[Determining the status of the cervical spine after whiplash injury].
The results of medical investigations following acceleration mechanism to the cervical spine (so called "soft tissue neck injury") are to be described in common diagnostic terms. Biomechanical and legal considerations are beyond medical competence. In certain cases, the clinical examination must be completed in cooperation with specialists. Within the entire medical context, the neuropsychological and neuropsychiatric assessment may contribute to a comprehensive understanding of the consequences. In cases of litigation, the full array of facts, like the patients' previous history, and differential diagnoses, have to be drawn to attention. At present, compensation takes place only exceptionally and in a limited range, if an impairment by an accompanying brain injury is excluded.


Epidemiology of skin event rates among users of pumps for the subcutaneous administration of drugs for chronic conditions.
To provide the epidemiology of skin events occurring during long-term administration of medications delivered by continuous subcutaneous infusion pump (CSIP) systems as background rates for the development of novel CSIP treatments to use in community-based settings. Using a United Kingdom general practice database, we conducted a study to assess the rates of skin events among new users of apomorphine and insulin delivered by CSIP in patients with Parkinson's disease or diabetes, respectively. Skin events included skin infections, skin nodules/localized swelling, dermatitis/eczema, urticaria/erythema, and rash/other non-specific skin eruptions. Five hundred and fifty-seven adults (age 30+) were included in this descriptive cohort. The median duration of CSIP use was 17 months among 255 apomorphine users and 41 months among 302 insulin users. By 60 months, ∼40% of both cohorts experienced skin events. Repeated skin events occurred in 11% of the apomorphine cohort and 14% of the insulin cohort at any time during follow-up. The overall skin event rate in the apomorphine cohort was 17 per 1000 person-months (PM) and 13 per 1000 PM in the insulin cohort. The most common skin events in both cohorts were infection and rash/unspecified skin eruptions. The highest rates of skin events occurred soon after apomorphine CSIP initiation (36 per 1000 PM in weeks 1-2 and 50 per 1000 PM in weeks 3-4), with lower rates after 4 weeks. Insulin CSIP users' skin event rates were consistent over the treatment duration. Clinically important skin events are common during long-term administration of medications by CSIP.


Myogenic differentiation of VCP disease-induced pluripotent stem cells: A novel platform for drug discovery.
Valosin Containing Protein (VCP) disease is an autosomal dominant multisystem proteinopathy caused by mutations in the VCP gene, and is primarily associated with progressive muscle weakness, including atrophy of the pelvic and shoulder girdle muscles. Currently, no treatments are available and cardiac and respiratory failures can lead to mortality at an early age. VCP is an AAA ATPase multifunction complex protein and mutations in the VCP gene resulting in disrupted autophagic clearance. Due to the rarity of the disease, the myopathic nature of the disorder, ethical and practical considerations, VCP disease muscle biopsies are difficult to obtain. Thus, disease-specific human induced pluripotent stem cells (hiPSCs) now provide a valuable resource for the research owing to their renewable and pluripotent nature. In the present study, we report the differentiation and characterization of a VCP disease-specific hiPSCs into precursors expressing myogenic markers including desmin, myogenic factor 5 (MYF5), myosin and heavy chain 2 (MYH2). VCP disease phenotype is characterized by high expression of TAR DNA Binding Protein-43 (TDP-43), ubiquitin (Ub), Light Chain 3-I/II protein (LC3-I/II), and p62/SQSTM1 (p62) protein indicating disruption of the autophagy cascade. Treatment of hiPSC precursors with autophagy stimulators Rapamycin, Perifosine, or AT101 showed reduction in VCP pathology markers TDP-43, LC3-I/II and p62/SQSTM1. Conversely, autophagy inhibitors chloroquine had no beneficial effect, and Spautin-1 or MHY1485 had modest effects. Our results illustrate that hiPSC technology provide a useful platform for a rapid drug discovery and hence constitutes a bridge between clinical and bench research in VCP and related diseases.


Association of Ocular Surface Immune Cells With Dry Eye Signs and Symptoms in the Dry Eye Assessment and Management (DREAM) Study.
Dry eye disease (DED) is a multifactorial, heterogeneous disease of the ocular surface with one etiology being ocular surface inflammation. Studies using animal models demonstrate the role of ocular surface immune cells in the inflammatory pathway leading to DED, but few have evaluated humans. This study described the white blood cell population from the ocular surface of patients with DED and assessed its association with DED signs and symptoms in participants of the Dry Eye Assessment and Management (DREAM) study. Participants were assessed for symptoms using the Ocular Surface Disease Index, signs via corneal staining, conjunctival staining, tear break-up time, and Schirmer test, and Sjögren's syndrome (SS) based on the 2012 American College of Rheumatology classification criteria. Impression cytology of conjunctival cells from each eye was evaluated using flow cytometry: T cells, helper T cells (Th), regulatory T cells (Tregs), cytotoxic T cells, and dendritic cells. We assessed 1049 eyes from 527 participants. White blood cell subtype percentages varied widely across participants. Significant positive associations were found for Th and conjunctival staining (mean score of 2.8 for 0% Th and 3.1 for >4.0% Th; P = 0.007), and corneal staining (mean score of 3.5 for 0% Th and 4.3 for >4.0% Th; P = 0.01). SS was associated with higher percent of Tregs (median 0.1 vs. 0.0; P = 0.01). Th were associated with more severe conjunctival and corneal staining, possibly indicating their role in inflammation leading to damage of the ocular surface. There is no consistent conclusion about Tregs in SS, but these results support that Tregs are elevated in SS.


LAG3 (CD223) as a cancer immunotherapy target.
Despite the impressive impact of CTLA4 and PD1-PDL1-targeted cancer immunotherapy, a large proportion of patients with many tumor types fail to respond. Consequently, the focus has shifted to targeting alternative inhibitory receptors (IRs) and suppressive mechanisms within the tumor microenvironment. Lymphocyte activation gene-3 (LAG3) (CD223) is the third IR to be targeted in the clinic, consequently garnering considerable interest and scrutiny. LAG3 upregulation is required to control overt activation and prevent the onset of autoimmunity. However, persistent antigen exposure in the tumor microenvironment results in sustained LAG3 expression, contributing to a state of exhaustion manifest in impaired proliferation and cytokine production. The exact signaling mechanisms downstream of LAG3 and interplay with other IRs remain largely unknown. However, the striking synergy between LAG3 and PD1 observed in multiple settings, coupled with the contrasting intracellular cytoplasmic domain of LAG3 as compared with other IRs, highlights the potential uniqueness of LAG3. There are now four LAG3-targeted therapies in the clinic with many more in preclinical development, emphasizing the broad interest in this IR. Given the translational relevance of LAG3 and the heightened interest in the impact of dual LAG3/PD1 targeting in the clinic, the outcome of these trials could serve as a nexus; significantly increasing or dampening enthusiasm for subsequent targets in the cancer immunotherapeutic pipeline.


Melatonin reverses tumor necrosis factor-alpha-induced metabolic disturbance of human nucleus pulposus cells via MTNR1B/Gαi2/YAP signaling.
Background: Intervertebral disc degeneration (IDD), the main cause of low back pain, is closely related to the inflammatory microenvironment in the nucleus pulposus (NP). Tumor necrosis factor-α (TNF-α) plays an important role in inflammation-related metabolic disturbance of NP cells. Melatonin has been proven to regulate the metabolism of NP cells, but whether it can protect NP cells from TNF-α-induced damage is still unclear. Therefore, this study aims to investigate the role and specific mechanism of melatonin on regulating the metabolism of NP cells in the inflammatory microenvironment. Methods: Western blotting, RT-qPCR and immunohistochemistry were used to detect the expression of melatonin membrane receptors (MTNR1A/B) and TNF-α in human NP tissues. In vitro, human primary NP cells were treated with or without vehicle, TNF-α and melatonin. And the metabolic markers were also detected by western blotting and RT-qPCR. The activity of NF-κB signaling and Hippo/YAP signaling were assessed by western blotting and immunofluorescence. Membrane receptors inhibitors, pathway inhibitors, lentiviral infection, plasmids transfection and immunoprecipitation were used to explore the specific mechanism of melatonin. In vivo, the rat IDD model was constructed and melatonin was injected intraperitoneally to evaluate its therapeutical effect on IDD. Results: The upregulation of TNF-α and downregulation of melatonin membrane receptors (MTNR1A/B) were observed in degenerative NP tissues. Then we demonstrated that melatonin could alleviate the development of IDD in a rat model and reverse TNF-α-impaired metabolism of NP cells in vitro. Further investigation revealed that the protective effects of melatonin on NP cells mainly rely on MTNR1B, which subsequently activates Gαi2 protein. The activation of Gαi2 could upregulate the yes-associated protein (YAP) level, resulting in anabolic enhancement of NP cells. In addition, melatonin-mediated YAP upregulation increased the expression of IκBα and suppressed the TNF-α-induced activation of the NF-κB pathway, thereby inhibiting the catabolism of NP cells. Conclusions: Our results revealed that melatonin can reverse TNF-α-impaired metabolism of NP cells via the MTNR1B/Gαi2/YAP axis and suggested that melatonin can be used as a potential therapeutic drug in the treatment of IDD.


A systematic literature review of the effect of insulin sensitizers on the cognitive symptoms of Alzheimer's Disease in transgenic mice.
Alzheimer's Disease (AD) presents as a gradual decline in cognitive function, with its characteristic pathology consisting of Amyloid β (Aβ) accumulation and hyperphosphorylated tau. Impaired insulin signalling was recently found in the brain in AD, and shown to increase AD pathology. Similar insulin resistance is found in type 2 diabetes and is currently treated with insulin sensitizers (IS). The aim of this literature review was to evaluate whether IS could effectively reduce AD's characteristic pathology and symptoms in models of AD in transgenic mice. The efficacy of an IS (Metformin, Rosiglitazone or Pioglitazone) at improving each characteristic in transgenic mice was evaluated. A variety of cognitive tests and measures of pathology were utilized to assess these outcomes, hindering comparison. Improvements in cognition, learning and Aβ pathology were demonstrated by some papers, and all papers reported a decrease in tau phosphorylation, but no effect on total tau levels.


Integrating traditional medicine into modern health care systems: examining the role of Chinese medicine in Taiwan.
Since the World Health Organization officially promoted traditional medicine in developing countries in 1978, there have been increasing interests among developing countries in integrating traditional medicine into a national health care system. Most of these policies, however, tend to be the policy of coexistence instead of integration. This paper focuses on the rationale, strategies, and process of integrating traditional medicine into a modern health care system by using the experience of Chinese medicine in Taiwan as an example. After briefly describing the changing roles of Chinese medicine in Taiwan, the author critically reviews the government policies and regulations on Chinese medicine. Research findings and government statistics on the demand and supply of Chinese medicine are also described to provide some insights for developing recommendations for an appropriate integration policy. To effectively integrate traditional medicine into a modern health care system, this paper suggests that such integration should begin at the grass roots level, that is with the training of physicians and practitioners. A successful, integrated health care system would facilitate more efficient use of domestic medical resources, and enhance self-sufficiency in health development for resource poor countries. Integrating traditional medicine into a modern health care system, moreover, can benefit industrialized nations as well. After recommending several strategies for integration, the author proposes a further development of a unified medical system as the final stage of full integration. This unified medical system should be an inclusive medical system, which could help countries to expand the available medical resources.


Alzheimer's disease amyloid beta and prion protein amyloidogenic peptides promote macrophage survival, DNA synthesis and enhanced proliferative response to CSF-1 (M-CSF).
Microglial cells, macrophage-lineage cells in the brain, are increased in amyloid-containing plaques in Alzheimer's disease (AD) and in the lesions of prion diseases. Recent studies suggest that microglia have a central role in turnover of amyloid in these diseases. We report here that synthetic amyloid beta (Abeta) 1-42 and prion protein (PrP) 106-126 peptides promote macrophage survival; they also induce macrophage DNA synthesis, particularly in the presence of sub-optimal concentrations of the growth factor, macrophage-colony stimulating factor (M-CSF or CSF-1). These responses are proposed to provide a means to increase brain microglia/macrophage numbers thereby enhancing subsequent inflammatory/immune responses. These fibrillogenic peptides join the list of aggregates having these effects on macrophages, indicating the generality of this type of response.


Experimental studies on possible regulatory role of nitric oxide on the differential effects of chronic predictable and unpredictable stress on adaptive immune responses.
The present study was designed to investigate the effects of chronic predictable stress (CPS) and chronic unpredictable stress (CUS) on immunological responses in KLH-sensitized rats and involvement of NOergic signaling pathways mediating such responses. Male Wistar rats (200-250g) were exposed to either CPS or CUS for 14days and IgG antibody levels and delayed type hypersensitivity (DTH) response was determined to assess changes in adaptive immunity. To evaluate the role of nitric oxide during such immunomodulation, biochemical estimation of stable metabolite of nitric oxide (NOx) and 3-nitrotyrosine (3-NT, a marker of peroxynitrite formation) were done in both blood and brain. Chronic stress exposure resulted in suppression of IgG and DTH response and elevated NOx and 3-NT levels, with a difference in magnitude of response in CPS vs CUS. Pretreatment with aminoguanidine (iNOS inhibitor) caused further reduction of adaptive immune responses and attenuated the increased NOx and 3-NT levels in CPS or CUS exposed rats. On the other hand 7-NI (nNOS inhibitor) did not significantly affect these estimated parameters. The results suggest involvement of iNOS and lesser/no role of nNOS during modulation of adaptive immunity to stress. Thus, the result showed that predictability of stressors results in differential degree of modulation of immune responses and complex NO-mediated signaling mechanisms may be involved during responses.


The role of olanzapine in the treatment of anorexia nervosa.
To evaluate the role of olanzapine in the treatment of anorexia nervosa. Literature was obtained through searches of MEDLINE (1966-December 2006), EMBASE (1980-4th Quarter 2006), and PsycINFO (1985-December 2006) and a bibliographic review of published articles. Key terms used in the searches included anorexia nervosa, antipsychotics, eating disorders, olanzapine, and Zyprexa. All English language articles that were identified from the search were evaluated. All primary literature was included in the review. In several case reports and most clinical trials, patients with anorexia nervosa successfully gained weight while being treated with olanzapine. Moreover, many patients treated with olanzapine achieved a healthy body weight. Case reports and trials identified additional benefits of olanzapine, including reduction in delusional thinking; improvement in body image, sleep, depressive symptoms, adherence to treatment, and eating-disorder symptoms; and decreased agitation and premeal anxiety. Preliminary evidence supports the use of olanzapine for treatment of anorexia nervosa by demonstrating that olanzapine 2.5-15 mg daily promotes weight gain and has positive effects on associated psychological symptoms. Limitations of the reported data include small sample size, low completion rate in clinical trials, and open-label trial design. Although olanzapine appears to have a potential role in the treatment of anorexia nervosa that has been unresponsive to other therapy, randomized, placebo-controlled studies with larger sample sizes are necessary to establish its role in therapy.


Cultured microglial cells have a distinct pattern of membrane channels different from peritoneal macrophages.
Microglia are the source of the resident macrophages of the brain and thus belong to one of the most reactive cell types in cerebral tissue. They are attributed to have an important role in a number of pathological conditions, such as multiple sclerosis, viral infections like AIDS, and in lethal or sublethal injuries of neurons where the blood-brain barrier is left intact (Streit et al., 1988; McGeer et al., 1988; Gendelman et al., 1989). Microglia share a number of macrophage characteristics but so far lack a distinguishing positive marker. In this study it is shown that microglia are distinguished from other macrophages by a unique pattern of ion channels. We compared membrane currents of microglial cells with those from peritoneal macrophages cultured under identical conditions. Although in macrophages a delayed outward K+ current was previously described (Randriamampita and Trautmann, 1987), microglial cells lacked any specific outward current. Instead, these cells were characterized by large inwardly rectifying currents, activated by hyperpolarizing voltage steps. The reversal potential in different K+ gradients and the sensitivity of the current to to Ba2+, TEA, and 4-AP indicates that this current is K+ selective. In single-channel recordings, a 30 pS K+ selective channel similar to the classical inward rectifier K+ channel was observed. Thus, the expression of membrane channels served not only to distinguish microglia from other cells inside and outside the brain, e.g., blood macrophages, but also suggests a unique functional state of this cell population.


Aortic root replacement for Takayasu arteritis associated with ulcerative colitis and ankylosing spondylitis--report of a case.
A 26-year-old man was admitted for treatment of congestive heart failure resulting from aortic regurgitation. The patient had been on medical treatment for ulcerative colitis (UC) since he was 14 years old and for ankylosing spondylitis (AS) since he was 20 years old. On admission, gradients of blood pressure among the extremities were observed. Echocardiography revealed marked dilation of the left ventricle (LV), hypokinetic wall motion of the LV, slightly prolapsed aortic cusps with annular dilatation, and severe aortic regurgitation. Computed tomographic scans demonstrated an aneurysmal dilation of the ascending aorta and thickening of the descending and abdominal aortic wall. Digital subtraction angiography demonstrated an aneurysmal dilation of the ascending aorta; however, there was no clear evidence of steno-occlusive lesions in the brachiocephalic vessels. Blood studies showed positive inflammatory signs and negative rheumatoid factor. HLA typing showed A2, 24(9), B27, 67, Cw1, 7, and DR1, 2. Based on these data, the diagnosis of Takayasu arteritis associated with UC and AS was made. Aortic root replacement was performed. Steroid therapy was restarted immediately after surgery. Histologic studies of the aortic wall showed findings compatible with Takayasu arteritis. The combination of these rare diseases suggests that they have a common pathophysiologic background.


Mitochondrial DNA variation within and among regional populations of longtail macaques (Macaca fascicularis) in relation to other species of the fascicularis group of macaques.
An 835 base pair (bp) fragment of mitochondrial DNA (mtDNA) was sequenced to characterize genetic variation within and among 1,053 samples comprising five regional populations each of longtail macaques (Macaca fascicularis) and rhesus macaques (Macaca mulatta), and one sample each of Japanese (M. fuscata) and Taiwanese (M. cyclopis) macaques. The mtDNA haplotypes of longtail macaques clustered in two large highly structured clades (Fas1 and Fas2) of a neighbor-joining tree that were reciprocally monophyletic with respect to those representing rhesus macaques, Japanese macaques, and Taiwanese macaques. Both clades exhibited haplotypes of Indonesian and Malaysian longtail macaques widely dispersed throughout them; however, longtail macaques from Indochina, Philippines, and Mauritius each clustered in a separate well-defined clade together with one or a few Malaysian and/or Indonesian longtail macaques, suggesting origins on the Sunda shelf. Longtail macaques from Malaysia and Indonesia were far more genetically diverse, and those from Mauritius were far less diverse than any other population studied. Nucleotide diversity between mtDNA sequences of longtail macaques from different geographic regions is, in some cases, greater than that between Indian and Chinese rhesus macaques. Approximately equal amounts of genetic diversity are due to differences among animals in the same regional population, different regional populations, and different species. A greater proportion of genetic variance was explained by interspecies differences when Japanese and Taiwanese macaques were regarded as regional populations of rhesus macaques than when they were treated as separate species. Rhesus macaques from China were more closely related to both Taiwanese and Japanese macaques than to their own conspecifics from India.


Targeting Neutrophil α9 Improves Functional Outcomes After Stroke in Mice With Obesity-Induced Hyperglycemia.
Obesity-induced hyperglycemia is a significant risk factor for stroke. Integrin α9β1 is expressed on neutrophils and stabilizes adhesion to the endothelium via ligands, including Fn-EDA (fibronectin containing extra domain A) and tenascin C. Although myeloid deletion of α9 reduces susceptibility to ischemic stroke, it is unclear whether this is mediated by neutrophil-derived α9. We determined the role of neutrophil-specific α9 in stroke outcomes in a mice model with obesity-induced hyperglycemia. α9Neu-KO (α9fl/flMRP8Cre+) and littermate control α9WT (α9fl/flMRP8Cre-) mice were fed on a 60% high-fat diet for 20 weeks to induce obesity-induced hyperglycemia. Functional outcomes were evaluated up to 28 days after stroke onset in mice of both sexes using a transient (30 minutes) middle cerebral artery ischemia. Infarct volume (magnetic resonance imaging) and postreperfusion thrombo-inflammation (thrombi, fibrin, neutrophil, phospho-nuclear factor kappa B [p-NFκB], TNF [tumor necrosis factor]-α, and IL [interleukin]-1β levels, markers of neutrophil extracellular traps) were measured post 6 or 48 hours of reperfusion. In addition, functional outcomes (modified Neurological Severity Score, rota-rod, corner, and wire-hanging test) were measured for up to 4 weeks. Stroke upregulated neutrophil α9 expression more in obese mice (P<0.05 versus lean mice). Irrespective of sex, deletion of neutrophil α9 improved functional outcomes up to 4 weeks, concomitant with reduced infarct, improved cerebral blood flow, decreased postreperfusion thrombo-inflammation, and neutrophil extracellular traps formation (NETosis) (P<0.05 versus α9WT obese mice). Obese α9Neu-KO mice were less susceptible to thrombosis in FeCl3 injury-induced carotid thrombosis model. Mechanistically, we found that α9/cellular fibronectin axis contributes to NETosis via ERK (extracellular signal-regulated kinase) and PAD4 (peptidyl arginine deiminase 4), and neutrophil α9 worsens stroke outcomes via cellular fibronectin-EDA but not tenascin C. Obese wild-type mice infused with anti-integrin α9 exhibited improved functional outcomes up to 4 weeks (P<0.05 versus vehicle). Genetic ablation of neutrophil-specific α9 or pharmacological inhibition improves long-term functional outcomes after stroke in mice with obesity-induced hyperglycemia, most likely by limiting thrombo-inflammation.


Factors Associated With Attainment of Specialty Board Qualifications and Doctor of Medical Science Degrees Among Japanese Female Doctors.
Specialty board qualifications or doctor of medical science (DMSc) degrees are essential for women's promotion to leadership positions in medicine in Japan. The authors examined what personal and professional characteristics of female doctors were associated with attainment of specialty board qualifications and DMSc degrees. This study was based on alumnae surveys of 13 private medical schools in Japan conducted from 2009 to 2011 and investigating 882 alumnae who had at least one child (mean age 47 years). Multinomial logistic regression models were applied to investigate factors associated with attainment of specialty board qualifications alone, DMSc degrees alone, and both, compared with attainment of neither specialty board qualifications nor DMSc degrees. In total, 34% of the sample obtained both specialty board qualifications and DMSc degrees, 33% obtained specialty board qualifications only, 9% obtained DMSc degrees only, and 24% obtained neither. A one-year increase in age at the time of first birth was associated with an increased likelihood of attaining a specialty board qualification and/or a DMSc versus having neither qualification (P < .0001). Women who resigned from their jobs instead of taking maternity leave at the time of first childbirth had a significantly lower likelihood ratio of obtaining specialty board qualifications either alone or in conjunction with DMSc degrees (P < .0001). Earlier age and job resignation at the time of first childbirth among physician-mothers in Japan were associated with failure to attain specialty board qualifications and DMSc degrees, with important implications for future career advancement.


Cellular tagging as a neural network mechanism for behavioural tagging.
Behavioural tagging is the transformation of a short-term memory, induced by a weak experience, into a long-term memory (LTM) due to the temporal association with a novel experience. The mechanism by which neuronal ensembles, each carrying a memory engram of one of the experiences, interact to achieve behavioural tagging is unknown. Here we show that retrieval of a LTM formed by behavioural tagging of a weak experience depends on the degree of overlap with the neuronal ensemble corresponding to a novel experience. The numbers of neurons activated by weak training in a novel object recognition (NOR) task and by a novel context exploration (NCE) task, denoted as overlapping neurons, increases in the hippocampal CA1 when behavioural tagging is successfully achieved. Optical silencing of an NCE-related ensemble suppresses NOR-LTM retrieval. Thus, a population of cells recruited by NOR is tagged and then preferentially incorporated into the memory trace for NCE to achieve behavioural tagging.


Prostaglandin E2 is an enhancer of interleukin-1beta-induced expression of membrane-associated prostaglandin E synthase in rheumatoid synovial fibroblasts.
Membrane-associated prostaglandin E synthase (mPGES) is a recently identified terminal enzyme of the arachidonic acid cascade, which converts PGH(2) to PGE(2) in rheumatoid arthritis synovial fibroblasts (RASFs). This study was undertaken to investigate factors regulating the expression of mPGES. RASFs were treated with interleukin-1beta (IL-1beta), indomethacin, NS-398, rofecoxib, or meloxicam. The effects of PGE(2) and selective agonists for PGE(2) receptor subtypes (EP1, EP2, EP3, and EP4) were also studied. Expression of mPGES messenger RNA (mRNA) and protein was measured by Northern and Western blot analysis, respectively. EP receptor mRNA expression in RASFs was determined by reverse transcriptase-polymerase chain reaction. Production of PGE(2) and cAMP was measured by enzyme-linked immunosorbent assay. The enhanced expression of mPGES mRNA and protein in IL-1beta-stimulated RASFs was attenuated by the addition of indomethacin, NS-398, rofecoxib, or meloxicam. This reduction of expression was reversed by PGE(2). IL-1beta-induced PGES activity, measured by conversion of PGH(2) to PGE(2), was decreased by rofecoxib. EP2 and EP4 receptor mRNA was detected in RASFs. EP2 and EP4 agonists, as well as PGE(2), restored the inhibitory effect of rofecoxib on mPGES expression. The effect of PGE(2) was mimicked by forskolin, a direct activator of adenylate cyclase. Intracellular cAMP was increased by IL-1beta and was inhibited by rofecoxib. Enhancement of mPGES expression by PGE(2) via the EP2/EP4 receptors with an increase in cAMP may play an important role in articular inflammation in patients with RA. It also seems that cyclooxygenase 2 (COX-2) inhibitors decrease PGE(2) production not only by direct inhibition of COX-2, but also by reducing mPGES expression in activated RASFs.


Cortisone in treatment of bronchial asthma.
Twenty patients with intractable asthma were treated with cortisone on various dosage schedules. Results indicated that a rapid improvement in the asthmatic state may be expected in four to five days with high level dosage of the hormone-usually a total dose exceeding 200 mg. per day at the beginning. If treatment is discontinued after a week, relapse usually will occur within a period of eight days. If small doses are given two or three times weekly, following initial response, relapse may not occur for 20 or 30 days. The interspersed administration of ACTH during an attempt to discontinue cortisone apparently was of no value. It therefore appears that cortisone control of intractable asthma is dependent on large dosage until clinical improvement is obtained, then approximately 100 mg. two or three times a week for maintenance of a reasonable state of health.


A Study on the Laser-Assisted Machining of Carbon Fiber Reinforced Silicon Carbide.
In recent years, as replacements for traditional manufacturing materials, monolithic ceramics and carbon fiber reinforced silicon carbide (C/SiC) ceramic matrix composites have seen significantly increased usage due to their superior characteristics of relatively low density, lightweight, and good high temperature mechanical properties. Demand for difficult-to-cut materials is increasing in a variety of area such as the automotive and aerospace industries, but these materials are inherently difficult to process because of their high hardness and brittleness. When difficult-to-cut materials are processed by conventional machining, tool life and quality are reduced due to the high cutting force and temperatures. Laser-assisted machining (LAM) is a method of cutting a workpiece by preheating with a laser heat source and lowering the strength of the material. LAM has been studied by many researchers, but studies on LAM of carbon-ceramic composites have been carried out by only a few researchers. This paper focuses on deducing the optimal machining parameters in the LAM of C/SiC. In this study, the Taguchi method is used to obtain the major parameters for the analysis of cutting force and surface roughness under various machining conditions. Before machining experiments, finite element analysis is performed to determine the effective depth of the cut. The cutting parameters for the LAM operation are the depth of cut, preheating temperature, feed rate, and spindle speed. The signal to noise (S/N) ratio and variance analysis (ANOVA) of the cutting force and surface roughness are analyzed, and the response optimization method is used to suggest the optimal machining parameters.


Novel device accurately measures graft resistance and compliance to ensure quality of coronary artery bypass.
The purpose of this study is to know the influence of coronary artery bypass grafting (CABG) on coronary circulation. In the present study, we evaluated CABG by using a novel flow analyzer that can calculate bypass graft resistance (Ra), resistance of the peripheral bed to which graft connects (Rp), the inertia of blood flow through the graft (L) and vascular wall compliance (C). We performed off-pump CABG surgery on fifteen pigs assigned to the following groups (n = 5 each): normal CABG, competitive flow grafts and constrictive grafts. The wave pattern of 3 groups showed a clearly different form. In normal CABG and competitive flow group, we accepted a statistical difference in Rp and flow. In normal CABG and constrictive grafts. We accepted a statistical difference in Ra and flow. We can know the relationship between CABG and coronary circulation by this device in detail. This device will be useful for evaluating graft performance during CABG.


Survey of grapevine Vitis vinifera stem polyphenols by liquid chromatography-diode array detection-tandem mass spectrometry.
Grapes and red wine prepared from Vitis vinifera L. contain a variety of polyphenols. Some information is available about the polyphenols of the seeds and leaves of grapevine, but considerably less is known about the polyphenols of woody stems. In this paper, we describe the results of a study of polyphenolic compounds in grapevine stems. We demonstrate how a combination of reversed phase high-performance liquid chromatography with ultraviolet-diode array detection and electrospray ionization-tandem mass spectrometry ion-trap detection enables characterization of a phytochemical mixture of considerable complexity. As the polyphenol source, the stems of three frost-hardy grapevine varieties [Hasaine (Hasansky) sladki, Zilga, and Yubilei Novgoroda] were used. The main group of methanol-extractable polyphenols of stems consists of trans-resveratrol and its derivatives including oligomers and glucosides. As minor components of the extract, stilbenoid piceatannol as well as a number of nonstilbenoid polyphenols, mostly flavan-3-ols and phenolic acids glucosides, were determined. The total polyphenol content of the grapevine stems depends on the variety, whereby the stems of cultivar Yubilei Novgoroda with white grapes contain significantly less of both groups of polyphenols.


Intraoral Pain Disorders.
Those experiencing intraoral pain associated with dental and oral diseases are likely to pursue treatment from medical and dental providers. The causes for intraoral pain include odontogenic, periodontal, oral mucosal, or contiguous hard and soft tissue structures to the oral cavity. Providers should be vigilant when diagnosing these, as they should be among the first in their differential diagnoses to be ruled out. This review provides brief overviews of frequently encountered oral/dental diseases that cause intraoral pain, originating from the teeth, the surrounding mucosa and gingivae, tongue, bone, and salivary glands and their causes, features, diagnosis, and management strategies.


Parity-time-symmetric microring lasers.
The ability to control the modes oscillating within a laser resonator is of fundamental importance. In general, the presence of competing modes can be detrimental to beam quality and spectral purity, thus leading to spatial as well as temporal fluctuations in the emitted radiation. We show that by harnessing notions from parity-time (PT) symmetry, stable single-longitudinal mode operation can be readily achieved in a system of coupled microring lasers. The selective breaking of PT symmetry can be used to systematically enhance the maximum attainable output power in the desired mode. This versatile concept is inherently self-adapting and facilitates mode selectivity over a broad bandwidth without the need for other additional intricate components. Our experimental findings provide the possibility to develop synthetic optical devices and structures with enhanced functionality.


Anti-leishmanial, anti-inflammatory and antimicrobial activities of phenolic derivatives from Tibouchina paratropica.
A new phenolic derivative, 2,8-dihydroxy-7H-furo[2,3-f]chromen-7-one (1), together with isoquercitrin (2), was isolated from the aerial parts of Tibouchina paratropica. Compound structures were elucidated by spectroscopic methods. Both compounds show antimicrobial activity towards a panel of bacterial and fungal pathogens, and compound 1 displayed potent anti-parasitic activity against Leishmania donovani (IC50 = 0.809 µg/mL). In addition, an 85% reduction in the secretion of the pro-inflammatory cytokine IL-6 was recorded when macrophages challenged with lipopolysaccharide were exposed to compound 1, but no effect on the anti-inflammatory IL-10 was observed. Compound 2 showed neither anti-parasitic nor anti-inflammatory properties. In addition, no cytotoxic activities were observed against the human-derived macrophage THP-1 cells.


[Mental dysontogeny as a clinicopathogenetic problem for pediatric psychiatry].
The concept of psychic dysontogenesis as a part of general post-natal dysontogenesis is formulated, and the principal types of the pathogenetic mechanisms of the psychic dysontogenesis and their clinical manifestations in the form of particular psychopathological syndromes and symptoms are described. The author believes that it is not reasonable to differentiate negative and productive psychopathological dysontogenetic disorders.


Drug-induced Interstitial Nephritis in a Patient with Ulcerative Colitis Treated with 5-Aminosalicylic Acid: A Case Report.
This report describes the case of a 76-year-old man with ulcerative colitis who developed interstitial nephritis after starting 5-aminosalicylic acid (5-ASA) therapy. The patient experienced an initial improvement in symptoms, but developed fatigue, anorexia, and severe renal dysfunction 2.5 months later. Renal biopsy confirmed drug-induced interstitial nephritis, and conservative treatment with fluid replacement and the discontinuation of 5-ASA improved the patient's condition. Clinicians should monitor patients receiving 5-ASA therapy for potential adverse effects, particularly renal injury, and promptly investigate symptoms of renal dysfunction. Early recognition and discontinuation of the offending agent may prevent further damage and improve patient outcomes.


Effects of race on responses and response latencies in the weapon identification task: a test of six models.
The authors consider six models of underlying process in the weapon identification task: The first two are response-time extensions of signal detection models; the last four, of the process dissociation model. Predictions for accuracy data, correct response latencies, and false response latencies are used to discriminate between models. In the present study, racial bias in responses and correct response latency was replicated. New findings were that the direction of bias was reversed in error latency and that errors were faster than correct responses. These findings rule out four models, in particular, the idea that race biases early perception and interpretation of targets. Implications for reducing errors in the weapon identification task and possibilities of discriminating between the remaining two models are discussed.


Molecular mechanisms in C-Phycocyanin induced apoptosis in human chronic myeloid leukemia cell line-K562.
C-Phycocyanin (C-PC), the major light harvesting biliprotein from Spirulina platensis is of greater importance because of its various biological and pharmacological properties. It is a water soluble, non-toxic fluorescent protein pigment with potent anti-oxidant, anti-inflammatory and anti-cancer properties. In the present study the effect of highly purified C-PC was tested on growth and multiplication of human chronic myeloid leukemia cell line (K562). The results indicate significant decrease (49%) in the proliferation of K562 cells treated with 50 microM C-PC up to 48 h. Further studies involving fluorescence and electron microscope revealed characteristic apoptotic features like cell shrinkage, membrane blebbing and nuclear condensation. Agarose electrophoresis of genomic DNA of cells treated with C-PC showed fragmentation pattern typical for apoptotic cells. Flow cytometric analysis of cells treated with 25 and 50 microM C-PC for 48 h showed 14.11 and 20.93% cells in sub-G0/G1 phase, respectively. C-PC treatment of K562 cells also resulted in release of cytochrome c into the cytosol and poly(ADP) ribose polymerase (PARP) cleavage. These studies also showed down regulation of anti-apoptotic Bcl-2 but without any changes in pro-apoptotic Bax and thereby tilting the Bcl-2/Bax ratio towards apoptosis. These effects of C-PC appear to be mediated through entry of C-PC into the cytosol by an unknown mechanism. The present study thus demonstrates that C-PC induces apoptosis in K562 cells by cytochrome c release from mitochondria into the cytosol, PARP cleavage and down regulation of Bcl-2.


A retrospective cohort study of intensive gastric variceal ligation versus endoscopic gastric variceal obturation in the management of gastric variceal bleeding.
Gastric variceal bleeding is often more serious and can be fatal. Currently, international consensus recommendations for the treatment of gastric variceal bleeding vary according to endoscopic classification. Few studies have investigated ligation versus gastric variceal obturation (GVO) for the treatment of gastric varices. The study included 79 patients with cirrhosis-induced bleeding from esophageal and fundal varices who were treated at the Second Hospital of Hebei Medical University between January 2016 and December 2020 and who met the inclusion criteria. Among them, 42 patients were included in the intensive gastric varices ligation (IGVL) group, and 37 were included in the GVO group. We conducted a retrospective cohort study to analyze the effectiveness and safety of these 2 treatments. The rebleeding rate after initial treatment was significantly lower in the IGVL group than in the GVO group (23.8% vs. 48.6%, P<0.05). No significant between-group difference was observed in overall mortality (14.3% vs. 32.4%), 6-week mortality (0.0% vs. 2.7%), or 1-year mortality (11.9% vs. 13.5%, all P>0.05). The >1-year mortality and bleeding-related mortality rates were significantly higher in the GVO group than in the IGVL group (23.3% vs. 2.7%, P<0.05; 27.0% vs. 9.5%, P<0.05). The incidence of adverse events was 57.1% in the IGVL group and 48.6% in the GVO group, with no significant difference (P>0.05). Independent predictors for rebleeding after initial treatment were the use of GVO as endoscopic treatment, total bilirubin >17.1 µmol/L, liver cancer, and diabetes. For mortality, the independent predictors were male sex, liver cancer, ascites, and rebleeding after initial treatment. Rebleeding after initial treatment was lower after IGVL than GVO. Independent predictors for rebleeding after initial treatment were endoscopic treatment method, total bilirubin >17.1 µmol/L, liver cancer, and diabetes. For mortality, the independent predictors were male sex, liver cancer, ascites, and rebleeding after initial treatment.


Clinical characterisation of severe hypoglycaemia--a prospective population-based study.
To determine the clinical characteristics of severe hypoglycaemia (SH) in a nonselected German population. SH was defined as an event requiring intravenous glucose or glucagon injection. The prospective population-based study screened sensitively for SH in a region with 200,000 inhabitants between 1997 and 2000. All 30,768 patients who presented to the regional central hospital emergency department, and 6,631 (85 %) of 7,804 patients attended by the emergency medical service in the region were given an initial blood glucose test to detect atypical hypoglycaemia. Altogether, 264 cases of SH were registered, which occurred either spontaneously (n = 14; 5 %), in subjects with type 1 (n = 92; 35 %) or type 2 diabetes (n = 148; 56 %), or in subjects with a non-classified form of diabetes (n = 10; 4 %). On the basis of the estimated local number of diabetic patients the annual rate of SH was 1.5 episodes per 100 patients in insulin-treated type 2 diabetics compared with a rate of 0.4 episodes per 100 patients for the overall group of type 2 diabetic patients. Nocturnal hypoglycaemia accounted for 44 % of episodes in patients with type 1 diabetes on intensified therapy but for only 25 % in patients with type 2 diabetes. 26 % of the hypoglycaemic individuals with type 1 diabetes had an impaired awareness of hypoglycaemia and thus recurrent hypoglycaemic episodes. Irrespective of the treatment, the most frequent contributing factors for SH in type 2 diabetic patients were advanced age (76 +/- 12 years), multimorbidity (3.6 +/- 2.6 concomitant diseases)--in particular renal impairment (54 % [80/148])--and polypharmacy (4 +/- 2.7 concomitant drugs). 34 % (50/148) of the subjects with type 2 diabetes lived in nursing homes or were cared for by a home nursing service. With standardised treatment zero mortality of SH in diabetic patients was achieved, only one non-diabetic died due to hepatic failure. In elderly, multimorbid patients approaching the insulin-deficient end of the spectrum of type 2 diabetes the risk of developing SH increases considerably, nearing that in patients with type 1 diabetes. In order to avoid SH in geriatric patients, the treatment targets should be defined critically, taking into account individual quality of life and life expectancy. Hypoglycaemia unawareness is a major risk factor for SH in type 1 diabetes.


Vitamin A transport in human vitamin A toxicity.
The plasma retinol transport system was studied in three patients with chronic hypervitaminosis A. The toxic state in each was associated with increased plasma concentrations of total vitamin A, and particularly of retinyl esters. The concentrations of plasma retinol-binding protein and prealbumin were, in contrast, non to retinol-binding protein. These limited clinical data support conclusions from detailed studies with hypervitaminotic rats, which suggest that vitamin A toxicity occurs when excessive amounts of vitamin A are presented to cell membranes in association with plasma lipoproteins, rather than specifically bound to retinol-binding protein. Retinol-binding protein may not only regulate the supply of retinol to tissues but also protect tissues from the surface-active properties of the vitamin.


Temporal rhythm of petal programmed cell death in Ipomoea purpurea.
Flowers are the main sexual reproductive organs in plants. The shapes, colours and scents of corolla of plant flowers are involved in attracting insect pollinators and increasing reproductive success. The process of corolla senescence was investigated in Ipomoea purpurea (Convolvulaceae) in this study. In the research methods of plant anatomy, cytology, cell chemistry and molecular biology were used. The results showed that at the flowering stage cells already began to show distortion, chromatin condensation, mitochondrial membrane degradation and tonoplast dissolution and rupture. At this stage genomic DNA underwent massive but gradual random degradation. However, judging from the shape and structure, aging characteristics did not appear until the early flower senescence stage. The senescence process was slow, and it was completed at the late stage of flower senescence with a withering corolla. We may safely arrive at the conclusion that corolla senescence of I. purpurea was mediated by programmed cell death (PCD) that occurred at the flowering stage. The corolla senescence exhibited an obvious temporal rhythm, which demonstrated a high degree of coordination with pollination and fertilization.


Medial canal fibrosis: surgical technique, results, and a proposed grading system.
To report the hearing and surgical results in patients with medial canal fibrosis. To describe the surgical technique for removal of medial canal fibrosis and to propose a classification for grading postoperative surgical outcome and to correlate this with hearing results. Tertiary university referral center. Retrospective case review. Twenty-one patients with mature medial canal fibrosis underwent a total of 26 operations at our institution from February 1994 to June 2003. Four patients underwent surgery for bilateral disease and another had a second operation for recurrence. According to the proposed grading system, 10 (38.5%) of the 29 ears operated on achieved a Grade I result (normal self-cleaning ears) and three (11.5%) had recurrence (Grade III). One patient was found to have external ear canal cholesteatoma. Postoperatively, 15 ears demonstrated closure of the air-bone gap to within 10 dB or improvement on four-frequency average pure-tone audiogram to better than 25 dB. The mean preoperative air-bone gap was 28.7 dB compared with 12.5 dB postoperatively (p < 0.001). When hearing results were correlated with postoperative grade, 90.0% of the ears with a Grade I result had significant hearing improvement, 46.2% in patients with Grade II and 33.3% in patients with Grade III results. Four patients complained of temporomandibular joint pain postoperatively. Surgery remains the treatment of choice for mature medial canal fibrosis. With proper surgical technique and meticulous postoperative care, a patent and functioning external ear canal can be achieved in a majority of patients. Absence of recurrence does not equate with improved hearing thresholds.


My friend is embarrassing me: exploring the guilty by association effect.
It is contended that people (known here as associates) erroneously believe that their social standing suffers when people with whom they are associated (offenders) act in socially inappropriate ways. Accordingly, the anticipated evaluations of associates and observers were contrasted in 6 studies. Study 1 participants read a second-person scenario from the perspective of an associate or an observer. Associates anticipated that observers would give them less positive ratings when the offender picked his or her nose (versus control), but observers' ratings were unaffected. In Study 2, associates erroneously anticipated that observers' ratings of them would vary systematically as a function of whether or not they were introduced as friends of an offender who had/had not committed academic misconduct. In Study 3, anticipated ratings of associates were negatively affected by the actions of an offender whom they did not know previously. Study 4 showed that perspective-taking is the key to attenuating the effect and reducing feelings of embarrassment. The last 2 studies clarified the role of physical proximity and felt closeness. Consistent with results of a scenario study (Study 5), Study 6 participants' anticipated ratings were negatively affected by a combination of increased physical proximity and felt closeness.


An unexpected case of Borrelia garinii liver infection.
Lyme borreliosis is the most prevalent arthropod-borne infection in the Northern Hemisphere. In Europe, Borrelia afzelii is predominantly involved in cutaneous manifestations, Borrelia garinii and Borrelia bavariensis in neurological manifestations, and Borrelia burgdorferi sensu stricto in articular ones. Liver impairement is not classical in Lyme borreliosis. Diagnosis is currently mainly based on serological testing, and is challenging in immunocompromised patients. We report the first case of B. garinii infection revealed by liver involvement in an immunocompromised man. A 73-year-old man with marginal zone lymphoma, treated with bendamustine and rituximab, developed intermittent fever and inflammatory syndrome. Microbial investigations were all negative and FDG-PET showed complete remission of the lymphoma. Three months later, liver biopsy was performed and histology revealed spirochetes-like bacteria. Microbial diagnosis was performed by 16S rDNA sequencing, flagellin (flaB) gene sequencing and multi-locus sequence typing and identified B. garinii. The patient recovered successfully after a three weeks course of antibiotics. Diagnosis was challenging because Borrelia hepatic involvement is unusual and no erythema migrans nor tick bite were notified. This case highlights that unexplained fever and inflammatory syndrome in immunocompromised patients warrants specific investigations to identify bacteria such as spirochetes.


[Colorectal nociceptive signal input facilitates impact of acupoint stimulation of "Zusanli" (ST 36) on electrical activities of wide dynamic range neurons in lumbar spinal cord in rats].
To observe changes of electrical activities of wide dynamic neurons (WDR) in the lumbar spinal cord after electroacupuncture (EA) stimulation of "Zusanli" (ST 36) during colorectal distension in rats, so as to analyze alternations of acupoint's functions under pathological conditions. Experiments were performed in male Sprague-Dawley rats. Visceral nociceptive information input was generated by colorectal distension (CRD). Extracellular discharges of WDR neu- rons in the dorsal horns of L(1-3) spinal cord were recorded using glass micropipettes and a microelectrode amplifier. EA stimulation (15 Hz, 1, 4, 7, 10 mA) was applied to ipsilateral "Zusanli" (ST 36) area. A total of 40 neurons were recorded in the present study. Under no CRD conditions, the firing rates of WDR neurons were significantly increased by (18.12 +/- 13.56)% (1 mA), (152.38 +/- 36.19)% (4 mA), (231.21 +/- 49.74)% (7 mA) and (331.54 +/- 61.89)% (10 mA) respectively after EA sti- mulation of ST 36. Under CRD conditions, the firing rates of these WDR neurons were increased by (226.78 +/- 39.59)% (1 mA), (282.80 +/- 47.54)% (4 mA), (343.06 +/- 58.35)% (7 mA), and (338.62 +/- 80.04)% (10 mA) respectively after EA stimulation. It showed a considerablely increased sensitivity of electrical activities of WDR neurons to EA stimulation during CRD nociceptive stimulation. colorectal distension (visceral nociceptive stimulation) can strengthen the sensitivity of acupoint-EA stimulation-induced increase of firing rates of WDR neurons in the dorsal horns of the lumbar spinal cord in rats, suggesting a potentiation of the acupoint action under visceral nociceptive signal inputs.


G-ROP criteria for predicting retinopathy of prematurity among neonates with different birth weight percentiles.
The Postnatal Growth and Retinopathy of Prematurity (G-ROP) Study showed that adding postnatal weight gain to birth weight and gestational age detected 100% of cases with type 1 retinopathy of prematurity (ROP) while reducing the ROP examinations by 30%. The purpose of this study was to investigate whether being small for gestational age (SGA) affects the sensitivity and specificity of the G-ROP model. We applied the G-ROP criteria for premature infants. The infants were classified as three subgroups: SGA, appropriate for gestational age (AGA), and large for gestational age (LGA). The performance of G-ROP criteria was assessed for each group for ROP. There were 41 (10.5%) SGA, 312 (80%) AGA, and 37 (9.5%) LGA neonates. Twenty-six (6.7%) neonates were treated for ROP, and the G-ROP model identified all of them. The sensitivity of the model for treatment-requiring ROP (TR-ROP) was found to be 100% in the whole patient group and for each subgroup. The specificity for TR-ROP was 46.4% for the whole group, 50% for SGA, 44% for AGA, and 63.6% for LGA. By applying the G-ROP model, the number of ROP examinations could be reduced by 25% for the whole group, 27% for SGA, 24% for AGA, and 31% for LGA, without missing TR-ROP. The sensitivity and specificity of the G-ROP model for TR-ROP in SGA infants were similar to the whole group. The model did not miss any cases of TR-ROP.


Investigating Parent Needs, Participation, and Psychological Distress in the Children's Hospital.
Greater parent participation in a child's hospital care is associated with better child outcomes in the hospital and after discharge. This study examined the relationships between perceived need fulfillment for parents, parent participation in hospital care, and parent psychological distress. We hypothesized that greater perceived need fulfillment would be associated with greater participation in hospital care and decreased psychological distress. In this prospective cohort study, 166 parents completed questionnaires on a pediatric (nonintensive care) floor. Eligible parents were fluent in English and had a child who was hospitalized ≥2 nights. Previously validated questionnaires were used to assess parent participation in hospital care and psychological distress (defined here as symptoms of anxiety/depression). A modified version of the Bereaved Parent Needs Assessment was used to assess perceived need fulfillment. The association between perceived need fulfillment and each outcome variable was examined using multiple linear regression analyses. Of 186 eligible parents, 166 were enrolled (1 declined, 19 missed/not present). In multivariable analyses, greater perceived need fulfillment was associated with greater participation in hospital care and fewer symptoms of depression, even after controlling for relevant covariates. Exploratory analyses identified needs that were differentially important within groups of parents at risk for distress. This study suggests that assessing and supporting parent needs during a child's hospitalization may improve parent and child outcomes by increasing parents' ability to participate in hospital care and decreasing psychological distress. Future research is needed to investigate the impact of interventions targeting specific parent needs.


Anterior cruciate ligament reconstruction with hamstring tendons and cross-pin femoral fixation compared with patellar tendon autografts.
To investigate the outcome of arthroscopic anterior cruciate ligament (ACL) reconstruction with hamstring autograft using femoral cross-pin fixation compared with patellar tendon autografts. Matched retrospective cohort. Twenty-one patients who underwent ACL reconstruction with hamstring autograft and femoral cross-pin fixation were evaluated at an average of 16.4 months postoperatively. Subjective data were collected using the International Knee Documentation Committee (IKDC) and the Cincinnati Knee Scale. Objective data included a comprehensive knee examination, plain radiographs, and KT-1000 measurements. The results were compared with 19 matched patients who had previously undergone ACL reconstruction using patellar tendon autograft. The average KT-1000 maximal manual side-to-side difference was 1.63 +/- 0.68 mm. Eighty-six percent of IKDC scores were normal or nearly normal. The average overall Cincinnati Knee Scale subjective symptom rating was 8.7 +/- 1.2. There was no significant difference in subjective or objective data between the 2 groups. ACL reconstruction using femoral cross-pin fixation is a reliable technique showing outcomes comparable to other established methods of fixation. Level IV, case series.


Independent clinical significance of HIV antigen determination and CD4 counts in anti-HIV positive patients.
HIV antigenemia was found in 52/243 HIV antibody positive individuals attending 2 AIDS-screening clinics, giving a prevalence of 13, 25 and 76% in CDC groups II, III and IV, respectively. No correlation was found to decreased CD4 lymphocyte values in the individual groups. HIV antigen therefore identified a separate subpopulation. For 138 asymptomatic patients followed prospectively both laboratory parameters predicted HIV-related events, the relative risk factor being 4 for low CD4 value and 6 for presence of HIV antigen. Individuals presenting with HIV antigen and decreased CD4 count all developed disease within 18 months, the relative risk factor being 24. Thus the 2 markers, when measured together, effectively separated asymptomatic HIV-infected patients into 1 of 3 risk categories.


Effects of isomerization on the measured thermochemical properties of deprotonated glycine/protic-solvent clusters.
The thermochemical properties associated with the formation of an isomeric distribution of ROHNH(2)CH(2)COO(-) clusters (R=H, CH(3), C(2)H(5)) are measured by using high-pressure mass spectrometry. A comparison of the measured properties with calculated values provides new insights into the thermochemical effects arising from the isomeric nature of this clustering system. When the distribution of isomers is correctly accounted for, the measured values of DeltaH degrees , DeltaS degrees , and DeltaG degrees (298) consistently agree, to a very high degree of accuracy, with those predicted by MP2(full)/6-311++G(d,p)//B3LYP/6-311++G(d,p) calculations.


Anti-Tumor Effect of Steamed Codonopsis lanceolata in H22 Tumor-Bearing Mice and Its Possible Mechanism.
Although previous studies confirmed that steaming and the fermentation process could significantly improve the cognitive-enhancement and neuroprotective effects of Codonopsis lanceolata, the anti-tumor efficacy of steamed C. lanceolata (SCL) and what mechanisms are involved remain largely unknown. The present study was designed to evaluate the anti-tumor effect in vivo of SCL in H22 tumor-bearing mice. The results clearly indicated that SCL could not only inhibit the tumor growth, but also prolong the survival time of H22 tumor-bearing mice. Besides, the serum levels of cytokines, such as interferon gamma (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-2 (IL-2), were enhanced by SCL administration. The observations of Hoechst 33258 staining demonstrated that SCL was able to induce tumor cell apoptosis. Finally, immunohistochemical analysis revealed that SCL treatment significantly increased Bax expression and decreased Bcl-2 and vascular endothelial growth factor (VEGF) expression of H22 tumor tissues in a dose-dependent manner. Moreover, LC/MS analysis of SCL indicated that it mainly contained lobetyolin and six saponins. Taken all together, the findings in the present study clearly demonstrated that SCL inhibited the H22 tumor growth in vivo at least partly via improving the immune functions, inducing apoptosis and inhibiting angiogenesis.


Mechanism of Longevity Extension of Caenorhabditis elegans Induced by Schizophyllum commune Fermented Supernatant With Added Radix Puerariae.
Schizophyllum commune (S. commune) fermented supernatant with added Radix Puerariae (SC-RP) showed significant antioxidant activity in our previous work. However, the possible lifespan and healthspan extending the capacity of Caenorhabditis elegans (C. elegans) and the underlying mechanism were not illuminated. In this study, the effect of SC-RP on extending the lifespan and improving stress resistance of C. elegans were examined. Additionally, the underlying lifespan extending molecular mechanisms of SC-RP were explored. Treated with SC-RP at 10 μg/mL, the lifespan of C. elegans increased by 24.89% (P < 0.01). Also, SC-RP prolonged the healthspan of the nematode, including reducing lipofuscin levels, improving mobility and enhancing resistance to oxidative stress and heat shock. Moreover, superoxide dismutase and catalase activities were increased for SC-RP treated C. elegans. Meantime the intracellular levels of thiobarbituric acid reactive substances (TBARS) and reactive oxygen species (ROS) were attenuated. Express levels of eight genes including daf-2, daf-16, sod-3, skn-1, gst-4, clk-1, age-1 and mev-1 were analyzed by RT-PCR method for possible C. elegan anti-aging mechanisms of SC-RP. Expression levels of key genes daf-2, gst-4 and sod-3 were up-regulated, while that of daf-16, skn-1, and clk-1 were down-regulated. The results suggest that SC-RP could extend the lifespan and healthspan of C. elegans significantly, and the IIS pathway, SKN-1/Nrf2 pathway and mitochondrial metabolism pathway were primarily considered associated. Thus, SC-RP is a potential component to improve aging and aging-related symptoms as new functional materials.


Brown adipose tissue. III. Effect of ethanol, nicotine and caffeine exposure.
Brown adipose tissue is known to be the most important organ for generating heat in non-shivering thermogenesis. Process of thermogenesis and thermoregulation may be affected by many drugs. The paper deals with actual literary data of effect of ethanol, nicotine and caffeine on brown adipose tissue, heat production and its regulation in experimental animals and in human.


The liver biopsy diagnosis of Wilson's disease. Methods in pathology.
The authors present a simple liver biopsy protocol that is a reliable and cost-effective method of diagnosing hepatic Wilson's disease. Biopsy specimens are obtained in routine fashion, without the need for copper-free solutions or instruments. The samples are then embedded in paraffin, stained for copper and copper-associated protein, and studied by light microscopy. Subsequently, a sample of hepatic parenchyma is excised from the paraffin block for chemical quantitation of tissue copper. This combination of methods generally yields reliable results and allows confirmation of the diagnosis in cases of Wilson's disease in which special stains for copper are negative. In most instances, electron-microscopic studies are not necessary.


A Participatory System for Preventing Pandemics of Animal Origins: Pilot Study of the Participatory One Health Disease Detection (PODD) System.
Aiming for early disease detection and prompt outbreak control, digital technology with a participatory One Health approach was used to create a novel disease surveillance system called Participatory One Health Disease Detection (PODD). PODD is a community-owned surveillance system that collects data from volunteer reporters; identifies disease outbreak automatically; and notifies the local governments (LGs), surrounding villages, and relevant authorities. This system provides a direct and immediate benefit to the communities by empowering them to protect themselves. The objective of this study was to determine the effectiveness of the PODD system for the rapid detection and control of disease outbreaks. The system was piloted in 74 LGs in Chiang Mai, Thailand, with the participation of 296 volunteer reporters. The volunteers and LGs were key participants in the piloting of the PODD system. Volunteers monitored animal and human diseases, as well as environmental problems, in their communities and reported these events via the PODD mobile phone app. LGs were responsible for outbreak control and provided support to the volunteers. Outcome mapping was used to evaluate the performance of the LGs and volunteers. LGs were categorized into one of the 3 groups based on performance: A (good), B (fair), and C (poor), with the majority (46%,34/74) categorized into group B. Volunteers were similarly categorized into 4 performance groups (A-D), again with group A showing the best performance, with the majority categorized into groups B and C. After 16 months of implementation, 1029 abnormal events had been reported and confirmed to be true reports. The majority of abnormal reports were sick or dead animals (404/1029, 39.26%), followed by zoonoses and other human diseases (129/1029, 12.54%). Many potentially devastating animal disease outbreaks were detected and successfully controlled, including 26 chicken high mortality outbreaks, 4 cattle disease outbreaks, 3 pig disease outbreaks, and 3 fish disease outbreaks. In all cases, the communities and animal authorities cooperated to apply community contingency plans to control these outbreaks, and community volunteers continued to monitor the abnormal events for 3 weeks after each outbreak was controlled. By design, PODD initially targeted only animal diseases that potentially could emerge into human pandemics (eg, avian influenza) and then, in response to community needs, expanded to cover human health and environmental health issues.


Practical Assessment and Management of Vulnerabilities in Older Patients Receiving Systemic Cancer Therapy: ASCO Guideline Update.
To update the ASCO guideline (2018) on the practical assessment and management of age-associated vulnerabilities in older patients undergoing systemic cancer therapy. An Expert Panel conducted a systematic review to identify relevant randomized clinical trials (RCTs), systematic reviews, and meta-analyses from January 2016 to December 2022. A total of 26 publications met eligibility criteria and form the evidentiary basis for the update. The Expert Panel reiterates its overarching recommendation from the prior guideline that geriatric assessment (GA), including all essential domains, should be used to identify vulnerabilities or impairments that are not routinely captured in oncology assessments for all patients over 65 years old with cancer. Based on recently published RCTs demonstrating significantly improved clinical outcomes, all older adults with cancer (65+ years old) receiving systemic therapy with GA-identified deficits should have GA-guided management (GAM) included in their care plan. GAM includes using GA findings to inform cancer treatment decision-making as well as to address impairments through appropriate interventions, counseling, and/or referrals. A GA should include high priority aging-related domains known to be associated with outcomes in older adults with cancer: physical and cognitive function, emotional health, comorbid conditions, polypharmacy, nutrition, and social support. Clinical adaptation of the GA based on patient population, resources, and time is appropriate.The Panel recommends the Practical Geriatric Assessment as one option for this purpose (https://old-prod.asco.org/sites/new-www.asco.org/files/content-files/practice-patients/documents/2023-PGA-Final.pdf; https://youtu.be/jnaQIjOz2Dw; https://youtu.be/nZXtwaGh0Z0).Additional information is available at www.asco.org/supportive-care-guidelines.


Vaccine Hesitancy Under the Magnifying Glass: A Systematic Review of the Uses and Misuses of an Increasingly Popular Construct.
Resistance to vaccines has hindered attempts to contain and prevent outbreaks of infectious diseases for centuries. More recently, however, the term "vaccine hesitancy" has been used to describe not necessarily outright resistance but also a delay in acceptance or uncertainty regarding vaccines. Given concerns about hesitancy and its impact on vaccine uptake rates, researchers increasingly shifted the focus from resistance to vaccines toward vaccine hesitancy. Acknowledging the urgency to accurately assess the phenomenon, it is critical to understand the state of the literature, focusing on issues of conceptualization and operationalization. To carry out this systematic review, we collected and analyzed all published empirical articles from 2000 to 2021 that explicitly included quantitative self-report measures of vaccine hesitancy (k = 86). Using a mixed-method approach, the review demonstrates and quantifies crucial inconsistencies in the measurement of the construct, lack of clarity in regard to the determination of who should or should not be defined as hesitant, and overreliance on unrepresentative samples. Crucially, our analysis points to a potential systematic bias toward exaggerating the level of hesitancy in the population. Modeling a vaccine hesitancy co-citation network, the analysis also points to the existence of insular academic silos that make it harder to achieve a unified measurement tool. Theoretical and practical implications for academics, practitioners, and policymakers are discussed.


Profile of a large sample of patients with social phobia: comparison between generalized and specific social phobia.
This study examines a large cohort of subjects with social phobia, as part of a larger naturalistic and longitudinal study of 711 subjects with anxiety disorders. We focused on 176 subjects who were in an episode of social phobia at intake. We were particularly interested in evaluating the diagnostic distinction between generalized and specific social phobia. We compared these two groups along demographic characteristics, comorbidities, psychosocial functioning (health, role functioning, social functioning, and emotional functioning) and global assessment scores. We found that generalized social phobics tended to have an earlier age of onset as compared to the specific group; however, this is not a statistically significant difference at this level of analysis. The two groups did not differ for the current comorbidities examined. We observed no differences in the treatment received by the two types of social phobia subjects, and the two groups functioned equally well in terms of health and fulfilling social roles. In addition, we examined adverse childhood events (i.e., death of a parent, childhood abuse) and found no evidence for any differential impact these events might have on the type of social phobia. Although we did observe significantly greater fear of public speaking among the specific compared to the generalized group, which may indicate a qualitative difference between the subtypes, our results suggest that for most parameters, generalized and specific social phobia represent a continuum of similar and overlapping entities.


Using Intervention Mapping to Develop Health Education and Health Policy Components to Increase Breast Cancer Screening and Chemotherapy Adherence Among Syrian and Iraqi Refugee Women in Beirut, Lebanon.
Introduction: Despite the continuous increase in the incidence of metastatic breast cancer among Syrian and Iraqi refugee women residing in camp settings in Lebanon, mammography and chemotherapy adherence rates remain low due to multiple social, economic, and environmental interfering factors. This in turn led to an alarming increase in breast cancer morbidity and mortality rates among the disadvantaged population. Methods: Intervention mapping, a systematic approach which guides researchers and public health experts in the development of comprehensive evidence-based interventions (EBIs) was used to plan a health education and health policy intervention to increase breast cancer screening and chemotherapy adherence among Iraqi and Syrian refugee women aged 30 and older who are residing in refugee camps within the Beirut district of Lebanon. Results: The generation of the logic model during the needs assessment phase was guided by an extensive review of the literature and reports published in peer-reviewed journals or by international/local organizations in the country to determine breast cancer incidence and mortality rates among refugee women of Syrian and Iraqi nationalities. The underlying behavioral and environmental determinants of the disease were identified from qualitative and quantitative studies carried out among the target population and also aided in assessing the sub-behaviors related to the determinants of breast cancer screening and chemotherapy completion as well as factors affecting policy execution to formulate performance objectives. We then developed matrices of change objectives and their respective methods and practical applications for behavior change at the intrapersonal, interpersonal, organizational, and societal levels. Both educational components (brochures, flyers) and technological methods (videos disseminated via Whats app and Facebook) will be adopted to apply the different methods selected (modeling, self-reevaluation, consciousness raising, persuasion, and tailoring). We also described the development of the educational and technological tools, in addition to providing future implementers with methods for pre-testing and pilot-testing of individual and environmental prototype components. Conclusion: The use of intervention mapping in the planning and implementation of holistic health promotion interventions based on information collected from published literature, case reports, and theory can integrate the multiple disciplines of public health to attain the desired behavioral change.


Blood flow velocity in the right coronary artery: assessment before and after angioplasty.
This study attempted 1) to assess the utility of rest measurements of intracoronary blood flow velocity for the physiologic assessment of coronary stenoses before and after right coronary artery angioplasty, and 2) to compare the phasic flow pattern in the right coronary artery proper with the phasic flow pattern in its major branches to the left ventricle. Previous investigations have demonstrated that a reduction in distal blood flow velocity and a loss of distal diastolic predominant flow are characteristic of physiologically significant stenoses and that these indexes normalize after successful coronary artery dilation. However, these studies were predominantly performed in the left coronary artery. The utility of monitoring rest velocity variables during angioplasty of the right coronary artery has not been studied. We studied 20 patients undergoing angioplasty of the right coronary artery with use of a Doppler angioplasty guide wire. Values were expressed as the mean value +/- 1 SD. The rest average peak velocity did not decrease distal to angiographically significant right coronary artery stenoses (23.3 +/- 9.4 cm/s proximal vs. 20.2 +/- 11.1 cm/s distal, p = 0.20). The proximal/distal velocity ratio was 1.4 +/- 0.9 before angioplasty and did not significantly decrease after angioplasty (p = 0.58). This study had a 99.4% power to detect a difference between proximal and distal average peak velocity. There was no relation between percent diameter stenosis and proximal/distal velocity ratios (r = 0.15, p = 0.55). Diastolic predominant flow was not observed in the proximal or distal right coronary artery. However, after angioplasty, diastolic predominant flow was observed in the posterolateral and posterior descending coronary arteries. Rest phasic Doppler flow velocity indexes are not useful for evaluating stenoses in the right coronary artery proper before or after angioplasty. In contrast to the right coronary artery proper, diastolic predominant flow is observed in the posterior descending and posterolateral coronary arteries. The utility of measuring hyperemic Doppler flow velocity indexes, such as distal coronary flow reserve, for assessing right coronary artery stenoses merits further investigation.


Novel Magnetic Resonance Imaging-Based Method for Accurate Diagnosis of Meniere's Disease.
Background: Pathologically, Meniere's disease symptoms are considered to be associated with endolymphatic hydrops. Examinations revealing endolymphatic hydrops can be useful for accurate Meniere's disease diagnosis. We previously reported a quantitative method for evaluating endolymphatic hydrops, i.e., by measuring the volume of the endolymphatic space using three-dimensional magnetic resonance imaging (MRI) of the inner ear. This study aimed to confirm the usefulness of our methods for diagnosing Meniere's disease. Here, we extracted new explanatory factors for diagnosing Meniere's disease by comparing the volume of the endolymphatic space between healthy volunteers and patients with Meniere's disease. Additionally, we validated our method by comparing its diagnostic accuracy with that of the conventional method. Methods and Findings: This is a prospective diagnostic accuracy study performed at vertigo/dizziness centre of our university hospital, a tertiary hospital. Eighty-six patients with definite unilateral Meniere's disease and 47 healthy volunteers (25 and 33 males, and 22 and 53 females in the control and patient groups, respectively) were enrolled. All participants underwent 3-Tesla MRI 4 h after intravenous injection of gadolinium to reveal the endolymphatic space. The volume of the endolymphatic space was measured and a model for Meniere's disease diagnosis was constructed and compared with models using conventional criteria to confirm the effectiveness of the methods used. The area under the receiver operating characteristic curve of the method proposed in this study was excellent (0.924), and significantly higher than that derived using the conventional criteria (0.877). The four indices, sensitivity, specificity, positive predictive value, and negative predictive value, were given at the threshold; all of these indices achieved higher scores for the 3D model compared to the 2D model. Cross-validation of the models revealed that the improvement was due to the incorporation of the semi-circular canals. Conclusions: Our method showed high diagnostic accuracy for Meniere's disease. Additionally, we revealed the importance of observing the semi-circular canals for Meniere's disease diagnosis. The proposed method can contribute toward providing effective symptomatic relief in Meniere's disease.


Exploratory factor analysis and convergent validity of the Dundee Provocation Inventory.
Background The prevalence and consequences of anger and aggression in people with intellectual disability (ID) are of great concern. It is essential that appropriate assessment tools are developed to aid formulation of treatments and to evaluate progress and outcomes. Method This study evaluates the Dundee Provocation Inventory (DPI), a 20-item assessment measure for anger provocation. A group of 114 participants were administered the DPI, and 62 of these were also administered the Novaco Anger Scale (NAS) and NAS Provocation Inventory (NAS-PI), two well-validated measures. Results Preliminary analysis revealed that the DPI correlated significantly with the NAS (r = .57) and NAS-PI (r = .77). The DPI had high internal consistency (alpha = .91) and moderate to high inter-item and item-to-total score correlations. Factor analysis revealed a 5-factor solution which accounted for 63% of the variance and was most easily interpreted. Conclusion The analysis suggests that the DPI is a suitable tool for assessing anger in people with ID. Further replication of the factor structure would be valuable.


Structure of lactococcal phage p2 baseplate and its mechanism of activation.
Siphoviridae is the most abundant viral family on earth which infects bacteria as well as archaea. All known siphophages infecting gram+ Lactococcus lactis possess a baseplate at the tip of their tail involved in host recognition and attachment. Here, we report analysis of the p2 phage baseplate structure by X-ray crystallography and electron microscopy and propose a mechanism for the baseplate activation during attachment to the host cell. This approximately 1 MDa, Escherichia coli-expressed baseplate is composed of three protein species, including six trimers of the receptor-binding protein (RBP). RBPs host-recognition domains point upwards, towards the capsid, in agreement with the electron-microscopy map of the free virion. In the presence of Ca(2+), a cation mandatory for infection, the RBPs rotated 200 degrees downwards, presenting their binding sites to the host, and a channel opens at the bottom of the baseplate for DNA passage. These conformational changes reveal a novel siphophage activation and host-recognition mechanism leading ultimately to DNA ejection.


Metagenome sequencing-based strain-level and functional characterization of supragingival microbiome associated with dental caries in children.
Studies of the microbiome associated with dental caries have largely relied on 16S rRNA sequence analysis, which is associated with PCR biases, low taxonomic resolution, and inability to accurately study functions. Here, we employed whole metagenome shotgun sequencing, coupled with high-resolution analysis algorithm, to analyze supragingival microbiomes from 30 children with or without dental caries. A total of 726 bacterial strains belonging to 406 species, in addition to 34 bacteriophages were identified. A core bacteriome was identified at the species and strain levels. Species of Prevotella, Veillonella, as yet unnamed Actinomyces, and Atopobium showed strongest association with caries; Streptococcus sp. AS14 and Leptotrichia sp. Oral taxon 225, among others, were overabundant in caries-free. For several species, the association was strain-specific. Furthermore, for some species, e.g. Streptococcus mitis and Streptococcus sanguinis, sister strains showed differential associations. Noteworthy, associations were also identified for phages: Streptococcus phage M102 with caries and Haemophilus phage HP1 with caries-free. Functionally, potentially relevant features were identified including urate, vitamin K2, and polyamine biosynthesis in association with caries; and three deiminases and lactate dehydrogenase with health. The results demonstrate new associations between the microbiome and dental caries at the strain and functional levels that need further investigation.


Penetration and stainability of modified Sato's lead staining solution.
The penetration and stainability of modified Sato's lead staining solution containing calcined lead citrate were studied. Modified Sato's lead solution was preserved for 1 week and for 2 years, each at room temperature and at 4 degrees C. Specimens were stained with these solutions to measure the stainability. After 2-min staining, specimens were stained to the depth of 1.0-1.2 microns even when there had been 2-year preservation of the staining solution. This modified solution could be preserved for a long time and good penetration and stainability could still be obtained. This solution is also suitable for the observation of semithin sections.


A Modified Tongue Crib Appliance for Correction of Tongue Thrusting.
Digit sucking and tongue thrusting are parafunctional habits that are commonly observed and are recognized as major etiological factors in the development of dental malocclusion. Treatment for these oral habits typically involves removal of the etiology, retraining exercises, and use of mechanical restraining appliances. A 13-year-old male patient reported a complaint of forwardly placed upper front teeth. The extraoral examination of the patient showed a convex profile, good facial symmetry, acute nasolabial angle, incompetent lips at rest, and a shallow mentolabial sulcus. Intraoral examination showed class I molar and canine relations on either side, a mild open bite tendency, a midline diastema, proclined upper and lower anteriors, an increased overjet, and tongue thrusting habit. A modification to the tongue crib was made by adding an acrylic bead in the center of the crib. The patient was trained to roll the bead posteriorly with the aim of retraining the tongue to posture away from the front teeth. Harmful forces of the tongue can result in excessive posterior teeth eruption, open bite, and increased overjet. Duration of appliance wear and type of appliance used are important considerations in treating patients with tongue thrust or open bite. A modified tongue crib was used for six months resulting in significant improvement in maxillary anterior dentition position, lip competence, arch forms, overbite, and midline diastema closure. A tongue crib is a useful tool for addressing tongue thrusting and digit-sucking behaviors by retraining the related muscles, providing physical restraint, and serving as a reminder to break the habit. It can be used in conjunction with a fixed appliance to improve its effectiveness.


Changes in Gait Variables in Patients with Intermittent Claudication.
Intermittent claudication (IC) is a pathological symptom with a particular effect on human gait patterns. Therefore, analyzing these patterns can facilitate rehabilitation or treatment through comparison of the values of kinematic and kinetic variables of patients with the normal values of healthy people. Therefore, the aim of this study was to find differences in the values of gait variables between patients with IC and healthy people. The study included 98 patients diagnosed with peripheral arterial disease with IC. The patients traveled a distance of 6 m at a voluntary gait velocity. Ground reaction forces while the foot contacted the ground and kinematic variables of lower limb movements were recorded. The values of normal gait variables were computed based on the results obtained in a group of 30 healthy people. Patients used a gait velocity below the norm for healthy people. The velocity during the lower limb swing and the step and stride length in patients with IC were below the norm. Differences were also found in the ranges of motion between patients with IC and healthy people for the pelvic obliquity, pelvic rotation, hip flexion-extension, hip abduction-adduction, hip internal-external rotation, knee flexion-extension, ankle dorsi-plantar flexion, and foot progression angles. The presented kinematic and kinetic characteristics measured by gait variables suggest differences between patients with IC and healthy people. Considering kinematic and kinetic gait variables during the rehabilitation process would facilitate the development of a more economic gait technique (with increased stride length and range of motion in the lower limb joints) to obtain the desired rehabilitation effects. Patients with IC should receive rehabilitation oriented towards improving mobility and increasing muscle strength in selected lower limb joints to increase gait velocity and stride length.


The microtubule-associated protein WDL4 modulates auxin distribution to promote apical hook opening in Arabidopsis.
The unique apical hook in dicotyledonous plants protects the shoot apical meristem and cotyledons when seedlings emerge through the soil. Its formation involves differential cell growth under the coordinated control of plant hormones, especially ethylene and auxin. Microtubules are essential players in plant cell growth that are regulated by multiple microtubule-associated proteins (MAPs). However, the role and underlying mechanisms of MAP-microtubule modules in differential cell growth are poorly understood. In this study, we found that the previously uncharacterized Arabidopsis MAP WAVE-DAMPENED2-LIKE4 (WDL4) protein plays a positive role in apical hook opening. WDL4 exhibits a temporal expression pattern during hook development in dark-grown seedlings that is directly regulated by ethylene signaling. WDL4 mutants showed a delayed hook opening phenotype while overexpression of WDL4 resulted in enhanced hook opening. In particular, wdl4-1 mutants exhibited stronger auxin accumulation in the concave side of the apical hook. Furthermore, the regulation of the auxin maxima and trafficking of the auxin efflux carriers PIN-FORMED1 (PIN1) and PIN7 in the hook region is critical for WDL4-mediated hook opening. Together, our study demonstrates that WDL4 positively regulates apical hook opening by modulating auxin distribution, thus unraveling a mechanism for MAP-mediated differential plant cell growth.


Lymphatic cyst of the descending colon: a report of a case.
A patient with a lymphatic cyst of the descending colon, treated by segmental colon resection, is reported. Lymphatic cysts of the colon are extremely rare, and there have been only fourteen previously reported cases. In no case has the diagnosis of lymphatic cyst of the colon been made prior to the excision of the lesion.


Experimental charge density study of estrogens: 17beta-estradiol.urea.
To relate the molecular electrostatic potential to the biological activities of estrogens, a comparative charge density study of different derivatives has been initiated. The second completed charge density analysis of this series for 17beta-estradiol*urea is presented here. This is a large organic system with 52 atoms in a noncentrosymmetric space group, therefore special tools such as an optimal coordinate system and slow, initially constrained refinement have been used to accomplish this study. Our results for the urea molecule reasonably agree with previous experimental and theoretical results. In the 17beta-estradiol molecule, the oxygen atoms appear to be close to sp3 in shape, exhibiting two consistent, distinct lone pairs despite different chemical environments. No significant interaction of the hydroxyl group oxygen with the orbitals of the aromatic ring is observed. Analysis of the electrostatic potential revealed that the negative potential in the lone pair region of the two oxygen atoms is quite different. The topological analysis of the electron density has been performed, and the atomic charges have been estimated.


Incidence of hyperkalemia in high risk patients during treatment with an angiotensin converting enzyme inhibitor (Lisinopril) versus an angiotensin II receptor blocker (Losartan).
Hyperkalemia is a known side effect during treatment with Angiotensin Converting Enzyme Inhibitors (ACEIs). The purpose of this study was to compare the effect of an ACEI (Lisinopril) to an Angiotensin II Receptor Blocker (Losartan) on serum potassium (K) level in patients with known history of high normal serum K (mean = 4.8) while on treatment with ACEIs or Angiotensin II Receptor Blockers (ARBs).


NLR family pyrin domain containing 3 (NLRP3) inflammasomes and peripheral neuropathic pain - Emphasis on microRNAs (miRNAs) as important regulators.
Neuropathic pain is caused by the lesion or disease of the somatosensory system and can be initiated and/or maintained by both central and peripheral mechanisms. Nerve injury leads to neuronal damage and apoptosis associated with the release of an array of pathogen- or damage-associated molecular patterns to activate inflammasomes. The activation of the NLR family pyrin domain containing 3 (NLRP3) inflammasome contributes to neuropathic pain and may represent a novel target for pain therapeutic development. In the current review, we provide an up-to-date summary of the recent findings on the involvement of NLRP3 inflammasome in modulating neuropathic pain development and maintenance, focusing on peripheral neuropathic conditions. Here we provide a detailed review of the mechanisms whereby NLRP3 inflammasomes contribute to neuropathic pain via (1) neuroinflammation, (2) apoptosis, (3) pyroptosis, (4) proinflammatory cytokine release, (5) mitochondrial dysfunction, and (6) oxidative stress. We then present the current research literature reporting on the antinociceptive effects of several natural products and pharmacological interventions that target activation, expression, and/or regulation of NLRP3 inflammasome. Furthermore, we emphasize the effects of microRNAs as another regulator of NLRP3 inflammasome. In conclusion, we summarize the possible caveats and future perspectives that might provide successful therapeutic approaches against NLRP3 inflammasome for treating or preventing neuropathic pain conditions.


[A comparison of the radioimmunologic and immunoenzyme methods of detecting HBsAg].
The frequency of HBsAg detection by these two methods is similar, but only half of positive results is confirmed by both methods. This discrepancy appears to be explained by inadequate technology of the reagent preparation or by impossibility to rule out false-positive results. Combinations of highly sensitive methods for HBsAg indication are recommended for clinical diagnosis of hepatitis B.


Fabrication of nanoscale rings, dots, and rods by combining shadow nanosphere lithography and annealed polystyrene nanosphere masks.
The application of shadow nanosphere lithography for the preparation of large-area, two-dimensional, metallic nanostructures of different shape is described. Through changing the mask morphology by temperature processing and varying the evaporation conditions, particles with morphologies such as rings, rods, and dots have been produced. This process allows outstanding control of the size and morphology of the particles. The efficient technique is shown to scale down the size of metallic nanoparticles from 200 to 30 nm, while preserving the original nanosphere spacing and order. The 150-nm-diameter Fe rings produced by this method show ferromagnetic behavior, which was predicted by theoretical simulation. All the experimental results were confirmed by computer simulations, which also showed the possibility of creating periodic arrays of any other geometrical shape.


Noninvasive cross-sectional imaging of proximal caries using swept-source optical coherence tomography (SS-OCT) in vivo.
The aim of this study was to determine the diagnostic accuracy of swept-source optical coherent tomography (SS-OCT) in detecting and estimating the depth of proximal caries in posterior teeth in vivo. SS-OCT images and bitewing radiographs were obtained from 86 proximal surfaces of 53 patients. Six examiners scored the locations according to a caries lesion depth scale (0-4) using SS-OCT and the radiographs. The results were compared with clinical observations obtained after the treatment. SS-OCT could detect the presence of proximal caries in tomograms that were synthesized based on the backscatter signal obtained from the proximal carious lesion through occlusal enamel. SS-OCT showed significantly higher sensitivity and larger area under the receiver operating characteristic curve than radiographs for the detection of cavitated enamel lesions and dentin caries (Student's t -test, p < 0.05). SS-OCT appears to be a more reliable and accurate method than bitewing radiographs for the detection and estimation of the depth of proximal lesions in the clinical environment.