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Heparin is widely used as an anticoagulant drug in clinics, especially in surgery and dialysis machines. For safe use of heparin, it is necessary to closely monitor its dosage during the application. However, this was determined to be a challenging task because the chemical structure of heparin is very complicated. As a matter of fact, some well-established methods such as activated clotting time assay (ACT) and activated partial thromboplastin time assay (aPTT) were indirect and not accurate enough for monitoring heparin concentration. Therefore, the development of fluorescence sensors for selective, quantitative and fast heparin sensing has attracted much attention. To date, small organic molecule-based sensors, organic-inorganic hybrid materials and supramolecular complexes have been reported for heparin sensing. In this review, the design strategy, working principle and sensing performance of chemical sensors for heparin are discussed in detail with representative examples that have been reported mainly within the past 15 years (up to early 2020). These examples are summarized according to their type of recognition unit and photophysical sensing mechanisms. | Partial Thromboplastin Time |
The ability to acquire iron directly from host Tf (transferrin) is an adaptation common to important bacterial pathogens belonging to the Pasteurellaceae, Moraxellaceae and Neisseriaceae families. A surface receptor comprising an integral outer membrane protein, TbpA (Tf-binding protein A), and a surface-exposed lipoprotein, TbpB (Tf-binding protein B), mediates the iron acquisition process. TbpB is thought to extend from the cell surface for capture of Tf to initiate the process and deliver Tf to TbpA. TbpA functions as a gated channel for the passage of iron into the periplasm. In the present study we have mapped the effect of TbpA from Actinobacillus pleuropneumoniae on pTf (porcine Tf) using H/DX-MS (hydrogen/deuterium exchange coupled to MS) and compare it with a previously determined binding site for TbpB. The proposed TbpA footprint is adjacent to and potentially overlapping the TbpB-binding site, and induces a structural instability in the TbpB site. This suggests that simultaneous binding to pTf by both receptors would be hindered. We demonstrate that a recombinant TbpB lacking a portion of its anchor peptide is unable to form a stable ternary TbpA-pTf-TbpB complex. This truncated TbpB does not bind to a preformed Tf-TbpA complex, and TbpA removes pTf from a preformed Tf-TbpB complex. Thus the results of the present study support a model whereby TbpB 'hands-off' pTf to TbpA, which completes the iron removal and transport process. | Transferrin-Binding Protein A |
The approach presented in this study is the first for the hemisynthesis of methylated anthocyanins. It was possible to obtain cyanidin-3-O-glucoside derivatives with different degrees of methylation. Cautious identification of 4'-, 5-, and 7-OH monomethylated derivatives was also accomplished. The methylation agent used was the green chemical" dimethyl carbonate (DMC), which is characterized by low human and ecological toxicity. The influence of the temperature, reaction time, and amount of the required diazabicyclo[5.4.0]undec-7-en (DBU) catalyst on the formation of the products was examined. Compared to conventional synthesis methods for methylated flavonoids using DMC and DBU, the conditions identified in this study result in a reduction of reaction time, and an important side reaction, so-called carboxymethylation, was minimized by using higher amounts of catalyst." | Formates |
BACKGROUND: Serum-based parameters are considered non-invasive biomarkers for cancer detection. In human studies, insulin-like growth factor-I and II (IGF-I and IGF-II) and insulin-like growth factor binding protein-3 (IGFBP-3) are useful as diagnostic or prognostic markers and potential therapeutic targets. OBJECTIVES: This study examined the diagnostic utility of circulating IGF-I, IGF-II, and IGFBP-3 levels in healthy dogs and dogs with tumors. METHODS: The serum concentrations of these biomarkers in 86 dogs with tumors were compared with those in 30 healthy dogs using an enzyme-linked immunosorbent assay (ELISA). RESULTS: The ELISA results showed no difference between healthy dogs and dogs with tumors in the serum IGF-II concentrations. On the other hand, there was a significant difference in the circulating IGF-I and IGFBP-3 levels between healthy dogs and dogs with tumors. The concentrations of serum IGF-I (median [interquartile range], 103.4 [59.5-175] ng/mL) in dogs with epithelial tumors were higher than those (58.4 ng/mL [43.5-79.9]) in healthy dogs. Thus, the concentrations of serum IGFBP-3 (43.4 ng/mL [33.2-57.2]) in dogs with malignant mesenchymal tumors were lower than those (60.8 ng/mL [47.6-70.5]) in healthy dogs. CONCLUSIONS: The serum IGF-I and IGFBP-3 levels can be used as diagnostic biomarkers in dogs with tumors." | Insulin-Like Growth Factor Binding Protein 3 |
An indirect hemagglutination was developed for the diagnosis of equine infectious anemia using sheep red blood cells coated with group specific virus antigen which had been highly purified by affinity chromatography. The presence of indirect hemagglutination antibodies was demonstrated in horses with equine infectious anemia since the cells were specifically agglutinated by all the serum samples obtained from experimentally infected horses. Antibodies appeared within 35 days after inoculation, and development of which coincided well with that of precipitating and complement fixing antibodies. Titer of indirect hemagglutination antibodies were ten to 320 times greater than those of precipitating antibodies. Test results could be read more clearly by the indirect hemagglutination test especially in weakly positive cases. Ninety-six samples from suspected field cases collected from every region of Japan which were positive on the immunodiffusion test were also positive on indirect hemagglutination test. Serum samples from 420 horses in one race track were examined by both the indirect hemagglutination and immunodiffusion tests to determine the reliability of the indirect hemagglutination test for diagnosis of equine infectious anemia. The same result was obtained on both tests. Based on this evidence, the indirect hemagglutination test can be employed as a very sensitive serological test for the diagnosis of equine infectious anemia." | Infectious Anemia Virus, Equine |
INTRODUCTION: Impairment of dermal elastic tissue occurs in different entities associated with immunoglobulins or immunoglobulin-derived protein-secreting clonal plasma cell proliferations, such as amyloid elastosis, anetodermic nodular amyloidosis or monoclonal gammopathy-associated cutis laxa. We report a case of cutaneous immunoglobulinemic amyloidosis revealed by a unique chalazodermic presentation and we review elastic tissue impairment in patients with monoclonal gammopathies. OBSERVATION: A 67-year-old woman consulted for non-infiltrated anetodermic lesions on the upper left quadrant of her abdomen present for ten years. She also had a chalazodermic plaque with abnormal skin wrinkling and laxity in her right axilla. Biopsies revealed deep dermal and subcutaneous amyloid deposits. Immunohistochemistry with lambda light chain was positive. Orcein staining and electron microscopy showed extensive elastolysis. The patient presented no signs of systemic involvement, but a very small amount of monoclonal IgGlambda gammopathy was detected during follow-up. DISCUSSION: This is a unique chalazodermic presentation of immunoglobulinemic amyloidosis that does not fit into a clearly-defined nosological setting. It highlights the complex interactions between immunoglobulin-derived proteins, including light and heavy chains, and elastic tissue components, leading to different types of impairment of the latter. We therefore suggest the unifying concept of immunoglobulinemic elastopathy, underscoring the need to screen for monoclonal gammopathy in patients presenting elastic tissue impairments. | Cutis Laxa |
Although the primary goals of federal welfare reform legislation were to move welfare mothers into the workforce and reduce births outside of marriage, promotion of responsible parenting was also an important underlying theme. Parenting is a complex, multifaceted phenomenon, however, encompassing a wide range of functions related to nurturing, discipline, stimulation, values, activities, and routines. This article provides a framework for assessing the impact of welfare reform on various dimensions of parenting, with the following key findings: Many aspects of life affect parenting and child development, such as parent characteristics, child characteristics, family economic resources, family structure, parental mental health, marital or partner relationships, and the quality of parents' kin and social networks. About two-thirds of states are using federal welfare funds to promote better parenting through programs such as home visits to new parents and parenting classes, but virtually no state parenting programs have been evaluated. Welfare reform appears to have limited effects on parenting. The only dimension of parenting significantly affected by some welfare demonstration programs was parents' choice of child care settings and extracurricular activities for their children. The programs with the greatest positive impact on parenting were those with more generous work supports and more flexible work requirements. Not only did these programs lead to different choices concerning child care and activities for preschool and school-age children, but they also resulted in more stable marriages and less violence between partners, which also could lead to improved parenting. The authors conclude that many important aspects of the connection between welfare reform and parenting have yet to be examined, and that further research is needed to identify the ways states' welfare programs can promote better parenting. | Public Assistance |
Scrub typhus is one of the leading causes of undifferentiated treatable febrile illness in Asia pacific region. It is grossly under diagnosed in many tropical countries of South Asia including Bangladesh, due to wide range of non-specific clinical presentations, low index of suspicion among clinicians, limited awareness and lack of accurate diagnostic facilities. This cross sectional observational study was conducted at department of Microbiology, Mymensingh Medical College, Mymensingh, Bangladesh from March 2019 to February 2020 enrolling 113 diagnosed cases of scrub typhus by Immunochromatographic test (ICT) and / or Nested PCR to characterize the socio-demographic and clinico-epidemiological features of scrub typhus in Mymensingh area. Majority of the scrub typhus cases came from rural areas (63.83%) and there was a slight female predominance (52.21%). The young (32.74%) and the young-adult age group (28.31%) were mostly affected. Most of the scrub typhus cases were housewives (30.98%), followed by farmers (23.89%) and students (21.23%). All the enrolled cases presented with fever. Other findings were myalgia (76.10%), headache (56.63%), cough (30.97%), vomiting (12.38%) and Respiratory distress (9.73%). Typical eschar of scrub typhus was present only in 9(7.96%) cases and 4(3.53%) patients had rashes on their skin. Few cases (3.53%) had jaundice and 15.96% cases were anaemic. Oliguria (7.96%) and neck rigidity (1.76%) were also documented. Most of the Nested PCR positive scrub typhus cases were documented during late rainy season and beginning of winter months. Findings of the study may offer increased awareness about high burden of scrub typhus as well as heightened suspicion among clinicians for early diagnosis, timely treatment and prevention of complications. | Scrub Typhus |
BACKGROUND AND OBJECTIVES: Disability-based discrimination in health care can lead to low quality of care, limited access to care, and negative health consequences. Yet, little is known regarding the experiences of disability-based discrimination in health care for children with medical complexity and disability. An understanding of disability-based discrimination in pediatrics is needed to drive change and improve care. METHODS: We conducted in-depth, semistructured interviews with caregivers of children with medical complexity and disability. Participants were purposefully recruited through national advocacy and research networks. Interviews were conducted via video conferencing, recorded, and transcribed. Data collection and analysis occurred iteratively. An inductive thematic analysis approach with constant comparison methods was used to identify themes that form a conceptual framework of disability-based discrimination in health care. RESULTS: Thirty participants from diverse backgrounds were interviewed. Six themes emerged, forming a conceptual framework of disability-based discrimination in health care. Three themes described drivers of discrimination: lack of clinician knowledge, clinician apathy, and clinician assumptions. Three themes described manifestations of discrimination: limited accessibility to care, substandard care, and dehumanization. CONCLUSIONS: Children with medical complexity may face disability-based discrimination in health care. Themes describing the drivers and manifestations of discrimination offer a conceptual framework of disability-based discrimination. Understanding the drivers and acknowledging perceived manifestations can provide insight into improving patient care for children with disabilities. | Perceived Discrimination |
OBJECTIVES: The deviation and spread of values measured by tensile strength tests should be significantly reduced by optimized axially pull-off-device. MATERIAL AND METHODS: Factors like geometry, roughness, surface texture and fit of the specimens, the luting procedure (mixing ratio, compacting pressure) were standardized and the precision of the axially load transmission during the tensile force application optimized. Copings of CoCr-alloy were luted using a provisional zinc-oxide eugenol and a glass-ionomer cement (nâ¯=â¯20 per group each) on 4 degrees , respectively 8 degrees titanium implant abutment analogs. 24â¯h after luting the copings were pulled off with the improved (IPD) and the previous non improved device (NIPD). Means, std. dev. and t-tests were calculated. RESULTS: The stress- strain curves produced by the IPD showed a clear and linear relationship between stress and strain. The curves of the NIPD were ragged and chaotic. For both luting agents the means of the retentive force were considerable higher (pâ¯>â¯0.000) with IPD. However, the standard deviation was unimproved for the zinc oxide eugenol cement: IPD: 27%; NIPD: 27%, but significantly improved with glass ionomer: IPD: 16%, NIPD: 28%. CONCLUSION: The results from luting agents, which react like a solid body, may benefit from the optimized pull-off-device. Despite the fact that many factors in this investigation have been controlled, unknown flow characteristics of non-Newtonian-fluids like luting agents may have a considerable influence on the standard deviation of pull-off tests. | Materials Testing |
Confusion over dorsolumbar kyphosis and Sheuermann's disease has existed in the literature since the first recorded episodes in 1921. The present article delineates an etiology of back pain that is frequently seen in the adolescent population and is not to be confused with the painless fixed kyphotic deformity so frequently mentioned in the scoliosis literature. These patients with a painful dorsolumbar Sheuermann's disease may well have a traumatic herniation of the disk into the bony vertebral body. This type of x-ray and clinical finding should become familiar to all clinicians dealing with an adolescent population. | Scheuermann Disease |
This article first reviews the literature on the development of ethical content within nursing curricula and its impact on nursing education. This is followed by a discussion of faculty responsibility for the preparation of ethically competent graduates. Faculty behaviors that appear to be related to ethically sound education practices are discussed along with examples of positive and negative behaviors. The article concludes with five principles to use in developing an ethical basis for student-teacher relationships. These principles include mutual respect, open communication, demonstration of linkages between ethical principles and behavior, facilitating students' understanding of their behaviors, and recognition of legitimate individual differences in ethical positions. | Ethics, Nursing |
Eosinophilia is a common finding in tropical developing countries, and is mainly caused by chronic helminth infections, predominantly of the gut. Although only a minority of infections is symptomatic, development during childhood can be impaired, and in some patients serious complications and sequelae may occur. Eosinophilia in helminth infection is typically associated with a strong Th2 immune response, and eosinophils can effectively kill or damage larvae and adult worms in vitro. However, in vivo, eosinophils are only partly effective in the control of helminth infection, and recent research has shown that eosinophils are involved in a range of immunomodulatory effects, such as increased production of the down-modulatory cytokines interleukin 10 and tumour growth factor beta, as well as stimulation of regulatory T cells and alternatively activated macrophages. Increasing evidence suggests that immunomodulation favours parasite survival and reduces immune pathology. On the other hand, immunomodulation induced by helminth infections may contribute to protection from allergic and autoimmune responses, as proposed by the 'hygiene hypothesis' to explain the increase in allergic diseases in the industrialised world. The predictive value of eosinophilia for the presence of helminth infections is limited and depends on the epidemiological background and the extent of the eosinophilia. It increases considerably in populations with a high prevalence of parasitic infections, as in developing tropical countries or in travellers to those areas. | Helminthiasis |
For the inactivation or removal of bacterial biofilms via chemical or physical processes, it is crucial to sufficiently wet the biofilm surface. However, many bacterial biofilms efficiently resist wetting by water, oil or even organic solvents. Here, we demonstrate how exposing the surface of mature biofilm colonies to concentrated ethanol, saline or glucose solutions results in topographical changes that enable their wettability. With this approach, even omniphobic biofilm colonies become wettable towards aqueous solutions and oils. As a result of this reduced liquid repellency, the biofilms become susceptible to erosion by water which allows for their removal from the substrate they have been grown on. Moreover, bacteria within pre-treated biofilms can now be inactivated with antibiotic solutions. Thus, the biofilm treatment strategy presented here presents a new stepping stone for fighting biofilms in either industrial or medical settings. | Hypertonic Solutions |
In this paper we present what is apparently the tenth published case of vulvitis circumscripta plasmacellularis (Zoon). The patient had eroded, red-brown, asymptomatic vulvar lesions that were recalcitrant to treatment. The characteristic histopathology--dense plasma cell infiltrate and deposition of hemosiderin--was present. | Vulvitis |
The keratin macromolecule in wool fiber may be found in alpha-helix or beta-sheet conformations besides a disordered portion. The physical and chemical treatments may cause transformations between alpha-helix and beta-sheet conformations. The aim of this study was to investigate the influence of lecithin treatment on the wool fiber using the micro-Raman spectroscopy and Fourier transform infrared spectroscopy. Characteristic bands found in the FTIR spectra of wool fibers including the amide A, amide B and amide I-III, which are assigned to the peptide bonds of wool keratin and arise from the amide bonds that link the amino acids. The lecithin treatment didn't affect the peak position of amide bands and only slightly influenced their intensity. It means that the lecithin treatment didn't change the chemical structure of wool fibers. The amide I and III regions, CC skeletal vibration region, and SS bonds vibration regions were analyzed with the Raman microscope. The results indicated the peak area of alpha-conformation increased gradually by lecithin treatment of the wool fiber, while the peak area of beta-conformation decreased. Therefore, it seems that lecithin treatment of the wool fiber resulted in transformation of beta-sheet to alpha-helix. | Wool |
PURPOSE OF REVIEW: Post dural puncture headache (PDPH) is a relatively common complication which may occur in the setting of inadvertent dural puncture (DP) during labor epidural analgesia and during intentional DP during spinal anesthetic placement or diagnostic lumbar puncture. Few publications have established the long-term safety of an epidural blood patch (EBP) for the treatment of a PDPH. RECENT FINDINGS: The aim of this pilot study was to examine the association of chronic low back pain (LBP) in patients who experienced a PDPH following labor analgesia and were treated with an EBP. A total of 146 patients were contacted and completed a survey questionnaire via telephone. The EBP group was found to be more likely to have chronic LBP (percentage difference 20% [95% CI 6-33%], RR 2.6 [95% CI 1.3-5.2]) and also LBP < 6 (percentage difference 24% [95% CI 9- 37%], RR 2.3 [95% CI 1.3-4.1]). There were no significant differences in the severity and descriptive qualities of pain between the EBP and non-EBP groups. Our findings suggest that PDPH treated with an EBP is associated with an increased prevalence of subsequent low back pain in parturients. The findings of this pilot study should spur further prospective research into identifying potential associations between DP, EBP, and chronic low back pain. | Post-Dural Puncture Headache |
Anorexia nervosa is a rare disorder in the elderly but should be thought of in the differential diagnosis of extreme weight loss, especially if there are accompanying psychological features and normal baseline investigations. Psychiatric opinion should be obtained and treatment, although of unproven value, considered, since improvement may increase mobility and reduce morbidity and mortality. | Isocarboxazid |
Aim:Cryptococcus neoformans is the major agent of cryptococcosis. The main virulence factor is the polysaccharide (PS) capsule. Changes in cryptococcal PS properties have been poorly elucidated. Materials & methods: We analyzed the mechanical properties of secreted PS and intact capsules, using dynamic light scattering and optical tweezers. Results: Storage and loss moduli showed that secreted PS behaves as a viscoelastic liquid, while capsular PS behaves as a viscoelastic solid. The secreted PS remains as a viscoelastic fluid at different temperatures with thermal hysteresis after 85 degrees C. Antibody binding altered the viscoelastic behavior of both secreted and capsular PS. Conclusion: Deciphering the mechanical aspects of these structures could reveal features that may have consequences in novel therapies against cryptococcosis. | Fungal Capsules |
Several in vitro models have been developed to recapitulate mouse embryogenesis solely from embryonic stem cells (ESCs). Despite mimicking many aspects of early development, they fail to capture the interactions between embryonic and extraembryonic tissues. To overcome this difficulty, we have developed a mouse ESC-based in vitro model that reconstitutes the pluripotent ESC lineage and the two extraembryonic lineages of the post-implantation embryo by transcription-factor-mediated induction. This unified model recapitulates developmental events from embryonic day 5.5 to 8.5, including gastrulation; formation of the anterior-posterior axis, brain, and a beating heart structure; and the development of extraembryonic tissues, including yolk sac and chorion. Comparing single-cell RNA sequencing from individual structures with time-matched natural embryos identified remarkably similar transcriptional programs across lineages but also showed when and where the model diverges from the natural program. Our findings demonstrate an extraordinary plasticity of ESCs to self-organize and generate a whole-embryo-like structure. | Embryonic Development |
Thevetia peruviana (T. peruviana) has been considered as a potentially important plant for industrial and pharmacological application. Among the number of compounds which are produced by T. peruviana, antioxidants and polyphenols are of particular interest due to their benefits on human health. Cell suspension cultures of T. peruviana were established under different conditions: 1) constant illumination (24h/day) at different light wavelengths (red, green, blue, yellow and white), 2) darkness and 3) control (12h/12h: day light/dark) to investigate their biomass, substrate uptake, polyphenols production and oxidizing activity. The results showed biomass concentrations between 17.1g dry weight (DW)/l (green light) and 18.2g DW/l (control) after 13days. The cultures that grew under green light conditions consumed completely all substrates after 10days, while other cultures required at least 13days or more. The total phenolic content was between 7.21 and 9.46mg gallic acid (GA)/g DW for all light conditions. In addition the ferric reducing antioxidant power and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid antioxidant activity ranged from 5.41-6.58mg ascorbic acid (AA)/g DW and 82.93-110.39mumol Trolox/g DW, respectively. Interestingly, the samples which grew under the darkness presented a higher phenolic content and antioxidant capacity when compared to the light conditions. All together, these results demonstrate the extraordinary effect of different lighting conditions on polyphenols production and antioxidant compounds by T. peruviana. | Thevetia |
The effects of bath therapy are complex and result from a unique interaction between the aquatic environment and the human body functions. The effect of bath therapy depends on both water temperature and chemical additives (mineral substances and humic substances). Varska Resort Centre, in south-eastern Estonia, uses for the balneotherapy the local curative mud and mineral water. The aim of the study was to evaluate and compare the effects of Varska's local mud bath and mineral water bath on moderate musculoskeletal pains in working-age people. The study involved 64 working-age subjects: within two weeks, 32 of them received five general mineral water baths, and another 32 received five general curative mud baths. Pain was assessed with the Nordic Musculosceletal Questionnaire, and muscle tension was measured with a myotonometer in m. erector spinae and m. trapezius. Measurements were performed three times: before the start of the study, immediately after the last procedure, and 2-3 weeks after the last procedure. Both the Varska curative mud bath and the Varska mineral water bath showed a positive effect on musculoskeletal pain and muscle tension. Both procedures can be recommended as drug-free interventions for mild to moderate musculoskeletal pain syndrome and muscle tensions, in both prevention and treatment. | Mud Therapy |
Podiatry as a medical specialty has received little sociological attention. This omission leaves a sizeable gap in our understanding of the total health care system. Given the functional importance of this speciality and the growing need for the services of podiatrists this report represents an attempt to increase our knowledge in this area. The paper attempts to fill that gap by presenting a discussion of the development of podiatry as a health profession; documenting the educational and political development and attempting to explain the reasons which have inhibited the process of professionalization. Our findings suggest that podiatry as a profession has been unable to attain full autonomy over its anatomical area of expertise and this along with other factors has prevented podiatry from attaining full professional status and recognition. | Podiatry |
This article discusses the emergence and reemergence of infectious diseases on the basis of a review of the literature. It shows the critical situations faced worldwide and in special Brazil's susceptible position due to its complexity, mostly represented by the mega-biodiversity of the country and its socio-economic problems directly affecting public health. It approaches the discussions around the issue with emphasis to the recommended investments in the health sector, directed to surveillance and to strengthening the epidemiological, laboratorial and clinical bases and centered on preventive and control measures in the affected areas including Biosafety." | Communicable Diseases, Emerging |
Fusarium graminearum species complex produces type B trichothecenes oxygenated at C-7. In axenic liquid culture, F. graminearum mainly accumulates one of the three types of trichothecenes, namely 3-acetyldeoxyinvalenol, 15-acetyldeoxyinvalenol, or mixtures of 4,15-diacetylnivalenol/4-acetylnivalenol, depending on each strain's genetic background. The acetyl groups of these trichothecenes are slowly deacetylated to give deoxynivalenol (DON) or nivalenol (NIV) on solid medium culture. Due to the evolution of F. graminearum FgTri1, encoding a cytochrome P450 monooxygenase responsible for hydroxylation at both C-7 and C-8, new derivatives of DON, designated as NX-type trichothecenes, have recently emerged. To assess the risks of emergence of new NX-type trichothecenes, we examined the effects of replacing FgTri1 in the three chemotypes with FgTri1_(NX chemotype), which encodes a cytochrome P450 monooxygenase that can only hydroxylate C-7 of trichothecenes. Similar to the transgenic DON chemotypes, the transgenic NIV chemotype strain accumulated NX-type 4-deoxytrichothecenes in axenic liquid culture. C-4 oxygenated trichothecenes were marginal, despite the presence of a functional FgTri13 encoding a C-4 hydroxylase. At present, outcrossing of the currently occurring NX chemotype with NIV chemotype strains of F. graminearum in the natural environment likely will not yield a new strain that produces a C-4 oxygenated NX-type trichothecene. | Axenic Culture |
Skeletal muscle atrophy is commonly associated with aging, immobilization, muscle unloading, and congenital myopathies. Generation of mature muscle cells from skeletal muscle satellite cells (SCs) is pivotal in repairing muscle tissue. Exercise therapy promotes muscle hypertrophy and strength. Primary cilium is implicated as the mechanical sensor in some mammalian cells, but its role in skeletal muscle cells remains vague. To determine mechanical sensors for exercise-induced muscle hypertrophy, we established three SC-specific cilium dysfunctional mouse models-Myogenic factor 5 (Myf5)-Arf-like Protein 3 (Arl3)(-/-), Paired box protein Pax-7 (Pax7)-Intraflagellar transport protein 88 homolog (Ift88)(-/-), and Pax7-Arl3(-/-)-by specifically deleting a ciliary protein ARL3 in MYF5-expressing SCs, or IFT88 in PAX7-expressing SCs, or ARL3 in PAX7-expressing SCs, respectively. We show that the Myf5-Arl3(-/-) mice develop grossly the same as WT mice. Intriguingly, mechanical stimulation-induced muscle hypertrophy or myoblast differentiation is abrogated in Myf5-Arl3(-/-) and Pax7-Arl3(-/-) mice or primary isolated Myf5-Arl3(-/-) and Pax7-Ift88(-/-) myoblasts, likely due to defective cilia-mediated Hedgehog (Hh) signaling. Collectively, we demonstrate SC cilia serve as mechanical sensors and promote exercise-induced muscle hypertrophy via Hh signaling pathway. | PAX7 Transcription Factor |
Balantidium coli is a protozoon that can cause dysentery in humans, pigs and nonhuman primates, with zoonotic potential. In the literature, there is still little information on the effectiveness of different laboratory techniques for diagnosing this disease. This study compared and evaluated the performance of the Lutz, modified Ritchie, Faust, modified Sheather and direct examination techniques for detecting cysts of this protozoon. Between 2012 and 2014, 1905 fecal samples were collected from captive animals in the state of Rio de Janeiro. Of these, 790 were obtained from the rectum of pigs and 1115 from enclosures occupied by nonhuman primates. B. coli cysts were most evident through direct examination (22.4% of the samples) and the Lutz technique (21%). Fair agreement (Kappa = 0.41; p < 0.05) was observed only between direct examination and Lutz. The flotation techniques (Faust and modified Sheather) did not show good recovery of cysts. A statistically significant difference (p < 0.05) in the frequency of cysts between pigs and nonhuman primates could only be observed through direct examination and the Lutz technique. The most efficient method for diagnosing this parasitosis was seen to an association between direct examination and the spontaneous sedimentation technique. | Trichostomatida |
Few are familiar with the neurological contributions of the German pathologist Theodor Langhans. Even fewer are aware of his significant and early contributions to the study of what is now known as the Chiari I malformation. In at least 4 cases, Langhans described the association between tonsillar ectopia and syringomyelia. Moreover, this early pioneer speculated that there was a cause and effect with hindbrain herniation resulting in improper flow at the craniocervical junction and consequent development of syringomyelia. These cases were reported prior to Hans Chiari's descriptions, and Langhans' theory of impeded foramen magnum flow as a cause of syringomyelia was novel and preceded the current understanding of this mechanism by almost a century. The authors discuss the life of Langhans and translate excerpts from his 1881 work regarding tonsillar ectopia and syringomyelia. | Arnold-Chiari Malformation |
OBJECTIVE: Long term exposure to gonadotoxic chemotherapy is becoming a major cause of premature ovarian failure/insufficiency (POF/POI) with the increasing cancer incidence among young women. The present study was designed to investigate the protective effects of human cord mesenchymal stem cells (HUCMSCs)-derived extracellular vesicles (EVs) on cisplatin (CDDP)-damaged granulosa cells (GCs) in vitro. MATERIALS AND METHODS: EVs were obtained from supernatant of cultured HUCMSCs by ultracentrifugation method, purified by Sucrose density gradient centrifugation, and then were co-cultured with cisplatin-damaged GCs of 3-weeks female Sprague-Dawley (SD) rats. PKH26 labeled EVs could be observed in normal and CDDP-damaged GCs after 6 h co-culture. RESULTS: The surviving GCs were significantly higher and apoptotic GCs were significantly lower in EVs + CDDP group compared with CDDP group. Meanwhile, the levels of E2 and StAR (the key gene related to synthesis of steroid hormone) were significantly higher in EVs + CDDP group compared with CDDP group. Furthermore, the mRNA expression of Caspase 3 was down-regulated significantly and the ratio of Bcl-2/Bax was up-regulated significantly in EVs + CDDP group. Moreover, the protective effect of EVs on CDDP-damaged GCs showed a dose-dependent effect. CONCLUSION: HUCMSCs-derived EVs could become incorporated to CDDP-damaged GCs, and increase the number of living cells, therefore playing important roles in promoting resistance to cisplatin-induced GCs apoptosis and restoring synthesis and secretion of steroid hormone in GCs. This study might provide a theoretical and experimental basis for use of mesenchymal stem cells (MSCs) derived EVs instead of MSCs as a cell-free therapeutic strategy for the patients with POI induced by chemotherapeutic agents. | Granulosa Cells |
OBJECTIVES: To review the methods for verifying the needle position while performing epidural anaesthesia in dogs, and to discuss the advantages, disadvantages, usefulness and reliability of each technique in the experimental and clinical research setting. DATABASES USED: PubMed, Scopus, Google Scholar and the Basel University Library online catalogues; the latter, which was provided by the University of Berne, were used as databases. The results were filtered manually based on the titles and abstracts in order to narrow the field. CONCLUSIONS: Besides some drawbacks, including the potential side effects of contrast medium injection, which may limit its routine use in clinical patients, epidurography should still be regarded as one of the most reliable techniques to verify needle position in dogs. Ultrasonography, electrical nerve stimulation, loss of resistance and the hanging drop technique are regarded as less invasive than epidurography and, for this reason, their use may be more applicable to clinical patients. However, these methods have been described in only a few published reports, all of which involved a limited number of dogs. Finally, the detection of epidural pressure waves has been investigated more extensively in dogs, and the findings of these studies suggest that this technique may be used to verify epidural needle placement for experimental and clinical research, on condition that all the negative subjects are excluded from the study. | Anesthesia, Epidural |
It was found that chromatin transcription in the neuronal nucleus of rat brain is inhibited by antisera to proteins HMG 14, HMG 17 and HMG 2. It is known that chromatin transcription of the neuronal nucleus and phosphorylation of chromosomal proteins are activated by etimizol. The phosphorylation of chromosomal proteins activated by etimizol is inhibited by the antiserum to HMG 14 (but not to HMG 17). The data obtained are suggestive of a possible role of HMG proteins and their phosphorylated forms in the regulation of transcription. | Etimizol |
The purine nucleoside adenosine (ADO) is an important modulator of cellular function in mammalian tissues, modulating cellular function and neuronal excitability via interactions with different cell surface receptor subtypes that are heterogeneously distributed in both the mammalian CNS and peripheral tissues. Four ADO receptor subtypes have been cloned and characterized. Described in this unit are three radioligand binding assays for pharmacological characterization of the high-affinity ADO receptor subtypes A1, A2A, and A3 receptors. Pharmacological characterization of the low-affinity A2B receptor has been enabled by the use of tritiated xanthine PSB-603. Because receptor localization is an important criterion for differentiation of receptor subtypes, a support protocol that describes the methodology for the localization of ADO receptors in rat brain tissue using autoradiography is also included." | Purinergic P1 Receptor Antagonists |
The pressing need for innovation in drug discovery is spurring the emergence of drugs that turn on protein function, as opposed to shutting activity down. Several pharmacophores usher protein target gain-of-function, for instance: PROTACs promote protein target degradation; other drug candidates have been reported to function through dominant-negative inhibition of their target enzyme. Such classes of molecules are typically active at low target occupancy and display numerous advantages relative to canonical inhibitors, whose function is intrinsically tied to achieving, or exceeding a threshold occupancy. However, our ability to generally tap into gain-of-function processes through small molecule interventions is overall in its infancy. Herein, I outline how chemical biology is poised to help us bring this powerful idea to fruition. I further outline means through which gain-of-function events can be identified and harnessed. | Small Molecule Libraries |
Irreversible inhibition of acetylcholinesterase (AChE) by organophosphates leads to many failures in living organism and ultimately in death. Organophosphorus compounds developed as nerve agents such as tabun, sarin, soman, VX and others belong to the most toxic chemical warfare agents and are one of the biggest threats to the modern civilization. Moreover, misuse of nerve agents together with organophosphorus pesticides (e.g. malathion, paraoxon, chlorpyrifos, etc.) which are annually implicated in millions of intoxications and hundreds of thousand deaths reminds us of insufficient protection against these compounds. Basic treatments for these intoxications are based on immediate administration of atropine and acetylcholinesterase reactivators which are currently represented by mono- or bis-pyridinium aldoximes. However, these antidotes are not sufficient to ensure 100 % treatment efficacy even they are administered immediately after intoxication, and in general, they possess several drawbacks. Herein, we have reviewed new efforts leading to the development of novel reactivators and proposition of new promising strategies to design novel and effective antidotes. Structure-activity relationships and biological activities of recently proposed acetylcholinesterase reactivators are discussed and summarized. Among further modifications of known oximes, the main attention has been paid to dual binding site ligands of AChE as the current mainstream strategy. We have also discussed new chemical entities as potential replacement of oxime functional group. | Cholinesterase Reactivators |
Ingestion of white snakeroot ( Ageratina altissima ) can cause trembles in livestock and milk sickness in humans. The toxicity has been associated with tremetol, a relatively crude, multicomponent lipophilic extract of the plant. In this study, 11 different compounds were isolated from white snakeroot-derived lipophilic extracts from 18 collections. Six of the isolated compounds have not been previously reported to be found in white snakeroot. High-performance liquid chromatography (HPLC) analysis indicated that there are three different chemotypes of white snakeroot from the plant samples analyzed. Elucidation of these chemotypes may explain the sporadic and unpredictable toxicity of white snakeroot to livestock and humans. | Milk Sickness |
Microorganisms play a crucial role in the biogeochemical processes of Dissolved Organic Matter (DOM), and the properties of DOM also significantly influence changes in microbial community characteristics. This interdependent relationship is vital for the flow of matter and energy within aquatic ecosystems. The presence, growth state, and community characteristics of submerged macrophytes determine the susceptibility of lakes to eutrophication, and restoring a healthy submerged macrophyte community is an effective way to address this issue. However, the transition from eutrophic lakes dominated by planktic algae to medium or low trophic lakes dominated by submerged macrophytes involves significant changes. Changes in aquatic vegetation have greatly affected the source, composition, and bioavailability of DOM. The adsorption and fixation functions of submerged macrophytes determine the migration and storage of DOM and other substances from water to sediment. Submerged macrophytes regulate the characteristics and distribution of microbial communities by controlling the distribution of carbon sources and nutrients in the lake. They further affect the characteristics of the microbial community in the lake environment through their unique epiphytic microorganisms. The unique process of submerged macrophyte recession or restoration can alter the DOM-microbial interaction pattern in lakes through its dual effects on DOM and microbial commu-----nities, ultimately changing the stability of carbon and mineralization pathways in lakes, such as the release of methane and other greenhouse gases. This review provides a fresh perspective on the dynamic changes of DOM and the role of the microbiome in the future of lake ecosystems. | Dissolved Organic Matter |
A longitudinal study was carried out to investigate the diversity and persistence of Mycoplasma hyopneumoniae (M. hyopneumoniae) strains in four infected pig herds. In each herd, 20 pigs were randomly selected and blood and/or bronchoalveolar lavage (BAL) fluid was collected at 6, 10, 14 and 26 weeks of age. In the BAL fluid, quantitative PCR and MLVA (multiple-locus variable number of tandem repeats (VNTR) analysis) testing were performed for detection and typing of M. hyopneumoniae strains, respectively. At 26 weeks of age, the prevalence and severity of lung lesions were recorded at slaughter (minimum 50 pigs belonging to the same batch as the investigated pigs). The percentage of pigs testing positive on qPCR increased from 35% at 6 weeks to 96% at 26 weeks of age. With MLVA testing, positive pigs were found from 14 weeks onwards. Within each herd, only one distinct strain was detected, although clonal variants were identified in two herds. In three of the herds, the strain remained present until slaughter age. The percentage of pigs with Mycoplasma-like lesions ranged from 38% to 98%, and the average pneumonia score ranged from 1.7 to 11.9, respectively. The present field study documented that within a herd, mainly one distinct M. hyopneumoniae strain was present that persisted in the same animals for at least 12 weeks. This implies that the immune response of the animals following infection is not able to rapidly clear the infection from the respiratory tract." | Pneumonia of Swine, Mycoplasmal |
In situ and in vitro degradation of glial fibrillary acidic (GFA) protein in mouse spinal cord was examined with electroblots stained for GFA protein by the peroxidase anti-peroxidase method. Non-degraded, intact GFA protein had a molecular weight of 48 Kdaltons and isoelectric points ranging from pH 5.8 to 6.4. The molecular weights of immunoreactive degradation products ranged from 47 to 28 Kdaltons. All of the degradation products had acid shifted isoelectric points (pH 5.8-5.2). Degradation was prevented by chelating calcium with EGTA. In contrast to in situ degradation, degradation in vitro with 3 mM CaCl2 occurred at a faster rate. The effect of pH and temperature on the degradation process were determined by incubating homogenized spinal cords in 3 mM CaCl2 solutions varying in pH from 4 to 10 and at 4, 37, and 60 degrees C. The greatest number of immunoreactive bands with the lowest molecular weights occurred at pH 8 and 37 degrees C. The results suggest that turnover of glial filaments is in part controlled by a calcium dependent proteinase active near neutral pH similar to that postulated for neurofilament turnover. | Mice, Jimpy |
The aims of this longitudinal study were to 1) identify categories of adverse childhood experiences (ACEs) (ie, neglect, abuse, household dysfunction in childhood) that increase risk for internalizing mental health problems, pain-related impairment, and poorer quality of life and 2) examine the moderating role of posttraumatic stress symptoms (PTSS) in these associations, in a clinical sample of youth with chronic pain. At 2 timepoints, youth (Nâ¯=â¯155; aged 10-18 years) completed measures of exposure to ACEs, PTSS, depressive and anxiety symptoms, pain intensity, pain interference, and quality of life. Multivariate analyses of variance, linear mixed modeling, and moderation analyses were conducted. Results from cross-sectional and longitudinal analyses were similar; youth with a history of 3+ ACEs reported significantly higher PTSS, depressive and anxiety symptoms, and poorer quality of life than youth with no ACE history. Results also revealed differences in functioning between youth exposed to different types of ACEs (ie, maltreatment only, household dysfunction only, both, none). Finally, PTSS was found to moderate the association between ACEs and anxiety and depressive symptoms. Findings underscore the influence that ACEs can have on the long-term functioning of youth with chronic pain as well as the important role of current PTSS in this association. PERSPECTIVE: This study found that the risk of poorer outcomes imposed by ACEs at baseline remains longitudinally and that posttraumatic stress symptoms (PTSS) moderate the relationship between ACEs and anxiety and depressive symptoms in youth with chronic pain. These results underscore the importance of assessing for ACEs and PTSS alongside chronic pain in youth. | Psychosocial Functioning |
BACKGROUND: Although many theories have been established to explain the mechanism of aneurysm development following steno-occlusive or hypertensive disease, the effect of the geometrical shape of the inner elastic membrane on the maximum dilatation capacity of arteries has not been adequately investigated so far. This subject was investigated. METHODS: This study was conducted in 24 rabbits. The rabbits were divided into 3 groups: as the control, (n = 5), the SHAM (n = 5), and the study group (n = 14). In the study group, BCCAL was performed. After decapitation, the basilar artery vasodilatation index (VDI) and the actual length of the inner elastic membrane (IEM) were estimated. The relationship between the true length of IEM and VDI values was compared statistically using the Mann-Witney -U test. RESULTS: Mean blood pressures were 113 +/- 7 mmHg in animals at the beginning of the experiment (n = 24), and 119 +/- 9 mmHg in GII and 122 +/- 11mmHg in GIII after BCCAL (n = 12). Before decapitation, the mean blood pressures were 115 +/- 10 mmHg in GI, 116 +/- 10 mmHg in GII, and 127 +/- 11mmHg GIII. The DADA values of animals were 20 +/- 4mm in GI; 28 +/- 6mm in GII and 37 +/- 9mm in GIII. The VDI value of BA was 1.390 +/- 0.220 in GI; 1.013 +/- 0.108 in GI; 0.019 +/- 0.011in GII group. CONCLUSION: An inverse relationship was discovered between the DADA/VDI values. BCCAL may lead to severe dangerous histopathological changes at the BA. Lower DADA or higher VDI values may lead to severe basilar enlargement, endothelial losing, inner elastic membrane rupture, and aneurysm formation after BCCAL. | Decapitation |
BACKGROUND AND AIM: The prospective, open-label, randomized study aims to compare the efficacy of lansoprazole, a fast orally disintegrating proton pump inhibitor (PPI), and dexlansoprazole, a dual delayed release PPI, in patients with atypical symptoms of gastroesophageal reflux disease (GERD). METHODS: Patients with atypical GERD symptoms with a total reflux symptom index score > 10 were eligible for enrollment. From February 2018 to December 2019, 232 subjects were randomly assigned (1:1 ratio) to receive oral lansoprazole, Takepron OD 30 mg, once daily before breakfast or oral dexlansoprazole, Dexilant 60 mg, once daily before breakfast for 8 weeks. The primary end-point is to compare the symptoms response rate after an 8-week PPI therapy between the two groups. RESULTS: There were 232 study subjects enrolling in this study. After the 8-week PPI therapy, dexlansoprazole-treated group had a significantly higher response rate than lansoprazole-treated group in cough (76.5% vs 38.0%) and globus (69.7% vs 30.8%) (P all < 0.05 by intention-to-treat). Multivariate logistic regression analysis showed that the use of dexlansoprazole, presence of dyslipidemia, and typical GERD symptoms (acid reflux and heartburn) were predictors for symptom response for cough; the use of dexlansoprazole and presence of erosive esophagitis were predictors for symptom response for globus (P all < 0.05). No predictor for therapy response to hoarseness was noted. CONCLUSIONS: There is a higher response rate for cough and globus symptoms in patients with atypical GERD after the 8-week PPI therapy with dexlansoprazole rather than lansoprazole. | Globus Sensation |
Rising interest in the mechanism and function of the proteasomes and the ubiquitin system revealed that it is hard to find any aspect of the cellular metabolic network that is not directly or indirectly affected by the degradation system. This includes the cell cycle, the "quality control" of newly synthesized proteins (ERAD), transcription factor regulation, gene expression, cell differentiation, immune response or pathologic processes like cancer, neurodegenerative diseases, lipofuscin formation, diabetes, atherosclerosis, inflammatory processes or cataract formation and in addition to that the aging process itself and the degradation of oxidized proteins, in order to maintain cell homeostasis. But also this seems to be only a small aspect of the general view. The various regulator proteins that are able to change the rate or specificity of proteolysis, fitting it out for highly specialized tasks, or the precise regulation of the half-life of cellular proteins by ubiquitin-mediated degradation shape the proteasome and the ubiquitin-proteasome system into a fascinating and essential part of cellular function in the three kingdoms of bacteria, plants and animals. This review tries to summarize the current knowledge on the proteasome and the ubiquitin-proteasomal system, including the cellular functions of this system." | Proteasome Endopeptidase Complex |
A comprehensive analysis of the X-chromosome led to the discovery of an important region found to be Xq22.1. Xq22.1 was analysed in detail to locate a credible gene carrying segment on it, which may be implicated in various disorders related to the X-chromosome. Finding genes in a genomic sequence is a fiddly problem. Hence, we developed a new in-silico approach to identify the novel gene, based on homology methods (extrinsic methods) and gene prediction methods (intrinsic methods). | Chromosomes, Human, X |
Folie a deux is a psychiatric illness involved in homicides. OBJECTIVE: To study the mechanisms leading to homicide and determine homicide risk factors in folie a deux patients through a literature review and the study of a complex clinical case. MATERIALS AND METHODS: We included articles available on PubMed, ScienceDirect or Cairn that address the forensic implications of folie a deux. Then, we analyzed the criminal psychiatric assessments of two murderers (husband and wife) of a child in a case of folie a deux. RESULTS: Seventeen articles were included. In the cases examined, homicides were committed with great violence, usually against a victim in the family circle, and were sometimes followed by suicide. The main risk factor for homicide was the combination of mystical and persecutory delusions. The homicides occurred in response to destabilization of the delusional dyads. Concerning the clinical case, we described the circumstances surrounding the killing and analyzed the four expert reports that permit us to infer the occurrence of induced psychosis, which is a form of folie a deux. DISCUSSION: Psychiatrists must attain a better knowledge of folie a deux to allow early identification of risk situations and to improve their assessments. | Shared Paranoid Disorder |
OBJECTIVES: To review cancer risk assessment and counseling, hereditary cancer syndrome risk factors, indicators for cancer predisposition testing, and interpretation of genetic test results. DATA SOURCES: Research studies, review articles, and authors' experience. CONCLUSION: Approximately 10% of those with a diagnosis of cancer may have a hereditary predisposition. In many cases genetic testing for susceptibility genes may be available. Knowledge of the results of genetic testing can be helpful when developing a plan for cancer prevention and early detection, and addressing concerns associated with genetic testing with the individual and family. IMPLICATIONS FOR NURSING PRACTICE: Nurses need to know how to access genetic resources and to identify, evaluate, and care for patients and families at risk of or diagnosed with common hereditary cancer syndromes." | Neoplastic Syndromes, Hereditary |
Trichotillomania is a form of hair loss characterized by an irresistible compulsion to pull out or twist and break off one's own hair. Extracted hairs are often manipulated, examined, or played with before being discarded or eaten. We report an obsessive-compulsive 65-year-old lady who exclusively ate the root of the hair she plucked, in a very selective type of trichophagia. We suggest the new term trichorrhizophagia which means eating the root of the hair" (from the Greek rhiza rho iota zeta alpha = root) to name this condition." | Trichotillomania |
The spatial segregation of informational molecules in the unfertilized egg and embryo has been hypothesized to be a necessary phenomenon for the normal progression of development leading to the determination of cellular phenotypes. This study describes the selection of a monoclonal antibody (Mab: 2G6) that identifies an antigen (Ag: 2G6) which is localized in the germinal vesicle of oocytes and has a discrete pattern of inheritance during embryogenesis. The antigen displayed biochemical and physical characteristics very similar to nucleoplasmin, which is the histone-binding and nucleosome-assembly protein previously described. Immunoblot analysis with purified oocyte nucleoplasmin confirmed this relationship. Indirect immunofluorescence was used to study the temporal expression and spatial distribution of nucleoplasmin. From early cleavage stages through gastrulation, it is preferentially localized in nuclei of blastomeres at the animal pole. By tadpole stages, it was detected only in nuclei of postmitotic cells of the central nervous system and in nuclei of striated muscle. It was not detected in adult tissues. Western blot analysis during embryogenesis revealed at least five immunologically related polypeptides that displayed distinct patterns of expression during development. The different species observed most likely represent different levels of phosphorylation of nucleoplasmin. The more acidic forms, known to be more active in nucleosome assembly, were present during cleavage stages. Analysis of labelled oocyte proteins by two-dimensional immunoblots and autoradiography revealed that synthesis of nucleoplasmin was first detected in stage-2 oocytes, reached 60% maximum levels at stage 3, peaked at stage 4 and was undetectable in stage-6 oocytes. The amount of nucleoplasmin message present does not follow a similar pattern during oogenesis. These results suggest that the message undergoes pronounced changes in translational efficiency during oogenesis. A comparative immunoblot analysis using proteins from a variety of adult tissues revealed that, whereas the polyclonal antisera against amphibian vitellogenic oocyte nucleoplasmin recognized several different, tissue-specific polypeptides, two different monoclonal antibodies (Mab: b7-1D1, Mab: 2G6) failed to recognize any of the adult tissues tested. We conclude that nucleoplasmin is a family of closely related proteins with distinct embryonic and adult members. | Nucleoplasmins |
PURPOSE: To study age-related changes in the refractive index distribution of the human ocular lens. METHODS: Biometric data collected on 48 eyes in subjects ranging in age from 19 to 31 years and 48 eyes in subjects ranging in age from 49 to 61 years allowed estimation of a single parameter related to the refractive index distribution of the crystalline lens. The authors selected a gradient index model of the lens characterized by a fixed index at the lens center, a somewhat lower fixed index at the surface, and a continuum of index values between center and surface depending on a single parameter, beta. This parameter was evaluated for each of the two age groups. RESULTS: The distributions of the gradient index parameter beta for the two age groups were found to be statistically well separated. On average, the older group was found to have an index gradient that was flatter near the lens center and steeper near the surface, implying a lower refractive power of about 2 D for representative lens surface curvatures. CONCLUSIONS: It has been observed that surface curvatures and thicknesses of the ocular lens increase with age, whereas other ocular dimensions apparently do not change, implying a trend toward myopia. This trend has not been observed. The authors' results are consistent with and strongly in support of the hypothesis that subtle index changes in the aging lens compensate to a large extent for changes in surface curvatures. | Lens, Crystalline |
Multiple myeloma (MM) is a currently incurable neoplasm of terminally differentiated B cells. The translocation and/or overexpression of c-MAF have been observed in human MM. Although c-MAF might function as an oncogene in human MM, there has been no report thus far describing the direct induction of MM by c-MAF overexpression in vivo. In this study, we have generated transgenic (TG) mice that express c-Maf specifically in the B-cell compartment. Aged c-Maf TG mice developed B-cell lymphomas with some clinical features that resembled those of MM, namely, plasma cell expansion and hyperglobulinemia. Quantitative RT-PCR analysis demonstrated that Ccnd2 and Itgb7, which are known target genes of c-Maf, were highly expressed in the lymphoma cells. This novel TG mouse model of the human MM t(14;16)(q32;q23) chromosomal translocation should serve to provide new insight into the role of c-MAF in tumorigenesis. | Proto-Oncogene Proteins c-maf |
A major biologic role of the ubiquitous mitochondrial P450 enzyme CYP27A1 is the generation of ligands such as 27-hydroxycholesterol and 3 beta-hydroxy-5-cholestenoic acid, which regulate the expression of nuclear receptors that govern many aspects of cholesterol homeostasis. We now report that sterol intermediates in cholesterol synthesis, beginning with the initial post-cyclization sterol, lanosterol, continuing with zymosterol, and ending with desmosterol are also substrates for the enzyme. Using the human enzyme expressed in Escherichia coli, we characterized the retention times and major mass fragments of these novel metabolites. Although sequestration of the enzyme in the inner mitochondrial membrane and normal subcellular organization probably greatly restrict the proportion of these and other intermediates in cholesterol synthesis that undergo side chain oxidation, disruption of compartmentalization can bypass cholesterol as the end product and give rise to potent ligands that further modify gene expression. | Cholestadienols |
We report design improvements for evanescently coupled Germanium photodetectors grown at low temperature. The resulting photodetectors with 10 mum Ge length manufactured in a commercial CMOS process achieve >0.8 A/W responsivity over the entire C-band, with a device capacitance of <7 fF based on measured data. | Germanium |
Elongation factor (EF) is a key regulation factor for translation in many organisms, including plants, bacteria, fungi, animals and insects. To investigate the nature and function of elongation factor 1beta' from Spodoptera exigua (SeEF-1beta'), its cDNA was cloned. This contained an open reading frame of 672 nucleotides encoding a protein of 223 amino acids with a predicted molecular weight of 24.04 kDa and pI of 4.53. Northern blotting revealed that SeEF-1beta' mRNA is expressed in brain, epidermis, fat body, midgut, Malpighian tubules, ovary and tracheae. RT-PCR revealed that SeEF-1beta' mRNA is expressed at different levels in fat body and whole body during different developmental stages. In RNAi experiments, the survival rate of insects injected with SeEF-1beta' dsRNA was 58.7% at 36 h after injection, which was significantly lower than three control groups. Other elongation factors and transcription factors were also influenced when EF-1beta' was suppressed. The results demonstrate that SeEF-1beta' is a key gene in transcription in S. exigua. | Peptide Elongation Factor 1 |
Despite much progress in regulations to improve paediatric drug development, there remains a significant need to develop better medications for children. For the design of oral dosage forms, a detailed understanding of the specific gastrointestinal (GI) conditions in children of different age categories and how they differ from GI conditions in adults is essential. Several review articles have been published addressing the ontogeny of GI characteristics, including luminal conditions in the GI tract of children. However, the data reported in most of these reviews are of limited quality because (1) information was cited from very old publications and sometimes low quality sources, (2) data gaps in the original data were filled with textbook knowledge, (3) data obtained on healthy and sick children were mixed, (4) average data obtained on groups of patients were mixed with data obtained on individual patients, and (5) results obtained using investigative techniques that may have altered the outcome of the respective studies were considered. Consequently, many of these reviews draw conclusions that may be incorrect. The aim of the present review was to provide a comprehensive and updated overview of the available original data on the ontogeny of GI luminal conditions relevant to oral drug absorption in the paediatric population. To this end, the PubMed and Web of Science metadatabases were searched for appropriate studies that examined age-related conditions in the oral cavity, esophagus, stomach, small intestine, and colon. Maturation was observed for several GI parameters, and corresponding data sets were identified for each paediatric age group. However, it also became clear that the ontogeny of several GI traits in the paediatric population is not yet known. The review article provides a robust and valuable data set for the development of paediatric in vitro and in silico biopharmaceutical tools to support the development of age-appropriate dosage forms. In addition, it provides important information on existing data gaps and should provide impetus for further systematic and well-designed in vivo studies on GI physiology in children of specific age groups in order to close existing knowledge gaps and to sustainably improve oral drug therapy in children. | Gastrointestinal Absorption |
Primary hepatic mucosa-associated lymphoid tissue (MALT) lymphoma is an extremely rare liver malignancy that usually lacks characteristic imaging findings and which is often misdiagnosed. We report a 63-year-old woman diagnosed with primary hepatic extranodal marginal zone B-cell lymphoma, MALT type. The patient underwent needle biopsy and radiofrequency ablation (RFA), and showed no signs of relapse during the 12-month postoperative follow-up. This case stresses the rarity of primary hepatic MALT-type lymphoma and the unique and effective treatment for this patient. Our patient received RFA, which showed good efficacy and which provides a new option for the treatment of hepatic MALT lymphoma. We also present our findings from a systematic review to improve the current understanding of this disease." | Lymphoma, B-Cell, Marginal Zone |
NTRK-rearranged spindle cell neoplasms (NTRK-RSCNs) represent an emerging group of rare tumours defined using molecular means. To the best of our knowledge, there have been no large series of reports about this tumour in the Chinese population in English full-text articles. Herein, we present 13 NTRK-RSCNs with peculiar characteristics. Ten of the 13 (77%) patients were children without sex differences. The tumour locations included six trunks, four extremities, two recta, and one small bowel. The histological morphology included four lipofibromatosis-like neural tumour (LPF-NT)-like, eight malignant peripheral nerve sheath tumours (MPNST)/fibrosarcoma-like, and one extremely rare myxofibrosarcoma-like pattern. Immunohistochemically, all cases were CD34, pan-TRK and TRK-A positive, SOX-10 negative, and H3K27me3 intact. S-100 protein expression was identified in 11 of 13 (85%) cases. Genetically, NTRK1 rearrangements were considered positive (7/13, 54%) or suspicious for positivity (6/13, 46%) by fluorescence in situ hybridisation. Next-generation sequencing and Sanger sequencing confirmed NTRK1 fusions with a variety of partner genes, including five LMNA, three TPM3, one SQSTM1, three novel CPSF6, IGR (downstream PMVK), and GAS2L1 genes. Interestingly, the last tumour concurrently harboured a second EWSR1-PBX1 fusion, which has never been reported. Four patients developed local recurrence and two of them suffered metastasis. In our study, NTRK-RSCNs had peculiar fusions that displayed unusual or complicated clinicopathological features. Histological clues and IHC helped streamline a small subset of potential candidates. Although FISH is a powerful technology for identifying NTRK rearrangements, RNA-/DNA-based NGS is recommended for highly suspected cases in which FISH signal patterns are not discernible as classic positive patterns, particularly if targeted therapy is considered. | Receptor, trkC |
Although the role of Helicobacter pylori infection on noncomplicated peptic ulcer disease has been definitively established, the precise relationship between the organism and complicated ulcer has hardly been studied. The mean prevalence of H. pylori infection in patients with perforated peptic ulcer is of only about 65-70%, which contrasts with the almost 90-100% figure reported in noncomplicated ulcer disease. However, H. pylori infection rates in various studies range markedly from 0% to 100%, suggesting that differences in variables as number and type of diagnostic methods used to diagnose H. pylori infection, or frequency of nonsteroidal anti-inflammatory drug intake, may be responsible for the low prevalence reported in some studies. Recurrent ulcer disease after peptic ulcer perforation mainly occurs in patients with H. pylori infection, which suggests that the microorganism plays an important role in this complication. All patients with perforated peptic ulcer should be treated by simple closure of the perforation and with therapy aimed at healing of the ulcer and eradicating the H. pylori infection, as disappearance of the organism prevents, or at least decreases, ulcer recurrence and ulcer perforation in patients with H. pylori-associated perforated ulcers after simple closure. Therefore, H. pylori eradicating treatment should be started during the immediate postoperative period. The patients with intractable recurrent symptoms of peptic ulcer despite adequate medical treatment, but without H. pylori infection (e.g. a patient using nonsteroidal anti-inflammatory drugs), is probably the only remaining indication for elective definitive surgical treatment of peptic ulcer disease. | Peptic Ulcer Perforation |
It was proposed that CYP7A1 expression is suppressed through the gut-hepatic signaling pathway fibroblast growth factor (FGF) 15/19-fibroblast growth factor receptor 4, which is initiated by activation of farnesoid X receptor in the intestine rather than in the liver. The present study tested whether portal bile acid flux alone without ileal FGF19 could downregulate CYP7A1 expression in rabbits. A rabbit model was developed by infusing glycodeoxycholic acid (GDCA) through the splenic vein to bypass ileal FGF19. Study was conducted in four groups of rabbits: control; bile fistula + bovine serum albumin solution perfusion (BF); BF + GDCA (by portal perfusion); and BF + GDCA-f (by femoral perfusion). Compared with only BF, BF + GDCA (6 h portal perfusion) suppressed CYP7A1 mRNA, whereas BF + GDCA-f (via femoral vein) with the same perfusion rate of GDCA did not show inhibitory effects. Meanwhile, there was a decrease in ileal FGF19 expression and portal FGF19 protein levels, but an equivalent increase in biliary bile acid outputs in both GDCA perfusion groups. This study demonstrated that portal bile acid flux alone downregulated CYP7A1 expression with diminished FGF19 expression and protein levels, whereas the same bile acid flux reaching the liver through the hepatic artery via femoral vein had no inhibitory effect on CYP7A1. We propose that bile acid flux through the portal venous system may be a kind of intestinal factor" that suppresses CYP7A1 expression." | Glycodeoxycholic Acid |
The failure of axons to regenerate in the damaged mammalian CNS is the main impediment to functional recovery. There are many molecules and structures in the environment of the injured nervous system that can inhibit regeneration, but even when these are removed or replaced with a permissive environment, most CNS neurons exhibit little regeneration of their axons. This contrasts with the extensive and vigorous axon growth that may occur when embryonic neurons are transplanted into the adult CNS. In the peripheral nervous system, the axons usually respond to axotomy with a vigorous regenerative response accompanied by a regenerative program of gene expression, usually referred to as the regeneration-associated gene (RAG) program. These different responses to axotomy in the mature and immature CNS and the PNS lead to the concept of the intrinsic regenerative response of axons. Analysis of the many mechanisms and issues that affect the intrinsic regenerative response is the topic of this special issue of Developmental Neurobiology. The review articles highlight the control of expression of growth and regeneration-associated genes, emphasizing the role of epigenetic mechanisms. The reviews also discuss changes within axons that lead to the developmental loss of regenerative ability. This is caused by changes in axonal transport and trafficking, in the cytoskeleton and in signaling pathways. | Axons |
The hospital sector in 2001 led the health care field in mergers and acquisitions. Most deals involved a network augmenting its presence within a specific region or in a market adjacent to its primary service area. Analysts expect M&A activity to increase in 2002. | Health Facility Merger |
Pre-exposure prophylaxis (PrEP) is an effective HIV prevention strategy. There is little scientific consensus about how to measure PrEP program implementation progress. We draw on several years of experience in implementing PrEP programs and propose a PrEP continuum of care that includes: (1) identifying individuals at highest risk for contracting HIV, (2) increasing HIV risk awareness among those individuals, (3) enhancing PrEP awareness, (4) facilitating PrEP access, (5) linking to PrEP care, (6) prescribing PrEP, (7) initiating PrEP, (8) adhering to PrEP, and (9) retaining individuals in PrEP care. We also propose four distinct categories of PrEP retention in care that include being: (1) indicated for PrEP and retained in PrEP care, (2) indicated for PrEP and not retained in PrEP care, (3) no longer indicated for PrEP, and (4) lost to follow-up for PrEP care. This continuum of PrEP care creates a framework that researchers and practitioners can use to measure PrEP awareness, uptake, adherence, and retention. Understanding each point along the proposed continuum of PrEP care is critical for developing effective PrEP interventions and for measuring public health progress in PrEP program implementation. | Pre-Exposure Prophylaxis |
The use of micelle polymers, a class of polysoaps with a polymerized hydrophobic interior and a charged hydrophillic exterior, as pseudostationary phases in electrokinetic chromatography has generated significant interest. Their stable structure has been shown to provide significant advantages over conventional micelles when used as pseudostationary phases. In previous studies, micelle polymers have had carboxylate and sulfate head groups. These chemistries have limitations: carboxylate micelle polymers precipitate out of solution at pH less than seven or eight and sulfate head groups are not stable to hydrolysis and are hydrolyzed during polymerization. Additionally, while the chemical selectivity of conventional micelles varies with head group chemistry, no significant differences in chemical selectivity were observed between analogous polymers with sulfate and carboxylate groups. To overcome the limitations of carboxylate and sulfate head groups, and to further investigate the chemical selectivity of micelle polymers, poly(sodium-N-undec-10-ene-1-oyl-taurate) and poly(sodium-N-undec-10-ene-1-oyl-ethyl-2-phosphonate) micellar polymers have been synthesized and characterized as pseudostationary phases. These polymers have amide functionality and stable, strongly acidic sulfonate and phosphonate head groups. These polymers did provide improved solubility at low pH, and are stable under the conditions studied. The chromatographic performance and chemical selectivity of the polymers has been studied by several methods, including linear solvation energy relationships. Poly(sodiumN-undec-10-ene-1-oyl-taurate) has greater electrophoretic mobility than other polymers of this type, and can be used for the separation of hydrophobic compounds. The polymers do exhibit unique selectivity, but the differences in selectivity are not significant for the majority of compounds studied. | Undecylenic Acids |
The phylogeny of 16 isolates from root nodules of Genista germanica, Genista tinctoria, Cytisus ratisbonensis, and Cytisus scoparius growing in southeast Poland was estimated by comparative sequence analysis of core (16S rDNA, atpD, glnII, recA) and symbiosis-related (nodC, nodZ, nifH) genes. All the sequences analyzed placed the studied rhizobia in the genus Bradyrhizobium. Phylogenetic analysis of individual and concatenated housekeeping genes showed that the Genisteae microsymbionts form a homogeneous group with Bradyrhizobium japonicum strains. The phylogeny of nodulation and nitrogen fixation genes indicated a close relationship of the examined rhizobia with B. japonicum, Bradyrhizobium canariense, Bradyrhizobium cytisi, Bradyrhizobium rifense and Bradyrhizobium lupini strains infecting other plants of the tribe Genisteae. For the first time, the taxonomic position of G. germanica and C. ratisbonensis rhizobia, inferred from multigenic analysis, is described. The results of the phylogenetic analysis based on the protein-coding gene sequences presented in this study also indicate potential pitfalls concerning the choice of marker and reference strains, which may lead to conflicting conclusions in species delineation. | Cytisus |
A critical link exists between an individual's ability to repair cellular DNA damage and cancer development, progression, and response to therapy. Knowledge gained about the proteins involved and types of damage repaired by the individual DNA repair pathways has led to the development of a variety of assays aimed at determining an individual's DNA repair capacity. These assays and their use in the analysis of clinical samples have yielded useful though somewhat conflicting data. In this review article, we discuss the major DNA repair pathways, the proteins and genes required for each, assays used to analyze activity, and the relevant clinical studies to date. With the recent results from clinical trials targeting specific DNA repair proteins for the treatment of cancer, accurate, reproducible, and relevant analysis of DNA repair takes on an even greater significance. We highlight the strengths and limitations of these DNA repair studies and assays, with respect to the clinical assessment of DNA repair capacity to determine cancer development and response to therapy. | Cytogenetics |
There are many osseous variants that occur around the elbow joint such as supracondylar process, supratrochlear foramen, accessory ossicles, and others. Scientific databases were searched for variants around the elbow joint. Elbow radiographs from our center demonstrating some of these findings were included in the study. The aim of the present review was to provide comprehensive information on the terminology, prevalence, history, etiology, and clinical importance of these variants. These anatomical variants are important for radiologists while interpreting radiographs, computed tomography, and magnetic resonance imaging for trauma and orthopedic surgeons during osteosynthesis at the distal humerus, proximal ulna, and radius. | Bones of Upper Extremity |
BACKGROUND: The majority of patients with uncontrolled severe CRSwNP, asthma and atopic dermatitis share a similar T helper 2 type inflammation linked to their underlying phenotype. This discovery has triggered new research around treatments targeting specific cytokines driving inflammation in CRSwNP like IL-4, IL-13, IL-5 and IgE. Biologicals are increasingly tested as additional tre- atment for patients suffering from severe chronic rhinosinusitis with nasal polyps (CRSwNP). Their efficacy has been demonstrated in multiple studies. All studies differ in terms of baseline characteristics of included patients and outcome parameters analysed. AIMS: A comparative analysis of the efficacy of reported biologicals for CRSwNP based on the published data for phase 2 and 3 studies. The aim was to provide a comprehensive overview across the different biologicals and outcome parameters. METHODS: In a first step we critically selected out of all available phase 2 and 3 clinical trials the ones containing the most rigorous and compatible study designs. Meaning studies that comply with a need for a clear definition of CRSwNP, at least two administra- tion doses, comparable timeframes and the same outcome parameters studied. This assessment was performed using a PRISMA search. We retained 7 studies with significant data for dupilumab, mepolizumab and omalizumab. In a second step the effect-sizes of treatment with those biologicals were compared for the most important outcome parameters both patient relevant (nasal con- gestion, smell loss and SNOT-22 scores) and patient irrelevant (CT scan Lund-Mackay, smell test and nasal polyp scores). Therapy duration of 16 to 25 weeks was chosen for evaluation of efficacy. RESULTS: A direct comparison of efficacy between dupilumab, mepolizumab and omalizumab is challenging given differences in inclusion criteria, outcome parameters and time-points of analyses. We have been able to conclude that effect sizes of dupilumab, mepolizumab and omalizumab seem large enough to reflect a major reduction in symptom burden as experienced by patients suffering from refractory CRSwNP. The effect size of dupilumab on both patient relevant and patient irrelevant parameters of smell loss are clearly significant and reflect the clinical experience of major reduction of smell impairment in treated patients. CONCLUSION: Despite the heterogeneity of protocols, dosages and time-points of analyses of biological trials in CRSwNP, this over- view highlights outcomes of biological treatment in CRSwNP in a comprehensive way. Real-life registries, comparative trials and/ or endotype-driven treatment plans are needed to provide the answers to the multiple questions that are still open today. | Nasal Polyps |
Most platelet transfusions are given to prevent bleeding in thrombocytopenic patients undergoing chemotherapy for malignancy or hematopoietic stem cell transplant. In stable, uncomplicated patients the risk of bleeding is similar until the platelet count falls to <5,000/microL. However, many patients have clinical complications that necessitate transfusion at higher counts. Therefore, the recommended indication for prophylactic transfusion is a platelet count of 10,000/microL. The usual dose of platelets is 1 apheresis unit or a pool of four to six concentrates from individual units of whole blood. The likelihood of bleeding is the same if half or double the usual dose is given, but half-dose transfusions must be given more often and double-dose transfusions less often than the standard dose. For patients with inherited defects of platelet function or acquired defects such as due to drugs or uremia, the platelet count is usually normal and prophylactic transfusion is not recommended. Transfusion may be helpful to treat serious bleeding. Patients undergoing cardiopulmonary bypass may be slightly thrombocytopenic but usually have platelet dysfunction. Transfusion is helpful to treat nonsurgical serious bleeding. In idiopathic thrombocytopenic purpura, platelet survival is short and transfusion is useful only for severe bleeding." | Purpura, Thrombotic Thrombocytopenic |
Ivy leaf is used for the treatment of respiratory diseases with the intensive mucus formation, respiratory infections, and irritating cough coming from the common cold. Conferring to clinical trials, the efficacy, and tolerability of ivy leaf is good. The main compounds accountable for biological activity are triterpene and saponins. Ivy leaves show convulsive/antispasmodic, anti-inflammatory, antimicrobial, analgesic, anthelmintic and anti-thrombin activity. Not only ivy but also marshmallow and mustard seeds are used for these indications. This study was conducted to evaluate the efficacy and safety of Cough (EMA; European Medicines Agency) granules used for upper respiratory disorders. This clinical trial was conducted on 150 patients, out of which 75received the Cough (EMA) granules and 75received the placebo. The age range of patients was 3 years to above 15 years. The sample paired t-test was applied to evaluate the significant level. Cough (EMA) granules were found effective in the treatment of cough, cold, and flu symptoms. The new treatment Cough (EMA) granules were safe and well tolerated in patient at given specific age group. The study recommends that Cough (EMA) granules can be used effectively in the treatment of upper respiratory tract infection. | Althaea |
Present paper is aimed at assessing the effect of hypoxic gaseous mixtures intended for the use as the fire suppression agents within closed volumes on the basis of argon with addition of carbonic acid on the body of mammalia. Three experiments were performed on the male white laboratory Wistar rats. It is indicated that argon adding to the hypoxic mixtures containing 4-5% volume increases animal survivability as compared to analogous nitrogen-based mixtures. An addition of 4-8% volume of carbonic acid impairs the of animal condition and reduces the survival rate. There noted a pronounced negative effect of the increased temperature on the survival time in the hypoxic media. One can draw inference about the principal possibility of using argon for formation of the hypoxic gaseous mixtures possessing fire suppression properties. | Hypoxia |
BACKGROUND: Pancreatic cancer has a poor prognosis because of its high refractoriness to chemotherapy and tumour recurrence, and these properties have been attributed to cancer stem cells (CSCs). MicroRNA (miRNA) regulates various molecular mechanisms of cancer progression associated with CSCs. This study aimed to identify the candidate miRNA and to characterise the clinical significance. METHODS: We established gemcitabine-resistant Panc1 cells, and induced CSC-like properties through sphere formation. Candidate miRNAs were selected through microarray analysis. The overexpression and knockdown experiments were performed by evaluating the in vitro cell growth and in vivo tumourigenicity. The expression was studied in 24 pancreatic cancer samples after laser captured microdissection and by immunohistochemical staining. RESULTS: The in vitro drug sensitivity of pancreatic cancer cells was altered according to the miR-1246 expression via CCNG2. In vivo, we found that miR-1246 could increase tumour-initiating potential and induced drug resistance. A high expression level of miR-1246 was correlated with a worse prognosis and CCNG2 expression was significantly lower in those patients. CONCLUSIONS: miR-1246 expression was associated with chemoresistance and CSC-like properties via CCNG2, and could predict worse prognosis in pancreatic cancer patients. | Cyclin G2 |
Nanotechnology is one of the most important and relevant disciplines today due to the specific electrical, optical, magnetic, chemical, mechanical and biomedical properties of nanoparticles. In the present study we demonstrate the efficacy of Cuphea procumbens to biogenerate silver nanoparticles (AgNPs) with antibacterial and antitumor activity. These nanoparticles were synthesized using the aqueous extract of C. procumbens as reducing agent and silver nitrate as oxidizing agent. The Transmission Electron Microscopy demonstrated that the biogenic AgNPs were predominantly quasi-spherical with an average particle size of 23.45 nm. The surface plasmonic resonance was analyzed by ultraviolet visible spectroscopy (UV-Vis) observing a maximum absorption band at 441 nm and Infrared Spectroscopy (FT IR) was used in order to structurally identify the functional groups of some compounds involved in the formation of nanoparticles. The AgNPs demonstrated to have antibacterial activity against the pathogenic bacteria Escherichia coli and Staphylococcus aureus, identifying the maximum zone of inhibition at the concentration of 0.225 and 0.158 microg/mL respectively. Moreover, compared to the extract, AgNPs exhibited better antitumor activity and higher therapeutic index (TI) against several tumor cell lines such as human breast carcinoma MCF-7 (IC(50) of 2.56 microg/mL, TI of 27.65 microg/mL), MDA-MB-468 (IC(50) of 2.25 microg/mL, TI of 31.53 microg/mL), human colon carcinoma HCT-116 (IC(50) of 1.38 microg/mL, TI of 51.07 microg/mL) and melanoma A-375 (IC(50) of 6.51 microg/mL, TI of 10.89 microg/mL). This fact is of great since it will reduce the side effects derived from the treatment. In addition, AgNPs revealed to have a photocatalytic activity of the dyes congo red (10(-3) M) in 5 min and malachite green (10(-3) M) in 7 min. Additionally, the degradation percentages were obtained, which were 86.61% for congo red and 82.11% for malachite green. Overall, our results demonstrated for the first time that C. procumbens biogenerated nanoparticles are excellent candidates for several biomedical and environmental applications. | Cuphea |
In the synthesis of dipeptides (Boc-AA(1)-AA(2)-OPac: AA(1) and AA(2) represent amino acids) protected by phenacyl (Pac) ester, amines and solid bases as the base for the conversion of the trifluoroacetic acid (TFA) salt of the amino component (TFA.H-AA(2)-OPac) into the corresponding free amino component (H-AA(2)-OPac) were examined. The synthesis of a dipeptide (Boc-Ala-Gly-OPac) using amines for the conversion afforded an unsatisfactory yield with by-products. On the other hand, the use of neutral alumina-supported Na(2) CO(3) (Na(2)CO(3) /n-Al(2)O(3)) as a solid base for the conversion provided the dipeptide in a quantitative yield without by-products. The application of Na(2)CO(3) /n-Al2 O3 to the synthesis of some dipeptides protected by Pac ester gave the desired peptides in excellent yields. | Esters |
Concerns about parenting adolescents are not new, but the rapid diffusion of digital technologies has heightened anxieties over digital parenting. Findings are decidedly mixed regarding the impact of digital technologies on adolescent well-being, and parents are left to navigate their concerns without an empirically based road map. A missing link for understanding the state of the science is a clear characterization of how digital parenting is measured, including an evaluation of which areas demand an outsized share of scientific attention and which have been overlooked. To address this gap, we undertook two interdisciplinary systematic reviews of the digital-parenting literature and characterized measurement across (a) quantitative surveys (n = 145 studies) and (b) qualitative focus groups, interviews, codesign studies, and user studies (n = 49). We describe previously popular areas of survey measurement that are of decreasing relevance to parenting of digital spaces (e.g., co-use, hovering). We likewise highlight areas that have been overlooked, including consideration of positive uses of digital technologies, acknowledgment of bidirectional influence, and attention to heterogeneity among families and to extraparental social ecologies of support and monitoring. We provide recommendations for the future of digital-parenting research and propose a more comprehensive approach to measuring how modern adolescents are parented. | Parenting |
The authors consider the issues concerning planning of pregnancy in patients with multiple sclerosis receiving pathogenetic and immunomodulatory therapy and provide descriptions of cases of pregnancy in patients with aggressively multiple sclerosis occurred during the treatment with natalizumab. | Natalizumab |
Transcutaneous immunization (TCI) is a promising alternative to vaccine delivery via the subcutaneous and intramuscular routes because of the unique immunological characteristics of the skin. However, the stratum corneum (SC) prevents entry of most therapeutic compounds into the body. Several physical devices have been developed to overcome the SC barrier, but still damage the skin. However, by targeting antigens to the abundant perifollicular antigen-presenting cells (APCs), the transfollicular route might be a promising approach for TCI without compromising the skin barrier. | Immunization |
Electrophoretic mobility shift assays (EMSA) are used to characterize interactions between nucleic acids and proteins in native conditions. This is based on the fact that the electrophoretic mobility of a nucleic acid becomes slower when it forms complexes with proteins. There are many different variants and applications of this methodology. In this chapter we describe a detailed EMSA protocol applied to the study of asthma." | Electrophoretic Mobility Shift Assay |
BACKGROUND AND AIM: DNA methylation is an important epigenetic modification that can promote the development of various cancers. The STAT1 and SOCS3 have been observed to be hypermethylated in tumor tissues and peripheral blood. This study aimed to explore the relationship between the methylation status of the STAT1 and SOCS3 in peripheral blood and gastric cancer (GC). METHODS: This hospital-based case-control study involved 372 patients with GC and 379 controls. The methylation status of the STAT1 and SOCS3 was semiquantitatively determined using the methylation-sensitive high-resolution melting method. Logistic regression analysis was used to analyze the relationship between the STAT1 and SOCS3 methylation status and GC susceptibility. Moreover, propensity scores were used to control confounding factors. RESULTS: Compared with negative methylation, the positive methylation of SOCS3 significantly increased the risk of GC (OR(a) = 1.820, 95% CI: 1.247-2.658, P = 0.002). This trend was also found via stratified analysis, and methylation positivity of the SOCS3 significantly increased the risk of GC in the < 60 years group, in the >/= 60 years group, and in the positive Helicobacter pylori infection group (OR(a) = 1.654, 95% CI: 1.029-2.660, P = 0.038; OR(a) = 1.957, 95% CI: 1.136-3.376, P = 0.016; OR(a) = 2.084, 95% CI: 1.270-3.422, P = 0.004, respectively). Additionally, no significant association was found between STAT1 methylation and GC risk (OR(a) = 0.646, 95% CI: 0.363-1.147, P = 0.135). This study found that the interaction between the methylation status of STAT1 and SOCS3 and environmental factors did not have an impact on GC risk. CONCLUSION: SOCS3 methylation may serve as a new potential biomarker for GC susceptibility. | STAT1 Transcription Factor |
PATH hosted the inaugural Vaccines Against Shigella and Enterotoxigenic Escherichia coli (VASE) Conference in Washington, DC in June 2016, bringing together experts from around the world for a highly collaborative forum to discuss progress in the development of new enteric vaccines. Diarrheal disease and long-term sequelae caused by infections with the bacterial pathogens Shigella and enterotoxigenic E. coli (ETEC) pose a significant public health burden in low-income communities. There are currently no licensed vaccines against these pathogens, and the global health community has recently prioritized their development. The 2016 VASE Conference aimed to accelerate communication and progress among those working in the enteric vaccine field to make Shigella and ETEC vaccines a reality as quickly as possible. Research presented in oral and poster presentations at the VASE Conference covered a range of topics, including: the global burden of disease and public health case for Shigella and ETEC vaccines; current vaccine candidates in development; immunology and host responses to the pathogens; and the rationale for and status of combined Shigella-ETEC vaccine candidates. This article reviews key points and highlighted research presented in each of the plenary conference sessions and poster presentations at the 2016 conference. Planning for the 2018 VASE Conference is underway and will likely provide an important platform for sharing the latest updates on Shigella and ETEC vaccine research efforts and maintaining the momentum for accelerating this work. It is also expected that the VASE Conference will continue to provide a unique opportunity for those in the enteric vaccine field to share ideas, make connections, and create workable plans to make Shigella and ETEC vaccines a reality. (Updates available at: www.vaseconference.org.). | Escherichia coli Vaccines |
BACKGROUND: heart rates generated by pulse oximeters and electronic sphygmomanometers in acutely ill patients may not be the same as those recorded by ECG. METHODS: heart rates recorded by an oximeter and an electronic sphygmomanometer were compared with electrocardiogram (ECG) heart rates measured on acutely ill medical patients. RESULTS: 1010 ECGs were performed on 217 patients while they were in the hospital. The bias between the oximeter and the ECG measured heart rate was -1.37 beats per minute (limits of agreement -22.6 to 19.9 beats per minute), and the bias between the sphygmomanometer and the ECG measured heart rate was -0.14 beats per minute (limits of agreement -22.2 to 21.9 beats per minute). Both devices failed to identify more than half the ECG recordings that awarded 3 NEWS points for heart rate. CONCLUSION: Heart rates of acutely ill patients are not reliably measured by pulse oximeter or electronic sphygmomanometers. | Sphygmomanometers |
Simple biomembrane models, namely micellar aggregates formed by enantiopure sodium N-acylprolinates, are able to convert the racemic mixture of bilirubin-IXalpha into an enantiomerically enriched mixture, thus suggesting a possible role of chirality in bilirubin toxicity due to the perturbation of neuron membrane dynamics. The length of alkyl chain does not influence the extent of equilibrium displacement, however, it affects the conformation of bilirubin, thus confirming the role of lipid structure in the membrane/bilirubin interaction, and suggesting a non-superficial main site of association. | Bile Pigments |
Three unrelated boys, ages 2, 6, and 10 years, who have congenital stationary night blindness with myopia and a Schubert-Bornschein-type electroretinogram finding, were found to show a paradoxical" pupillary constriction in darkness. When examining room lights are turned out, the patient's pupils briskly constrict and slowly dilate. Older night blind male relatives of these boys did not show this abnormal constriction to darkness." | Night Blindness |
The development of the iliosacral joint (ISJ) in tetrapods represented a crucial step in the evolution of terrestrial locomotion. This structure is responsible for transferring forces between the vertebral column and appendicular skeleton, thus supporting the bodyweight on land. However, most research dealing with the water-to-land transition and biomechanical studies in general has focused exclusively on the articulation between the pelvic girdle and femur. Our knowledge about the contact between the pelvic girdle and vertebral column (i.e. the ISJ) at a tissue level is restricted so far to human anatomy, with little to no information available on other tetrapods. This lack of data limits our understanding of the development and evolution of such a key structure, and thus on the pattern and processes of the evolution of terrestrial locomotion. Therefore, we investigated the macro- and microanatomy of the ISJ in limb-bearing squamates that, similar to most non-mammalian, non-avian tetrapods, possess only two sacral ribs articulating with the posterior process of the ilium. Using a combination of osteology, micro-computed tomography and histology, we collected data on the ISJ apparatus of numerous specimens, sampling different taxa and different ontogenetic stages. Osteologically, we recorded consistent variability in all three processes of the ilium (preacetabular, supracetabular and posterior) and sacral ribs that correlate with posture and locomotion. The presence of a cavity between the ilium and sacral ribs, abundant articular cartilage and fibrocartilage, and a surrounding membrane of dense fibrous connective tissue allowed us to define this contact as a synovial joint. By comparison, the two sacral ribs are connected to each other mostly by dense fibrous tissue, with some cartilage found more distally along the margins of the two ribs, defining this joint as a combination of a syndesmosis and synchondrosis. Considering the intermediary position of the ISJ between the axial and appendicular skeletons, the shape of the articular surfaces of the sacral ribs and ilium, and the characteristics of the muscles associated with this structure, we argue that the mobility of the ISJ is primarily driven by the movements of the hindlimb during locomotion. We hypothesize that limited torsion of the ilium at the ISJ happens when the hip is abducted, and the joint is likely able to absorb the compressional and extensional forces related to the protraction and retraction of the femur. The mix of fibres and cartilage between the two sacral ribs instead serves primarily as a shock absorber, with the potential for limited vertical translation during locomotion. | Sacrum |
Unregulated inflammation during bovine mastitis is characterized by severe mammary tissue damage with systemic involvement. Vascular dysfunction underlies tissue pathology because of concurrent oxidative stress mediated by several inflammatory mediators. We recently demonstrated increased production of 20-hydroxyeicosatetraenoic acid (20-HETE), a cytochrome P450-derived (CYP) oxylipid that correlated with oxidative stress during severe bovine coliform mastitis. The hypothesis for this study was that 20-HETE-induced oxidative stress disrupts barrier function of endothelial cells. Primary endothelial cells from the bovine aorta were utilized to investigate the effects of 20-HETE on barrier integrity in an in-vitro model of oxidative stress. The effects of various antioxidants on modulating the 20-HETE barrier integrity effects also were investigated. Our results showed that 20-HETE decreased endothelial barrier integrity, which was associated with increased reactive metabolite production and decreased total glutathione. The antioxidant, vitamin E, partially delayed the loss of endothelial resistance upon exposure to 20-HETE but did not prevent complete loss of barrier integrity. The decrease in barrier resistance due to 20-HETE was neither associated with oxidative stress as assessed by oxidative protein or lipid damage nor endothelial cell apoptosis; however, selenium supplementation conferred resistance to loss of barrier integrity suggesting a role for shifts in redox status. Specific mechanisms by which 20-HETE alters vascular barrier integrity require further investigation to identify targets for therapy during inflammatory conditions with enhanced CYP450 activity. | Hydroxyeicosatetraenoic Acids |
The data are presented on changes in the rat arcuate nuclear neuron ultrastructure after using cyproheptadine (peritol, Egyt Pharmaceutical Works, Hungary) in a water suspension at a dose of 20 mg/kg once daily during 7 successive days and twice a day within 10 days. It was shown that cyproheptadine decreases the functional activity of the arcuate nuclear neurons, depending on the total amount of the drug used. Cyproheptadine-induced inhibition of the forming neurohormone release from neurons is likely to be one of the mechanisms of its therapeutic effect in Itsenko-Cushing's disease." | Arcuate Nucleus of Hypothalamus |
Currently, liver transplantation is the only available remedy for patients with end-stage liver disease. Conservation of transplanted liver graft is the most important issue as it directly related to patient survival. Carbonyl reductase 1 (CBR1) protects cells against oxidative stress and cell death by inactivating cellular membrane-derived lipid aldehydes. Ischemia-reperfusion (I/R) injury during living-donor liver transplantation is known to form reactive oxygen species. Thus, the objective of this study was to investigate whether CBR1 transcription might be increased during liver I/R injury and whether such increase might protect liver against I/R injury. Our results revealed that transcription factor Nrf2 could induce CBR1 transcription in liver of mice during I/R. Pre-treatment with sulforaphane, an activator of Nrf2, increased CBR1 expression, decreased liver enzymes such as aspartate aminotransferase and alanine transaminase, and reduced I/R-related pathological changes. Using oxygenglucose deprivation and recovery model of human normal liver cell line, it was found that oxidative stress markers and lipid peroxidation products were significantly lowered in cells overexpressing CBR1. Conversely, CBR1 knockdown cells expressed elevated levels of oxidative stress proteins compared to the parental cell line. We also observed that Nrf2 and CBR1 were overexpressed during liver transplantation in clinical samples. These results suggest that CBR1 expression during liver I/R injury is regulated by transcription factor Nrf2. In addition, CBR1 can reduce free radicals and prevent lipid peroxidation. Taken together, CBR1 induction might be a therapeutic strategy for relieving liver I/R injury during liver transplantation. | Carbonyl Reductase (NADPH) |
Cardiac implantable devices are commonly used for superior vena cava stenosis, but there have been few reports of electrode replacement in the stenosed superior vena cava. A 73-year-old man was diagnosed with second-degree type II atrioventricular block and a permanent dual-chamber, rate-modulated pacing pacemaker was implanted 10 years previously. Because of depletion of the pacemaker battery and an increase in the ventricular pacing threshold, replacement of the pacemaker and ventricular electrode was required. During the operation, we found that the patient had severe superior vena cava stenosis on angiography, and this caused obstruction when a common guidewire was used to pass through the superior vena cava. After attempting various methods, we successfully passed through the vascular stenosis with a super slide guidewire and a long sheath, and completed replacement of the pacemaker and ventricular electrode. We summarize the related literature of superior vena cava stenosis related to a cardiac implantable device, and discuss the replacement strategy of this complication and other treatment options. | Vena Cava, Superior |
OBJECTIVES: To evaluate the effect of microblepharon exfoliation on the number of eyelid bacteria and their lipase activity and the relationship of these to contact lens discomfort. METHODS: Thirty experienced contact lens wearers had their eyelid margin physiology, tear properties, and comfort scores assessed. The number, type, and frequency of lower eyelid margin bacteria, and their lipase activity, were measured. Eyelids were treated with a foam cleanser or microblepharon exfoliation. Clinical and microbiological tests were repeated at each visit. Changes and correlations were examined. RESULTS: Symptomatic lens wearers had a higher ratio for the number and frequency of gram-positive rods and cocci. Microblepharon exfoliation reduced the number and ratio of gram-positive rods to cocci from baseline for symptomatic wearers that lasted 7 to 10 days after treatment (P<0.05). Numbers of bacteria, the ratio of rods to cocci, and lipase activity correlated with lash contamination (r>/=0.385; P</=0.046) and anterior blepharitis (r>/=0.359; P</=0.048). Bacterial lipase correlated with meibomian gland secretions (r=0.422; P=0.038) and the tear evaporation rate (r=0.479; P=0.022). Microblepharon exfoliation produced a significant reduction in CLDEQ-8 scores and converted 10 symptomatic into asymptomatic lens wearers. CONCLUSIONS: There was dysbiosis in the lid microbiome of symptomatic lens wearers. Microblepharon exfoliation reduced the number, frequency of isolation, and ratio of gram-positive rods and cocci. Bacterial numbers and their lipase production correlated with changes to clinical signs and symptoms. Symptomatic lens wearers could be converted to asymptomatic lens wearers after microblepharon exfoliation. | Demulcents |
Observations have resolved the satellite Charon from its parent planet Pluto, giving separate spectra of the two objects from 1.0 to 2.5 micrometers. The spectrum of Charon is found to be different from that of Pluto, with water ice in crystalline form covering most of the surface of the satellite. In addition, an absorption feature in Charon's spectrum suggests the presence of ammonia ices. Ammonia ice-water ice mixtures have been proposed as the cause of flowlike features observed on the surfaces of many icy satellites. The existence of such ices on Charon may indicate geological activity in the satellite's past. | Pluto |
Smoothelin is a smooth muscle-specific cytoskeletal protein exclusively found in differentiated smooth muscle cells. This contrasts with other smooth muscle proteins (eg, h-caldesmon, alpha-smooth muscle actin, desmin, smooth muscle myosin), which are expressed in proliferative (early) stages of smooth muscle development and occasionally in other cell types (striated muscle, myofibroblasts, myoepithelial cells, pericytes). Smoothelin has been shown to be expressed predominantly in visceral smooth muscle and to a lesser extent in vascular smooth muscle. Smoothelin expression in mesenchymal tumors of the gastrointestinal (GI) tract has not been evaluated earlier. The purpose of this study was to determine whether immunostaining for smoothelin could help distinguish smooth muscle neoplasms from their morphologic mimics, particularly KIT-negative gastrointestinal stromal tumors (GISTs), desmin-positive GISTs, and desmoid fibromatosis. A total of 150 mesenchymal neoplasms of the GI tract, abdominal cavity, and retroperitoneum were retrieved from consult and surgical pathology archives, including 54 GISTs (8 KIT-negative; 13 desmin-positive), 17 GI leiomyosarcomas (LMS), 11 GI mural leiomyomas, 13 leiomyomas of the muscularis mucosae, 12 gastric schwannomas, 15 inflammatory myofibroblastic tumors, 9 cases of mesenteric desmoid fibromatosis, 10 dedifferentiated liposarcomas, and 9 malignant peripheral nerve sheath tumors. Immunostaining for smoothelin was performed on all cases. Cytoplasmic and nuclear staining was recorded. Cytoplasmic expression of smoothelin was present in all 24 (100%) benign smooth muscle tumors (mural leiomyomas and leiomyomas of the muscularis mucosae). In contrast, only 4 (24%) GI LMS showed cytoplasmic staining for smoothelin. None of the GISTs, desmoid tumors, inflammatory myofibroblastic tumors, schwannomas, dedifferentiated liposarcomas, or malignant peripheral nerve sheath tumors showed cytoplasmic reactivity for smoothelin. Interestingly, 7 (41%) GI LMS and 12 (22%) GISTs (all except 2 with an epithelioid component) showed multifocal, exclusively nuclear staining for smoothelin. Nuclear expression of smoothelin was not detected in any of the other tumor types examined. In summary, diffuse cytoplasmic staining for smoothelin is highly sensitive and specific for benign leiomyomas of the GI tract. Aberrant nuclear expression is common in GI LMS and may also be seen in GISTs, especially epithelioid and mixed-type tumors. These findings suggest that the extent and pattern of smoothelin expression may help differentiate between benign and malignant mesenchymal tumors of the GI tract, and may be useful in distinguishing leiomyomas from KIT-negative and/or desmin-positive GISTs. | Smooth Muscle Tumor |
Postsynaptic scaffold proteins immobilize neurotransmitter receptors in the synaptic membrane opposite to presynaptic vesicle release sites, thus ensuring efficient synaptic transmission. At inhibitory synapses in the spinal cord, the main scaffold protein gephyrin assembles in dense molecule clusters that provide binding sites for glycine receptors (GlyRs). Gephyrin and GlyRs can also interact outside of synapses, where they form receptor-scaffold complexes. Although several models for the formation of postsynaptic scaffold domains in the presence of receptor-scaffold interactions have been advanced, a clear picture of the coupled dynamics of receptors and scaffold proteins at synapses is lacking. To characterize the GlyR and gephyrin dynamics at inhibitory synapses, we performed fluorescence time-lapse imaging after photoconversion to directly visualize the exchange kinetics of recombinant Dendra2-gephyrin in cultured spinal cord neurons. Immuno-immobilization of endogenous GlyRs with specific antibodies abolished their lateral diffusion in the plasma membrane, as judged by the lack of fluorescence recovery after photobleaching. Moreover, the cross-linking of GlyRs significantly reduced the exchange of Dendra2-gephyrin compared with control conditions, suggesting that the kinetics of the synaptic gephyrin pool is strongly dependent on GlyR-gephyrin interactions. We did not observe any change in the total synaptic gephyrin levels after GlyR cross-linking, however, indicating that the number of gephyrin molecules at synapses is not primarily dependent on the exchange of GlyR-gephyrin complexes. We further show that our experimental data can be quantitatively accounted for by a model of receptor-scaffold dynamics that includes a tightly interacting receptor-scaffold domain, as well as more loosely bound receptor and scaffold populations that exchange with extrasynaptic pools. The model can make predictions for single-molecule data such as typical dwell times of synaptic proteins. Taken together, our data demonstrate the reciprocal stabilization of GlyRs and gephyrin at inhibitory synapses and provide a quantitative understanding of their dynamic organization. | Receptors, Amino Acid |
Salt tolerance and the possible functions of suberization on salt exclusion and secretion were examined in a dominant mangrove plant, Avicennia marina. The results showed that low salinities (10 per thousand and 20 per thousand) almost has no negative effect on A. marina, however significant growth inhibitions were observed in the seedlings grown in higher salinities (30 per thousand and 40 per thousand). With the increases of salinity, increased tissue Na(+) content and enhanced salt secretion by glands were observed. Obvious suberization thickening were detected both in the exodermis and endodermis of the roots after salt pretreatment when compared to the roots without salt treatment. More importantly, the present data further confirmed that these root apoplastic barriers would directly decrease Na(+) loading into xylem. Higher salt tolerance was observed in the seedlings pre-cultivated by salty tide when compared to fresh water cultivated A. marina. In summary, this study suggests a barrier property of suberization in dealing with salt exclusion in mangroves, a moderate salt pre-treatment may benefit plant withstanding high salinity. | Salt Tolerance |
The surface proteins of several Bordetella strains and their modulated derivatives were examined by surface radioiodination, cell fractionation, and Western blotting. A surface protein with a high Mr, missing in a mutant lacking the filamentous hemagglutinin, was identified in virulent Bordetella pertussis and Bordetella parapertussis cells and was absent in avirulent B. pertussis strains. The electrophoretic profiles of lipopolysaccharide and the 40,000-Mr anion-selective porin were not determinants which correlated with phase variation or phenotypic modulation. At least three envelope proteins (91,000, 32,000, and 30,000 molecular weight) were found only in virulent B. pertussis strains and were absent or diminished in the avirulent phase and most phenotypically modulated strains. Two transposon-induced mutants unable to produce hemolysin, dermonecrotic toxin, pertussis toxin, and filamentous hemagglutinin also lacked these three envelope proteins, confirming that virulence-associated envelope proteins were genetically regulated with other virulence-associated traits. | Bordetella pertussis |
Deoxycytidine metabolism was investigated in light density human tonsillar lymphocytes using 5-3H-deoxycytidine as extracellular precursor. A significant portion of the deoxycytidine (more than 50% of ethanol soluble pool) was found to incorporate into dCDP-choline and dCDP-ethanolamine beside the well-known pathway i.e. incorporation into DNA in form of dCMP and dTMP. Hydroxyurea increased the labeling of the deoxyliponucleotides from 5-3H-deoxycytidine in spite of its inhibition of DNA synthesis. | Deoxycytidine Monophosphate |
Our understanding of human early development is severely hampered by limited access to embryonic tissues. Due to their close evolutionary relationship with humans, nonhuman primates are often used as surrogates to understand human development but currently suffer from a lack of in vivo datasets, especially from gastrulation to early organogenesis during which the major embryonic cell types are dynamically specified. To fill this gap, we collected six Carnegie stage 8-11 cynomolgus monkey (Macaca fascicularis) embryos and performed in-depth transcriptomic analyses of 56,636 single cells. Our analyses show transcriptomic features of major perigastrulation cell types, which help shed light on morphogenetic events including primitive streak development, somitogenesis, gut tube formation, neural tube patterning and neural crest differentiation in primates. In addition, comparative analyses with mouse embryos and human embryoids uncovered conserved and divergent features of perigastrulation development across species-for example, species-specific dependency on Hippo signalling during presomitic mesoderm differentiation-and provide an initial assessment of relevant stem cell models of human early organogenesis. This comprehensive single-cell transcriptome atlas not only fills the knowledge gap in the nonhuman primate research field but also serves as an invaluable resource for understanding human embryogenesis and developmental disorders. | Primitive Streak |
The myocardial performance index (MPI) is a simple quantitative, non-geometric index of ventricular function and is readily applicable for evaluation of the right and left ventricle function. The aim of the study was to assess normal MPI values in healthy children. We studied 38 healthy children from 3 to 18 years of age. The normal values of both, the left ventricular and right ventricular MPI were 0.32 +/- 0.07 and 0.27 +/- 0.09, respectively. Measurement of the MPI is non-invasive and easily obtainable and does not prolong the time required for examination. It is independent from ventricular geometry, blood pressure, heart rate and it appears to be of great prognostic value in many different clinical settings (Tab. 2, Fig. 1, Ref. 14). Full Text in free PDF www.bmj.sk." | Echocardiography, Doppler, Pulsed |
Serotonin and its receptors have been shown to play critical regulatory roles in cancer biology. Nevertheless, the contributions of 5-hydroxytryptamine 1D (5-HT1D), an indispensable member of the serotonergic system, to hepatocellular carcinoma (HCC) remain unknown. The present study demonstrated that the 5-HT1D expression level was significantly up-regulated in HCC tissues and cell lines. The 5-HT1D expression level was closely correlated with unfavorable clinicopathological characteristics. Survival analyses show that elevated 5-HT1D expression level predicts poor overall survival and high recurrence probability in HCC patients. Functional studies revealed that 5-HT1D significantly promoted HCC proliferation, epithelial-mesenchymal transition, and metastasis in vitro and in vivo. Mechanistically, 5-HT1D could stabilize PIK3R1 by inhibiting its ubiquitin-mediated degradation. The interaction between 5-HT1D and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) enhanced the expression of FoxO6 through the PI3K/Akt signaling pathway; FoxO6 could also be directly transcriptionally activated by 5-HT1D in an Akt-independent manner. MicroRNA-599 was found to be an upstream suppressive modulator of 5-HT1D. Additionally, 5-HT1D could attenuate tryptophan hydroxylase 1 expression through the PI3K/Akt/cut-like homeobox 1 axis in HCC. Conclusion: Herein, we uncovered the potent oncogenic effect of 5-HT1D on HCC by interacting with PIK3R1 to activate the PI3K/Akt/FoxO6 pathway, and provided a potential therapeutic target for HCC. | Receptor, Serotonin, 5-HT1D |
Transposons are DNA sequences capable of moving in genomes. Early evidence showed their accumulation in many species and suggested their continued activity in at least isolated organisms. In the past decade, with the development of various genomic technologies, it has become abundantly clear that ongoing activity is the rule rather than the exception. Active transposons of various classes are observed throughout plants and animals, including humans. They continue to create new insertions, have an enormous variety of structural and functional impact on genes and genomes, and play important roles in genome evolution. Transposon activities have been identified and measured by employing various strategies. Here, we summarize evidence of current transposon activity in various plant and animal genomes." | Interspersed Repetitive Sequences |
Since the discovery of the RGD sequence motif as the essential cell attachment site in Fn (fibronectin), RGD-dependent ligand recognition by integrins has been the major focus of many integrin researches. Although many integrins recognize RGD-containing ligands, it is believed that residues outside the RGD motif provide specificity as well as high affinity for each integrin-ligand pair. These 'secondary' sites are generally assumed to interact directly with the alpha subunit of integrin, whereas the RGD motif binds primarily to the beta subunit. This necessitates that the integrin-ligand interface comprises a relatively large, or even scattered, area. Molecular electron microscopy and single-particle analysis were performed on a headpiece fragment of integrin alpha5beta1 in the presence and absence of bound ligand (Fn fragment), and revealed a marked shape change of the beta subunit hybrid and I-like domains that is linked with the ligand docking. Furthermore, electron microscopy images revealed a focal rather than a large contact area at the alpha5beta1-Fn interface, raising a question about '2-site docking model'. Kinetic analysis of real-time binding data showed that the synergy site greatly enhances kon but has little effect on the stability or koff of the complex, suggesting that the synergy site exerts its positive effect on alpha5beta1 binding by facilitating the initial encounter, rather than by contributing to the protein-protein interaction surface. Thus the ligand recognition mechanism by integrins needs further refinement through more structural analyses of the complexes as well as kinetic analysis of binding data. | Integrin alpha5beta1 |
Our previous studies (Pattison, S. E., and Dunn, M. F. (1975), Biochemistry 14, 2733) have shown that the reaction of divalent metal ion chelators with the 140 000 mol wt mouse submaxillary nerve growth factor protein (7S NGF) activates the iota-subunit esteropeptidase activity ca. sevenfold. Ultraviolet-visible spectral studies with the chelator 2,2',2''-terpyridine (terpyridine) and fluorescence emission studies with 8-hydroxyquinoline-5-sulfonic acid (HQSA) in combination with both conventional and rapid-mixing stopped-flow kinetic techniques have been employed in the present study to investigate (a) the mechanism of the chelator-induced activation process, and (b) the identity of the divalent metal ion involved. The spectral studies confirm the presence of stoichiometrically significant amounts of tightly bound zinc ion in native 7S NGF (1-2 g-atoms of An2+/mol of 7S NGF). The kinetic studies show that the reaction of terpyridine with 7S NGF occurs via a two-step process involving first a rapid, apparent second-order step (k1 = 1 x 10(6) M-1 s-1) to form a 7S NGF-Zn2+-chelator monocomplex, then a slow step to form a bis(terpyridine)-Zn(II) complex and activated 7S NGF in an apparent first-order process (kobsd = 0.10 min-1). This rate is, within experimental error, identical with the apparent first-order rate constant for the chelator-induced activation process (monitored by the rate of change in the steady-state rate of hydrolysis of chromophoric substrate, alpha-N-benzoyl-D,L-arginine-p-nitroanilide). Kinetic studies of the reaction of HQSA with native 7S NGF show that, under the same conditions of concentration, the rate of formation of the tris(HQSA)-Zn(II) complex is identical with the rate of the HQSA-induced activation of the 7S NGF esteropeptidase. Thus, these studies unambiguously establish that zinc ion is the metal ion involved in the chelator-induced activation process, and that activation involves removal of zinc ion from native 7S NGF. | Oxyquinoline |
Tryptophan, serotonin, N-acetylserotonin, melatonin, 5-hydroxyindoleacetic acid and 5-hydroxytryptophol have been determined in rat and human pineal glands. The compounds were measured by directly injecting centrifuged tissue homogenates into a liquid chromatographic-fluorometric system. Normal ranges are reported for these compounds and upper limits established for several other indoles. | Hydroxytryptophol |
One hundred years have passed since the discovery of insulin-an achievement that transformed diabetes from a fatal illness into a manageable chronic condition. The decades since that momentous achievement have brought ever more rapid innovation and advancement in diabetes research and clinical care. To celebrate the important work of the past century and help to chart a course for its continuation into the next, the Canadian Institutes of Health Research's Institute of Nutrition, Metabolism and Diabetes and the U.S. National Institutes of Health's National Institute of Diabetes and Digestive and Kidney Diseases recently held a joint international symposium, bringing together a cohort of researchers with diverse interests and backgrounds from both countries and beyond to discuss their collective quest to better understand the heterogeneity of diabetes and thus gain insights to inform new directions in diabetes treatment and prevention. This article summarizes the proceedings of that symposium, which spanned cutting-edge research into various aspects of islet biology, the heterogeneity of diabetic phenotypes, and the current state of and future prospects for precision medicine in diabetes." | National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) |
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