone exposure, as it offers a different timeline of hormone incorporation than scalp hair, and may be obtainable from populations in which hair either is lacking or is unavailable for cultural reasons. Moreover, there is established precedent for using fingernail clippings to attain biomarker data. However, the value of nail hormone assessment for psychological research is currently unknown due to a paucity of information on the relations between nail hormone concentrations and environmental or psychological variables. In the present study, we collected data from a low income, minority population (N = 47; 97% African American) to demonstrate feasibility and acceptability of nail collection and analysis of the adrenal steroids CORT and DHEA. Participants reported on perceived stress, sleep and self-control abilities. Correlational analyses suggest that exposure to stressful events, disturbances in sleep and waking were associated with higher levels of nail DHEA, while self-control was associated with higher levels of nail CORT. We discuss the potential importance of this methodology for investigating biological, behavioral, and subjective indices of stress and well-being.


Total cardiovascular risk for next 10 years among rural population of Nepal using WHO/ISH risk prediction chart.
Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality globally. Primary prevention of CVD based on total CVD risk approach using WHO/ISH risk prediction chart would be more effective to stratify population under different risk levels, prioritize and utilize the scarce resources of low and middle-income countries. This study estimated total 10-year CVD risk and determined the proportion of population who need immediate drug therapy among the rural population of Nepal. A community based cross-sectional study conducted among 345 participants aged 40-80 years in rural villages of Lamjung District of Nepal. They were selected randomly from total eighteen wards. Data were collected using WHO STEPS questionnaires. WHO/ISH risk prediction chart for SEAR D was used to estimate total cardiovascular risk. Chi-square and independent t-test were used to test significance at the level of p < 0.05 in SPSS version 16.0. Of the total participants, 55.4% were female. The mean age (standard deviation) of the participants was 53.5 ± 10.1 years. According to WHO/ISH chart proportions of low, moderate and high CVD risk were 86.4%, 9.3%, and 4.3%, respectively. Eleven percent of participants were in need of immediate pharmacotherapy. Age (p = 0.001), level of education (p = 0.01) and occupation (p = 0.001) were significantly associated with elevated CVD risk. A large proportion of Nepalese rural population is at moderate and high CVD risk. Immediate pharmacological interventions are warranted for at least one in every ten individuals along with lifestyle interventions. Both population-wise and high-risk approaches are required to minimize CVD burden in the future.


[Atrial lead placement in the right atrial appendage during recent or chronic arrhythmia].
An atrial arrhythmia could be encountered during the atrial lead implantation. The lead placement must subsequently be delayed after restitution of the sinus rhythm or completely abandoned. The authors investigate the atrial lead placement during atrial arrhythmia and the lead performance at 6-month follow-up. The study population was 65 patients aged 78.5 years, 42 males and 28 structural heart diseases. They were implanted for sick sinus syndrome (n=14), atrioventricular block (n=44), infra-hisian conduction abnormality (n=7) in association with an atrial fibrillation (63.1%), an atrial flutter (24.6%) or an atrial tachycardia (12.3%). The onset of the arrhythmia was < or = 7 days (47.7%) or > 7 days (52.3%). An atrial lead was placed in the right atrial appendage under fluoroscopic control. If the sinus rhythm was not restored at 1 month, an electrical cardioversion was performed. The per-implantation atrial signal amplitude was 2.2+/-1.5 mV (range 0.5 mV to 7 mV). Sinus rhythm was restored in 54 patients. At 1 month, one patient was in an incessant atrial fibrillation. The 53 patients in sinus rhythm had a good atrial lead performance. Out of 46 patients who completed the 6-month follow-up, 4 had an arrhythmia recurrence. The 42 patients in sinus rhythm had a good atrial lead performance. At 1 and 6-month follow-up, the atrial pacing threshold (1.1+/-0.7 V vs 1.2+/-1.0 V, ns) and the atrial signal amplitude (2.1+/-1.0 mV and 2.1+/-0.9 mV, ns) were stable. Comparing the patients with a recent or a chronic arrhythmia, the pacing thresholds (1.2+/-1.1 V vs 1.14+/-0.8 V, ns), the atrial signal amplitudes (2.17+/-0.9 mV vs 2.05+/-0.9 mV, ns) and the proportion of satisfactory pacemaker performance in DDD(R) mode for the patients in sinus rhythm (100% vs 100%, ns) did not statistically differ between the two groups at 6 months. In conclusion, the placement of an atrial lead in the right atrial appendage during an atrial arrhythmia is feasible with a good lead performance at 6 months in sinus rhythm regardless the onset time of the arrhythmia and provides a satisfactory atrial-based pacing with the preservation of the atrioventricular synchrony.


Post-traumatic trapped dislocations of the proximal interphalangeal joint.
This paper deals with the uncommon and frequently unrecognized problem of trapped dislocations of the proximal interphalangeal joint. These may be dorsal or volar. Soft tissue forming a noose, or interposed in the joint, is implicated. There is injury to one or more of the following structures: 1) extensor mechanism, 2) collateral ligament, 3) volar plate, 4) flexor tendon sheath, and 5) skin (compound dislocations). Open reduction and appropriate soft tissue repair are mandatory the essential features of diagnosis and management are discussed and four illustrative cases are presented.


Adenosine A1 antagonists. 3. Structure-activity relationships on amelioration against scopolamine- or N6-((R)-phenylisopropyl)adenosine-induced cognitive disturbance.
The effects of a variety of adenosine A1 and A2 antagonists on N6-((R)-phenylisopropyl)adenosine (R-PIA)- and scopolamine-induced amnesias were investigated in rodents in order to clarify the role of adenosine receptors in learning and memory. Some of the selective adenosine A1 antagonists exhibited antiamnesic activities at several doses where they did not induce an increase of spontaneous locomotion. These results suggest that the blockade of A1 receptors is more important than that of A2 receptors in learning and memory. Detailed studies of structure-activity relationships of adenosine A1 antagonists in two amnesia models demonstrated that there were three types of adenosine A1 antagonists: (A) Compounds 3-5 (8-substituted 1,3-dipropylxanthines) ameliorated the shortened latency in both models. (B) Compounds 7-11 (8-substituted 1,3-dialkylxanthines) and 19-21 (imidazo[2,1-i]purin-5(4H)-one derivatives) ameliorated the shortened latency in the (R)-PIA-induced amnesia model but not in the scopolamine-induced amnesia model. (C) Compounds 14-16 ameliorated the shortened latency in the scopolamine model but not in the (R)-PIA model. Aminophenethyl-substituted compounds C did not exhibit adenosine A1 antagonism in vivo presumably due to rapid metabolism. The dramatic change in the activities of A and B could not be explained by their simple pharmacokinetic differences because both types of compounds showed clear blockade of central adenosine A1 receptors in the (R)-PIA model. 8-(3-Dicyclopropylmethyl)-1,3-dipropylxanthine (5) (KF15372) was chosen for further studies and is currently under preclinical development as a cognition enhancer.


Abrogation of skin disease in LUPUS-prone MRL/FASlpr mice by means of a novel tylophorine analog.
To test the therapeutic effect of DCB-3503, a synthetic compound derived from a natural product that inhibits NF-kappaB, on end-organ disease in the MRL-Fas(lpr) murine model of systemic lupus erythematosus (SLE). Eight-week-old female MRL/Fas(lpr) mice were treated intraperitoneally with a low (2 mg/kg) or high (6 mg/kg) dose of DCB-3503 for 10 weeks. Control groups were administered vehicle treatment alone (negative control) or 25 mg/kg cyclophosphamide (positive control). Mice were bled before (8 weeks) and during (13 weeks) treatment, and when they were killed (20 weeks), and serum samples were analyzed for total IgM and IgG levels and autoantibody titers. When the mice were killed, spleen and lymph nodes (axillary, brachial, and cervical) were examined by flow cytometric analysis. The presence of skin and renal disease was determined by histopathologic analysis. DCB-3503 reduced anti-double-stranded DNA and antichromatin autoantibodies and nearly abrogated inflammatory skin disease in MRL/Fas(lpr) mice; however, it had little effect on histologic kidney disease. Treated mice did not have hematologic or hepatic toxicity. These data indicate that end-organ disease in MRL/Fas(lpr) mice responds differentially to NF-kappaB inhibitor. DCB-3503 causes significant abrogation of skin disease in MRL/Fas(lpr) mice and may potentially be beneficial in the treatment of inflammatory skin disease in SLE.


Surface Presentation of Hyaluronic Acid Modulates Nanoparticle-Cell Association.
Nanoparticle (NP) drug carriers have revolutionized medicine and increased patient quality of life. Clinically approved formulations typically succeed because of reduced off-target toxicity of the cargo. However, increasing carrier accumulation at disease sites through precise targeting remains one of the biggest challenges in the field. Novel multivalent ligand presentations and self-assembled constructs can enhance cell association, but an inability to draw direct comparisons across formulations has hindered progress. Furthermore, how nanoparticle structure influences function often is unclear. In this report, we leverage the well-characterized hyaluronic acid (HA)-CD44 binding pair to investigate how the surface architecture of modified NPs impacts their association with ovarian cancer cells that overexpress CD44. We functionalized anionic liposomes with 5 kDa HA by either covalent conjugation via surface coupling or electrostatic self-assembly using the layer-by-layer (LbL) adsorption method. Comparing these two methods, we observed a consistent enhancement of NP-cell association with the self-assembly LbL technique, particularly with higher molecular weight (≥10 kDa) HA. To further optimize association, we increased the surface-available HA. We synthesized a bottlebrush glycopolymer composed of a polynorbornene backbone and pendant 5 kDa HA and layered this macromolecule onto NPs. Flow cytometry revealed that the LbL HA bottlebrush NP outperformed the LbL linear display of HA. Cellular visualization by deconvolution optical microscopy corroborated results from all three constructs. Using exogenous HA to block NP-CD44 interactions, we found the LbL HA bottlebrush NP had a 4-fold higher binding avidity than the best-performing LbL linear HA NP. We further observed that decreasing the density of HA bottlebrush side chains to 75% had minimal impact on LbL NP stability or cell association, though we did see a reduction in binding avidity with this side-chain-modified NP. Our studies indicate that LbL surfaces are highly effective for multivalent displays, and the mode in which they present a targeting ligand can be optimized for NP cell targeting.


[Prognostic indicators in stage I non-small cell lung cancer].
Determinating the prognosis of patients with stage I non-small cell lung cancer (NSCLC) is a challenge. Since up to 30% of patients who have undergone surgical resection experience recurrence, generally in distant organs, it is reasonable to postulate that neo-adjuvant or adjuvant treatments might be useful. Better knowledge of prognostic factors could perhaps define which patient populations should be targeted with such treatments. Numerous potential prognostic factors, relating to the disease (TNM classification, histology, tumor size, blood vessels invasion, micro-metastasis, serum or molecular markers), the patient (gender, age, co-morbidity) as well as the treatment (delay, resection, lymph node dissection, neo-adjuvant and adjuvant treatments), are discussed. These prognostic factors should be integrated into the design of future clinical trials of chemotherapy and/or radiotherapy attempting to evaluate the effectiveness of various combinations of neo-adjuvant or adjuvant therapies. These factors may offer the opportunity to clinically and biologically characterize the different subgroups of patients, leading to a more rational, and perhaps individualized, choice of therapy.


Postoperative adjuvant radio(chemo)therapy for rectal cancer: an appraisal.
Rectal cancer can be considered a broad-spectrum disease, where the surgeon, radiation oncologist and medical oncologist have a peculiar and specific place in order to work harmoniously as a good orchestra. The reality in common general hospitals is far from that of comprehensive cancer centers, particularly for postoperative approaches. The adjuvant therapy of rectal cancer is not codified worldwide, and it is strongly dependent on preoperative staging procedures, surgeon's acts and pathologist's decisions. Starting from our 10-year experience, we analyzed the various steps of postoperative approaches, defining possible decision errors, the incongruity of some attitudes, and the lack of knowledge of recent achievements of science in this disease. A total of 194 patients with advanced surgically removed rectal cancer (pT3-4 pN0-any pT pN+) treated with postoperative radio(chemo)therapy was reviewed retrospectively. Anterior resection was performed in 126, abdominoperineal resection in 48, and other surgical procedures in 20 patients. Irradiation was conducted with a single daily fraction of 1.8 Gy until 45 Gy, and chemotherapy consisted of the combination of 5-fluorouracil and folinic acid (Machover schedule): 47% of patients with positive nodes did not receive chemotherapy. Five-year overall survival was 60.6% and relapse-free survival was 55.5%. The main prognostic factors were pathological T and N stages. The principal route of progression was distant metastases. Acute toxicity was severe in 1 case (drug toxic hepatitis) and very severe in 16 patients, and late severe sequelae appeared in 13 patients. The outcome of rectal cancer patients has not changed during the last decade, and this was confirmed in our study. The improvement of radiotherapy techniques has reduced the adverse acute and late toxicity. The best postsurgical approach for pT3pN0 cancer remains unsolved, as the good chemotherapy combination and the real solution could be the application of a new Consensus Conference.


Variable regions V13 and V3 of Saccharomyces cerevisiae contain structural features essential for normal biogenesis and stability of 5.8S and 25S rRNA.
The homologous ribosomal RNA species of all organisms can be folded into a common "core" secondary structure. In addition, eukaryotic rRNAs contain a large number of segments, located at fixed positions, that are highly variable in size and sequence from one organism to another. We have investigated the role of the two largest of these variable regions in Saccharomyces cerevisiae 25S rRNA, V13, and V3, by mutational analysis in a yeast strain that can be rendered completely dependent on the synthesis of mutant (pre-)rRNA. We found that approximately half of variable region V13 can be deleted without any phenotypic effect. The remaining portion, however, contains multiple structural features whose disturbance causes serious growth defects or lethality. Accumulation of 25S rRNA is strongly reduced by these mutations, at least in part because they inhibit processing of ITS2. Removal of even a relatively small portion of V3 also strongly reduces the cellular growth rate and larger deletions are lethal. Interestingly, some of the deletions in V3 cause accumulation of 27S(A) pre-rRNA and, moreover, appear to interfere with the close coupling between the processing cleavages at sites A3 and B1(S). These results demonstrate that both variable regions play an important role in 60S subunit formation.


[Prevalence betel nut abuse and its related factors among residents in Haikou City from 2013 to 2014].
From 2013 to 2014, the age of 924 residents recruited in Haikou City was (38±13) years old, of which 57.3% (529) were males. Those who chewed betel nuts accounted for 17.4% (161). According to the diagnostic criteria of substance abuse in the Fourth Edition of the Diagnostic and Statistical Manual of Mental Disorders, the detection rate of betel nut abuse was 7.0% (65). Compared with those who were>30 years old, educated>6 years and non-smokers, people aged 15 to 30 years, education level less than 6 years and smoking behavior had higher risk of betel nut abuse, with the OR (95%CI) about 4.21 (1.48-11.99), 7.81 (1.92-31.69), and 13.53 (4.15-44.11), respectively.


Calculation of absolute protein-ligand binding free energy using distributed replica sampling.
Distributed replica sampling [T. Rodinger et al., J. Chem. Theory Comput. 2, 725 (2006)] is a simple and general scheme for Boltzmann sampling of conformational space by computer simulation in which multiple replicas of the system undergo a random walk in reaction coordinate or temperature space. Individual replicas are linked through a generalized Hamiltonian containing an extra potential energy term or bias which depends on the distribution of all replicas, thus enforcing the desired sampling distribution along the coordinate or parameter of interest regardless of free energy barriers. In contrast to replica exchange methods, efficient implementation of the algorithm does not require synchronicity of the individual simulations. The algorithm is inherently suited for large-scale simulations using shared or heterogeneous computing platforms such as a distributed network. In this work, we build on our original algorithm by introducing Boltzmann-weighted jumping, which allows moves of a larger magnitude and thus enhances sampling efficiency along the reaction coordinate. The approach is demonstrated using a realistic and biologically relevant application; we calculate the standard binding free energy of benzene to the L99A mutant of T4 lysozyme. Distributed replica sampling is used in conjunction with thermodynamic integration to compute the potential of mean force for extracting the ligand from protein and solvent along a nonphysical spatial coordinate. Dynamic treatment of the reaction coordinate leads to faster statistical convergence of the potential of mean force than a conventional static coordinate, which suffers from slow transitions on a rugged potential energy surface.


Which factors predict outcome in the treatment program of anterior knee pain?
The goal of this prospective study was to determine the outcome-predictive role of various parameters in the nonoperative treatment of chronic anterior knee pain patients. Thirty patients followed a five-week treatment program, which consisted out of only closed kinetic chain exercises. Prior to this treatment all subjects were evaluated on muscular characteristics, subjective symptoms, weight, sex, duration of symptoms and functional performance. A multiple stepwise regression analysis revealed that the reflex response time of m. vastus medialis obliquus (VMO) (P=0.041; 0.026), and the duration of symptoms (P=0.019; 0.045) were the only two parameters which were significantly associated with the outcome (evaluated by the Kujala score) at five weeks, and at three months. The shorter the duration of symptoms, or the faster the reflex response time of VMO prior to the treatment, the better the outcome after a closed kinetic chain exercise program. The statistical significance of these parameters in this study may be seen as an indication of the importance of these variables as predictors of the outcome of a closed kinetic chain strengthening program. Using this information, it seems clinically important to begin the treatment program before the anterior knee pain becomes more chronic and treatment results become less good.


Reading component skills in dyslexia: word recognition, comprehension and processing speed.
The cognitive model of reading comprehension (RC) posits that RC is a result of the interaction between decoding and linguistic comprehension. Recently, the notion of decoding skill was expanded to include word recognition. In addition, some studies suggest that other skills could be integrated into this model, like processing speed, and have consistently indicated that this skill influences and is an important predictor of the main components of the model, such as vocabulary for comprehension and phonological awareness of word recognition. The following study evaluated the components of the RC model and predictive skills in children and adolescents with dyslexia. 40 children and adolescents (8-13 years) were divided in a Dyslexic Group (DG; 18 children, MA = 10.78, SD = 1.66) and control group (CG 22 children, MA = 10.59, SD = 1.86). All were students from the 2nd to 8th grade of elementary school and groups were equivalent in school grade, age, gender, and IQ. Oral and RC, word recognition, processing speed, picture naming, receptive vocabulary, and phonological awareness were assessed. There were no group differences regarding the accuracy in oral and RC, phonological awareness, naming, and vocabulary scores. DG performed worse than the CG in word recognition (general score and orthographic confusion items) and were slower in naming. Results corroborated the literature regarding word recognition and processing speed deficits in dyslexia. However, dyslexics can achieve normal scores on RC test. Data supports the importance of delimitation of different reading strategies embedded in the word recognition component. The role of processing speed in reading problems remain unclear.