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Autophagy is an evolutionarily conserved mechanism by which cytoplasmic elements are degraded intracellularly. Autophagy has also emerged as a major regulator of cardiac homeostasis and function. Autophagy preserves cardiac structure and function under baseline conditions and is activated during stress, limiting damage under most conditions. It reduces injury and preserves cardiac function during ischemia. It also reduces chronic ischemic remodeling and mediates the cardiac adaptation to pressure overload by restricting misfolded protein accumulation, mitochondrial dysfunction, and oxidative stress. Impairment of autophagy is involved in the development of diabetes and aging-induced cardiac abnormalities. Autophagy defects contribute to the development of cardiac proteinopathy and doxorubicin-induced cardiomyopathy. However, massive activation of autophagy may be detrimental for the heart in certain stress conditions, such as reperfusion injury. In this review, we discuss recent evidence supporting the important role of autophagy and mitophagy in the regulation of cardiac homeostasis and adaptation to stress. | Mitophagy |
This work outlines an approach to creating a catalyst for cyclic polymer synthesis using readily available materials in only one or two steps. Combining commercially available molybdenum-alkylidene 1 with two equivalents of ene-ol proligand 2 rapidly produces, in quantitative yield ((1)H NMR spectroscopy), the double tethered metallacyclobutane complex 3. Characterized by variable temperature NMR studies and nuclear Overhauser effect spectroscopy (NOESY) experiments, complex 3 exhibits fluxional behavior in solution. Determined by single crystal X-ray diffraction, the solid-state structure of complex 3 reveals metrical parameters indicating that the metallacyclobutane is not predicted to undergo rapid retro-cycloaddition. However, complex 3 is a precatalyst for the polymerization of norbornene to produce cyclic polynorbornene. An NMR spectrum of a test polymerization indicates that only a small fraction of the precatalyst is activated upon exposure to monomer. Quantifying the active catalyst is possible by measuring vinyl resonances that appear in the (1)H NMR spectrum. The vinyl resonances are attributable to the release of one of the tethers upon norbornene addition. Confirmation of the polymer cyclic topology comes from gel permeation chromatography (GPC), dynamic light scattering (DLS), and intrinsic viscosity (eta) measurements. The double tethered metallacyclobutane complex is a novel design for catalytic cyclic polymer synthesis. The synthetic approach suggests that catalyst tuning is possible by a choice of the commercial alkylidene and alteration of the ene-ol proligand. | Norbornanes |
The studyTesfaye S, Sloan G, Petrie J, et al. Comparison of amitriptyline supplemented with pregabalin, pregabalin supplemented with amitriptyline, and duloxetine supplemented with pregabalin for the treatment of diabetic peripheral neuropathic pain (OPTION-DM): a multicentre, double-blind, randomised crossover trial. Lancet 2022;400:680-90.To read the full NIHR Alert, go to: https://evidence.nihr.ac.uk/alert/combination-therapy-for-painful-diabetic-neuropathy-is-safe-and-effective/. | Pregabalin |
We report about our experience in five patients who suffered from a mandibular micrognathia after ancylosis of the temporomandibular joint. At first the ancylosis was removed using a costochondral graft. About one year later, the mandible was cut by an osteotomy behind the last visible toothbud and a distractor was inserted. The mandible was to a slide overcorrection. This has to be taken into account to compensate a certain relapse. At first we used an unidirectional device, for one and a half years we have used a bidirectional device (Normed from Tuttlingen/Germany) which enables us to correct mandibular hypoplasias more adequately. Up to now our experience shows, that gradual callus-distraction leads to stable normalization of mandibular hypoplasias. Functional problems concerning chewing and speech are solved, the dramatical improvement of the profile of the face may avoid psycho-social problems for these patients. | Micrognathism |
Rapp-Hodgkin syndrome is a rare form of ectodermal dysplasia involving the hair, eyes, sweat glands, nails, teeth and palate. This syndrome is characterized by stiff sparse hair with the appearance of steel wool, sparse eyebrows and lashes, cleft palate, absence of lacrimal punctae, epiphora, a decreased number of sweat glands, and dystrophic nails. Cleft palate, hypodontia, abnormal tooth shape, multiple caries, delayed eruption of teeth are the main oral manifestations. In this paper we describe the clinical and dental findings of this syndrome in a 7 year old girl referred to the dental clinic because of severe tooth ache. The dental treatment included root canal treatment, composite restorations, extractions and removable prostheses. This paper highlights features of Rapp-Hodgkin Syndrome and its dental rehabilitation." | Ectodermal Dysplasia 3, Anhidrotic |
The complex anatomy of the larynx is a consequence of its various airway functions. The aim of the present study was to evaluate which anatomical structures of the larynx soft tissues could be defined using MRI, and to investigate the feasibility of using this technique to assess the dynamic functions of the larynx. MRI images of the larynx of six healthy volunteers during speech production were obtained in vivo. The volunteers were asked to breathe out long and deep in order to prolong in a normal voice the emission of the vowels [i] (as in key) and [a] (as in car) and the consonant [ch] (as in ship). We demonstrated the modification of the larynx position, which is high for [i] and low for [a], and the modification of the vocal folds which is adducted and abducted in [i] and kept abducted in [ch]. Dynamic MRI allows the possibility of multiplanar high-resolution imaging. It can provide information about the anatomy of the larynx and, it also has the ability to image moving laryngeal structures and to analyze vocal fold vibrations during phonation. | Phonation |
The role of cooking on health and wellbeing is a recent area of scientific interest. In order to investigate this role, a cooking program that is suitable for each target population is needed e.g., a program designed for American or Australian children might not be appropriate for teenagers in New Zealand. As there was no similar previously evaluated program already available, the study’s purpose was to test an intensive cooking intervention on cooking confidence and knowledge amongst a group of adolescents from Dunedin, New Zealand, and to assess its acceptability to participants. This five-day program comprised interactive cooking sessions and informal nutrition education and ran from 9 a.m. to 3:30 p.m., Monday to Friday during school holidays. Participants completed questionnaires on cooking skills and confidence at baseline and the end of intervention and took part in a group interview, which aimed to investigate the acceptability and outcome of the program. Twenty-one participants aged between 12 and 16 years old completed the program. At the end of the program, significant increases were seen in both skills and confidence levels, and feedback from the group interview indicated that the participants enjoyed the program and that it provided additional results other than those that were cooking related. | Child Nutrition Sciences |
Diffuse noxious inhibitory control (DNIC) is a phenomenon to reflect descending pain modulation in animals. Conditioned pain modulation (CPM) is the human counterpart of DNIC and is reduced in patients with several chronic pain conditions. Duloxetine is a serotonin and noradrenaline reuptake inhibitor that ameliorates CPM impairment in patients with diabetic neuropathy. Although some studies have reported the effects of different pharmacological agents on CPM, few studies have compared the effects of some analgesics in both humans and rodents. Therefore, we established a stable evaluation method for DNIC in rats and determined whether duloxetine and other specific analgesics affect DNIC impairment in rat models of peripheral neuropathic pain and osteoarthritis pain, two types of chronic pain. As a conditioning stimulus, capsaicin was injected into the forepaw of rats. The paw withdrawal threshold (PWT) in response to mechanical pressure was measured for the hindpaw. Peripheral neuropathic pain and osteoarthritis pain models were developed by partial sciatic nerve ligation (PSNL) and the intra-articular injection of 2â¯mg monoiodoacetate (MIA), respectively. Capsaicin (30-100â¯mug/site) increased the PWT, in a dose-dependent manner, in naive rats. The threshold significantly increased at 30â¯mug and reached its maximal level at 100â¯mug. The change in PWT following capsaicin injection was significantly reduced in PSNL-treated rats, but the threshold was increased by the subcutaneous administration of duloxetine (10â¯mg/kg). The oral administrations of pregabalin (10â¯mg/kg) and celecoxib (3â¯mg/kg) did not affect the PWT in PSNL-treated rats. Similarly, MIA-injected rats also showed a reduced change in PWT following capsaicin injection. Duloxetine, but not pregabalin and celecoxib, significantly increased the PWT in MIA-injected rats. These results suggested that duloxetine can directly ameliorate DNIC impairment in rat models of chronic pain. Duloxetine may be useful for modulating chronic pain by restoring function to the endogenous, descending, inhibitory pathway." | Diffuse Noxious Inhibitory Control |
Caspase-3 plays irreplaceable roles in apoptosis and related diseases. An imbalance in the measured levels of Caspase-3 is implicated in irreversible apoptosis. Therefore, the detection of Caspase-3 is of great significance for apoptosis imaging and the evaluation effect of early tumor treatment and other diseases. Herein, advances in the recent innovations of Caspase-3 response fluorescence biosensors, including molecular probes and nanoprobes, are systematically summarized in sections corresponding. The performances of various luminescence probes in Caspase-3 detection are discussed intensively in the design strategy of chemical structure, response mechanism and biological application. Finally, the current challenges and prospects of the design of new Caspase-3 responsive fluorescence probes for apoptosis imaging, or similar molecular event are proposed. | Caspases, Effector |
Nanoscale zero-valent iron (NZVI) represents a promising approach for source zone control, but concerns over its reactive lifetime might limit application. Here, we demonstrate that dithionite (S(2)O(4)(2)(-)), a reducing agent for in situ redox manipulation, can restore the reducing capacity of passivated NZVI. Slurries of NZVI were aged in the presence (3 days) and absence (60 days) of dissolved oxygen over a range of pH values (6-8). Upon loss of reactivity toward model pollutants1,1,1,2-tetrachloroethane, hexavalent chromium [Cr(VI)], nitrobenzene, aged suspensions were reacted with dithionite, and the composition and reactivity of the dithionite-treated materials were determined. NZVI aging products generally depended on pH and the presence of oxygen, whereas the amount of dithionite influenced the nature and reducing capacity of products generated from reaction with aged NZVI suspensions. Notably, air oxidation at pH >/= 8 quickly exhausted NZVI reactivity despite preservation of significant Fe(0) in the particle core. Under these conditions, formation of a passive surface layer hindered the complete transformation of NZVI particles into iron(III) oxides, which occurred at lower pH. Reduction of this passive layer by low dithionite concentrations( 1 g/g of NZVI) restored suspension reactivity to levels equal to, and occasionally greater than, that of unaged NZVI. Multiple dithionite additions further improved pollutant removal, allowing at least a 15-fold increase in Cr(VI) removal [ approximately 300 mg of Cr(VI)/g of NZVI] relative to that of as-received NZVI [ approximately 20 mg of Cr(VI)/g of NZVI]. | Dithionite |
With the help of a factorial design of experiments, the optimum conditions for preparing aminophenazone granules in a fluidized bed were established by which high quality tablets were obtained with a minimum energy expenditure. Granules with given technological properties could be prepared by controlling the regime of the granulation process. By varying the experimental conditions, a reproducible correlation was found between the parameters of optimization (mean granule diameter and work of compression) and the factors controlling the granulation process (pressure of compressed air, velocity and temperature of fluidizing air and binder concentration). The effect of the granule quality on tablet physical properties was discussed. Recommendations were given for the exploitation of fluidized bed units in the practice of granulation and tableting. | Aminopyrine |
A research chemist (non-smoker) worked for two years on an investigation where bis(chloromethyl)ether (BCME) and chloromethyl methyl ether (CMME) were by-products. Twelve years after completion of the study he died of a pulmonary adenocarcinoma that had metastasized to both the bones and soft tissue. The relatively large scale (1--2 mol) on which the chemical reaction was conducted resulted in his inhalation of high doses of both BCME and CMME for this two year period. His case history is discussed with reference to other such reported instances. | Bis(Chloromethyl) Ether |
Multiple endocrine neoplasia type 2 (MEN2) is a autosomal dominat inherited tumour-syndrome caused by germline activating mutations of the RET proto-oncogene on chromosome 10. It is clinically characterized by the presence of medullary thyroid carcinoma (MTC), bilateral pheochromocytoma and primary hyperparathyroidism (MEN2A) within a single patient. Three distinct clinical forms have been described depending on the phenotype: the classical MEN 2A, MEN 2B, an association of MTC, pheochromocytoma and mucosal neuroma, (FMTC) familial MTC with a low incidence of other endocrinopathies. Each variant of MEN2 results from different RET gene mutation, with a good genotype phenotype correlation. Genetic testing detects nearly 100% of mutation carriers and is considered the standard of care for all first degree relatives of patients with newly diagnosed MTC. Recommendations on the timing of prophylactic thyroidectomy and extent of surgery are based on a classification into four risk levels utilizing the genotype-phenotype correlations. MEN 2 gives a unique model for early prevention and cure of cancer and for stratified roles of mutation-based diagnosis of carriers." | Multiple Endocrine Neoplasia Type 2a |
Objective To present the case of a Latin man 68 years of age who presented to the emergency department with a rash to the right side of his groin 10 weeks after switching from simvastatin 40 mg daily to atorvastatin 40 mg daily. Background Prior to switching to atorvastatin, the patient had been taking simvastatin for 21 years without rash. The rash progressed bilaterally to his arms and hands, legs, buttocks, back, and trunk before the patient was seen by dermatology and atorvastatin was discontinued. Results Within six weeks of discontinuation of atorvastatin, the rash resolved with remaining pigmentation changes. The adverse effect was documented in the patient's chart, and dermatology recommended avoiding other statins in the future. Settings Ambulatory clinic pharmacy practice, emergency room, or urgent care centers. Practice Considerations Atorvastatin is a 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitor or statin that has been FDA approved for the prevention of atherosclerotic cardiovascular disease (ASCVD) and treatment of hypercholesterolemia since 1996. Despite widespread use of atorvastatin over many years, only a handful of published cases report drug eruption from its use. Previous case reports have found that retrial of statins may cause similar drug eruption. Conclusion Pharmacists should consider HMG-CoA reductase inhibitors as a possible cause of new onset rash and should not retrial an alternative statin. | Tinea cruris |
The dinoflagellate Karlodinium veneficum has worldwide distribution and is associated with harmful algal blooms through the production of karlotoxins. We investigated the allelopathy and toxicity to explore the potential ecological implications. Prorocentrum donghaiense was inhibited significantly when grown either in co-cultures or in culture filtrate of K. veneficum. In addition, the effect of the co-occurring microalga species (P. donghaiense) on the hemolytic activity of K. veneficum was also evaluated. P. donghaiense did not inhibit the growth of K. veneficum but increased the hemolytic activity. The culture of K. veneficum was loaded onto an RP-C18 column and eluted with different percentages of aqueous methanol solution. 80% methanol fraction not only inhibited the growth of P. donghaiense by allelopathy but also exhibited strong hemolytic activity, indicating that the allelochemicals and toxins of K. veneficum might be the same components. Furthermore, KmTx 3 (C(68)H(124)O(24)) was identified using HPLC-HRMS from this fraction. | Allelopathy |
Particularly, but not exclusively, in Germany, concerns are uttered as to the consequences of modern biotechnological advances and their range of applications in the field of human genetics. Whereas the proponents of this research are mainly focussing on the possible knowledge that could be gained by understanding the causes of developmental processes and of disease on the molecular level, the critics fear the beginnings of a new eugenics movement. Without claiming a logical relationship between genetic sciences and eugenics movements, it is nevertheless suggested in this article that a connection between both can become established when the distinction between scientifically validated statements on one hand and guiding hypotheses and assumptions on the other hand is blurred, as is observed particularly when scientists report their results to the public. This claim is demonstrated in comparisons between the current state of scientific knowledge on the role of genes in development and causation of diseases, and the way this is presented to the public. It is required that a debate on biotechnology should include reflections on the validity of claims made by scientists. | Genetic Determinism |
Through the ages, hysteria has been considered to be a female disease. The author explores the historical record and concludes that the hysterical (histrionic) personality is a caricature of femininity. It develops under the influence of cultural forces, particularly male domination, and is not a natural attribute of women. He then inquires whether the concept of a distinct femininity is itself a stereotype or is based on inborn personality differences between the sexes. Citing current biological and ethological evidence, he favors the latter explanation. He suggests that the hypothesis of sex role distortion include not only the equation femininity-caricature-hysterical personality but also the cognate one, masculinity-caricature-"machoism."" | Histrionic Personality Disorder |
Counterfeit medicines are a global public health risk. We assess counterfeit reports involving the legitimate supply chain using 2009-2011 data from the Pharmaceutical Security Institute Counterfeit Incident System (PSI CIS) database that uses both open and nonpublic data sources. Of the 1,510 identified CIS reports involving counterfeits, 27.6% reported China as the source country of the incident/detection. Further, 51.3% were reported as counterfeit but the specific counterfeit subcategory was not known or verifiable. The most prevalent therapeutic category was anti-infectives (21.1%) with most reports originating from health-related government agencies. Geographically, Asian and Latin American regions and, economically, middle-income markets were most represented. A total of 127 (64.8%) of a total of 196 countries had no legitimate supply chain CIS counterfeit reports. Improvements in surveillance, including detection of security breaches, data collection, analysis, and dissemination are urgently needed to address public health needs to combat the global counterfeit medicines trade. | United Nations |
Thirty-two dogs with naturally occurring multicentric lymphosarcoma were randomly assigned to one of two treatment groups. One half of the animals received combination chemotherapy plus vitamin injections (controls) while the other half received indentical chemotherapy plus injections of chemically-modified tumor cell extract in Freund's complete adjuvant (vaccinates). Clinical staging revealed no bias between groups but showed that prognosis could be closely correlated with the severity of disease at initial presentation. Twenty dogs (62%), including 11 vaccinates and 9 controls, responded favorably to chemotherapy and were evaluated for length of first remission and total survival time. Both parameters were significantly longer in vaccinated dogs than in controls. These data suggest that immunological stimulation may be a helpful adjunct to conventional therapy in selected types of cancer when immunological principles are observed. | Freund's Adjuvant |
OBJECTIVE: To determine the usefulness of critical-incident reports in facilitating reflective learning and the types of experiences that learners found meaningful on a general medicine service. DESIGN: Team members wrote about their most meaningful patient of the month and what was learned from the patient. They shared their narratives during teaching rounds at the end of each month. The written reports were collected and subjected to qualitative thematic analysis. SETTING: General medicine teaching service of an academic medical center. PATIENTS/PARTICIPANTS: Medical students, residents, and attending physicians. MEASUREMENTS AND MAIN RESULTS: Ninety-eight reports were collected over 10 months and subjected to thematic analysis. Reports were coded for six major themes, with a mean of 2.09 themes per narrative. The number of reports containing each theme was 47 for biomedical, 46 for communication with patients and families, 38 for psychosocial, 32 for the physician's role, 30 for personal feelings, and 14 for ethics. Communication issues constituted the theme most frequently reported by third-year students; biomedical and psychosocial themes by interns; biomedical by supervising residents; and the physician's role by attending physicians. Reports from men and women contained a similar mean number (men 2.101; women 2.128) and distribution of themes. CONCLUSIONS: The critical-incident technique promoted reflection on the meaning of clinical experiences. Qualitative thematic analysis revealed the diversity of meaningful experiences on a general medicine service and the high frequency of nonbiomedical themes. This study suggests that reflective exercises can provide a window into the experience of students and residents. | Clinical Medicine |
Eleven specimens of chronic submandibular sialadenitis were examined. A reduction in secretory material in acinar cells was seen with increasing atrophy until the acini resembled intercalary ducts. Myoepithelial cells and basement membrane were sometimes more conspicuous. Striated ducts showed a reduction of the folding of the plasma membranes in the basal part, and striated and excretory ducts showed a reduction in mitochondria. This possibly represents a functional atrophy secondary to reduced salivary flow. Very atrophic parenchyma largely consisted of simple cells. Phagosomes and apoptotic bodies were occasionally seen, and appear to be involved in the atrophy. Thiamine pyrophosphatase in the Golgi apparatus and acid phosphatase in the GERL were demonstrated in moderately atrophic parenchyma. This is similar to normal and indicates continuing synthetic activity. Acid phosphatase was demonstrated in lysosomes, which appear to be involved in the atrophy by their role in phagy. Alkaline phosphatase was occasionally demonstrated at luminal surfaces, and is likely to be involved in resorption of obstructed luminal contents. The changes are similar to those seen in experimentally obstructed glands and indicate that much of the parenchyma survives by adaptation to the altered environment which forms the basis for the successful results following conservative therapy. | Thiamine Pyrophosphatase |
We reviewed the cases of 11 patients with cryptococcosis and idiopathic CD4 lymphocytopenia (ICL) referred to our institution in the previous 12 years, as well as 42 similar cases reported in the literature, to assess the characteristics of the infection in this population. Cryptococcosis in 53 patients with ICL had features in common with cryptococcosis in previously normal patients. ICL patients had a slight male predominance (1.2:1) and a median age of presentation of 41 years (range, 4.5-85 yr). Initial cerebrospinal fluid findings showed glucose below 40 mg/dL in 60% of the patients, a median pleocytosis of 59 white blood cells/mm (range, 0-884), and protein of 156 mg/dL (range, 25-402 mg/dL). The median CD4 count at diagnosis of ICL and at the last available measurement was 82 (range, 7-292) and 132 (range, 13-892) cells/mm, respectively, for an average follow-up of 32 months in 46 patients. Unlike previously normal patients with cryptococcosis, those with ICL had an excess incidence of dermatomal zoster (7 episodes in 46 ICL cases). Pneumocystis pneumonia was rare (1 case), casting doubt on the need for prophylaxis in patients with ICL. A favorable outcome (cured or improved) may be more common in ICL patients than in previously normal patients with cryptococcal meningitis and no predisposing factors. Identification of ICL in patients who were apparently normal before the onset of cryptococcosis appears to be useful because it predicts a favorable outcome. Patients with cryptococcal infection and ICL have an increased likelihood of developing dermatomal zoster. The long-term follow-up of these patients offers some reassurance regarding favorable prognosis." | T-Lymphocytopenia, Idiopathic CD4-Positive |
In an attempt to clarify the role of endogenous opioid in peripheral I2-imidazoline receptors activation for improvement of insulin action, bilateral adrenalectomy was carried out in rats with insulin resistance induced by 4-week fructose-rich chow feeding. Single intravenous (i.v.) injection of agmatine (1mg/kg) for 30 min increased the plasma beta-endorphin-like immunoreactivity (BER) in a way parallel to the reduction of plasma glucose in sham-operated fructose chow-fed rats; this action of agmatine was totally abolished by BU224 at sufficient dosage (1mg/kg, i.v.) to block I2-imidazoline receptors. The plasma glucose lowering effect of agmatine was markedly reduced but not totally deleted by adrenalectomy in fructose chow-fed rats. A direct effect of agmatine on glucose homeostasis can thus be considered. The hyperinsulinemic-euglycemic clamp technique was performed to evaluate insulin sensitivity. The effect of agmatine on elevation of the average rate of glucose infusion at the glucose clamp steady state in sham-operated fructose chow-fed rats was lessen in adrenalectomized fructose chow-fed rats, but was completely abolished by BU224. The obtained results suggest that the improvement of insulin sensitivity by agmatine is produced by two mechanisms, stimulation of adrenal gland to enhance beta-endorphin secretion and a direct activation of peripheral I2-imidazoline receptor in tissues, for the amelioration of insulin action. | Imidazoline Receptors |
OBJECTIVE: To evaluate healing of pinch-grafted wounds on the distal aspect of the limbs of ponies bandaged with equine amnion or a standard nonadherent wound dressing material. ANIMALS: 6 ponies. PROCEDURE: A 2.5x2.5-cm full-thickness section of skin was removed from the dorsal aspect of each limb at the midpoint of the metacarpus or metatarsus. Six days later, wounds were grafted with partial-thickness pinch grafts. Half the wounds were bandaged with amnion, and the other half were bandaged with a nonadherent dressing. Bandages were changed every 3 days until wound healing was complete. At each bandage change, numbers of grafts lost were recorded, and wounds were measured. RESULTS: Percentage of grafts lost from wounds bandaged with amnion was not significantly different from percentage lost from wounds bandaged with the nonadherent dressing. Median healing time for wounds bandaged with amnion (30 days) was significantly less than median healing time for wounds bandaged with the nonadherent dressing (39 days). All wounds were healed by day 45. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that amnion can be used for bandaging pinch-grafted wounds on the distal aspect of the limbs of ponies. | Occlusive Dressings |
This article investigates ethical challenges cancer patients face in the end stages of life including doctors' responsibilities, patients' rights, unexpected desires of patients and their relatives, futile treatments, and communication with patients in end stages of life. These patients are taken care of through palliative rather than curative measures. In many cases, patients in the last days of life ask their physician to terminate their illness via euthanasia which has many ethical considerations. Proponents of such mercy killing (euthanasia) believe that if the patient desires, the physician must end the life, while opponents of this issue, consider it as an act of murder incompatible with the spirit of medical sciences. The related arguments presented in this paper and other ethical issues these patients face and possible solutions for dealing with them have been proposed. It should be mentioned that this paper is more human rational and empirical and the views of the legislator are not included, though in many cases human intellectual and empirical comments are compatible with those of the legislator. | Right to Die |
Renal tubular cells respond to mechanical stimuli generated by urinary flow to regulate the activity and transcript abundance of important genes for ion handling, cellular homeostasis, and proper renal development. The primary cilium, a mechanosensory organelle, is postulated to regulate this mRNA response. The aim of this study is to reveal the transcriptome changes of tubular epithelia in response to fluid flow and determine the role of primary cilia in this process. Inner-medullary collecting duct (CD) cells were subjected to either static or physiologically relevant fluid flow ( approximately 0.6 dyn/cm(2)). RNA-sequencing analysis of ciliated cells subjected to fluid flow showed up-regulation of 1379 genes and down-regulation of 1294 genes compared with static control cells. Strikingly, only 54 of these genes were identified as gene candidates sensitive to primary cilia sensing of fluid flow, of which 16 were linked to ion or water transport pathways in the CD. Validation by quantitative real-time PCR revealed that only the expression of transferrin receptor, which is involved in iron transport; and tribbles pseudokinase 3, which is involved in insulin signaling, were unequivocally regulated by primary cilia sensing of fluid flow. This study shows that the involvement of primary cilia in ion transport in the collecting duct is exceptionally specific.-Mohammed, S. G., Arjona, F. J., Verschuren, E. H. J., Bakey, Z., Alkema, W., van Hijum, S., Schmidts, M., Bindels, R. J. M., Hoenderop, J. G. J. Primary cilia-regulated transcriptome in the renal collecting duct. | Kidney Tubules, Collecting |
2,2'-Anhydro-1-(3'-O-acetyl-beta-D-arabinofuranosyl)-5-iodocytosine (anhydro-araIC 3'-acetate), previously synthesized and isolated as a crude product by Moffatt and his coworkers, was purified and characterized. The availability of pure anhydro-araIC 3'-acetate made possible a comparative study of the antineoplastic, antiviral and biochemical potencies of anhydro-araIC 3'-acetate with the structurally related agents 2,2'-anhydro-1-(3'-O-acetyl-beta-D-arabinofuranosyl)cytosine (anhydro-araC 3'-acetate) and 2,2'-anhydro-1-(beta-D-arabinofuranosyl)-5-iodocytosine (anhydro-araIC). The presence of the 5-iodo substituent and/or the 3'-O-acetyl group on 2,2'-anhydro1-(beta-D-arabinofuranosyl)cytosine (anhydro-araC) did not alter the capacity of these agents to exert cytotoxic and antineoplastic activity against L1210, P388, L5178Y and human leukemia cells and against human colon and rectal carcinomas, as well as antiviral activity against herpes simplex virus Type 1. All of the compounds caused inhibition of [3H]thymidine incorporation into the DNA of L1210 cells in culture, with anhydro-araIC 3'-acetate being significantly less inhibitory than the other derivatives. Little or no interference with RNA and protein synthesis was produced by these pyrimidine nucleosides. Both anhydro-araIC 3'-acetate and anhydro-araIC were potent inhibitors of the activity of DNA polymerase alpha from the L1210 leukemia at the nucleoside level, while anhydro-araC 3'-acetate and anhydroaraC were non-inhibitory; none of the agents caused inactivation of DNA polymerase beta. The findings suggest that the antineoplastic and antiviral activities of the 2,2'-anhydro-arabinosylcytosine nucleosides may be the result of biochemical actions different from those of araC. | Leukemia L5178 |
Nylidrin HCl lowered the blood pressure and increased the heart rate of conscious, spontaneously hypertensive rats (SHR), Goldblatt hypertensive rats, and DOCA hypertensive rates. In SHR, the minimum effective dose was 0.5 mg/kg, s.c. At that dose, the anti-hypertensive activity of nylidrin lasted more than 3 hours. Propranolol reversed both effects on blood pressure and heart rate by nylidrin, whereas atenolol, a specific cardiac beta 1 blocker, only blocked or reversed the tachycardia caused by nylidrin but did not block the anti-hypertensive effect of the compound. In normotensive rats of Wistar/Kyoto strain (WKY) and Holtzman strain, nylidrin at 5 or 10 mg/kg, s.c., produced a transient hypotensive effect which lasted less than an hour and tachycardia that persisted for several hours. In WKY, atenolol prolonged the hypotensive activity of the compound by partially reversing the tachycardia. These observations indicate that SHR is more sensitive than WKY to the anti-hypertensive activity of nylidrin, which is probably caused by vasodilatation mediated by beta 2 receptors. | Nylidrin |
Immunomodulatory drugs (IMiDs) such as thalidomide, lenalidomide and pomalidomide are antitumor compounds that have direct tumoricidal activity and indirect effects mediated by multiple types of immune cells in the tumor microenvironment (TME). IMiDs have shown remarkable therapeutic efficacy in a set of B-cell neoplasms including multiple myeloma, B-cell lymphomas and chronic lymphocytic leukemia. More recently, the advent of immunotherapy has revolutionized the treatment of these B-cell neoplasms. However, the success of immunotherapy is restrained by immunosuppressive signals and dysfunctional immune cells in the TME. Due to the pleiotropic immunobiological properties, IMiDs have shown to generate synergetic effects in preclinical models when combined with monoclonal antibodies, immune checkpoint inhibitors or CAR-T cell therapy, some of which were successfully translated to the clinic and lead to improved responses for both first-line and relapsed/refractory settings. Mechanistically, despite cereblon (CRBN), an E3 ubiquitin ligase, is considered as considered as the major molecular target responsible for the antineoplastic activities of IMiDs, the exact mechanisms of action for IMiDs-based TME re-education remain largely unknown. This review presents an overview of IMiDs in regulation of immune cell function and their utilization in potentiating efficacy of immunotherapies across multiple types of B-cell neoplasms. | Immunomodulating Agents |
Dengue is the commonest arboviral illness caused by four antigenically distinct dengue virus serotypes (DEN-1 through DEN-4). The clinical spectrum of the disease ranges from asymptomatic or mild infection to catastrophic dengue shock syndrome (DSS). In last few years, neurological manifestations of dengue infection have been increasingly observed and reported mainly with serotypes DEN-2 and DEN-3. The pathogenesis of neurological manifestations includes: neurotrophic effect of the dengue virus, related to the systemic effects of dengue infection, and immune mediated. Encephalopathy and encephalitis are the most frequently reported neurological manifestations followed by meningitis, myositis, hypokalemic periodic paralysis, stroke, Guillain-Barre syndrome and transverse myelitis. Acute disseminated encephalomyelitis (ADEM) associated with dengue infection is rarely reported. We herein report a case of ADEM associated with classic dengue fever. Favourable clinical outcome occurred after a five-day course of intravenous methylprednisolone therapy." | Encephalomyelitis, Acute Disseminated |
The purpose of the current study was to develop syndrome-specific standardized growth curves for growth hormone-treated Prader-Willi syndrome (PWS) individuals aged 0 to 18 years. Anthropometric growth-related measures were obtained on 171 subjects with PWS who were treated with growth hormone for at least 40% of their lifespan. They had no history of scoliosis. PWS standardized growth curves were developed for 7 percentile ranges using the LMS method for weight, height, head circumference, weight/length, and BMI along with normative 3rd, 50th, and 97th percentiles plotted using control data from the literature and growth databases. Percentiles were plotted on growth charts for comparison purposes. Growth hormone treatment appears to normalize stature and markedly improves weight in PWS compared with standardized curves for non-growth hormone-treated PWS individuals. Growth chart implications and recommended usage are discussed. | Prader-Willi Syndrome |
Control of serum phosphorus levels is a central goal in the management of patients with chronic renal failure. Inadequate control of serum phosphorus leads to elevated levels of the calcium-phosphorus product. This plays a pivotal role in vascular calcification, cardiovascular disease, calciphylaxis, and death. Elevated phosphorus and elevated levels of the calcium-phosphorus product are both significant predictors of cardiovascular mortality, at phosphorus and calcium-phosphorus product levels that were considered safe until recently. A lowering of levels such that phosphorus is maintained between 2.2 and 5.5 mg/dl, calcium-phosphorus product is below 55 mg(2)/dl(2), and serum calcium is at 9.2-9.6 mg/dl, respectively, might well be the goal of therapeutic management strategies." | Phosphorus Metabolism Disorders |
Parkinsonism can be psychogenic, and psychogenic parkinsonism is about 10% of psychogenic movement disorder patients. Patients can present with any feature or combination of features of organic Parkinson's disease. There are clinical clues that can lead to the correct diagnosis, and laboratory testing with clinical neurophysiology or DAT (dopamine transporter) scanning can be helpful as well. Patients may have both organic Parkinson's disease and psychogenic parkinsonism, and this might be considered a psychologically induced aggravation of the organic disorder. | Parkinsonian Disorders |
We studied the characteristics of acute blocking of supination of the distal radioulnar joint caused by triangular fibrocartilage complex injuries. Twenty-four patients who were treated for acute blocking of supination were retrospectively assessed. Supination was suddenly blocked after minor trauma to the wrist. Active and passive supination was severely restricted with a mean preoperative range of motion (11 degrees ), whereas pronation was almost normal. The cause was identified arthroscopically or at open operation. It was found to be a result of avulsion of the dorsal or palmar portion of the radioulnar ligament, which blocked movement of the ulnar head. Blocking was reduced manually in four cases, by arthroscopic surgery in eight cases and by open surgery in 12 cases. After treatment, forearm supination improved to 84 degrees of the mean range of motion. Distal radioulnar joint blocking from a ruptured triangular fibrocartilage complex should be considered in the differential diagnosis of loss of forearm supination.Level of evidence: IV. | Triangular Fibrocartilage |
INTRODUCTION: The study of natural products is one of the strategies implemented for the discovery of new compounds that can be used in cancer therapy. Aromatic herbs and medicinal plants found in Algeria and their anti-angiogenesis and cytotoxic potentials against cancer have not been much explored. OBJECTIVES: Our work aimed to evaluate the antioxidant, anti-inflammatory and anticancer properties of the essential oil (EO) extracted from rose-scented geranium (Pelargonium graveolens) and its major (citronellol) and characteristic (linalool) constituents. RESULTS: The chemical composition of EO was determined with chromatographic analysis and revealed the presence of citronellol as the major compound (25.84%). A strong chelating power of terpene alcohols (IC50=1.58+/-0.23mg/mL for citronellol) was found, with a significant difference (P<0.05) compared with the standard antioxidants used (L-ascorbic acid and butylated hydroxyanisole). The EO is distinguished by an interesting anti-inflammatory effect with the lowest IC(50) (4.63+/-0.3mg/mL), and it constitutes a good stabilizer of the erythrocyte membrane. Citronellol also exhibited the best anti-inflammatory effect (IC50=0.74+/-0.09mg/mL). We also assessed the anticancer effect of EO on two main pathways involved in cancer development, angiogenesis and cell proliferation, using in ovo bioassays with a chorio-allantoic membrane (CAM) of chicken eggs and in vitro assays of its cytotoxicity on different metastatic breast cancer (MDA-MB-231), gastric (AGS) and melanoma (MV3) cell lines. In the CAM model, the density of micro-vessels is 75+/-10 in the group supplemented with EO compared to 140+/-9 for the control group (b-FGF). In addition, the EO significantly reduced the number of newly formed vessels. The cytotoxicity was evaluated using the cell proliferation inhibition method and cell viability was measured using the MTT test. Results revealed that the treatment of cancer lines with different concentrations of EO reduces the rate of cell viability in a dose-dependent manner. EO showed the greatest cytotoxicity on the AGS line with an inhibition rate of 92.87+/-0.13% at the highest dose (4muL/mL), followed by the MV3 line (88.76+/-0.96%). CONCLUSION AND PROSPECTS: Data demonstrated that rose-scented geranium EO has an antitumor potential on metastatic cancer cell lines. It is distinguished by its antiproliferative, anti-angiogenic, and anti-inflammatory activities. Medicinal plants might contain new molecules, with new structures, which could become lead candidate among future anticancer drugs. | Pelargonium |
Viroids are structurally, functionally and evolutionarily different from viruses. Despite their small, non-protein-encoding, single-stranded circular RNA genome, viroids can infect higher plants and cause certain diseases. Members of the two viroid families, Pospiviroidae and Avsunviroidae, have evolved to usurp the transcriptional machinery of their host nuclei and chloroplasts, respectively, in which replication proceeds through a rolling-circle mechanism involving RNA polymerization, cleavage and ligation. Remarkably, viroids subvert certain DNA-dependent RNA polymerases to transcribe RNA templates, and, in the family Avsunviroidae, post-transcriptional cleavage is catalysed by hammerhead ribozymes. Viroids are models for studying RNA evolution and for analysing RNA transport in plants, because they can move intracellularly, intercellularly through plasmodesmata and to distal parts of the plant through the vascular system. Viroids elicit RNA-silencing phenomena, which might mediate some of their biological properties, including pathogenesis. As some viroids behave as catalytic RNAs, they are regarded as remnants of the RNA world. | Plant Viruses |
The embryonic stem cell- (ESC) specific transcription factor Oct4 is a well-known master regulator of pluripotency. The aim of this study was to identify upstream regulators of Oct4 and explore their functional link in regulating lincRNA expression in ESCs. By quantitative real-time PCR (RT-qPCR) analysis upon CCCTC-binding factor (CTCF) or Oct4 knockdown, here, we found that the chromatin insulator CTCF transcriptionally controls Oct4 gene expression in mouse ES cells. Furthermore, co-immunoprecipitation assays showed that CTCF physically interacts with Oct4. By analyzing CTCF and Oct4 ChIP-seq datasets in mouse ES cells and investigating their genomic occupancies, we demonstrated that CTCF and Oct4 share overlapping regulatory functions and are required for active transcription of long intergenic non-coding RNAs (lincRNAs) linc1253 and linc1356, which were reported to repress cellular lineage programs and maintain a pluripotent state. In summary, we propose an integrated model of transcriptional control mediated by CTCF, the master weaver of the genome, for the upstream regulation of Oct4-and ESC-associated genes. These results connect the chromatin insulator CTCF and the pluripotency factor Oct4 in the regulation of lincRNAs in pluripotent cells. | CCCTC-Binding Factor |
Standard microelectrode techniques were used to evaluate the effect of d-tubocurarine chloride on membrane potential of junctional and extrajunctional areas of muscle fibers in a potassium-free Ringer solution. The experiments were made on frogs after inactivation of acetylcholinesterase. d-Tubocurarine chloride hyperpolarized the membrane of muscle fibers only in the junctional area. Blockade of axoplasmic transport with colchicine did not affect the magnitude of the hyperpolarization response of the membrane end plate to the presence of d-tubocurarine chloride, but at the same time it significantly reduced the membrane rest potential of muscle fibers, and gave rise to the appearance of extrajunctional sensitivity to acetylcholine. It is concluded that the blockade of axoplasmic transport does not affect the pattern of non-quantum acetylcholine release from nerve terminals. Therefore, this is unlikely to cause denervation-like changes in the muscle under the conditions described. | Armin |
Toxoplasma gondii is an apicomplexan parasite that affects both humans and livestock. Transmitted to humans through ingestion, it is the second-leading cause of foodborne illness-related death. Currently, there exists no approved vaccine for humans or most livestock against the parasite. DNA vaccines, a type of subunit vaccine which uses segments of the pathogen's DNA to generate immunity, have shown varying degrees of experimental efficacy against infection caused by the parasite. This review compiles DNA vaccine efforts against Toxoplasma gondii, segmenting the analysis by parasite antigen, as well as a review of concomitant adjuvant usage. No single antigenic group was consistently more effective within in vivo trials relative to others. | Microneme |
One hundred and fifty-one nulligravid women and 63 parous women stopped taking low-dose sequential oral contraceptives in order to become pregnant. During the first post-Pill cycle, 39% of the nulligravid and 54% of the parous women conceived. These figures have been compared with data from the Royal College of General Practitioners survey in England, in which 13% of nulligravid and 17% of parous women conceived in the first cycle after ceasing to take combined oral contraceptives. The percentage of nulligravid women not pregnant six months after withdrawal of low-dose sequential formulations was 19% compared with 32% after withdrawal of combined oral contraceptives. The corresponding figures for parous women were 5% and 21%. Available data suggest that after withdrawal of low-dose sequential oral contraceptives, the incidence of post-Pill infertility is lower than that after withdrawal of combined oral contraceptives. The extent of this difference is 16% three months after withdrawal of the Pill and 10% six months after attempting pregnancy." | Contraceptives, Oral, Sequential |
SNAIL is a key transcriptional regulator in embryonic development and cancer. Its effects in physiology and disease are believed to be linked to its role as a master regulator of epithelial-to-mesenchymal transition (EMT). Here, we report EMT-independent oncogenic SNAIL functions in cancer. Using genetic models, we systematically interrogated SNAIL effects in various oncogenic backgrounds and tissue types. SNAIL-related phenotypes displayed remarkable tissue- and genetic context-dependencies, ranging from protective effects as observed in KRAS- or WNT-driven intestinal cancers, to dramatic acceleration of tumorigenesis, as shown in KRAS-induced pancreatic cancer. Unexpectedly, SNAIL-driven oncogenesis was not associated with E-cadherin downregulation or induction of an overt EMT program. Instead, we show that SNAIL induces bypass of senescence and cell cycle progression through p16(INK4A)-independent inactivation of the Retinoblastoma (RB)-restriction checkpoint. Collectively, our work identifies non-canonical EMT-independent functions of SNAIL and unravel its complex context-dependent role in cancer." | Snail Family Transcription Factors |
Separate age groups of C57BL/6 and autoimmune New Zealand Black (NZB) mice were compared for diazepam-induced ataxia and barbiturate-induced loss of righting reflex. Between 1 and 3 months of age, both strains showed a similar age-related decrease in ED50 for diazepam-induced ataxia. However, between 3 and 12 months the decrease in ED50 was markedly greater in NZB mice. In contrast, age-related increases in the durations of loss of righting reflex following hexobarbital or barbital were similar in both strains. The results suggest that NZB mice show relatively accelerated age-related increases in sensitivity to benzodiazepine, but not to barbiturates. | Mice, Inbred NZB |
Proline oxidase (POX) is a novel mitochondrial tumor suppressor that can suppress proliferation and induce apoptosis through the generation of reactive oxygen species (ROS) and decreasing hypoxia-inducible factor (HIF) signaling. Recent studies have shown the absence of expression of POX in human cancer tissues, including renal cancer. However, the mechanism for the loss of POX remains obscure. No genetic or epigenetic variation of POX gene was found. In this study, we identified the upregulated miR-23b in renal cancer as an important regulator of POX. Ectopic overexpression of miR-23b in normal renal cells resulted in striking downregulation of POX, whereas POX expression increased markedly when endogenous miR-23b was knocked down by its antagomirs in renal cancer cells. Consistent with the POX-mediated tumor suppression pathway, these antagomirs induced ROS, inhibited HIF signaling and increased apoptosis. Furthermore, we confirmed the regulation of miR-23b on POX and its function in the DLD1 Tet-off POX cell system. Using a luciferase reporter system, we verified the direct binding of miR-23b to the POX mRNA 3'-untranslated region. In addition, pairs of human renal carcinoma and normal tissues showed a negative correlation between miR-23b and POX protein expression, providing its clinical corroboration. Taken together, our results suggested that miR-23b, by targeting POX, could function as an oncogene; decreasing miR-23b expression may prove to be an effective way of inhibiting kidney tumor growth. | Proline Oxidase |
Tax incentives can provide a large financial impetus to change behavior. Current U.S. law establishes a substantial discontinuity in the amount of estate tax that many patients will have to pay in 2010: During this year only, the tax rate drops to zero. This article discusses concerns regarding the sharp change in tax rate and the incentives it creates for persons who are nearing the end of life and provides estimates of the number of people affected by this issue. | Taxes |
The scales covering the elytra of the male Hoplia coerulea beetle contain fluorophores embedded within a porous photonic structure. The photonic structure controls both insect colour (reflected light) and fluorescence emission. Herein, the effects of water-induced changes on the fluorescence emission from the beetle were investigated. The fluorescence emission peak wavelength was observed to blue-shift on water immersion of the elytra whereas its reflectance peak wavelength was observed to red-shift. Time-resolved fluorescence measurements, together with optical simulations, confirmed that the radiative emission is controlled by a naturally engineered photonic bandgap while the elytra are in the dry state, whereas non-radiative relaxation pathways dominate the emission response of wet elytra. | Light |
Viral M-dsRNAs encoding yeast killer toxins share similar genomic organization, but no overall sequence identity. The dsRNA full-length sequences of several known M-viruses either have yet to be completed, or they were shorter than estimated by agarose gel electrophoresis. High-throughput sequencing was used to analyze some M-dsRNAs previously sequenced by traditional techniques, and new dsRNAs from atypical killer strains of Saccharomyces cerevisiae and Torulaspora delbrueckii. All dsRNAs expected to be present in a given yeast strain were reliably detected and sequenced, and the previously-known sequences were confirmed. The few discrepancies between viral variants were mostly located around the central poly(A) region. A continuous sequence of the ScV-M2 genome was obtained for the first time. M1 virus was found for the first time in wine yeasts, coexisting with Mbarr-1 virus in T. delbrueckii. Extra 5'- and 3'-sequences were found in all M-genomes. The presence of repeated short sequences in the non-coding 3'-region of most M-genomes indicates that they have a common phylogenetic origin. High identity between amino acid sequences of killer toxins and some unclassified proteins of yeast, bacteria, and wine grapes suggests that killer viruses recruited some sequences from the genome of these organisms, or vice versa, during evolution. | Killer Factors, Yeast |
Uveal melanoma is very rare in children, and in both adults and children it can in rare cases develop intralesional cavities resembling an intraocular cyst. The presence of a solid mass at the base and a thick wall surrounding the cavity can assist in differentiating cavitary melanoma from a benign cyst. We report the case of a 5-year-old girl who presented with a large intraocular pigmented mass in the left eye, showing multiple hollow cavities on ocular ultrasonography, CT scan, and MRI. The patient was treated by enucleation and the pathology confirmed the diagnosis of choroidal melanoma. FISH revealed no aberration in chromosome 3. | Choroid Neoplasms |
Recent research suggests that when we lack a sense of control, we are prone to motivational failures and early quitting in competitions. Testosterone, on the other hand, is thought to boost competitiveness. Here we investigate the interaction between these factors, testing the testosterone's potential to enhance persistence in a competition against a stronger opponent, depending on experimentally manipulated perceived control. Healthy participants were administered a single dose of testosterone or placebo. They first underwent a task designed to either induce low or high perceived control and then entered a costly competition against a progressively stronger opponent that they could quit at any time. In the placebo group, men with low perceived control quitted twice as early as those with high perceived control. Testosterone countered this effect, making individuals with low control persist in the competition for as long as those with high perceived control, and did so also despite raising participants' explicit awareness of the opponents' advantage. This psychoendocrinological effect was not modulated by basal cortisol levels, CAG repeat polymorphism of the androgen receptor gene, or trait dominance. Our results provide the first causal evidence that testosterone promotes competitive persistence in humans and demonstrate that this effect depends on the psychological state elicited prior to the competition, broadening our understanding of the complex relationships between testosterone and social behaviors. | Competitive Behavior |
Carbamoyl-phosphate synthase gene expression is found to be primarily regulated by conditions that enhance hepatic glucocorticosteroid levels (hormone injections) and cyclic AMP levels (induction of diabetes). After birth, changes in the level of carbamoyl-phosphate synthase protein follow changes in the level of carbamoylphosphate synthase mRNA, suggesting a pretranslational control mechanism. In fetal rats, carbamoyl-phosphate synthase gene expression is regulated by the same factors as in adults. However, both the level to which carbamoyl-phosphate synthase mRNA can accumulate and the extent to which mRNA can be translated appear to be limited, indicating control mechanisms at the pretranslational and translational level. Finally, in the immediate postnatal period, a transient but pronounced decrease in the rate of degradation of carbamoyl-phosphate synthase protein may play a role in the accumulation of the enzyme." | Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) |
Increasing evidence shows changes in gut microbiota composition in association with psychiatric disorders, including anxiety and depression. Moreover, it has been reported that perturbations in gut microbe diversity and richness influence serotonergic, GABAergic, noradrenergic, and dopaminergic neurotransmission. Among these, dopamine is regarded as a main regulator of cognitive functions such as decision making, attention, memory, motivation, and reward. In this work, we will highlight findings that link alterations in intestinal microbiota and dopaminergic neurotransmission, with a particular emphasis on the mesocorticolimbic circuit, which is involved in reward to natural reinforcers, as well as abuse substances. For this, we reviewed evidence from studies carried out on germ-free animals, or in rodents subjected to intestinal dysbiosis using antibiotics, and also through the use of probiotics. All this evidence strongly supports that the microbiota-gut-brain axis is key to the physiopathology of several neuropsychiatric disorders involving those where dopaminergic neurotransmission is compromised. In addition, the gut microbiota appears as a key player when it comes to proposing novel strategies to the treatment of these psychiatric conditions. | Gastrointestinal Microbiome |
Smk1 is a mitogen-activated protein kinase (MAPK) family member in the yeast Saccharomyces cerevisiae that controls the postmeiotic program of spore formation. Ssp2 is a meiosis-specific protein that activates Smk1 and triggers the autophosphorylation of its activation loop. A fragment of Ssp2 that is sufficient to activate Smk1 contains two segments that resemble RNA recognition motifs (RRMs). Mutations in either of these motifs eliminated Ssp2's ability to activate Smk1. In contrast, deletions and insertions within the segment linking the RRM-like motifs only partially reduced the activity of Ssp2. Moreover, when the two RRM-like motifs were expressed as separate proteins in bacteria, they activated Smk1. We also find that both motifs can be cross-linked to Smk1 and that at least one of the motifs binds near the ATP-binding pocket of the MAPK. These findings demonstrate that motifs related to RRMs can directly activate protein kinases. | RNA Recognition Motif |
Apical periodontitis caused by root canal infection is the most frequent pathological lesion in the jaws, mainly manifested as periapical granulomas and cysts. Understanding of the formation and progression of apical periodontitis as well as the identification of inflammatory biomarkers can help increase the knowledge of pathogenic mechanisms, improve the diagnosis and provide support for different therapeutic strategies. The objective of the present article is to review inflammatory biomarkers such as cytokines, chemokines, inflammatory cells, neuropeptides, RANK/RANKL/OPG system and other inflammatory markers and to relate these systems to the development and progression of pathological conditions related to apical periodontitis. | Osteoprotegerin |
The emergence of pathogens and toxins with resistance against conventional drugs, vaccines, and host defense peptides and proteins warrants novel countermeasures that can efficiently capture and rapidly clear them. This article examines the utility of chimeric proteins with capture and clearance domains as a novel countermeasure against pathogens and their toxins. The capture and clearance domains are chosen from the large repertoire of host defense peptides and proteins. Although individual capture and clearance domains are rendered ineffective by pathogenic resistance mechanisms, chimeric scaffolds can be designed to retain their antimicrobial activity, even in the face of pathogenic resistance. Here, initial studies on the design of chimeric proteins targeted against (1) intact bacteria such as Xylella fastidiosa (plant pathogens), Salmonella spp. (food-borne pathogens), and Staphylococcus aureus (blood-borne pathogens); and (2) lethal toxins from Bacillus anthracis are described. | Recombinant Fusion Proteins |
The plasma disposition of fenbendazole (FBZ), oxfendazole (OFZ) and albendazole (ABZ); and the enantiospecific disposition of OFZ, and ABZSO produced were investigated following an oral administration (50 mg/kg) in dogs. Blood samples were collected from 1 to 120 h post-administration. The plasma samples were analysed by high performance liquid chromatography (HPLC). The plasma concentration of FBZ, OFZ, ABZ and their metabolites were significantly different from each other and depended on the drug administered. The sulphone metabolite (FBZSO2) of FBZ was not detected in any plasma samples and the parent molecule ABZ did not reach quantifiable concentrations following FBZ and ABZ administration, respectively. OFZ and its sulphone metabolite attained a significantly higher plasma concentration and remained much longer in plasma compared with FBZ and ABZ and their respective metabolites. The maximum plasma concentrations (Cmax), area under the concentration time curve (AUC) and mean residence time (MRT) of parent OFZ were more than 30, 68 and 2 times those of FBZ, respectively. The same parameters for ABZSO were also significantly greater than those of FBZSO. The ratio for total AUCs of both the parent drug and the metabolites were 1:42:7 for following FBZ, OFZ and ABZ administration, respectively. The enantiomers were never in racemic proportions and (+) enantiomers of both OFZ and ABZSO were predominant in plasma. The AUC of (+) enantiomers of OFZ and ABZSO was, respectively more than three and seven times larger than that of (-) enantiomers of both molecules. It is concluded that the plasma concentration of OFZ was substantially greater compared with FBZ and ABZ. The data on the pharmacokinetic profile of OFZ presented here may contribute to evaluate its potential as an anthelmintic drug for parasite control in dogs. | Fenbendazole |
Injectable hydrogels provide a powerful and non-invasive approach for numerous applications in cell transplantation, growth factor delivery, tissue regeneration and so forth. The properties of injectable hydrogels should be well-tuned for specific applications, where their overall design should ensure biocompatibility, non-toxicity, robust mechanical properties, and most importantly the ability to promote vascularization and integration with the host tissue/organ. Among these criteria, vascularization remains a key design element in the development of functional therapeutic hydrogels for successful translation into clinical settings. To that end, there is still a critical need for the development of the next generation of injectable hydrogels with precisely tuned biophysical and biochemical properties which could simultaneously promote tissue vascularization. In this work, we developed a temperature responsive, dual-crosslinking, biohybrid hydrogels, modified with a vasculogenic peptide for applications in regenerative medicine, specifically tissue vascularization. The synthesized hydrogels consisted of poly(N-isopropylacrylamide)-based copolymer, functionalized gelation and angiogenic VEGF-mimetic QK peptide with enhanced shear-thinning and injectability properties. QK peptide is a VEGF-mimetic vasculogenic peptide which binds to VEGF receptors and activates intercellular pathway for vascularization. Apart from the presence of QK peptide, the mechanical properties of the hydrogels were precisely tuned by altering the polymer concentration, enabling successful assembly and endothelial cell network formation. Extended in vitro studies demonstrated successful encapsulation and homogeneous distribution of endothelial cells within the three-dimensional (3D) environment of the hydrogel matrix with significantly enhanced vascularization in presence of the QK peptide as early as 3 days of culture. A small, preliminary in vivo study in mice showed a trend of increased blood vessel formation in hydrogels that incorporated the QK peptide. Overall, our study presents the design and characterization of injectable, dual-crosslinking and vasculogenic hydrogels with controlled properties which could be utilized for numerous applications in regenerative medicine, minimally invasive cell and drug delivery as well as fundamental studies on tissue vascularization and angiogenesis. STATEMENT OF SIGNIFICANCE: In this work, we synthesized a new class of temperature responsive, dual-crosslinking, biohybrid injectable hydrogels with enhanced vascularization properties for broad applications in regenerative medicine and minimally invasive cell/drug delivery. The developed hydrogels properly accommodated 3D culture, assembly and network formation of endothelial cells, as evidenced by in vitro and in vivo studies. | Polyhydroxyethyl Methacrylate |
OBJECT: A systematic investigation on cortical reorganization in patients with hemiparesis of a subcortical origin, with special emphasis on functional correlates, was conducted using functional magnetic resonance (fMR) imaging performed on a 3-tesla system specifically optimized for fMR imaging investigation. METHODS: The study group included 46 patients with hemiparesis (25 with right and 21 with left hemiparesis) and 30 age-matched healthy volunteers as controls. All study participants were originally right handed. The characteristics of the lesion were putaminal hemorrhage in 19 patients, thalamic hemorrhage in 10 patients, and striatocapsular bland infarction in 17 patients. Functional recovery in subcortical hemiparesis showed two distinct phases of the recovery process involving entirely different neural mechanisms. Phase I is characterized by the process of recovery and/or reorganization of the primary system. Successful recovery of this system is typically reached within 1 month after stroke onset. Its clinical correlate is a rapid recovery course and significant recovery of function within 1 month of stroke onset. Failure of recovery of the primary system shifts the recovery process to Phase II, during which reorganization involving the ipsilateral pathway takes place. The clinical correlate of Phase II is a slow recovery course with variable functional outcome. CONCLUSIONS: Effective functional organization of the ipsilateral pathway, as identified by linked activation of the ipsilateral primary sensorimotor cortex and contralateral anterior lobe of the cerebellum, is correlated with a good prognostic outcome for patients in the slow recovery group. A high degree of connectivity between supplementary motor areas, bilaterally, appears to influence functional recovery adversely." | Basal Ganglia Cerebrovascular Disease |
Isotope renography and excretory urography were perfored routinely before and 3 months after an operation on 21 patients with hydronephrosis. A year postoperatively all patients again underwent renography. Renography is a valuable and reliable method to estimate the results of an operation. By 3 months postoperatively the renograms revealed improved renal function and drainage in 75 per cent of the cases. | Hydronephrosis |
The present study describes, for the first time, the glycosidic content of boar bulbourethral glands using lectin histochemistry. Fourteen horseradish peroxidase- or digoxigenin-labelled lectins with different carbohydrate specificities were used in samples obtained from 3 healthy Landrace boars. The results obtained indicate that endpiece and duct cells synthesize and secrete mainly O-glycoproteins with alpha- and beta-D-N-acetylgalactosamine, beta-D-galactose-beta(1-->3)-D-N-acetylgalactosamine, D-N-acetylglucosamine and neuraminic acid residues. Glycoproteins secreted by bulbourethral glands have a role in the protection and lubrication of the urethra. In addition, they may be also involved in the regulation of the sperm metabolic activity and in the maintenance of the structural integrity of acrosomal and plasma membranes. | Bulbourethral Glands |
OBJECTIVE: To evaluate patients' experiences of shortened hospitalization in relation to bone grafting of unilateral alveolar clefts with mandibular symphyseal bone grafts. DESIGN: Prospective cohort questionnaire study. SETTING: Department of Oral and Maxillofacial Surgery, Aarhus University Hospital, Denmark. PATIENTS: Thirty-nine (male n = 26, female n = 13) patients with unilateral residual clefts after primary reconstruction, mean age 10.4 years. INTERVENTIONS: All patients underwent a standardized procedure with closure of the alveolar defect using mandibular symphyseal bone grafts. Patients were discharged within a day after surgery. Within 24 hours after discharge from surgery, patients and their parents filled in a 14-item psychometric questionnaire assessing the quality of their recovery. For all questions, a visual analogue scale (VAS) (0-10) was used. MAIN OUTCOME MEASURE: Patients' experience of shortened hospitalization in relation to secondary bone grafting of alveolar defects. Factors influencing the overall experience were measured using a VAS scale. RESULTS: A significant correlation between Information from the hospital" and feeling worried and anxious was found (P = .04). Additionally, the ability to sleep correlated with pain (P = .003) and with nausea (P = .001). CONCLUSIONS: Although this study included a limited number of patients, the findings suggest that treatment of alveolar residual cleft with bone grafting from the mandibular symphyseal region in a day care surgery setting is characterized by very high patient satisfaction." | Alveolar Bone Grafting |
Beta-galactosidase, encoded by the lacZ gene in E. coli, can cleave lactose and structurally related compounds to galactose and glucose or structurally related products. Its activity can be measured using an artificial substrate, o-nitrophenyl-beta-D-galactopyranoside (ONPG). Miller firstly described the standard quantitative assay of beta-galactosidase activity in the cells of bacterial cultures by disrupting the cell membrane with the permeabilization solution instead of preparing cell extracts. Therefore, beta-galactosidase became one of the most widely used reporters of gene expression in molecular biology to reflect intracellular gene expression difference. But the Miller assay procedure could not monitor the beta-galactosidase reaction in real time and its results were greatly influenced by some operations in the Miller procedure, such as permeabilization time, reaction time and concentration of the cell suspension. A scanning method based on the Miller method to determine the intracellular beta-galactosidase activity in E. coli Tuner (DE3) expressing -galactosidase in real time was developed and the permeabilization time of cells was optimized for that. The comparison of 3 assays of beta-galactosidase activity (Miller, colorimetric and scanning) was made. The results proved that scanning method for the determination of enzyme activity with using ONPG as substrate is simple, fast and reproducible. | Nitrophenylgalactosides |
INTRODUCTION: Juvenile myoclonic epilepsy (JME) is a genetic generalized epilepsy syndrome. Under appropriate antiepileptic drugs (AED) up to 85% of patients become seizure-free, but many may have a relapse after AED withdrawal. METHODS: We retrospectively studied 242 patients with JME at the Department of Neurology, Medical University Innsbruck, Austria (1975-2006). We analyzed age at seizure onset, age at last follow up, seizure types, photosensitivity, seizure outcome and neuroimaging findings; inclusion criterion was a medical treatment period of >2 years; exclusion criteria were traumatic or infectious brain injury before the onset of JME and/or gross structural pathology on neuroimaging. RESULTS: We identified 175 patients (111 women) with a median age at seizure onset of 15 years, (range 3-46) and a median age at follow-up (FU) of 38 years (range 14-87; median FU 8 years, range 2-38). Fourteen percent showed (24/175) photosensitivity on routine EEG. Seizure outcome: 62% (109/175) were seizure-free of myoclonic seizures (MS), generalized tonic clonic seizures (GTCS) and absence seizures (AS) for >1 year, and 53% (94/175) for >2 years, including 16 patients (9%) without AEDs. Thirty-one percent (54/175) were seizure-free between 2 and 5 years, 15% (26/175) between 6 and 10, and 8% (14/175) >10 years; 38% (66/175) were not seizure-free. Not seizure-free patients had more often MS, AS and GTCS within the first year of epilepsy than those who were seizure-free at last FU (11% vs. 3%, Chi(2)=4.679, df=1, p=0.043). Seizure-free patients had more often MS and GTCS as last seizure types in the year before becoming seizure-free (37% vs. 15%, p=0.003), whereas in not seizure-free group MS only and GTCS only persisted. CONCLUSIONS: JME does not always need lifelong treatment, as a substantial minority of patients remain seizure-free without AEDs. AS, MS and GTCS at onset of the disease are indicators of poor long-term seizure control. | Myoclonic Epilepsy, Juvenile |
Contact zones provide important insights into the evolutionary processes that underlie lineage divergence and speciation. Here, we use a contact zone to ascertain speciation potential in the red-eyed treefrog (Agalychnis callidryas), a brightly coloured and polymorphic frog that exhibits unusually high levels of intraspecific variation. Populations of A. callidryas differ in a number of traits, several of which are known sexual signals that mediate premating reproductive isolation in allopatric populations. Along the Caribbean coast of Costa Rica, a ~100 km contact zone, situated between two phenotypically and genetically divergent parent populations, contains multiple colour pattern phenotypes and late-generation hybrids. This contact zone provides the opportunity to examine processes that are important in the earliest stages of lineage divergence. We performed analyses of colour pattern variation in five contact zone sites and six parental sites and found complex, continuous colour variation along the contact zone. We found discordance between the geographic distribution of colour pattern and previously described genomic population structure. We then used a parental site and contact zone site to measure assortative mating and directional selection from naturally-occurring amplectant mating pairs. We found assortative mating in a parental population, but no assortative mating in the contact zone. Furthermore, we uncovered evidence of directional preference towards the adjacent parental phenotype in the contact zone population, but no directional preference in the parent population. Combined, these data provide insights into potential dynamics at the contact zone borders and indicate that incipient speciation between parent populations will be slowed. | Reproductive Isolation |
Two pyrrolidine compounds (1 and 2) were isolated from photo-degradation of Bi-Sifrol tablets. Compound 1 was esterified to p-bromophenacyl ester as single-crystal, and then the structure was elucidated by single-crystal X-ray study. Compound 2 was determined by 2D NMR and mass spectra. Otherwise, we established that the photo-degradation of pramipexole was smoothly carried out in the methanol solution, and elucidate the degradation mechanism. | Pramipexole |
Knowledge of composition of beverages volatile fraction is essential for understanding their sensory attributes. Analysis of volatile compounds predominantly resorts to gas chromatography coupled with mass spectrometry (GC-MS). Often a previous concentration step is required to quantify compounds found at low concentrations. This work presents a liquid-liquid microextraction method combined with GC-MS (LLME/GC-MS) for the analysis of compounds in fermented beverages and spirits. The method was validated for a set of compounds typically found in fermented beverages comprising alcohols, esters, volatile phenols, and monoterpenic alcohols. The key requirements for validity were observed, namely linearity, sensitivity in the studied range, accuracy, and precision within the required parameters. Robustness of the method was also evaluated with satisfactory results. Thus, the proposed LLME/GC-MS method may be a useful tool for the analysis of several fermented beverages, which is easily implementable in a laboratory equipped with a GC-MS. | Fermented Foods |
AIM: The aim of this study was the evaluation of risk among the couples various types of Robertsonian translocations. METHODS: Cytogenetic diagnosis has been carried out according to the Moorhead and Seabright method. RESULTS: Cytogenetics diagnosis was performed in 17 couples having Robertsonian translocations. Among our examined cases, the most frequent (82.3%) cases were with Robertsonian translocations formed by aberrant fusion between heterologous chromosomes 13q and 14q. Three out of seventeen couples affected with Robertsonian translocation 13q;14q suffered from primary infertility. The total number of pregnancy among the couples with Robertsonian translocation has been 45. Of these 80% of pregnancies resulted in spontaneous miscarriages, while 20% of others have gave birth to alive or dead children. In one couple a Robertsonian translocation was caused as a result of fusion of two homologous chromosomes 15q;15q. A patient with this translocation has had 7 pregnancies and all of them ended with abortions. CONCLUSION: Robertsonian translocation caused the primary infertility in three couples and lowering reproductive abilities in 14 others. Robertsonian translocation between 15q;15q caused intrauterine death and spontaneous failures of all pregnancies of the carrier with this translocation. | Chromosomes, Human, Pair 13 |
The label cancer in itself leads to complex psychological reactions in patients that are closely related to previous experiences and self-image. A cancer diagnosis can lead to increased distress and subsequent mental comorbidity such as depression or anxiety disorders. The responsibility of the pathologist, as the person who first uses the label cancer, is high. The pathologist must be conscious and focus not only on the accuracy of the anatomical pathology, but also on the potential influences the wording may have on the mental health of the patient. The word carcinoma" should only be used in the case of tumors with the respective biological behavior. The example of non-invasive follicular thyroid neoplasm with papillary-like nuclear features shows that changing a label can lead to an improvement in distress and quality of life." | Psychology, Medical |
Evidence-based medicine that is designed to guide benefit/risk drug therapy decisions does not exist for pregnant women. The types of studies that do exist are usually conducted in animals, which may not reflect human benefits and risks. The types of studies that do exist in humans are typically limited and, at best, may show an association" between a particular drug therapy and an undesirable effect. This review outlines the difficulties that are associated with the assessment of the benefits/risks of drug therapy during pregnancy, the history of the Food and Drug Administration regulations for labeling prescription drugs, and the strengths and weaknesses of the current Food and Drug Administration pregnancy labeling system. Proposed changes to the current system are reviewed." | Drug Labeling |
Two-month-old male offspring of rats injected intravenously on day 19 of gestation with antiserum to synaptic membrane fraction showed marked behavioral deficits on a DRL (differential reinforcement at low rates) training paradigm. These behavioral deficits included perseveration, slow acquisition rates, and poor retention. Offspring of pregnant rats injected with antiserum to galactocerebroside or isotonic saline did not show these behavioral effects. | Synaptic Membranes |
One-anastomosis gastric bypass is an alternative to the gold-standard" Roux-en-Y gastric bypass. This technique appears to be safe and efficient, but controversy remains regarding the long-term theoretical risk of subsequent biliary reflux and its possible complications, such as cancer. The aim of the present narrative review was to summarize some of the current thoughts on biliary reflux. Research has established that exposure to chronic bile reflux in humans and rats (outside the "bariatric surgery" box) induce esophageal intestinal metaplasia and esophageal adenocarcinoma. Although one-anastomosis gastric bypass can theoretically induce chronic biliary reflux, the incidence of biliary reflux and risk of cancer have not been prospectively evaluated. Clarification of this controversial issue is urgently needed." | Gastric Bypass |
In the 1970s, the public’s need for Japanese herbal medicine increased, and the Ministry of Health and Welfare was flooded with applications for Japanese herbal extracts as OTC drugs. In 1975, the ministry of Health issued the guidebook of the approval standards for Kampo products for 210 prescriptions. But, although Kampo has already been partially incorporated into the healthcare system, this does not mean that clinical research is not being conducted or that evidence-based medicine (EBM) is being taken lightly. | Medicine, Kampo |
BACKGROUND: In the last decade, many new avenues of cancer treatment have opened up but the costs of treatment have sky-rocketed too. Hence, screening of indigenously available plant and animal resources for anti-carcinogenic potential is an important branch of anticancer research. The effort has been made through this comprehensive review to highlight the recent developments of anticancer therapies using different parts of papaya plant extract. METHODS: In search of the naturally existing animals and plants for anticarcinogenic potential, papaya plant has been exploited by the scientist working in this research field. A widespread literature search was performed for writing this review. RESULTS: Different constituents of Carica papaya responsible for anticancer activities have been discussed. Papaya extract for the treatment of breast, liver, blood, pancreas, skin, prostate, and colon cancer have also been reported. Finally, the various formulation approach using Carica papaya extract have been highlighted. CONCLUSION: The information provided in this review might be useful for researchers in designing of novel formulation of Carica papaya extract for the treatment of cancer. | Carica |
Although serine acetyltransferase (SAT) from Escherichia coli is homologous with a number of bacterial enzymes that catalyze O-acetyl transfer by a sequential (ternary complex) mechanism, it has been suggested, from experiments with the nearly identical enzyme from Salmonella typhimurium, that the reaction could proceed via an acetyl-enzyme intermediate. To resolve the matter, the E. coli gene for SAT was overexpressed and the enzyme purified 13-fold to homogeneity. The results of a steady-state kinetic analysis of the forward reaction are diagnostic for a ternary complex mechanism, and the response of SAT to dead-end inhibitors indicates a random order for the addition of substrates. The linearity of primary double-reciprocal plots, in the presence and absence of dead-end inhibitors, argues that interconversion of ternary complexes is not significantly faster than kcat, whereas substrate inhibition by serine suggests that breakdown of the SAT.CoA binary complex is rate-determining. The results of equilibrium isotope exchange experiments, for both half-reactions, rule out a ping-pong" mechanism involving an acetyl-enzyme intermediate, and a pre-steady-state kinetic analysis of the turnover of AcCoA supports such a conclusion. Kinetic data for the reverse reaction (acetylation of CoA by O-acetylserine) are also consistent with a steady-state random-order mechanism, wherein both the breakdown of the SAT*serine complex and the interconversion of ternary complexes are partially rate-determining." | Serine O-Acetyltransferase |
INTRODUCTION: Online health information seeking has been verified to play a crucial role in improving public health and has received close scholarly attention. However, the seeking behavior of older adults, especially the underlying mechanism through which they are motivated to seek health information online, remains unclear. This study addresses the issue by proposing a theoretical model leveraging social cognitive theory. METHODS: IT self-efficacy and IT innovativeness were identified as personal factors and professional support and social support were identified as environmental factors. We conducted a survey that included 347 older people in China and examined the research hypotheses with a structural equation model. RESULTS: IT self-efficacy and IT innovativeness facilitate older adults to seek health information online by increasing their perceived benefit of using the internet. Additionally, professional support and social support enhanced older adults' online seeking behavior by promoting their health awareness. We also found that perceived benefit displayed a stronger impact than health awareness on older adults' behavior related to searching for health information online. CONCLUSION: This study reveals that IT self-efficacy, IT innovativeness, professional support, and social support will promote older adults to seek health information online by enhancing their health awareness and perceived benefit. The findings of this study provide significant theoretical and practical implications. | Information Seeking Behavior |
We are using the domestic ram as an experimental model to examine the role of aromatase in the development of sexual partner preferences. This interest has arisen because of the observation that as many as 8% of domestic rams are sexually attracted to other rams (male-oriented) in contrast to the majority of rams that are attracted to estrous ewes (female-oriented). Our findings demonstrate that aromatase expression is enriched in a cluster of neurons in the medial preoptic nucleus called the ovine sexually dimorphic nucleus (oSDN). The size of the oSDN is associated with a ram's sexual partner preference, such that the nucleus is 2-3 times larger in rams that are attracted to females (female-oriented) than in rams that are attracted to other rams (male-oriented). Moreover, the volume of the oSDN in male-oriented rams is similar to the volume in ewes. These volume differences are not influenced by adult concentrations of serum testosterone. Instead, we found that the oSDN is already present in late gestation lamb fetuses (approximately day 135 of gestation) when it is approximately 2-fold greater in males than in females. Exposure of genetic female fetuses to exogenous testosterone during the critical period for sexual differentiation masculinizes oSDN volume and aromatase expression when examined subsequently on day 135. The demonstration that the oSDN is organized prenatally by testosterone exposure suggests that the brain of the male-oriented ram may be under-androgenized during development. | Aromatase |
OBJECTIVE: To investigate the pharmacological effect of Yifuzhixue Pill (YFZXP). METHODS: PPT, RT, PT, platelet counts and platelet adhesive rate were examined after administration of YFZXP. In other hand, the functions of isolated rabbit's uteri were also examined to determine whether they were responsible to the administration of YFZXP. RESULTS: YFZXP could enhance the intrinsic blood coagulating function and stimulate the contraction of smooth muscles of uterus including increasing the rhythms and strength. The stimulation effect of YFZXP on smooth muscles of uterus exhibited no selections between the uteri treated with or without estradiol. It was speculated that the increased intrinsic blood coagulating and uterus' contraction induced by YFZXP were contributed to its anti-bleeding effect in uterus. | Codonopsis |
ASP7962 is a small molecule inhibitor for the nerve growth factor (NGF) receptor, tropomyosin-related kinase A (TrkA). NGF contributes to the survival of sensory and sympathetic neurons through TrkA receptor activation. Gross, microscopic, and quantitative effects to the nervous system were evaluated following oral ASP7962 administration to Sprague Dawley rats for 4 weeks and 13 weeks and after a recovery period. Histopathological findings included reversible neuronal atrophy but no neuronal death in the sympathetic ganglia (cervicothoracic ganglion, cranial mesenteric ganglion or superior [cranial] cervical ganglion). Stereological analysis showed reversible decreased ganglion volume and/or decreased neuron size in the superior (cranial) cervical ganglion in both the 4-week and the 13-week repeated dose studies. There were no test article related changes in the brain, dorsal root ganglia with spinal nerve roots or trigeminal ganglia and no functional deficits. ASP7962 did not cause any detectable dysfunction of the sympathetic and sensory nervous system in either study. | Superior Cervical Ganglion |
A phage Mu-driven two-plasmid system for DNA integration in Escherichia coli genome has been adjusted for Methylophilus methylotrophus. Constructed helper plasmids with broad-host-range replicons carry thermo-inducible genes for transposition factors MuA and MuB. Integrative plasmids that are only replicated in E. coli could be mobilized to M. methylotrophus and contained mini-Mu unit with a short terminus of Mu DNA, Mu-attL/R. Mini-Mu unit was integrated in the M. methylotrophus genome via mobilization of the integrative plasmid to the cells carrying the helper in conditions of thermo-induced expression of MuA and MuB. In this system, mini-Mu unit was mainly integrated due to replicative transposition, and the integrated copy could be amplified in the M. methylotrophus chromosome in the presence of helper plasmid. A kan-gene flanked by FRT sites was inserted in one of the mini-Mu units, and it could be readily excised by yeast FLP recombinase that is encoded by the designed plasmid. The multiple Mu-driven gene insertion was carried out by integration of the Bacillus amyloliquefaciens alpha-amylase gene followed by curing the KmR marker before integration of the second mini-Mu unit with Pseudomonas putida xylE gene encoding catechol 2,3-dioxygenase (C23O). | Methylophilus methylotrophus |
We studied the mechanism that may explain the relative resistance of thyrocytes to H(2)O(2) compared to other cell types. Ability to degrade H(2)O(2), glutathione peroxidase (GPx) activity, heme oxygenase-1 (HO-1) expression, cell survival and capacity to repair DNA damage after H(2)O(2) exposure or irradiation were measured in human thyrocytes in primary culture and compared to the values obtained in human T-cells and different cell lines. Compared to other cell types, thyrocytes presented a low mortality rate after H(2)O(2) exposure, rapidly degraded extracellular H(2)O(2) and presented a high basal seleno-dependent GPx activity. Only in thyrocytes, H(2)O(2) up-regulated GPx activity and expression of HO-1 mRNA. These effects were not reproduced by irradiation. DNA damage caused by H(2)O(2) was more slowly repaired than that caused by irradiation and not repaired at all in T-cells. Our study demonstrates that the thyrocyte has specific protective mechanisms against H(2)O(2) and its mutagenic effects. | Thyroid Epithelial Cells |
We described an association between a strain of the nematode Caenorhabditis briggsae, i.e. KT0001, and the bacteria Serratia sp. SCBI (South African Caenorhabditis briggsae isolate), which was able to kill the insect Galleria. Here we show that the Serratia sp. SCBI lines the gut of the nematode, similar to the Heterorhabditis-Photorhabdus complex, indicating that the association is possibly internal. We also expand on the relevance of this tripartite, i.e. insect-nematode-bacteria, interaction in the broader evolutionary context and Caenorhabditis natural history. | Serratia |
Rho-associated protein kinase (ROCK) is a serine-threonine kinase and is a major downstream effector of the small GTPaseRhoA. Upon activation, Rho/ROCK cell signaling pathway regulates cell morphology, polarity, and cytoskeletal remodeling. Recent years have highlighted the role of ROCK signaling pathway in the replication of diverse group of viruses. Cell contractions and membrane blebbing induced by certain group of viruses is mediated via ROCK signaling and facilitates virus replication by sequestration of cellular factors and anchoring them at replication sites (viral factories). Besides, ROCK signaling also stabilizes the nascent viral mRNA for its efficient transcription and translation and, regulates trafficking of the viral proteins. In addition, ROCK signaling is also involved in modulating the immune response to viral infections. This review describes the regulation of virus replication by ROCK signaling with the basic aim of defining it as a target for the development of novel antiviral therapeutics. | rho-Associated Kinases |
OBJECTIVES: To examine the point prevalence and correlates of prolonged grief disorder (PGD) in a nationally-representative sample of United States (U.S.) veterans. METHODS: Data were analyzed from the National Health and Resilience in Veterans Study, a nationally representative study of 2,441 U.S. veterans. RESULTS: A total of 158 (weighted 7.3%) veterans screened positive for PGD. The strongest correlates of PGD were adverse childhood experiences, female sex, non-natural causes of death, knowing someone who died from coronavirus disease 2019, and number of close losses. After adjusting for sociodemographic, military, and trauma variables, veterans with PGD were 5-to-9 times more likely to screen positive for post-traumatic stress disorder, major depressive disorder, and generalized anxiety disorder. After additional adjustment for current psychiatric and substance use disorders, they were 2-3 times more likely to endorse suicidal thoughts and behaviors. CONCLUSIONS: Results underscore the importance of targeting PGD as an independent risk factor for psychiatric disorders and suicide risk. | Prolonged Grief Disorder |
Cryptosporidium spp. are obligate protozoan parasites of the gastrointestinal tract of vertebrates, including humans. In the majority of human cases, the diarrheal disease cryptosporidiosis is caused by either the human-adapted species Cryptosporidium hominis or the zoonotic Cryptosporidium parvum 'bovine genotype' (also known as Cryptosporidium pestis). The infectious stage, environmentally resilient Cryptosporidium oocysts, are shed by the infected host. Cryptosporidium parasites are transmitted by the fecal-oral route and are one of the major water-borne pathogens. The cryptic nature of the microscopic Cryptosporidium oocysts coupled with the existence of several host-adapted and zoonotic species requires molecular tools to identify Cryptosporidium spp. in either fecal or environmental samples. This unit describes methods for Cryptosporidium identification and typing using genotyping based on nuclear loci. We also provide a protocol for morphological confirmation of Cryptosporidium oocysts based on antibody labeling of the Cryptosporidium oocyst wall and a protocol for purification of oocysts from fecal material. (c) 2017 by John Wiley & Sons, Inc. | Cryptosporidiidae |
The fine structure of the parathyroid of the macaque is described, and is correlated with classical parathyroid cytology as seen in the light microscope. The two parenchymal cell types, the chief cells and the oxyphil cells, have been recognized in electron micrographs. The chief cells contain within their cytoplasm mitochondria, endoplasmic reticulum, and Golgi bodies similar to those found in other endocrine tissues as well as frequent PAS-positive granules. The juxtanuclear body of the light microscopists is identified with stacks of parallel lamellar elements of the endoplasmic reticulum of the ergastoplasmic or granular type. Oxyphil cells are characterized by juxtanuclear bodies and by numerous mitochondria found throughout their cytoplasm. Puzzling lamellar whorls are described in the cytoplasm of some oxyphil cells. The endothelium of parathyroid capillaries is extremely thin in some areas and contains numerous fenestrations as well as an extensive system of vesicles. The possible significance of these structures is discussed. The connective tissue elements found in the perivascular spaces of macaque parathyroid are described. | Oxyphil Cells |
DNA topoisomerase II completely removes DNA intertwining, or catenation, between sister chromatids before they are segregated during cell division. How this occurs throughout the genome is poorly understood. We demonstrate that in yeast, centromeric plasmids undergo a dramatic change in their topology as the cells pass through mitosis. This change is characterized by positive supercoiling of the DNA and requires mitotic spindles and the condensin factor Smc2. When mitotic positive supercoiling occurs on decatenated DNA, it is rapidly relaxed by topoisomerase II. However, when positive supercoiling takes place in catenated plasmid, topoisomerase II activity is directed toward decatenation of the molecules before relaxation. Thus, a topological change on DNA drives topoisomerase II to decatenate molecules during mitosis, potentially driving the full decatenation of the genome. | Catenanes |
A high-performance liquid chromatographic method with fluorescence detection for the determination of methamphetamine and its related compounds is reported. Methamphetamine, amphetamine, norephedrine, p-hydroxymethamphetamine and 1-phenylethylamine as an internal standard were extracted from human urine, derivatized with fluorescein-4-isothiocyanate, and then separated on a reversed-phase column within 36 min. The fluorescence intensity of the effluent was monitored at excitation and emission wavelengths of 496 and 518 nm, respectively. Calibration curves were confirmed to be linear up to at least 100 pmol on the column with a correlation coefficient (r) of 0.994-0.999 for the target compounds. The detection limits (S/N=3) were 55-105 fmol per 20-microl injection. The method was successfully applied to urine samples taken from methamphetamine addicts. | p-Hydroxynorephedrine |
PURPOSE: There is still a lack of robust data on the epidemiology of cardiac arrest during anesthesia. We investigated the frequency and risk factors of cardiac arrest during anesthesia over the past two decades at a tertiary care university hospital in Japan. METHODS: We retrospectively analyzed 111,851 anesthesia records of patients who underwent surgery under anesthesia between 2000 and 2019. Cardiac arrest cases were classified according to the patient's background, surgical status, main cause and initial rhythm of cardiac arrest, and the presence of the return of spontaneous circulation (ROSC). Univariate and multivariate logistic regression analyses were used to identify the risk factors of cardiac arrest and failure to achieve ROSC. RESULTS: Ninety cardiac arrest cases during anesthesia were identified. The incidence of cardiac arrest was 8.05 per 10,000 anesthetics (95% CI, 6.54-9.90). There were 6 anesthesia-related cardiac arrests and 9 anesthesia-contributory cardiac arrests. The most common cause of cardiac arrest was blood loss. American Society of Anesthesiologists physical status 4-5, emergency surgery, and cardiovascular surgery were identified as independent risk factors of cardiac arrest. American Society of Anesthesiologists physical status 4-5, blood loss-induced cardiac arrest, and non-shockable rhythm were independently associated with failure to achieve ROSC. CONCLUSION: Blood loss was the most common cause of cardiac arrest and blood loss-induced cardiac arrest was independently associated with failure to achieve ROSC. Further improvements in treatment strategies for bleeding may reduce the future incidence of cardiac arrest and death during anesthesia." | Return of Spontaneous Circulation |
The number of nucleolar silver stained granules representing nucleolus organizer regions in interphase nuclei was studied in Yoshida ascitic sarcoma cells without and after the inhibition of the nucleolar RNA synthesis with actinomycin D or cyclophosphamide. The results demonstrated that the number of nucleolar silver stained granules decreased after the inhibition of the nucleolar RNA synthesis with these drugs disregarding the mode of their action. In addition, the decrease of nucleolar silver stained granules in number produced by actinomycin D was dose dependent. Similarly, the number of nucleoli without silver stained granules increased depending on the dose of the administered actinomycin D. | Sarcoma, Yoshida |
Elevated concentration of homocysteine (Hcy) in the blood plasma, hyperhomocysteinemia (HHcy), has been implicated in various disorders, including cardiovascular and neurodegenerative diseases. Accumulating evidence indicates that pathophysiology of these diseases is linked with mitochondrial dysfunction. In this review, we discuss the current knowledge concerning the effects of HHcy on mitochondrial homeostasis, including energy metabolism, mitochondrial apoptotic pathway, and mitochondrial dynamics. The recent studies suggest that the interaction between Hcy and mitochondria is complex, and reactive oxygen species (ROS) are possible mediators of Hcy effects. We focus on mechanisms contributing to HHcy-associated oxidative stress, such as sources of ROS generation and alterations in antioxidant defense resulting from altered gene expression and post-translational modifications of proteins. Moreover, we discuss some recent findings suggesting that HHcy may have beneficial effects on mitochondrial ROS homeostasis and antioxidant defense. A better understanding of complex mechanisms through which Hcy affects mitochondrial functions could contribute to the development of more specific therapeutic strategies targeted at HHcy-associated disorders. | Homocysteine |
Historically, CGRP receptors have been classified as CGRP(1) or CGRP(2) subtypes, chiefly depending on their affinity for the antagonist CGRP(8-37). It has been shown that the complex between calcitonin receptor-like receptor (CRLR or CL) and receptor activity modifying protein (RAMP) 1 provides a molecular correlate for the CGRP(1) receptor; however, this does not explain the range of affinities seen for CGRP(8-37) in isolated tissues. It is suggested that these may largely be explained by a combination of methodological factors and CGRP-responsive receptors generated by CL and RAMP2 or RAMP3 and complexes of RAMPs with the calcitonin receptor. | Receptors, Peptide |
BACKGROUND: To describe some sociodemographic and educational characteristics of oral health technicians (OHTs) in public primary health care teams in the state of Minas Gerais, Brazil. METHODS: A cross-sectional descriptive study was performed based on the telephone survey of a representative sample comprising 231 individuals. A pre-tested instrument was used for the data collection, including questions on gender, age in years, years of work as an OHT, years since graduation as an OHT, formal schooling, individual income in a month, and participation in continuing educational programmes. The descriptive statistic was developed and the formation of clusters, by the agglomerative hierarchy technique based on the furthest neighbour, was based on the age, years of work as an OHT, time since graduation as an OHT, formal schooling, individual income in a month, and participation in continuing educational programmes. RESULTS: Most interviewees (97.1%) were female. A monthly income of USD 300.00 to 600.00 was reported by 77.5% of the sample. Having educational qualifications in excess of their role was reported by approximately 20% of the participants. The median time since graduation was six years, and half of the sample had worked for four years as an OHT. Most interviewees (67.6%) reported having participated in professional continuing educational programmes. Two different clusters were identified based on the sociodemographic and educational characteristics of the sample. CONCLUSIONS: The Brazilian OHTs in public primary health care teams in the state of Minas Gerais are mostly female who have had little time since graduation, working experience, and formal schooling sufficient for professional practice. | Dental Technicians |
The etiology of secondary retention is not well understood, but ankylosis is often considered to be an important factor in primary molars. Data concerning the mechanism of secondary retention in the permanent dentition are insufficient, although a possible role of ankylosis has been suggested. In order to analyze the frequency of occurrence and localization of ankylosis in secondarily retained permanent teeth, 26 secondarily retained molars and for comparison six normal molars were studied histologically. These data were compared with the clinical and radiographic findings. Areas of ankylosis were observed along the roots of all secondarily retained molars. In 81% of the cases these areas were located at the bifurcation and interradicular root surface. No signs of ankylosis were found in normal molars. When these results were compared with the clinical and radiographic data, it was obvious that the latter gave many false negative results, because the areas of ankylosis were often too small to be detected clinically or radiographically. | Hypercementosis |
BACKGROUND: Clinical services evaluation with specific indicators are very helpful to identify improvable points. This study was conducted to analyze the factors affecting the quality of clinical nursing services and offer practical solutions for accreditation of clinical nursing services. METHODS: The present study was conducted using Delphi method with two rounds. At the beginning of the study a questionnaire was prepared using results of another project (clinical nursing services audit). This questionnaire was sent to 47 nursing and accreditation professionals. After the first round, causes and solutions were categorized. Then participants were asked to comment on the significance of each strategy on the prepared questionnaire. RESULTS: In the first round of Delphi in response to the question about the main causes and solutions of low quality of nursing clinical services, 394 causes and 212 solutions were mentioned by the participants. In the second round, considering moralists and specialization in the selection of nursing managers, staffing according to workload and attendance in comprehensive exam after graduation and before entering clinical fields attained the most importance. CONCLUSION: Mismatch of human resources with workload and lack of clarity with regard to duties have maximum correlation with poor quality of care. Organizational structure and communication program categories gained the highest and lowest importance respectively. This information could be used by nursing managers and policy makers to plan programs in order to improve the quality of clinical nursing services. | Nursing Services |
Matrix formulations of Eudragit E 100: NE 40D polymers (100:0, 70:30, 60:40, 50:50% w/w) with 20% w/w of triacetine and 5% w/w of atenolol were prepared by film casting method with different solvents (methanol, 2-propanol and acetone). In vitro release of atenolol from the films were studied by vertical Franz diffusion cells in HEPES buffer (pH 7.4) for 78 h. Direct currents of 0.1 and 0.5 mA/cm2 were applied for 6 h to the formulations with Ag/AgCl electrodes. Also, transdermal application for the Eudragit E 100: NE 40 D (70:30% w/w) formulation was compared by iontophoresis or oleic acid (2.5% w/v) with control group on Wistar rats. As a result, the in vitro release rate of atenolol from films were increased with iontophoresis by increasing the current density (from 0.240 to 0.424 mg/cm2 for 70:3% w/w formulation) and also increased with the amount of Eudragit NE 40D (from 0.646 to 1.30 mg/cm2 at the end of 78 h). It is obtained from the in vivo studies that oleic acid provided a higher plasma and skin concentration (0.825 mg/mL and 12.5 mg/cm2, respectively) than iontophoresis treatment (0.399 mg/mL and 1.81 mg/cm2, respectively) due to the different mechanisms. However, the results showed that iontophoresis is a good alternative for enhancing the transdermal delivery of atenolol. | Triacetin |
Four cases of gastric diverticula following subtotal gastrectomy are described. This type of diverticula associated with partial gastrectomy are probably true, acquired, pulsion diverticula. In two of our patients the diverticula were associated with significant prolapse of gastric mucosa causing obstruction at the anastomosis. | Diverticulum, Stomach |
BACKGROUND: The unbranched filamentous green alga Spirogyra (Streptophyta, Zygnemataceae) is easily recognizable based on its vegetative morphology, which shows one to several spiral chloroplasts. This simple structure falsely points to a low genetic diversity: Spirogyra is commonly excluded from phylogenetic analyses because the genus is known as a long-branch taxon caused by a high evolutionary rate. RESULTS: We focused on this genetic diversity and sequenced 130 Spirogyra small subunit nuclear ribosomal DNA (SSU rDNA) strands of different origin. The resulting SSU rDNA sequences were used for phylogenetic analyses using complex evolutionary models (posterior probability, maximum likelihood, neighbor joining, and maximum parsimony methods). The sequences were between 1672 and 1779 nucleotides long. Sequence comparisons revealed 53 individual clones, but our results still support monophyly of the genus. Our data set did not contain a single slow-evolving taxon that would have been placed on a shorter branch compared to the remaining sequences. Out of 130 accessions analyzed, 72 showed a secondary loss of the 1506 group I intron, which formed a long-branched group within the genus. The phylogenetic relationship to the genus Spirotaenia was not resolved satisfactorily. The genetic distance within the genus Spirogyra exceeded the distances measured within any other genus of the remaining Zygnemataceae included in this study. CONCLUSION: Overall, we define eight distinct clades of Spirogyra, one of them including the genus Sirogonium. A large number of non-homoplasious synapomorphies (NHS; 114 NHS in total) was found for Spirogyra (41 NHS) and for each clade (totaling 73 NHS). This emphasizes the high genetic diversity of this genus and the distance to the remaining Zygnematophyceae. | Zygnematales |
The survey was carried out at one hospital to evaluate the nutrient content of the food served to and consumed by eight female patients. A weighed food intake was undertaken on the subjects chosen, over three days. Observations were also recorded regarding the nursing and catering practices relating to meals. The results showed that the food served to this group of patients was deficient in energy, folic acid, iron and vitamin D and that this group of patients failed to achieve an adequate vitamin C, protein, calcium and fibre intake. Problems also existed with the ordering and service procedure for meals, timing of meals, quantities of food delivered to the ward and procedure of patients who are eating poorly. Although the numbers in the survey were too small for statistical analysis, it was felt that the results were as representative as possible. This survey was felt to be very worthwhile and highlighted the need for all members of staff involved in the care of these patients to work together to consider ways that the patients' food intake could be improved in the future. The study, carried out by a dietitian is particularly relevant to the work of nurses in this field, as they are often the key persons affecting the patient's choice and consumption of food. | Dietary Services |
OBJECTIVE: The purpose of this study was to test the hypothesis that abnormalities in the parvalbumin-containing subclass of local circuit neurons contribute to altered gamma-aminobutyric acid (GABA) neurotransmission in the prefrontal cortex of schizophrenic subjects. METHOD: Profile counts and somal size measures were made of parvalbumin-immunoreactive neurons in areas 9, 46, and 17 from 15 matched pairs of schizophrenic and normal comparison subjects. RESULTS: No differences in relative density, laminar distribution, or somal size of labeled neurons were found in any region. CONCLUSIONS: These findings suggest that altered GABA neurotransmission in schizophrenia is due to either abnormalities in other sub-populations of prefrontal cortical GABA neurons or abnormalities in the parvalbumin-containing subclass that could not be detected in the present study. | Parvalbumins |
The hematoxylin and eosin (H&E) stained tissue section is the cornerstone of anatomical pathology diagnosis. The H&E procedure stains the nucleus and cytoplasm contrasting colors to readily differentiate cellular components. However, staining results are dependent on proper specimen processing, which involves tissue preservation, dehydration, clearing, and paraffin infiltration. While improvements in instrumentation for both tissue processing and staining have been beneficial, limitations in the chemical reagents used must always be considered. | Hematoxylin |
Imaging techniques, including magnetic, optical, acoustic and nuclear imaging, are gaining popularity as a research tool and clinical diagnostics. The advent of imaging agents-incorporated nanosystems (NSs), with sufficient contrast and high resolution, facilitates better monitoring of disease progression, targeted delivery and therapeutic process. Of note, the size of NSs remarkably affects imaging performance, while both large and small NSs enjoy respective features and superiority for imaging aspect, including penetration depth, signal-to-background ratio and spatiotemporal resolution. In this review, after a systematic summary of the basic knowledge of imaging techniques and its relation with size-tunable strategies, we further provide insights into the opportunities and challenges facing size-transformable NSs of the future for bio-imaging application and clinical translation. | Photoacoustic Techniques |
Gastropods (class Gastropoda) form the largest of the classes in the phylum Mollusca and inhabit terrestrial, fresh water and marine environments. A large number of these species are of major conservation importance and are an essential component of ecosystems. Gastropods may be deemed as pests, having a negative impact in horticulture and agriculture, whereas others may be used as a food source for human consumption and therefore are beneficial. Gastropods are susceptible to primary diseases and also act as intermediate hosts for diseases which affect other animals, including humans. The diseases described include two that are notifiable to the World Organisation for Animal Health (OIE): Xenohaliotis californiensis and Abalone viral ganglioneuritis caused by Haliotid herpesvirus-1 (HaHV-1). Research into the diseases of gastropods has often focused on those species that act as intermediate disease hosts, those that are used in research or those cultured for food. In this paper we review the viral, bacterial, fungal, parasitic and miscellaneous conditions that have been reported in gastropods and mention some of the factors that appear to predispose them to disease. The pathogenicity of a number of these conditions has not been fully ascertained and more research is needed into specifying both the etiological agent and significance in some of the diseases reported. | Host Microbial Interactions |
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