text
stringlengths 11
9.77k
| label
stringlengths 2
104
|
|---|---|
The period of palliative care is a difficult time for parents and caregivers because they are all weakened by the proximity of death. First of all, because of religious and cultural differences, parents and families cannot easily express their beliefs or the rituals they are required to develop; second, this impossibility results in conflicts between the caregiver team and the family with consequences for both. Caregivers are concerned to allow the expression of religious beliefs and cultural demands because it is assumed that they may promote the work of mourning by relating the dead child to its family and roots. However, caregivers' fear not knowing the cultural context to which the family belongs and having inappropriate words or gestures, as sometimes families dare not, cannot, or do not wish to describe their cultural background. We attempt to differentiate what relates to culture and to religion and attempt to identify areas of potential disagreement between doctors, staff, and family. Everyone has to work with the parents to open a space of freedom that is not limited by cultural and religious assumptions. The appropriation of medical anthropology concepts allows caregivers to understand simply the obligations imposed on parents by their culture and/or their religion and open access to their wishes. Sometimes help from interpreters, mediators, ethnopsychologists, and religious representatives is needed to understand this reality. | Attitude to Death |
Curiosity as a clinical entity has been a neglected subject in the psychoanalytic literature. Freud never addressed the issue of curiosity systematically. His interest was in trying to account for children's sexual questioning. Nevertheless, hinderance to internal curiosity--this is to say, that which intimidates and abates the appetite for an exploration of one's motives--is part and parcel of psychoanalytic inquiry. And, arguably, there is no greater clinical challenge for the analyst than trying to treat an analysand who appears to lack an interest in the underlying causes of his unhappiness. The problem of impeded self-inquiry is usually exacerbated in people with more serious emotional disturbances. My position here is that in studying the conditions that mitigate against curiosity in a seriously disturbed patient, we gain access to an enlarged version of the curiosity problems of our less disturbed patients. Here I interpret my clinical impressions about problems with curiosity with ideas from the writings of Martin Buber and Albert Camus. | Escape Reaction |
We had a forensic autopsy case in which drugs were detected in a cadaver that had been stored in a cold and wet condition for 5 years. The skin of the cadaver was hard, and the color was partly whitish or dark brown. Though the cadaver had transformed into adipocere in the wet and cold condition, QuEChERS extraction and LC-MS/MS revealed the presence of sulpiride and estazolam in the femoral muscle and bone marrow. The concentrations of sulpiride and estazolam in the femoral muscle were 10.6 ng/g and 39.9 ng/g, respectively. The result of a drug screening test led not only to the cause of death but also to the personal identification of the cadaver. The individual had a history of drug taking, which had been stored in his medical records at the hospital for a long time. The fact of taking sulpiride and estazolam at the same time was characteristic, and it was useful in identifying the cadaver in this case. The progress in analytical technology has made possible the detection of particle drugs from old or adipoceratous cadavers, but there have been no reports of particle drugs being detected in a cadaver that had been dead for 5 years and had transformed to adipocere, as in our present case. The analytical results by LC-MS/MS were certainly important for the diagnosis of the cause of death, and, moreover, they were useful for the purpose of personal identification. | Estazolam |
The mitochondria are the major intracellular source of reactive oxygen species (ROS), which are generated during cellular respiration. The role of peroxiredoxin (Prx) III, a 2-Cys Prx family member, in the scavenging of mitochondrial H(2)O(2) has recently been emphasized. While eliminating H(2)O(2), Prx can become overoxidized and inactivated by modifying the active cysteine into cysteine sulfinic acid (Cys-SO(2)H). When 2-Cys Prxs are inactivated in vitro, sulfiredoxin (Srx) reduces the cysteine sulfinic acid to cysteines. However, whereas Srx is localized in the cytoplasm, Prx III is present exclusively in the mitochondria. Although Srx reduces sulfinic Prx III in vitro, it remains unclear whether the reduction of Prx III in cells is actually mediated by Srx. Our gain- and loss-of-function experiments show that Srx is responsible for reducing not only sulfinic cytosolic Prxs (I and II) but also sulfinic mitochondrial Prx III. We further demonstrate that Srx translocates from the cytosol to mitochondria in response to oxidative stress. Overexpression of mitochondrion-targeted Srx promotes the regeneration of sulfinic Prx III and results in cellular resistance to apoptosis, with enhanced elimination of mitochondrial H(2)O(2) and decreased rates of mitochondrial membrane potential collapse. These results indicate that Srx plays a crucial role in the reactivation of sulfinic mitochondrial Prx III and that its mitochondrial translocation is critical in maintaining the balance between mitochondrial H(2)O(2) production and elimination. | Peroxiredoxin III |
The gastric acidity of young to elderly Japanese subjects from 1989 to 1999 was assessed and compared with that obtained in 1984, using GA-Test capsules containing acid-dissolving granules of riboflavin. The percentage of achlorhydric subjects increased with age as observed before, however, an over all decrease in all age categories year by year was noted. The percentage of achlorhydric subjects aged 50 years in 1995-1999 was about 40%, which was lower than that (60%) in 1984. However, such a chronological change was not observed when the percentage of achlorhydric subjects was determined according to birth year, indicating that it is related to the birth year of subjects. The percentage of achlorhydric subjects correlated with infection by Helicobacter pylori. Considering the high percentage of achlorhydric elderly, bioavailability and bioequivalence studies should be performed taking into consideration the effects of gastric acidity on the in vivo performance of drug products. | Achlorhydria |
Bell palsy should be suspected in patients with acute onset of unilateral facial weakness or paralysis involving the forehead in the absence of other neurologic abnormalities. The overall prognosis is good. More than two-thirds of patients with typical Bell palsy have a complete spontaneous recovery. For children and pregnant women, the rate of complete recovery is up to 90%. Bell palsy is idiopathic. Laboratory testing and imaging are not required for diagnosis. When other causes of facial weakness are being considered, laboratory testing may identify a treatable cause. An oral corticosteroid regimen (prednisone, 50 to 60 mg per day for five days followed by a five-day taper) is the first-line treatment for Bell palsy. Combination therapy with an oral corticosteroid and antiviral may reduce rates of synkinesis (misdirected regrowth of facial nerve fibers manifesting as involuntary co-contraction of certain facial muscles). Recommended antivirals include valacyclovir (1 g three times per day for seven days) or acyclovir (400 mg five times per day for 10 days). Treatment with antivirals alone is ineffective and not recommended. Physical therapy may be beneficial in patients with more severe paralysis. | Bell Palsy |
The red panda (Ailurus fulgens) is distributed primarily in the Himalayas and southern China. It is classified as a vulnerable species by the International Union for Conservation of Nature. The aim of this study was to describe the normal osteology and radiographic anatomy of the thoracic limb of the red panda. Radiography of the right thoracic limb was performed in seven captive adult red pandas. Radiographic findings were correlated with bone specimens from three adult animals. The scapula was wide craniocaudally and presented with a large area for the origin of the teres major muscle. The square-shaped major tubercle did not extend proximal to the head of the humerus. The medial epicondyle was prominent. A supracondylar foramen was present. The radial tuberosity and sesamoid bone for the abductor digiti I longus were prominent. The accessory carpal bone was directed palmarolaterally. Metacarpal bones were widely spread. The thoracic limb morphology of the red panda evidenced by osteology and radiography indicated flexibility of the thoracic limb joints and well-developed flexor and supinator muscles, which are important in arboreal quadrupedal locomotion. Knowledge gained during this study may prove useful in identifying skeletal material or remains and diagnosing musculoskeletal diseases and injuries of the thoracic limb. | Ailuridae |
We challenged six patients suffering from acute neuroleptic-induced akathisia (NIA) with intravenous benztropine (2 mg), propranolol (1 mg), and placebo (saline) using a random, double-blind cross-over design to examine the effects of the drugs on the subjective, objective, and global manifestations of NIA. Benztropine produced a significant amelioration of NIA, more apparent in its subjective component. Propranolol failed to produce a significant improvement overall in any of the akathisia measures, with only one patient showing clinical improvement. The patients demonstrated considerable placebo effect and marked variation in their responses to the drugs. | Akathisia, Drug-Induced |
MDA was indicated in the death of a 35-year-old male. Blood, tissue, and urine concentrations of MDA were measured by ultraviolet spectrophotometry after identification by gas chromatography/mass spectrometry. The concentrations found were within the range of previously reported fatal MDA levels. | Amphetamines |
OBJECTIVE: To evaluate the efficacy of gabexate mesilate (GM) in reducing surgical stress after esophagectomy. METHODS: In a prospective, randomized, clinical study, 11 patients with squamous cell carcinoma of the esophagus were randomly assigned to two groups: 5 patients were continuously administered gabexate mesilate 1.5 mg/kg per hour from the beginning of anesthesia until the third postoperative day (preop GM group); and 6 patients were administered gabexate mesilate 1.5 mg/kg per hour continuously from the end of surgery and for the same postoperative period (postop GM group). Blood samples were taken from all patients before surgery, immediately after it, and 3 days after surgery. Serum interleukin-6 (IL-6) level, tumor necrosis factor-alpha (TNF-alpha) production, and Mac-1 antigen expression of peripheral blood monocytes were measured. Clinical courses of patients in the two groups were compared. RESULTS: Time courses of serum IL-6 levels in the preop GM group were significantly lower than those in the postop GM group. Ex vivo TNF-alpha production by lipopolysaccharide (LPS) stimulated monocyte was much higher than that by monocyte without LPS stimulation. Gabexate mesilate showed a little inhibition of TNF-alpha production by monocyte without LPS stimulation. On the other hand, gabexate mesilate significantly inhibited TNF-alpha production by LPS stimulated monocyte. Mac-1 antigen expression by monocyte immediately after operation in the preop GM group was significantly lower than that in the postop GM group. Duration of systemic inflammatory response syndrome was significantly shorter in the preop GM group than in the postop GM group. CONCLUSIONS: Reduction of systemic inflammatory response syndrome duration after esophagectomy by the continuous administration of gabexate mesilate started before operation may be through the suppression of TNF-alpha production capacity and Mac-1 expression on monocytes immediately after operation, and to suppression of increase in serum IL-6 level. | Gabexate |
Life on Earth is found in a wide range of environments as long as the basic requirements of a liquid solvent, a nutrient source, and free energy are met. Previous hypotheses have speculated how extraterrestrial microbial life may function, among them that particle radiation might power living cells indirectly through radiolytic products. On Earth, so-called electrophilic organisms can harness electron flow from an extracellular cathode to build biomolecules. Here, we describe two hypothetical mechanisms, termed direct electrophy" and "indirect electrophy" or "fluorosynthesis," by which organisms could harness extracellular free electrons to synthesize organic matter, thus expanding the ensemble of potential habitats in which extraterrestrial organisms might be found in the Solar System and beyond. The first mechanism involves the direct flow of secondary electrons from particle radiation to a microbial cell to power the organism. The second involves the indirect utilization of impinging secondary electrons and a fluorescing molecule, either biotic or abiotic in origin, to drive photosynthesis. Both mechanisms involve the attenuation of an incoming particle's energy to create low-energy secondary electrons. The validity of the hypotheses is assessed through simple calculations showing the biomass density attainable from the energy supplied. Also discussed are potential survival strategies that could be used by organisms living in possible habitats with a plentiful supply of secondary electrons, such as near the surface of an icy moon. While we acknowledge that the only definitive test for the hypothesis is to collect specimens, we also describe experiments or terrestrial observations that could support or nullify the hypotheses. Key Words: Radiation-Electrophiles-Subsurface life. Astrobiology 18, 73-85." | Solar System |
The Ras/MAPK syndromes ('RASopathies') are a class of developmental disorders caused by germline mutations in 15 genes encoding proteins of the Ras/mitogen-activated protein kinase (MAPK) pathway frequently involved in cancer. Little is known about the molecular mechanisms underlying the differences in mutations of the same protein causing either cancer or RASopathies. Here, we shed light on 956 RASopathy and cancer missense mutations by combining protein network data with mutational analyses based on 3D structures. Using the protein design algorithm FoldX, we predict that most of the missense mutations with destabilising energies are in structural regions that control the activation of proteins, and only a few are predicted to compromise protein folding. We find a trend that energy changes are higher for cancer compared to RASopathy mutations. Through network modelling, we show that partly compensatory mutations in RASopathies result in only minor downstream pathway deregulation. In summary, we suggest that quantitative rather than qualitative network differences determine the phenotypic outcome of RASopathy compared to cancer mutations. | ras Proteins |
Forensic nurses are faced with unique challenges in their attempt to deliver nursing care in a custodial environment. * The impact of such challenges on the cultural dynamic of forensic nursing and consequently on healthcare delivery is largely unknown. * The aim of this ethnographic study was to explore the nursing culture within an Australian prison hospital and the migration of the culture over a 12-month period. * At the end of the study, the nursing culture was found to be one of hope, although with no clearly articulated vision of nurse-hood or patient-hood and model within which to practice nursing. * The ability to articulate practice is central to the development of mental health nursing in any context. Abstract Forensic nurses are faced with unique challenges in their attempt to deliver nursing care in a custodial environment. The impact of such challenges on the cultural dynamic of forensic nursing and consequently on healthcare delivery is largely unknown. The aim of this ethnographic study was to explore the nursing culture within an Australian prison hospital and the migration of the culture over a 12-month period. At the end of the study the nursing culture was found to be one of hope, although with no clearly articulated vision of nurse-hood or patient-hood and model within which to practice nursing. | Forensic Nursing |
Inflammatory fasciitis without infection include different entity like eosinophilic fasciitis, the syndrome of eosinophilia-myalgia after tryptophan ingestion, toxic oil syndrome, exposure to trichlorethylene, phenylketonuria skin changes, the syndrome of palmar fasciitis, fasciitis in chronic graft-versus-host disease and fasciitis secondary to an adjacence process. The diagnosis of all these scleroderma-like skin changes is sometimes not easy because the clinical and sometimes the histopathological changes are bordeline manifestations with scleroderma. The most characteristic markers for non infectious fasciitis is eosinophilia and the infiltration of the fascia with eosinophilis, but it may be unremarkable or absent, only frequently present at the onset of the disease. Anamnesis is most important to guide the diagnosis. The eosinophils, but not only, may play a major role in the pathogenesis of this entity. | Fasciitis |
Assessment and treatment of the stressors associated with major medical illness such as CHD without regard to gender overlooks women's issues in some extremely fundamental ways. To ensure that rehabilitation formats are relevant for women, more qualitative studies are needed so that women can give voice to the story of an MI recovery from a feminine perspective. It is vital to understand the psychologic contribution to the development and treatment of CHD both as described by women in their own words and as evaluated by distinctly feminine constructs. Assessment of psychosocial factors should be an essential component of a CHD diagnostic evaluation. Although little can be done about a genetic predisposition to CHD, education and personal support can help women make needed lifestyle changes to forestall further cardiac damage and to improve a woman's level of functioning. The capacity to take charge of one's life and social support are strong counterpoints to negative psychosocial symptoms of CHD. There is a strong need to make rehabilitation programs for women with CHD contextually congruent. Strategies to involve women in cardiac rehabilitation must take into account a woman's needs, providing both age-appropriate physical exercise and psychologic social support for women at times convenient to their schedules. Women must be given permission to let go of normally performed duties after a major cardiac event and to seek out what is meaningful. Group formats that offer women essential social support, an opportunity to verbally process the meaning of a life-threatening diagnosis, an opportunity to share their experiences with other women, and the ability to reconstruct a new sense of self based on feminine constructs may be as important for women as other lifestyle structural components in effective rehabilitation programs. Society must reclassify the CHD disease process as one that equally affects women. Research studies with women as primary subjects and key informants can provide needed direction in the identification of psychosocial risk factors and appropriate treatments to reduce alarming morbidity and mortality of CHD in women. More data are needed about the psychosocial mechanisms that aggravate and mediate physiologic responses in CHD in women. | Stress, Psychological |
Enhancing citizens' and communities' resilience is critical to adapt successfully to ongoing challenges faced by communities, as well as acute shocks resulting from disasters. While significant progress has been made in this area, several research and practice gaps remain. A crucial next step to advance resilience is the development of a resilience-oriented workforce. This narrative review examines existing literature to determine key components of a resilience-oriented workforce, with a focus on organizational structures, training and education, and leadership models. Reviewed articles spanned a variety of study types, including needs assessments of existing workforce, program evaluations, and reviews/commentaries. A resilience-oriented workforce spans many disciplines and training programs will need to reflect that. It requires a collaborative organizational model that promotes information sharing structures. Leadership models should foster a balance between workforce autonomy and operation as a collective entity. Optimal strategies to develop a resilience-oriented workforce have yet to be realized and future research will need to collect and synthesize data to promote and evaluate the growth of this field. | Resilience, Psychological |
Yeast killer viruses are widely distributed in nature. Several toxins encoded in double-stranded RNA (dsRNA) satellites of the L-A totivirus have been described, including K1, K2, K28, and Klus. The 4.6-kb L-A genome encodes the Gag major structural protein that forms a 39-nm icosahedral virion and Gag-Pol, a minor fusion protein. Gag-Pol has transcriptase and replicase activities responsible for maintenance of L-A (or its satellite RNAs). Recently we reported a new killer toxin, Klus. The L-A virus in Klus strains showed poor hybridization to known L-A probes, suggesting substantial differences in their sequences. Here we report the characterization of this new L-A variant named L-A-lus. At the nucleotide level, L-A and L-A-lus showed only 73% identity, a value that increases to 86% in the amino acid composition of Gag or Gag-Pol. Two regions in their genomes, however, the frameshifting region between Gag and Pol and the encapsidation signal, are 100% identical, implying the importance of these two cis signals in the virus life cycle. L-A-lus shows higher resistance than L-A to growth at high temperature or to in vivo expression of endo- or exonucleases. L-A-lus also has wider helper activity, being able to maintain not only Mlus but also M1 or a satellite RNA of L-A called X. In a screening of 31 wine strains, we found that none of them had L-A; they carried either L-A-lus or a different L-A variant in K2 strains. Our data show that distinct M killer viruses are specifically associated with L-As with different nucleotide compositions, suggesting coevolution. | Helper Viruses |
Cataract and uveitis are rare in newborns but potentially blinding. Three newborns with cataract and severe anterior uveitis underwent cataract surgery. Spiroplasma ixodetis was detected in lens aspirates using bacterial 16S-rRNA PCR and transmission electron microscopy. These findings, which suggest maternal-fetal infection, are consistent with previous experimental Spiroplasma-induced cataract and uveitis. | Entomoplasmatales |
OBJECTIVE: To describe a novel method of safe and effective intensive management of inpatient hyperglycemia with use of cost-effective protocols directed by a glucose management service (GMS). METHODS: An intravenous insulin protocol was designed to achieve a glycemic target of 80 to 110 mg/dL. When stable inpatients were transferred from the intravenous protocol to a subcutaneous insulin protocol, which consisted of basal long-acting and prandial and supplemental rapid-acting insulins, the blood glucose target was 80 to 150 mg/dL. Glucose levels were reviewed by the GMS at least daily for protocol adjustments, when necessary. RESULTS: The intravenous insulin protocol was used in 276 patients, and 4,058 capillary blood glucose levels were recorded. Glycemic target levels (80 to 110 mg/dL) were achieved, on average, 10.6 +/- 5.2 hours after initiation of insulin drip therapy. The mean capillary blood glucose level during the study interval was 135.3 +/- 49.9 mg/dL. Hypoglycemia (< or = 60 mg/dL) was recorded in 1.5% of glucose values, and hyperglycemia (> or = 400 mg/dL) was recorded in only 0.06%. The subcutaneous insulin protocol was used in 922 patients, and 18,067 capillary glucose levels were documented. The mean blood glucose level was 145.6 +/- 55.8 mg/dL during the study period. The blood glucose target of 80 to 150 mg/dL was achieved in 58.6%, whereas 74.3% of glycemic values were in the clinically acceptable range (80 to 180 mg/dL). Hypoglycemia (< or = 60 mg/dL) occurred in 1.3% of capillary blood glucose values, and hyperglycemia (> or = 400 mg/dL) occurred in 0.4% of values. CONCLUSION: Validated protocols dedicated to the achievement of strict glycemic goals were implemented by a GMS and resulted in substantial improvements in glycemic control on the surgical inpatient services, with a reduced frequency of hypoglycemia. The protocols and the GMS have been well received by the inpatient nursing and surgical staff members, and all of this has been done in a cost-effective manner." | Management Service Organizations |
This paper combines new and old data in order to offer a modified perspective of the mechanism of organophosphate-induced delayed polyneuropathy. Neuropathy target esterase (NTE) is though to be the molecular target and neuropathy to be initiated with a two-step mechanism: progressive inhibition of NTE and aging of the phosphorylated enzyme. When neuropathic organophosphates modify more than 70% of NTE in this way, neuropathy develops 2 weeks later. Other chemicals producing an inhibited NTE, which is incapable of aging, were thought to be not neuropathic. When given before a challenging dose of a neuropathic organophosphate they protect animals from neuropathy. However, recent evidence indicates that aging may not always be essential in causing neuropathy. In fact, mipafox and methamidophos as well as certain classic protective inhibitors such as carbamate and sulfonyl fluoride form an inhibited NTE which apparently does not age and yet produces neuropathy. We propose that all NTE inhibitors may have the potential to cause neuropathy. In analogy with pharmacological models of drug-receptor interactions, NTE inhibitors might have variable intrinsic activities to initiate neuropathy once attached to the protein. Strong neuropathic chemicals require about 70% inhibition of NTE, others 80-90%, and the least potent almost 100%. These differences have been amplified by means of promotion. Different levels of NTE inhibition as caused by different compounds were promoted by the same dose of phenylmethanesulfonyl fluoride to similar degrees of ataxia. Conversely nearly complete NTE inhibitions obtained in chicks with different chemicals were promoted to varying severities of ataxia. Protection from delayed polyneuropathy by the least neuropathic inhibitors can be explained by their weak intrinsic activity: occupying NTE, they prevent the binding of more neuropathic compounds. Methamidophos represents a particular example because it is protective at lower doses and neuropathic at high doses. Moreover, the levels of NTE inhibited by methamidophos which can be promoted to neuropathy are lower than those required for classic protective chemicals and higher than those of classic neuropathic OPs. This suggests that methamidophos has an intermediate position between the most and the least neuropathic NTE inhibitors. | Carboxylic Ester Hydrolases |
Acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia, is the prototype of a cancer that can be cured by differentiation therapy using combined retinoic acid (RA) and chemotherapy. Acute promyelocytic leukemia is caused by chromosomal translocations, which in the large majority of cases generate the prototypic promyelocytic leukemia-retinoic-acid receptor alpha (PML-RARalpha) an oncogenic fusion protein formed from the retinoic-acid receptor alpha and the so-called PML protein. The fusion protein leads to the deregulation of wild type PML and RARalpha function, thus inducing the differentiation block and an altered survival capacity of promyelocytes of affected patients. A plethora of studies have revealed molecular details that account for the oncogenic properties of acute promyelocytic leukemia fusion proteins and the events that contribute to the therapy-induced differentiation and apoptosis of patients' blasts. Illustrating the beneficial mechanisms of action of retinoids for acute promyelocytic leukemia patients this review goes on to discuss a plethora of recently recognized molecular paradigms by which retinoids and rexinoids, alone or in combination with other compounds, regulate growth, differentiation and apoptosis also in non-acute promyelocytic leukemia cells, highlighting their potential as drugs for cancer therapy and prevention. | Retinoids |
Invariant natural killer T (iNKT) cells are innate-like T lymphocytes cells that recognize glycolipid antigens associated with CD1d, non-classical antigen presenting proteins. They can drive either pro-inflammatory (Th-1) or anti-inflammatory (Th-2) immune microenvironment through the production of both Th-1 and Th-2 type cytokines upon activation, thus play a vital role in cancer, infection, and autoimmune diseases. Adoptive cell therapy using ex vivo expanded iNKT cells is a promising approach to enhance anti-tumor immunity or immunosuppression. However, overcoming phenotypic and functional heterogeneity and promoting in vivo persistency of iNKT cells remains to be a challenge. Here, we compared various methods for ex vivo expansion of human iNKT cells and assessed the quality of expansion, phenotype, and cytokine production profile of expanded iNKT cells. While a direct stimulation of iNKT cells in peripheral blood mononuclear cells with agonist glycolipid led to the expansion of iNKT cells in varying degrees, stimulation of enriched iNKT cells by irradiated autologous peripheral blood mononuclear cells or allogeneic dendritic cells resulted in consistent expansion of highly pure iNKT cells. Interestingly, the mode of antigenic stimulation influenced the dominant subtype of expanded iNKT cells. Further, we evaluated whether additional IL-7 or IL-15 during antigenic stimulation with allogeneic dendritic cells can improve the phenotypic heterogeneity and modify cytokine production profile of iNKT cells expanded from 18 consecutive donors. The presence of IL-7 or IL-15 during antigenic stimulation did not affect the fold of expansion or purity of expanded iNKT cells. However, IL-7, but not IL-15, led to a better expansion of CD4(+) iNKT cells, enhanced Th-2 type cytokine production of CD4(+) iNKT cells, and maintained the expansion of central memory (CD45RA(-)CD62L(+)) CD4(+) iNKT cells. Our results suggest the addition of IL-7 during antigenic stimulation with allogeneic dendritic cells can promote the expansion of CD62L(+)Th-2(+)CD4(+) human iNKT cells that can be used as novel immunotherapeutic to control excessive inflammation to treat various autoimmune diseases. | Allogeneic Cells |
Stem cells have received a great deal of interest from the research community as potential therapeutic tools" for a variety of chronic debilitating diseases that lack clinically effective therapies. Stem cells are also of interest for the regeneration of tooth-supporting tissues that have been lost to periodontal disease. Indeed, substantial data have demonstrated that the exogenous administration of stem cells or their derivatives in preclinical animal models of periodontal defects can restore damaged tissues to their original form and function. As we discuss here, however, considerable hurdles must be overcome before these findings can be responsibly translated to novel clinical therapies. Generally, the application of stem cells for periodontal therapy in clinics will not be realized until the best cell(s) to use, the optimal dose, and an effective mode of administration are identified. In particular, we need to better understand the mechanisms of action of stem cells after transplantation in the periodontium and to learn how to preciously control stem cell fates in the pathological environment around a tooth. From a translational perspective, we outline the challenges that may vary across preclinical models for the evaluation of stem cell therapy in situations that require periodontal reconstruction and the safety issues that are related to clinical applications of human stem cells. Although clinical trials that use autologous periodontal ligament stem cells have been approved and have already been initiated, proper consideration of the technical, safety, and regulatory concerns may facilitate, rather than inhibit, the clinical translation of new therapies." | Periodontium |
Isolate RS1(T) isolated from used metalworking fluid was found to be a Gram-negative, motile, and non-spore forming rod. Based on phylogenetic analyses with 16S rRNA, isolate RS1(T) was placed into the mendocina sublineage of Pseudomonas. The major whole cell fatty acids were C(18:1)omega7c (32.6%), C(16:0) (25.5%), and C(15:0) ISO 2OH/C(16:1)omega7c (14.4%). The sequence similarities of isolate RS1(T) based on gyrB and rpoD genes were 98.9 and 98.0% with Pseudomonas pseudoalcaligenes, and 98.5 and 98.1% with Pseudomonas oleovorans, respectively. The ribotyping pattern showed a 0.60 similarity with P. oleovorans ATCC 8062(T) and 0.63 with P. pseudoalcaligenes ATCC17440(T). The DNA G + C content of isolate RS1(T) was 62.2 mol.%. The DNA-DNA relatedness was 73.0% with P. oleovorans ATCC 8062(T) and 79.1% with P. pseudoalcaligenes ATCC 17440(T). On the basis of morphological, biochemical, and molecular studies, isolate RS1(T) is considered to represent a new subspecies of P. oleovorans. Furthermore, based on the DNA-DNA relatedness (>70%), chemotaxonomic, and molecular profile, P. pseudoalcaligenes ATCC 17440(T) and P. oleovorans ATCC 8062(T) should be united under the same name; according to the rules of priority, P. oleovorans, the first described species, is the earlier synonym and P. pseudoalcaligenes is the later synonym. As a consequence, the division of the species P. oleovorans into two novel subspecies is proposed: P. oleovorans subsp. oleovorans subsp. nov. (type strain ATCC 8062(T) = DSM 1045(T) = NCIB 6576(T)), P. oleovorans subsp. lubricantis subsp. nov. (type strain RS1(T) = ATCC BAA-1494(T) = DSM 21016(T)). | Pseudomonas oleovorans |
In recent years hospitals have been creating materials management departments to effect cost controls and to increase efficiency. In some instances, it has been suggested that responsibility for maintenance of drug inventories should be shifted from the director of pharmacy to the director of materials management. Legal aspects of this shift in responsibility may preclude such changes. The Joint Commission on Accreditation of Hospitals' Standards clearly state that this responsibility is to rest with the pharmacy service. State law may also bear on the issue. Both state pharmacy acts and board of pharmacy regulations may contain provisions which are relevant to the issue. Pennsylvania law is used as an example of the points to be evaluated when considering the question. Clearly, this responsibility must continue to fall within the jurisdiction of the director of pharmacy." | Materials Management, Hospital |
Captive baboons of three age groups were experimentally infected with Herpesvirus SA 8-strain 0430. Intravenous inoculation of the virus induced minor, transient, interstitial pneumonia of a nonspecific type in newborn baboons. Intratracheal inoculation, in contrast, invariably produced multifocal or diffuse necrotizing inclusion body bronchopneumonia within two days in newborn, two months and one year old baboons. Differences in the outcome of the experimental intratracheal infections were noticed, depending on the animals age. All the newborns either died from the extensive pulmonary damage or had to be sacrificed because of serious illness. Older animals, in contrast, survived the initial impact with only minor clinical symptoms and repair of the necrotic and inflammatory lesions. The healing stages were characterized by interstitial fibrosis and transient tumorlike bronchial and bronchiolar epithelial proliferations, which lasted for approximately two months. Intranuclear inclusion bodies in ganglionic cells, ganglioneuritis and neuritis in different parts of the pulmonary plexus in intratracheally infected animals suggested the viral invasion of the pulmonary autonomous nervous system. | Bronchopneumonia |
Retroviruses package their genome as RNA dimers linked together primarily by base-pairing between palindromic stem-loop (psl) sequences at the 5' end of genomic RNA. Retroviral RNA dimers usually melt in the range of 55 degrees C-70 degrees C. However, RNA dimers from virions of the feline endogenous gammaretrovirus RD114 were reported to melt only at 87 degrees C. We here report that the high thermal stability of RD114 RNA dimers generated from in vitro synthesized RNA is an effect of multiple dimerization sites located in the 5' region from the R region to sequences downstream from the splice donor (SD) site. By antisense oligonucleotide probing we were able to map at least five dimerization sites. Computational prediction revealed a possibility to form stems with autocomplementary loops for all of the mapped dimerization sites. Three of them were located upstream of the SD site. Mutant analysis supported a role of all five loop sequences in the formation and thermal stability of RNA dimers. Four of the five psls were also predicted in the RNA of two baboon endogenous retroviruses proposed to be ancestors of RD114. RNA fragments of the 5' R region or prolonged further downstream could be efficiently dimerized in vitro. However, this was not the case for the 3' R region linked to upstream U3 sequences, suggesting a specific mechanism of negative regulation of dimerization at the 3' end of the genome, possibly explained by a long double-stranded RNA region at the U3-R border. Altogether, these data point to determinants of the high thermostability of the dimer linkage structure of the RD114 genome and reveal differences from other retroviruses. | Gammaretrovirus |
The present study examines postoperative pain experience following 243 gingivectomies in Norwegian patients using possible combinations of 3 local anaesthetics (lidocaine-adrenalin, prilocaine-felypressin or mepivacaine) and 3 periodontal dressings (Coe-pak, Wondrpak or Nobetec). When Coe-pak was used, the mean pain score was higher (P less than 0.05) in the group treated with lidocaine-adrenalin 4 to 6 h after gingivectomy than the groups treated with prilocaine-felypressin or mepivacaine. There was no significant difference between the groups treated with prilocaine-felypressin or mepivacaine. When Wondrpak or Nobetec were used, there was no significant difference between any of the local anaesthetics used. The present finding shows that the local anaesthetic combination of lidocaine-adrenalin (1:80,000) gives rise to a higher mean postoperative pain experience after gingivectomy than prilocaine-felypressin or mepivacaine. However, the relative difference in pain experience seen after gingivectomy when using the present local anaesthetic agents is masked when using an eugenol-containing periodontal dressing. Thus, the higher pain experience reported after lidocaine-adrenalin may only be clinically important when using periodontal dressings without local anaesthetic components such as eugenol. | Gingivectomy |
tRNA genes are transcribed as precursors and RNase P generates the matured 5' end of tRNAs. It has been suggested that residue - 1 (the residue immediately 5' of the scissile bond) in the pre-tRNA interacts with the well-conserved bacterial RNase P RNA (RPR) residue A(248) (Escherichia coli numbering). The way A(248) interacts with residue - 1 is not clear. To gain insight into the role of A(248), we analyzed cleavage as a function of A(248) substitutions and N(-1) nucleobase identity by using pre-tRNA and three model substrates. Our findings are consistent with a model where the structural topology of the active site varies and depends on the identity of the nucleobases at, and in proximity to, the cleavage site and their potential to interact. This leads to positioning of Mg(2+) that activates the water that acts as the nucleophile resulting in efficient and correct cleavage. We propose that in addition to be involved in anchoring the substrate the role of A(248) is to exclude bulk water from access to the amino acid acceptor stem, thereby preventing non-specific hydrolysis of the pre-tRNA. Finally, base stacking is discussed as a way to protect functionally important base-pairing interactions from non-specific hydrolysis, thereby ensuring high fidelity during RNA processing and the decoding of mRNA. | Ribonuclease P |
The availability of complete fungal genomes is expanding rapidly and is offering an extensive and accurate view of this kingdom." The scientific milestone of free access to more than 1000 fungal genomes of different species was reached, and new and stimulating projects have meanwhile been released. The "1000 Fungal Genomes Project" represents one of the largest sequencing initiative regarding fungal organisms trying to fill some gaps on fungal genomics. Presently, there are 329 fungal families with at least one representative genome sequenced, but there is still a large number of fungal families without a single sequenced genome. In addition, additional sequencing projects helped to understand the genetic diversity within some fungal species. The availability of multiple genomes per species allows to support taxonomic organization, brings new insights for fungal evolution in short-time scales, clarifies geographical and dispersion patterns, elucidates outbreaks and transmission routes, among other objectives. Genotyping methodologies analyze only a small fraction of an individual's genome but facilitate the comparison of hundreds or thousands of isolates in a small fraction of the time and at low cost. The integration of whole genome strategies and improved genotyping panels targeting specific and relevant SNPs and/or repeated regions can represent fast and practical strategies for studying local, regional, and global epidemiology of fungi." | Mycological Typing Techniques |
The study of muscle reinnervation has been difficult because of lack of an accurate, reproducible method to monitor return of function. Visual assessment relies on subjective interpretation. Histology provides anatomic, not functional, information. Electromyography and anatomic tracing have been most effective in evaluating physiologic return of muscle function. It has been difficult to assess the timing of functional return electromyographically because measurements are intermittent and electrode placement varies. A method was designed to allow long-term monitoring of electromyographic (EMG) activity in the facial musculature of the rabbit. Sixteen rabbits were monitored for at least 1 month or until return of normal EMG activity was identified. Various levels of injury (nerve crush, transection without repair, and transection with immediate end-to-end anastomosis) were evaluated. EMG evidence of reinnervation was seen in all animals with nerve crush injuries as well as those with anastomoses. Physiologic continuity of the nerves was then evaluated by retrograde transport of horseradish peroxidase. All muscles showing return of EMG activity had uptake of HRP into the appropriate brain stem motor neurons. The denervated muscles showed no HRP uptake. The information gained in this study shows potential for use of this technique in comparing functional return of muscle activity between different reinnervation methods. | Nerve Crush |
Expression of various membrane receptors on human eosinophils for immunoglobulin, complement, certain cytokines and chemotaxis factors, and adherence molecules as well as CD4 and class II major histocompatibility complex antigens has led to a reconsideration of the role of the eosinophil in the immune response. Eosinophils are able to present antigen and become infected by HIV. Eosinophils are not to only source of cytotoxic and proinflammatory mediators but can also release different cytokines and growth factors including their own differentiation factors. The recent demonstration that eosinophils can express IgE-binding molecules belonging to different multigenic families as well as two different IgA receptors which participate equally to the protective and to the pathological inflammatory responses reinforces the concept of a dual functionality for the eosinophil. | Eosinophils |
Clozapine is the only antipsychotic that is effective in treatment-resistant schizophrenia. However, in certain clinical situations, such as the emergence of serious adverse effects, it is necessary to discontinue clozapine. Stopping clozapine treatment poses a particular challenge due to the risk of psychotic relapse, as well as the development of withdrawal symptoms. Despite these challenges for the clinician, there is currently no formal guidance on how to safely to discontinue clozapine. We assessed the feasibility of developing evidence-based recommendations for (1) minimizing the risk of withdrawal symptoms, (2) managing withdrawal phenomena, and (3) commencing alternatives treatment when clozapine is discontinued. We then evaluated the recommendations against the Appraisal of Guidelines for Research and Evaluation (AGREE) II criteria. We produced 19 recommendations. The majority of these recommendation were evidence-based, although the strength of some recommendations was limited by a reliance of studies of medium to low quality. We discuss next steps in the refinement and validation of an evidence-based guideline for stopping clozapine and identify key outstanding questions. | Drug Substitution |
The widely accepted model for tumor necrosis factor 1 (TNFR1) signaling is that ligand binding causes receptor trimerization, which triggers a reorganization of cytosolic domains and thus initiates intracellular signaling. This model of stoichiometrically driven receptor activation does not account for the occurrence of ligand independent signaling in overexpressed systems, nor does it explain the constitutive activity of the R92Q mutant associated with TRAPS. More recently, ligand binding has been shown to result in the formation of high molecular weight, oligomeric networks. Although the dimer, shown to be the preligand structure, is thought to remain present within ligand-receptor networks, it is unknown whether network formation or ligand-induced structural change to the dimer itself is the trigger for TNFR1 signaling. In the present study, we investigate the available crystal structures of TNFR1 to explore backbone dynamics and infer conformational transitions associated with ligand binding. Using normal-mode analysis, we characterize the dynamic coupling between the TNFR1 ligand binding and membrane proximal domains and suggest a mechanism for ligand-induced activation. Furthermore, our data are supported experimentally by FRET showing that the constitutively active R92Q mutant adopts an altered conformation compared to wild-type. Collectively, our results suggest that the signaling competent architecture is the receptor dimer and that ligand binding modifies domain mobilities intrinsic to the receptor structure, allowing it to sample a separate, active conformation mediated by network formation." | Receptors, Tumor Necrosis Factor, Type I |
Large-scale single-cell arrays are urgently required for current high-throughput screening of cell function and heterogeneity. However, the rapid and convenient generation of large-scale single-cell array in a multiplex and universal manner is not yet well established. In this paper, we report a simple and reliable method for the generation of a single-cell array by combining pneumatic microvalve arrays (PmuVAs) and hydrodynamic single-cell trapping sites in a single microfluidic device. The PmuVAs, which can be precisely controlled by actuated pressures, were designed to guide multiple types of cells being trapped in the corresponding single-cell trapping sites located in the fluidic channel. According to the theoretical demonstration and computational simulation, we successfully realized a multiplex single-cell array with three different types of cells by a step-by-step protocol. Furthermore, the analysis of cellular esterase heterogeneity of the three types of cells was concurrently implemented in the device as a proof-of-concept experiment. All the results demonstrated that the method developed in the current study could be applied for the generation of large-scale single-cell array with multiple cell types, which would be also promising and helpful for single-cell-based high-throughput drug test, multipurpose immunosensor and clinical diagnosis. | Esterases |
Over the years, many antibodies have been successfully generated to treat patients with life-threatening diseases, most notably cancer. While the first generation of antibodies, originating from mice, caused severe side effects and were relatively inefficient, technological advances have made it possible to obtain fully human antibodies for therapeutic use. 'Heavy-chain only' antibodies have recently been discovered in the blood of camelids. Because of their size, the antigen-binding units of these antibodies comprising only a single Ig fold are called Nanobodies. These antibody fragments have several remarkable features that make them ideal candidates as next-generation cancer therapeutics. Particularly appealing is their ability to simultaneously inhibit various crucial growth factor receptors or their ligands with a single molecule. In addition, they are easy to clone and express on the tip of filamentous phage, which opens the possibility to select for Nanobodies inducing particular biological effects. Nanobodies have potential to become important cancer therapeutics in the near future, displaying unequalled and unprecedented efficacies in treatment. | Immunoglobulin Heavy Chains |
1. DNA synthesis was determined at midnight and noon in mammary tissue from 13-day pregnant mice (C3H, C57B110 and BALB/c) and 14-day pregnant golden hamsters and Sprague-Dawley rats. 2. Mammary tissue from the hamster and the three mouse strains had elevated DNA synthesis at midnight compared with noon. 3. In contrast, DNA synthesis in mammary tissue from the rat was not different at these two time periods. | Rodentia |
N,N',N -triethylenethiophosphoramide (thioTEPA) is a trifunctional alkylating agent with a broad spectrum of antitumour activity developed in the 1950s. The drug is now experiencing renewed interest as it appears to be one of the most effective anticancer drugs in high dose regimens. Despite many years of experience with thioTEPA, pharmacologic data are incomplete and controversy remains with respect to the dose-dependent pharmacokinetics of thioTEPA. In recent years greater insight has been obtained into the metabolism of thioTEPA, but there is still a gap between the total urinary excretion of thioTEPA and metabolites and the alkylating activity. In vivo and in vitro studies show that alkylation of DNA by thioTEPA can follow two pathways, but it remains unclear which pathway represents the precise mechanism of action. The currently available sensitive analytical methods for thioTEPA and its metabolites can be used to elucidate the many questions that still exist even so many years after its introduction. An overview is given of the chemistry, pharmacology, clinical use and toxicity of thioTEPA as well as its pharmacokinetics and analytical methods for thioTEPA and its metabolites." | Triethylenephosphoramide |
BACKGROUND: We have previously shown that essential hypertension in humans and spontaneously hypertensive rats (SHR), is associated with increased levels of ceramide and marked alterations in sphingolipid biology. Pharmacological elevation of ceramide in isolated carotid arteries of SHR leads to vasoconstriction via a calcium-independent phospholipase A(2), cyclooxygenase-1 and thromboxane synthase-dependent release of thromboxane A(2). This phenomenon is almost absent in vessels from normotensive Wistar Kyoto (WKY) rats. Here we investigated whether lowering of blood pressure can reverse elevated ceramide levels and reduce ceramide-mediated contractions in SHR. METHODS AND FINDINGS: For this purpose SHR were treated for 4 weeks with the angiotensin II type 1 receptor antagonist losartan or the vasodilator hydralazine. Both drugs decreased blood pressure equally (SBP untreated SHR: 191+/-7 mmHg, losartan: 125+/-5 mmHg and hydralazine: 113+/-14 mmHg). The blood pressure lowering was associated with a 20-25% reduction in vascular ceramide levels and improved endothelial function of isolated carotid arteries in both groups. Interestingly, losartan, but not hydralazine treatment, markedly reduced sphingomyelinase-induced contractions. While both drugs lowered cyclooxygenase-1 expression, only losartan and not hydralazine, reduced the endothelial expression of calcium-independent phospholipase A(2). The latter finding may explain the effect of losartan treatment on sphingomyelinase-induced vascular contraction. CONCLUSION: In summary, this study corroborates the importance of sphingolipid biology in blood pressure control and specifically shows that blood pressure lowering reduces vascular ceramide levels in SHR and that losartan treatment, but not blood pressure lowering per se, reduces ceramide-mediated arterial contractions. | Group VI Phospholipases A2 |
Genetic information plays a pivotal role in species recognition and delimitation, but rare or extinct animals can be difficult to obtain genetic samples from. While natural history wet collections have proven invaluable in the description of novel species, the use of these historical samples in genetic studies has been greatly impeded by DNA degradation, especially because of formalin-fixation prior to preservation. Here, we use recently developed museum genomics approaches to determine the status of an isolated population of the elapid snake genus Hemachatus from Zimbabwe. We used multiple digestion phases followed by single strand sequencing library construction and hybridisation capture to obtain 12S and 16S rDNA sequences from a poorly preserved tissue sample of this population. Phylogenetic and morphological analyses in an integrated taxonomic framework demonstrate that the Zimbabwean rinkhals population represents an old and highly distinct lineage, which we describe as a new species, Hemachatus nyangensis sp. nov. Our phylogenetic dating analysis is compatible with venom spitting having evolved in response to the threat posed by early hominins, although more data are required for a robust test of this hypothesis. This description demonstrates the power of museum genomics in revealing rare or even extinct species: Hemachatus from Zimbabwe are only known from a small area of the Eastern Highlands known for high endemism. No living specimens have been seen since the 1980s, most likely due to dramatic land-use changes in the Eastern Highlands, suggesting that the species could be extinct. In view of its recognition as a highly distinct lineage, urgent action is required to determine whether any populations survive, and to safeguard remaining habitat. | Hemachatus |
A male baby with bilateral cryptophthalmos without eyebrows, distorted anterior hairline, bifid nasal tip, low-set ears, hypertelorism and low anorectal anomaly who was phenotypically diagnosed with Manitoba oculo-tricho-anal syndrome (mutation in FREM1 gene) had an overlapping genotypic diagnosis of autosomal recessive Fraser syndrome 2 because of the presence of a closely related mutation in FREM2 This heterozygous variant was likely to be sporadic. Another mutation was identified in the CEP85L gene indicating lissencephaly 10. This genetic condition has abnormal gyri pattern in the occiput area. This form of lissencephaly is characterised by phenotypic heterogeneity whereby some patients have only mild mental retardation, while others have a very complex clinical picture.In conclusion, this rare condition with the overlap of genetics between several conditions highlights the need for genetic testing even in an low middle income country (LMIC). | Fraser Syndrome |
Pyloric atresia (PA) is a rare congenital anomaly that constitutes approximately 1% of all intestinal atresias, and its incidence is approximately 1 in 100,000 live births. PA may occur as an isolated condition or associated with other abnormalities, the most common being Junctional epidermolysis bullosa (JEB). Evidence suggests that PA-EB (Pyloric Atresia - Epidermolysis Bullosa) Syndrome is a distinct entity. In this report, we present three cases of pyloric atresia, one of which was associated with Junctional epidermolysis bullosa. The literature on the subject is also reviewed. | Pylorus |
BACKGROUND: To investigate whether combining 0.01% atropine with orthokeratology (AOK) has a better effect in retarding axial elongation, compared with orthokeratology alone (OK) over two years. METHODS: A total of 96 Chinese children aged six to < 11 years with myopia (1.00 - 4.00 D, inclusive) were randomized into either the AOK or OK group in a 1:1 ratio. Axial length (the primary outcome), and secondary outcomes (e.g. pupil size and choroidal thickness) were measured at 1-month and at 6-monthly intervals after commencement of treatment. RESULTS: Both intention-to-treat and per-protocol analyses showed significantly slower axial elongation in the AOK group than OK group over two years (P = 0.008, P < 0.001, respectively). AOK subjects had statistically slower axial elongation (adjusted mean [standard error], 0.17 [0.03] mm vs 0.34 [0.03] mm, P < 0.001), larger increase in mesopic (0.70 [0.09] mm vs 0.31 [0.09] mm, P = 0.003) and photopic pupil size (0.78 [0.07] mm vs 0.23 [0.07] mm, P < 0.001), and greater thickening of the choroid (22.6 [3.5] microm vs -9.0 [3.5] microm, P < 0.001) than OK subjects over two years. Except for a higher incidence of photophobia in the AOK group (P = 0.006), there were no differences in the incidence of any other symptom or adverse events between the two groups. Slower axial elongation was associated with a larger increase in the photopic pupil size and a greater thickening in the choroid in the AOK group. CONCLUSIONS: Slower axial elongation following 2-year AOK treatment may result from increased pupil dilation and a thickening in the choroid observed in the AOK group. | Orthokeratologic Procedures |
Indigo Snakes (genus Drymarchon) occur from northern Argentina northward into to the United States, where they inhabit southern Texas and disjunct populations in Mississippi, Florida and Georgia. Based on allopatry and morphological differences Collins (1991) hypothesized that the two United States taxa-the Western Indigo Snake, D. melanurus erebennus (Cope, 1860), and the Eastern Indigo Snake, D. couperi (Holbrook, 1842)-deserved full species recognition. Building upon this hypothesis with molecular and morphological analyses we illustrate that D. couperi is split into two distinct lineages. Based on the General Lineage Concept of Species, we describe the lineage that occurs along the Gulf coast of Florida and Mississippi as a new species, Drymarchon kolpobasileus. The new species is distinguished from D. couperi by a suite of morphological features, including a shorter and shallower head, deeper and shorter 7(th) infralabial scales, and shorter temporal scales. Overall, the presence of a deep 7(th) infralabial scale provides the best univariate identifier of D. kolpobasileus sp. nov. This study illustrates the usefulness of using both morphological and genetic data in refining accurate descriptions of geographical distributions. | Colubridae |
Three years ago, scientists reported that CRISPR technology can enable precise and efficient genome editing in living eukaryotic cells. Since then, the method has taken the scientific community by storm, with thousands of labs using it for applications from biomedicine to agriculture. Yet, the preceding 20-year journey--the discovery of a strange microbial repeat sequence; its recognition as an adaptive immune system; its biological characterization; and its repurposing for genome engineering--remains little known. This Perspective aims to fill in this backstory--the history of ideas and the stories of pioneers--and draw lessons about the remarkable ecosystem underlying scientific discovery. | Haloferax mediterranei |
Natural melanin features many interesting properties, including the ability to shield electromagnetic radiation, the ability to act as scavenger for radical and reactive oxygen species and the capacity to chelate different metal ions. For these reasons, melanin is becoming increasingly relevant for the development of functional materials with potential applications in cosmetics, drug delivery, and water purification. However, the extraction and purification of melanin from conventional sources (e.g., sepia ink, hair, and wool) is inefficient and not easily scalable, hence diverting its technological applications. Some fungal species, especially wood-decay basidiomycetes, can be regarded as promising sources of melanin. In the present study, we screened different fungi in regard to their melanin-biosynthesis abilities using l-tyrosine as a precursor, and we found that an Armillaria cepistipes strain (Empa 655) produced the highest yield of melanin (27.98 g L(-1)). Physicochemical characterization of the obtained fungal melanin revealed a typical eumelanin structure. The method for the biosynthesis of fungal melanin we propose is efficient, scalable, and sustainable and has the potential to provide support for further technological exploitation. | Melanins |
Pressurised liquid extraction (PLE) was used to extract DDT [1,1,1,-trichloro-2,2-bis(p-chlorophenyl)ethane] and its metabolites, DDD [1,1-dichloro-2,2-bis(p-chlorophenyl)ethane] and DDE [1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene] from an aged, contaminated soil. Using three sequential static phases, PLE removed an equivalent quantity of DDT and its metabolites as Soxhlet extraction, in less time and with less solvent. Recovery was almost quantitative, implying appropriate sample work-up and manipulation." | Dichlorodiphenyldichloroethane |
OBJECTIVES: To study the occurrence of cords accident (nuchal cords, prolapse, and braces) after external cephalic version according to its failure or success. METHODS: Retrospective study between 1998-2015 comparing in the cord accident diagnosed at delivery (by midwife or doctors according to mode of delivery): Patients with attempt ECV: Group 1 cephalic presentation after successful ECV with trial of labor, and Group 2 failed ECV followed by elective cesarean or trial of labor. Patients with no attempt ECV Group 3 spontaneous cephalic presentation matching for delivery date, maternal age, parity, body mass index, and delivery history with group 1, Group 4 Breech presentation without attempt ECV with trial of labor. RESULTS: A total of 776 women with breech presentation were included (198 in group 1, 446 in group 2, 396 in group 3 and 118 in group 4). The prevalence of cord accident did not differ according to ECV attempt (17.08 % versus 18.9 %), to cephalic presentation (group 1: 24.7 % versus group 3: 25 %) and to breech presentation (group 2: 16.9 % versus group 4: 17.2 %). The trial of labor after failed ECV did not increase the risk of cord accident when compared with elective cesarean (17.4 % versus 16 %). A prolapse cord was only observed after trial of labor, i.e. in groups 1, 2 and 4 without difference (respectively 1, 0.8 and 1.7 %). In each group, the rate of cesarean was not different according to the presence of nuchal cord. CONCLUSION: Success or failed External cephalic version is not associated with an increased risk of cord accident. | Nuchal Cord |
Darier-White disease is a relatively common autosomal dominant genodermatosis caused by mutation in the ATP2A2 gene. It is characterized by multiple warty papules coalescing into plaques in the seborrheic areas and by specific histological skin changes. Palm and sole involvement in Darier-White disease is usually mild, mainly featuring discrete and small keratotic papules. We present a unique case of Darier-White disease presenting with a diffuse, mutilating hystrix-like palmoplantar keratoderma. | Keratoderma, Palmoplantar |
OBJECTIVE: To conduct a systematic review and meta-analysis of the effects of preload/meal energy density on energy intake in a subsequent meal(s). METHODS: Multiple databases were searched for studies published through December 2016 on the effects of preload/meal energy density on energy intake in a subsequent meal(s). We extracted information on mean energy intake in a subsequent meal(s) and on variables that could contribute to between-subject heterogeneity. RESULTS: Forty and Thirty nine eligible studies were identified for our systematic review and meta-analysis, respectively. The meta-analysis showed that preload/meal energy density did not affect energy intake in a subsequent meal(s) (95% CI:-21.21, 21.29). As heterogeneity was remarkable among studies, we stratified the studies by intervention type into meal" or "preload" classifications. In the "preload" subgroup, studies used either fixed energy or fixed weight preloads. The results reveal that in comparison to a high energy-dense (HED) preload, consuming a low energy-dense (LED) preload with same weight resulted in higher energy intake in a subsequent meal (95% CI: 9.72, 56.19). On the other hand, decreased energy intake was observed after consuming an LED preload compared to after consumption of an HED preload with same energy content (95% CI: -138.71, -57.33). In the "meal" subgroup, studies were categorized by different subsequent meal (i.e., "afternoon or evening", "lunch" and "dinner or post-dinner"). Meta-analysis showed that an LED meal resulted in more energy intake only in afternoon or evening meals (95% CI: 14.82, 31.22). CONCLUSION: In summary, the current analysis revealed that we can restrict the energy intake by consuming an LED preload. Moreover, consuming an LED preload could favorably affect preload+meal energy intake." | Energy Intake |
The His-Asp phosphorelay signal transduction system has been identified in most organisms, including bacteria, yeasts, fungi, and plants, except for animals. This system is important in adaptation to stress, control of cell growth, and induction of development in response to environmental changes. On the basis of genomic information, it has been found that Aspergillus nidulans, a model species of fungi, includes 15 histidine kinases (HKs), one histidine-containing phosphotransmitter protein (HPt), and four response regulators (RRs) as factors related to the signal transduction system. In this review, it is explain that the His-Asp phosphorelay system is important in controlling cell growth (responses to fungicides, the induction of asexual and sexual development, and so on) under different growth conditions with reference to A. nidulans. | Aspergillus nidulans |
In this work, a wild-type T4 bacteriophage based micro electrochemical sensor (T4B-MES) was developed for specific and sensitive detection of viable pathogenic bacteria. Recently, bacteriophage has been widely applied as recognition elements for bacteria detection due to its low cost, high stability and specificity. Firstly, a systematic study was proposed in this paper to investigate the synergy of externally applied electric field and chemical functionalization on phage immobilization, involving several key factors such as Debye length. According to our experiments, the capture efficiency of the deposited phages had reached the maximum when the Debye length was comparable to the phage size. With the optimized immobilization protocol, the sensitivity of the T4B-MES was then determined with Differential Pulse Voltammetry (DPV), providing a quite low detection limit of 14 +/- 5 cfu/mL and a wide dynamic range of 1.9 x 10(1)-1.9 x 10(8) cfu/mL. In addition, the T4B-MES demonstrated the ability to distinguish viable and dead bacteria cells with high specificity, making it a promising solution in a variety of applications, e.g., water quality monitoring. | Bacteriophage T4 |
Although HBV has the potential to generate an almost limitless spectrum of quasispecies during chronic infection, the viability of the majority of these quasispecies is almost certainly impaired due to constraints imposed by the remarkably compact organization of the HBV genome. On the other hand, single mutations may affect more than one gene and result in complex and unpredictable effects on viral phenotype. Better understanding of the constraints imposed by gene overlap and of genotype-phenotype relationships should help in the development of improved antiviral strategies and management approaches. Although the probability of developing viral resistance is directly proportional to the intensity of selection pressure and the diversity of quasispecies, potent inhibition of HBV replication should be able to prevent development of drug resistance because mutagenesis is replication dependent. If viral replication can be suppressed for a sufficient length of time, viral load should decline to a point where the continued production of quasispecies with the potential to resist new drug treatments no longer occurs. Clinical application of this concept will require optimization of combination therapies analogous to highly active antiretroviral therapy (HAART) for HIV infection. Total cure of hepatitis B will require elimination of the intranuclear pool of viral minichromosomes, which will probably only be achieved by normal cell turnover, reactivation of host immunity, or elucidation of the antiviral mechanisms operating during cytokine clearance in acute hepatitis B (see Fig. 1). | Orthohepadnavirus |
Secreted phospholipase A2 (sPLA2) molecules constitute a family of proteins that are involved functionally in many biological processes. In particular, they participate in diverse pathophysiological settings as enzymes that release free fatty acids and lysophospholipids from phospholipids in biological membranes, or as ligands for various cellular receptors. In this review the confirmed or expected functions of sPLA2s in the mammalian immune system are surveyed. Some of the twelve mammalian sPLA2 molecules constitute part of the so-called innate immune system by virtue of their antibacterial, antiviral and antifungal activities. They are also involved in acute inflammation, a protective reaction of the body to infection or injury. The acute inflammation sometimes escapes regulation, becomes chronic and can evolve into a severe pathology. One or more types of sPLA2 are involved in asthma, rheumatoid arthritis, sepsis, atherosclerosis, myocardial infarction, Crohn's disease, ulcerative colitis and cancer. sPLA2s are thus important therapeutic targets as well as biotherapeutic molecules. Improving the selectivity of inhibitors of sPLA2s to be able to target a particular sPLA2 could therefore be one of the most important tasks for future research. | Phospholipases A2 |
OBJECTIVE: To assess rates of successful testicular sperm retrieval and intracytoplasmic sperm injection (ICSI) outcome in cancer survivors affected by non-obstructive azoospermia (NOA) or retrograde ejaculation (RE)/failure of emission (FOE). METHODS: A retrospective analysis of cancer survivors who did not cryopreserve sperm prior to treatment undergoing testicular sperm extraction (TESE). Non-cancer NOA patients and neurologic RE/FOE were the control group. RESULTS: A total of 97 cancer survivors were offered TESE and 88 (91%) accepted. Sperm was retrieved and cryopreserved in 34/67 patients with NOA (50.7%) and in 21/21 patients affected by RE/FOE (100%). Sperm retrieval rates were similar in the control group (44.9% in NOA and 100% in RE/FOE). The ICSI cumulative pregnancy rate (60%) and live birth rate (40%) per couple in 30 NOA men did not differ from controls (50.0 and 46.5%, respectively; p = 0.399/0.670). The cumulative pregnancy rate (66.7%) and live birth rate (55.6%) in 18 RE/FOE men did not differ from the control group (38.9 and 33.3%, respectively; p = 0.181/0.315). The cancer type and the resulting infertility disorder (NOA or RE/FOE) were not associated with ICSI outcomes. Female partner age was inversely related to the cumulative live birth rate, being fourfold lower (11.5%) in women >/= 40 years and 48.8% in younger women (p = 0.0037). CONCLUSIONS: The rate of successful TESE and the ICSI outcome in cancer survivors with NOA and RE/FOE is the same as non-cancer azoospermic patients. Female partner age (older than 40 years) was associated with a significant reduction in live birth rates after TESE-ICSI procedures. | Sperm Retrieval |
In the tumor microenvironment, inflammation and necrosis cause the accumulations of ATP extracellularly, and high concentrations of ATP can activate P2X7 receptors (P2X7R), which leads to the influx of Na(+) , K(+) , or Ca(2+) into cells and trigger the downstream signaling pathways. P2X7R is a relatively unique ligand-gated ion channel, which is over-expressed in most tumor cells. The activated P2X7R facilitates the tumor growth, invasion, and metastasis. Inhibition of the P2X7R activation can be applied as a potential anti-tumor therapy strategy. There are currently no anti-tumor agents against P2X7R, though several P2X7R antagonists for indications such as anti-inflammatory and anti-depression were reported. In this study, we combined homology modeling (HM), virtual screening, and EB intake assay to characterize the structural features of P2X7R and identify several novel antagonists, which were chemically different from any other known P2X7R antagonists. The identified antagonists could effectively prevent the pore opening of P2X7R with IC50 values ranging from 29.14 to 35.34 muM. HM model showed the area between ATP-binding pocket, and allosteric sides were hydrophobic and suitable for small molecule interaction. Molecular docking indicated a universal binding mode, of which residues R294 and K311 were used as hydrogen bond donors to participate in antagonist interactions. The binding mode can potentially be utilized for inhibitor optimization for increased affinity, and the identified antagonists can be further tested for anti-cancer activity or may serve as chemical agents to study P2X7R related functions. | Receptors, Purinergic P2X7 |
Sheep function as effective endozoochorous seed vectors in grasslands. Recent laboratory-based studies showed that this important function can be impaired by macrocyclic lactone anthelmintics, which are used to control parasites and enter into the environment mainly via faeces; however, there is a lack of in vivo studies. We conducted a seed-feeding experiment with sheep that included four temperate grassland species from four different families (Achillea ptarmica, Asteraceae; Agrostis capillaris, Poaceae; Dianthus deltoides, Caryophyllaceae; Plantago lanceolata, Plantaginaceae). A series of three feeding trials was carried out after one of two groups of sheep received a single administration of a common oral formulation of the macrocyclic lactone moxidectin. Faeces were collected to determine seedling emergence rate and emergence timing as well as moxidectin concentration via HPLC. Seedling emergence differed significantly between the anthelmintic-treated sheep and the control group. This impact depended on time of seed uptake after anthelmintic administration. Number of emerging seedlings was significantly reduced (27.1 %) when faeces moxidectin concentrations were high (on average 3153 ng g(-1); 1 d post treatment) and significantly increased (up to 68.8 %) when moxidectin concentrations were low (</=86 ng g(-1); 7, 14 d pt). Mean emergence time was significantly lowered at low moxidectin concentrations. These results demonstrate dose-related effects of deworming on seedling emergence which might affect endozoochory and eventually plant population dynamics in grasslands. | Anthelmintics |
Quinupristin/dalfopristin (Q/D) is a novel streptogramin antibiotic for the treatment of severe gram-positive infections. The purpose of this open, nonrandomized, parallel-group, phase I trial was to evaluate Q/D pharmacokinetics after single and repeated doses under the two different dosing regimens corresponding to the effective doses and to evaluate tolerability. Two groups of 10 healthy volunteers received multiple 1-hour intravenous infusions of 7.5 mg/kg Q/D either every 8 or 12 hours for 4 or 5 days, respectively. Plasma concentrations of Q, D, and metabolites were determined using high-performance liquid chromatography and selective microbiological assays. The two regimens q8h and q12h lead to the same disposition profile after single and repeated administration. Single-dose data confirmed the high plasma clearances of Q and D (about 0.90 l/h/kg) obtained previously. Unchanged drugs were the main components in plasma, with each of the three metabolites representing about 20% (in terms of the AUC ratio) of the parent drugs. Comparable steady-state concentrations were reached from day 2 of both regimens. A similar moderate increase in Cmax and AUC (about 20%) of parent drugs was observed between the first and last day of treatment. This phenomenon, which was also observed for the metabolites, was not expected considering the short terminal disposition half-lives of the parent drugs and trough plasma concentrations of all components mostly below the limits of quantitation at steady state, whatever the dosing regimen. The clearances of parent drugs at steady state were about 20% lower as compared with that observed following the first drug administration (statistically significant difference). No trend suggesting a treatment effect on any laboratory parameter, vital signs, or electrocardiographic parameters was identified. However, 80% of subjects reported venous adverse events probably related to treatment. | Virginiamycin |
Lipodystrophies are a heterogeneous group of diseases affecting adipose tissue distribution. Familial partial lipodystrophy of the Dunnigantype (FPLD) is a rare autosomal, dominant disorder caused by missense mutations in lamin A/C (LMNA) gene where selective loss of subcutaneous adipose tissue from the limbs and trunk, and accumulation of fat in the neck and face, is usually associated with a variety of metabolic disorders including insulin resistance, diabetes mellitus, dyslipidemia, hepatic steatosis and high blood pressure.In this report we present clinical and molecular features of three Polish women with FLPD phenotype coming from one family (a motherand her two daughters). FPLD was recognised under the circumstances of diabetes treatment, where sequencing of LMNA gene revealed heterozygous R482W mutation. In order to be able to recognise monogenic diabetes associated with lipodystrophy, it is important to bevery precise in physical examination while diagnosing diabetes and to be aware of the necessity of performing genetic testing. Diabetes appropriate differential diagnosis is essential for the treatment strategy, anticipation of the disease progression, and determination of the prognosis. It is necessary for an individual mutation carrier to look carefully at the patient's family." | Diabetes Mellitus, Lipoatrophic |
A new, multisyringe flow injection set-up has been developed for the completely automated determination of trace thiazide compounds with diuretic action in different types of samples. The proposed instrumental set-up exploits for the first time, a low pressure on-line solid phase extraction-liquid chromatography-chemiluminescence detection method. This novel combination of sample treatments in flow systems expands the current applicability of low pressure liquid chromatography due to the isolation/preconcentration of the target compounds, besides high selectivity and sensitivity. For the determination of three thiazide compounds named hydroflumethiazide, furosemide and bendroflumethiazide, the proposed set-up provided with the preconcentration of only 1mL of sample, limits of detection of 3, 60 and 40microgL(-1), respectively. Furthermore wide linear dynamic ranges of 6-4000, 140-20,000 and 90-40,000microgL(-1), respectively, were obtained. Besides of this, a high injection throughput of 12h(-1) was also achieved. As in sports, thiazide diuretics are prohibited substances, the proposed method has been applied to their determination in urine samples. Furthermore the potential of the proposed method as a fast-screening approach for emerging contaminants in waters has been also tested by applying it to well water and leachates from a solid waste landfill." | Sodium Chloride Symporter Inhibitors |
PREMISE OF THE STUDY: This study of Zamia in Puerto Rico is the most intensive population genetics investigation of a cycad to date in terms of number of markers, and one of few microsatellite DNA studies of plants from the highly critical Caribbean biodiversity hotspot. Three distinctive Zamia taxa occur on the island: Z. erosa on the north coast, and Z. portoricensis and Z. pumila, both in the south. Their relationships are largely unknown. We tested three hypotheses about their genetic diversity, including the possibility of multiple introductions. METHODS: We used 31 microsatellite loci across 10 populations and analyzed the data with AMOVA, Bayesian clustering, and ABC coalescent modeling. KEY RESULTS: Puerto Rican zamias exhibit an amalgam of patterns of genetic differentiation that have been reported for cycads. Overall, the taxa are slightly inbred, with high infra-populational variation and little evidence of recent bottlenecks. Zamia erosa exhibits a more than threefold greater degree of population differentiation than the other two taxa. Admixture is evident only between Z. portoricensis and Z. pumila. Zamia portoricensis is inferred to be the youngest taxon on the island, on the basis of estimates of coalescence time and effective population size. A selective sweep may be underway in a small population of Z. erosa in a saline environment. CONCLUSIONS: Zamia erosa may represent an independent introduction into Puerto Rico; Z. portoricensis and Z. pumila fit a scenario of allopatric speciation. This will be explored further in the context of genetic analysis across the entire Caribbean region. | Zamiaceae |
Influenza A viruses of the H2N2 subtype sparked a pandemic in 1957 and circulated in humans until 1968. Because A/H2N2 viruses still circulate in wild birds worldwide and human population immunity is low, the transmissibility of six avian A/H2N2 viruses was investigated in the ferret model. None of the avian A/H2N2 viruses was transmitted between ferrets, suggesting that their pandemic risk may be low. The transmissibility, receptor binding preference and haemagglutinin (HA) stability of human A/H2N2 viruses were also investigated. Human A/H2N2 viruses from 1957 and 1958 bound to human-type alpha2,6-linked sialic acid receptors, but the 1958 virus had a more stable HA, indicating adaptation to replication and spread in the new host. This increased stability was caused by a previously unknown stability substitution G205S in the 1958 H2N2 HA, which became fixed in A/H2N2 viruses after 1958. Although individual substitutions were identified that affected the HA receptor binding and stability properties, they were not found to have a substantial effect on transmissibility of A/H2N2 viruses via the air in the ferret model. Our data demonstrate that A/H2N2 viruses continued to adapt during the first year of pandemic circulation in humans, similar to what was previously shown for the A/H1N1pdm09 virus." | Influenza A Virus, H2N2 Subtype |
We tested the hypothesis that suppression of epoxyeicosatrienoic acid (EET) metabolism via genetic knockout of the gene for soluble epoxide hydrolase (sEH-KO), or female-specific downregulation of sEH expression, plays a role in the potentiation of pulmonary hypertension. We used male (M) and female (F) wild-type (WT) and sEH-KO mice; the latter have high pulmonary EETs. Right ventricular systolic pressure (RVSP) and mean arterial blood pressure (MABP) in control and in response to in vivo administration of U46619 (thromboxane analog), 14,15-EET, and 14,15-EEZE [14,15-epoxyeicosa-5(z)-enoic acid; antagonist of EETs] were recorded. Basal RVSP was comparable among all groups of mice, whereas MABP was significantly lower in F-WT than M-WT mice and further reduced predominantly in F-KO compared with M-KO mice. U46619 dose dependently increased RVSP and MABP in all groups of mice. The increase in RVSP was significantly greater and coincided with smaller increases in MABP in M-KO and F-WT mice compared with M-WT mice. In F-KO mice, the elevation of RVSP by U46619 was even higher than in M-KO and F-WT mice, associated with the least increase in MABP. 14,15-EEZE prevented the augmentation of U46619-induced elevation of RVSP in sEH-KO mice, whereas 14,15-EET-induced pulmonary vasoconstriction was comparable in all groups of mice. sEH expression in the lungs was reduced, paralleled with higher levels of EETs in F-WT compared with M-WT mice. In summary, EETs initiate pulmonary vasoconstriction but act as vasodilators systemically. High pulmonary EETs, as a function of downregulation or deletion of sEH, potentiate U46619-induced increases in RVSP in a female-susceptible manner. | Arterial Pressure |
An uptake and translocation study of azole compounds was performed in lamb's lettuce (Valerianella locusta L.) grown in nutrient solution fortified with different azoles. Three azoles, (clotrimazole, fluconazole and propiconazole), which have different physico-chemical properties and are ubiquitous in the aquatic environment, were the compounds selected. An analytical method, based on matrix solid phase dispersion (MSPD) followed by LC-MS/MS determination, was developed to quantify these compounds in aqueous solution and in roots and leaves. The physicochemical properties of azoles are the main factors governing the uptake and plant accumulation. These azoles were detected in leaves indicating their transport within lamb's lettuce. Translocation from nutrient solution to the aerial part of lamb's lettuce was found to be highly dependent on the hydrophobicity of the azole. Clotrimazole accumulates in roots causing necrosis in roots and leaves, whereas fluconazole was the azole with the highest concentration in leaves without causing apparent phytotoxicity symptoms. The assessment of the levels of these azoles in leaves indicates that the risk for human health is negligible. | Valerianella |
The Enterobacter cloacae complex (ECC) has become a major opportunistic pathogen with antimicrobial resistance issues. Temocillin, an old" carboxypenicillin that is remarkably stable toward beta-lactamases, has been used as an alternative for the treatment of multidrug-resistant ECC infections. Here, we aimed at deciphering the never-investigated mechanisms of temocillin resistance acquisition in Enterobacterales. By comparative genomic analysis of two clonally related ECC clinical isolates, one susceptible (Temo_S [MIC of 4 mg/L]) and the other resistant (Temo_R [MIC of 32 mg/L]), we found that they differed by only 14 single-nucleotide polymorphisms, including one nonsynonymous mutation (Thr175Pro) in the two-component system (TCS) sensor histidine kinase BaeS. By site-directed mutagenesis in Escherichia coli CFT073, we demonstrated that this unique change in BaeS was responsible for a significant (16-fold) increase in temocillin MIC. Since the BaeSR TCS regulates the expression of two resistance-nodulation-cell division (RND)-type efflux pumps (namely, AcrD and MdtABCD) in E. coli and Salmonella, we demonstrated by quantitative reverse transcription-PCR that mdtB, baeS, and acrD genes were significantly overexpressed (15-, 11-, and 3-fold, respectively) in Temo_R. To confirm the role of each efflux pump in this mechanism, multicopy plasmids harboring mdtABCD or acrD were introduced into either Temo_S or the reference strain E. cloacae subsp. cloacae ATCC 13047. Interestingly, only the overexpression of acrD conferred a significant increase (from 8- to 16-fold) of the temocillin MIC. Altogether, we have shown that temocillin resistance in the ECC can result from a single BaeS alteration, likely resulting in the permanent phosphorylation of BaeR and leading to AcrD overexpression and temocillin resistance through enhanced active efflux." | Enterobacter cloacae |
This article comments on: Raees Khan, Robert S. Hill, Veit M. Dorken and Ed Biffin, Detailed seed cone morpho-anatomy of the Prumnopityoid clade: an insight into the origin and evolution of Podocarpaceae seed cones, Annals of Botany, Volume 130, Issue 5, 1 November 2022, Pages 637-655 https://doi.org/10.1093/aob/mcac097 | Plant Cone |
AIM: We studied the effect on neurodevelopment of infants who are exposed to thimerosal in tetanus-diphtheria (Td) vaccines during pregnancy. METHODS: We compared Gesell Developmental Schedules (GDS) of exclusive breastfed infants at 6 months born to mothers who received Td (1 to 3 doses) against those who were born to mothers who did not take such vaccines. RESULTS: Compared with the group of infants not exposed to ethylmercury in utero, the infants of exposed mothers showed no significant difference in neurodevelopment delays. Although there was a significant correlation between hair-Hg of mothers and hair-Hg of neonates (Spearman r = 0.353; p = 0.0011), there was no significant correlation between the level of in utero exposure to ethylmercury in Td vaccines and neonate's hair-Hg concentrations (Spearman r = 0.060; p = 0.5922). However, regression analysis showed that GDS at 6 months was significantly associated with total mercury concentration of neonate's hair but was not sensitive to the number of vaccines taken by the mother. CONCLUSION: Early neurodevelopment of exclusively breastfed infants is sensitive to in utero exposure to mercury, but maternal thimerosal exposure in tetanus-diphtheria vaccines per se cannot portend clinical neurodevelopment delays measured by GDS at 6 months. | Thimerosal |
Mitral valve disease remains common, and requires regular clinical and echocardiographic review. Surgery is indicated soon after the development of symptoms or at the first sign of left ventricular decompensation in mitral regurgitation or of the right ventricle in mitral stenosis. | Mitral Valve Insufficiency |
Acute appendicitis is discussed from the etiologic standpoint, symptoms and signs. The origin and the shift of the pain is explained. The importance of shifting pain, anorexia and point tenderness, is stressed. The altered picture seen in retrocecal, retroilececal and low lying pelvic appendicitis is described and diagnostic measures pointed out. The limited, but very helpful radiologic findings in some cases are mentioned. | Appendicitis |
Wasting of skeletal muscle is a characteristic of many conditions besides those involving primary muscle disease, for example, cancer, cachexia and postoperative catabolism. There is now strong evidence from studies in animals, normal men and in patients with a variety of diseases to suggest that the muscle mass is regulated primarily by alterations in the protein synthetic rate and that changes in muscle protein degradation are largely secondary and adaptive. If this is so, attention should be focused on possible means of therapeutic intervention to increase protein synthesis rather than on ways of decreasing protein degradation. | Muscular Atrophy |
The most recent medical literature has emphasized the notion that catatonia is a syndrome rather than a disease and, on this basis it is associated with a wide variety of medical, neurological and psychiatric conditions. The authors report on five cases of catatonic patients with a favorable response to Lorazepam and analyze the possible mechanisms of action of this Benzodiazepine in catatonic syndrome. | Catatonia |
Three weeks after a surgical operation, a 74-year old woman was admitted to hospital for severe haemolytic anaemia. A strongly positive IgG type direct Coombs test pointed to a iatrogenic origin, but a search for anti-molecule antibodies directed against all medicines taken by the patient after surgery was negative. We extended our immunological investigations and were able to demonstrate the presence of IgG type antibodies directed against an ex vivo metabolite of glafenine. | Glafenine |
AIM: To study the pharmacokinetics and accumulation of an Escherichia coli expressed His-tag fused recombinant human endostatin (rh-endostatin) in Rhesus monkeys. METHODS: Rh-endostatin was iv or sc injected in Rhesus monkeys, and the rh-endostatin concentration in serum samples was determined by an enzyme immunoassay (EIA) method. The serum drug concentration-time data were analyzed by compartmental analysis using the practical pharmacokinetic program 3p97. RESULTS: Following iv administration at a dose rate of 1.5, 4.5, and 13.5 mg/kg in rhesus monkeys, the concentration-time curves of rh-endostatin were best fitted to a three-compartment open model. AUC(0-infinity) linearly increased with dose, while Cls exhibited no significant difference among different dose groups. The terminal half-lives (lambda3) were 8+/-8, 3.1+/-1.4, and 20+/-14 h, respectively. After sc administration at a dose rate of 1.5 mg/kg, the concentration-time curve was best fitted to a two-compartment open model, with a terminal half-life (T(1/2beta)) of 8+/-3 h. Bioavailability following sc injection was approximately 70%+/-3%. After consecutive iv injection of rh-endostatin at a dose rate of 1.5 mg.kg(-1).d(-1) for 7 d, the AUC(0-24 h) substantially increased from 22+/-13 mg.h.L(-1) (d 1) to 50+/-29 mg.h.L(-1) (d 7), with an accumulation factor of 2.3+/-0.6 (P < 0.05). CONCLUSION: The pharmacokinetic behavior of rh-endostatin in Rhesus monkeys complies with linear kinetics within the examined dose range. It tends to be accumulated in bodies after repeated administration at a dose level of 1.5 mg.kg(-1).d(-1) for more than 7 consecutive days. | Angiostatic Proteins |
The main goals of reorganization of sanatorium-and-spa facilities and their activities under current economic conditions should be standardization of services provided to the patients, improvement of their quality, efficacious exploitation of the available resources, and motivation of the personnel. | Health Resorts |
In human subjects sustained static contractions of the quadriceps femoris in one leg were performed with the same absolute and the same relative intensity before and after partial neuromuscular blockade with either decamethonium or tubocurarine which reduced strength to about 50% of the control value. During the contractions performed with the same absolute force, the magnitude of the cardiovascular responses (heart rate and blood pressure) was greater during neuromuscular blockade than during control contractions. During the contractions involving the same relative force the magnitude of the cardiovascular responses was almost the same with and without neuromuscular blockade. These findings were independent of the drug used. The metabolic part of the exercise pressor reflex was assessed by the application of an arterial cuff 1/2 min before cessation of exercise and for the following 3 min of rest. Although heart rate and blood pressure decreased after cessation of exercise, application of the tourniquet resulted in higher post-exercise values and this effect was seen both with and without neuromuscular blockade. Muscle biopsies from the subjects' m. vastus lateralis were analysed for fast- and slow-twitch fibre composition showing 27-66% slow-twitch fibres. No correlation was found between cardiovascular responses to static exercise, with or without neuromuscular blockade, and fibre type predominance. The results suggest that the involvement of fast- or slow-twitch muscle fibres does not play a dominant role in the cardiovascular responses to static exercise in man. Both central command and reflex neural mechanisms are of importance, and it appears that these two control mechanisms are redundant and that neural occlusion may be operative. However, when partial neuromuscular blockade induces a disproportion between an increase in central command and a constant or decreasing muscle tension and metabolism, the larger signal arising from central command determines the magnitude of the cardiovascular responses. | Decamethonium Compounds |
The inter- and intrasubject variability of the orocecal transit time assessed by the salicylazosulphapyridine/sulphapyridine test was examined. Nine healthy males attended on 3 occasions. Between-days comparison gives highly reproducible transit times for the subjects considered as a group (median values and their 95%-confidence limits): 4.0 (3.5-4.5), 4.5 (3.5-5.0), and 4.5 (3.0-4.5) hours, respectively. Fifty-nine per cent of the individual transit times amounts to 4.0 or 4.5 hours. Within subject comparison revealed marked differences for 4 of the volunteers. The maximum between-days differences observed were 1.0 (3 subjects) and 2.5 hours, respectively. Similar results of variability become evident regarding the area under the sulphapyridine concentration-time curves. In conclusion, it appears reasonable to use this method in assessing e.g. the effects of drugs on the transit time in crossover studies. | Sulfapyridine |
New analogs of the opiate peptides containing novel substitutions were compared in terms of their metabolic stability in the presence of an ultrafiltrate of mouse brain. The enkephalin analog FK 33-824 was more stable at short incubation periods (30 min) than Met-enkephalin but less stable than D-Ala2-enkephalinamide at longer periods (180 min) as shown by the complete release of N-terminal Tyr. In contrast, D-Ala2-enkephalinamide substituted in position 4 with pentafluorophenylalanine was completely stable at the time periods tested. A dimer of D-Ala2-enkephalin was relatively stable at short periods but subject to a 30% hydrolysis (vs. 100% for FK 33-824) in terms of Tyr release at longer periods of incubation. A doubly substituted human beta-endorphin (D-Leu17, D-Lys29-beta-endorphin) showed greater stability than the native peptide based on release of internal residues after incubation with the ultrafiltrate of brain. The presence of D-Leu17 blocked release of intermediate sized endorphins but did not affect liberation of Tyr. The additional presence of D-Thr in position 6 of a triply substituted beta-endorphin (D-Thr6, D-Leu17, D-Lys29-beta-endorphin) did not affect liberation of Tyr, indicating that formation of gamma-endorphin (cleavage of Leu17-Phe) and of enkephalin (cleavage of Met5-Thr) need not occur before the action of brain peptidases. The results demonstrate the feasibility of altering the resistance of analogs of enkephalin and endorphin to degradation by brain enzymes. | beta-Endorphin |
BACKGROUND: The house dust mite Suidasia pontifica (Sp) is an important source of allergens in tropical regions that trigger IgE-mediated allergic reactions such as allergic asthma, atopic dermatitis and allergic rhinitis. Detection of Sp-specific proteins are important in the management and prevention of allergic diseases. OBJECTIVE: The study aimed to provide a proof of concept for a gold nanoparticle-labeled sandwich format Lateral Flow Immunoassay (LFIA) kit for the detection of Sp-specific proteins. METHODS: Protein A chromatography-purified rabbit anti-Sp polyclonal antibodies were labeled with gold nanoparticles (AuNP) synthesized from chloroauric acid using the citrate reduction method, then dispensed on a glass fiber pad. Unlabeled antibodies and anti-rabbit IgG were immobilized onto nitrocellulose membrane as test line and control line respectively. Cellulose fiber pad, glass fiber, and the nitrocellulose membrane pad were then assembled as LFIA kit. RESULTS: Protein-A affinity chromatography purification with pre-concentration yielded 1.45 mg/mL of anti-Sp polyclonal antibodies. Synthesized AuNPs with ~20 nm sizes observed under transmission electron microscope were used for antibody conjugation at an optimal pH of 8.5 (borate buffer) and an optimal ratio of 10 micro L 50microg/mL antibody:100 micro L AuNP. Optimal color intensity and fastest migration time were observed with the treatment of 0.05% Tween20 and 10% sucrose in the conjugate pads; 5% BSA and 0.05% Tween20 in the sample pads, and 1% BSA in the test pads. The limit of detection of the LFIA Sp-specific proteins is 0.076 microg/mL. The sensitivity of the Sp LFIA kit is 83% while the specificity is 100%. CONCLUSION: This is the first report of a prototype for a cost-effective, rapid, and equipment-free detection of the house dust mite Suidasia pontifica. | Collodion |
Many quality assurance workers have been concerned about undertransfusion since acquired immune deficiency syndrome was first shown to be transmitted by blood transfusion. Physicians may be reluctant to order transfusions, and patients may be hesitant to receive blood therapy, even in situations meeting established guidelines for transfusion therapy. Transfusion guidelines are reviewed and compared to actual practices in a tertiary care hospital. Clinical cases between the limits set by the guidelines are examined and shown not to meet the definition of undertransfusion. | Blood Transfusion |
During wound healing and inflammation, fibroblasts express elevated alkaline phosphatase (ALP), but are not in contact with collagen fibrils in the fibronectin (FN)-rich granulation tissue. We hypothesized that the extracellular matrix (ECM) environment might influence the induction of ALP in fibroblasts. Here we tested this hypothesis by studying the ALP-inductive response of normal human gingival fibroblasts to ascorbic acid (AsA). AsA induced ALP activity and protein in cells in conventional monolayer culture. This induction was inhibited by blocking-antibodies to the FN receptor alpha 5 beta 1 integrin and by the proline analog 3,4-dehydroproline (DHP). DHP prevented cells from arranging FN fibrils into a pericellular network and reduced the activity of cell spreading on FN. Plating of cells on FN facilitated the up-regulation by AsA of ALP expression, but did not substitute for AsA. In contrast, AsA did not cause ALP induction in cells cultured on and in polymerized type I collagen gels. Collagen fibrils inhibited the up-regulation by AsA of ALP expression in cells plated on FN. These results indicate that the ECM regulates the induction of ALP expression by AsA in fibroblasts: FN enables them to express ALP in response to AsA through interaction with integrin alpha 5 beta 1, whereas type I collagen fibrils cause the suppression of ALP expression and overcome FN. | Receptors, Fibronectin |
There are several isomers of carotene, the main ones being alpha and beta carotene (i.e., alpha-carotene and beta-carotene). The latter serves as a precursor for vitamin A, and is thus a well-studied carotenoid in health, food, and nutrition research. A German special character, the Eszett (uppercase or capital áºÂ; lowercase ss), has been confused with the Greek, lowercase beta (beta) in some papers in the biomedical literature, and when the lowercase Eszett is written in italics, it looks even more similar to the Greek letter beta. Curiously, this linguistic error has given rise to a new" form of carotene, Eszett (ss)-carotene, which does not exist. A search on PubMed, Elsevier's sciencedirect.com, and Springer Nature's SpringerLink platforms reveals that there are potentially dozens, if not hundreds of cases or more of this false-positive carotene "isomer," which was supposed to represent beta-carotene, but has, through a typographic error, represented a "new" and non-existent form of carotene, ss-carotene. This clearly represents erroneous literature that needs correction." | Hydrocarbons, Alicyclic |
Postoperative pulmonary embolism continues to be a problem in patient care, especially in high-risk patients. This study was designed to evaluate a combined pharmacologic approach to the prophylaxis of postoperative deep venous thrombosis (DVT) by mediating at least two and probably three of Virchow's predisposing factors. Patients 40 years of age and older undergoing operations greater than 45 minutes under general anesthesia were placed in one of five treatment groups and studied by a prospective randomized, double-blind protocol. Study drugs were the following: (1) 0.5 mg of dihydroergotamine plus 5000 IU of sodium heparin (DHE 5000), (2) 0.5 mg DHE plus 2500 IU heparin (DHE 2500), (3) 5000 IU of HEP (HEP 5000), (4) 0.5 mg of DHE (DHE 0.5), and (5) a placebo. Study medications were administered 2 hours preoperatively and continuously thereafter every 12 hours postoperatively subcutaneously in the anterior abdominal wall for 5 to 7 days or until a positive radiofibrinogen uptake test (RFUT). The RFUT was performed according to standardized technique and was used to establish the presence or absence of DVT. This report is an analysis of the major subgroup of patients undergoing intra-abdominal operations. Results showed a highly statistically significant prophylactic benefit from DHE 5000 compared with the placebo (p less than 0.003) and all other treatment groups (p less than 0.05). There was no significant benefit from DHE 2500, HEP 5000 (p greater than 0.13), and DHE 0.5 (p greater than 0.3). All patients who entered the study had two or more risk factors for postoperative DVT, and high-risk patients were distributed equally throughout all treatment groups.(ABSTRACT TRUNCATED AT 250 WORDS) | Dihydroergotamine |
An organism is a dynamic system, and its life history results from underlying processes in time. The effects of biological and chemical stressors on this system therefore also change temporally. In the present short communication, we emphasize the importance of including time as a factor in stress ecology and ecotoxicology and argue that current standard test protocols may benefit considerably from this, improving data interpretation and thus also risk assessment and risk management. | Ecotoxicology |
Unspecific abdominal complaints including bloating and irregular bowel movements may be caused by carbohydrate malabsorption syndromes, e.g., lactose and fructose malabsorption. These symptoms were investigated with hydrogen (H2) breath tests and correlated to carbohydrate malabsorption. During performing these H2-breath tests the patient presented with an acute, localized, non-migratory pain in the left lower abdominal quadrant. Primary epiploic appendagitis is a rare cause of abdominal acute or subacute complaints and diagnosis of primary epiploic appendagitis (PEA) is made when computed tomography reveals a characteristic lesion. We report on a patient with co-occurrence of lactose and fructose malabsorption, which was treated successfully with a diet free of culprit carbohydrates, with PEA recovering without medication or surgical treatment within few days. Since the abdominal unspecific symptoms had been present for months, they appeared not to be correlated to the acute localized abdominal pain, therefore we speculate on a random co-occurrence of combined carbohydrate malabsorption and PEA. | Malabsorption Syndromes |
Surgeon wellness, and the means by which it may be realized, has recently come to the forefront as awareness of burnout among orthopaedic surgeons has increased. Individual surgeons face unique challenges toward finding their own path to thrive. It is important to incorporate varying perspectives regarding potential solutions to surgeons' stresses in both work and extracurricular life. Specifically, the goal is to initiate a discussion regarding wellness by providing insight into the challenges facing surgical residents, supplemented with the perspectives of women and minorities within the field. Peer coaching plays an essential role in optimizing mental health. | Surgeons |
Despite numerous improvements in the palatoplasty procedure, speech dysfunction tends to develop in many patients, requiring another surgery. In addition, vomer flaps have been used in palatoplasty in various shapes and on purposes. Nonetheless, they have been used mostly to cover the defect in wide and complete type of cleft palate. We introduce the vomopalatoplasty procedure that uses a vomer flap to reduce the nasopharyngeal space in incomplete or submucous type of cleft palate patients.The mucoperiosteal flaps on the nasal and oral sides were elevated by the conventional palatoplasty procedure, which subsequently elevated the bilateral vomer flaps to the posterior edge of vomer. Then, the vomer flap was sutured with the mucoperiosteal flap of the nasal side to the anterior half of the soft palate, and thus, the soft palate was fixed in more posterosuperior direction than in conventional palatoplasty. For patients whose junction of vomer and hard palate had to be exposed, a part of the bone at the bifid posterior nasal spine of the hard palate may be removed sometimes.Ostectomy of the bifid posterior nasal spine or the posterior end of the hard palate was performed in 11 patients. Another 12 patients did not need ostectomy. After the surgery, the surgical wounds healed well in all patients without any major complications such as dehiscence or loss of flap.Our vomopalatoplasty is easy to perform, and the procedure could be combined to the conventional palatoplasty procedure. Thus, we consider vomopalatoplasty as a useful procedure that could reduce the nasopharyngeal space in patients with incomplete or submucous type of cleft palate. | Velopharyngeal Sphincter |
The knowledge of the molecular basis of factor XIII deficiency has improved significantly in recent years. Almost 20 different mutations have been described in the gene coding for the factor A-subunit and 3 mutations in the gene coding for the B-subunit. Half of the mutations in the factor XIIIa A-subunit gene are nonsense mutations that result in premature termination of translation. Three of them are frameshift mutations that are caused by minor deletions. Two of them are splicing mutations and 3 are stop mutations that are caused by single nucleotide substitutions. Ten of the mutations are missense mutations caused by nucleotide transitions leading to amino acid substitutions. In the factor XIII B-subunit gene, the 3 mutations are an amino acid substitution, a splicing mutation, and a trinucleotide insertion. These mutations explain the disease in the two families reported to have XIII B-subunit deficiency. In factor XIII A-subunit deficiency, the genetic defects have been characterized so far only in a minority of cases. In most of the reports of factor XIII A-subunit mutations, each family carries its own mutation/mutations. However, in some populations such as Finns and Arabs some enrichment of specific mutations has occurred. Some international migration of a few mutations has also been noted. The structural and functional effects of the mutations have been analyzed by studying the expression of the factor XIII subunits on mRNA and protein levels in vivo or in vitro, and by utilizing the three-dimensional model of crystallized factor XIII A-subunit in modeling of the missense mutations. | Factor XIII Deficiency |
OBJECTIVES: This report presents detailed pregnancy rates for 1990-2004, updating a national series of rates extending since 1976. Data from the National Survey of Family Growth (NSFG) are used to interpret trends in teenage pregnancy and in total pregnancy and fertility rates. METHODS: Tabular and graphical data on pregnancy rates by age, race and Hispanic origin, and by marital status are presented and described. Birth data are from the birth registration system for all births registered in the United States and reported by state health departments to the National Center for Health Statistics; abortion data are from the Guttmacher Institute and the National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention; and fetal loss estimates are from pregnancy history information collected by the NSFG. RESULTS: In 2004 an estimated 6,390,000 pregnancies resulted in 4.11 million live births, 1.22 million induced abortions, and 1.06 million fetal losses. The estimated pregnancy rate for 2004 was 103.0; the rate varied little between 1995 and 2004. The teenage pregnancy rate dropped 38 percent during 1990-2004, reaching an historic low of 72.2 pregnancies per 1,000 women aged 15-19 years. Rates for younger teenagers declined relatively more than for older teenagers. | Pregnancy Rate |
INTRODUCTION: Optimism-the expectation that good things will happen-has emerged as a promising health asset, as it appears to be related to healthier behaviors and reduced disease risk. Growing research finds that higher optimism is associated with lower mortality, yet it is critical to understand whether this prolonged longevity is accompanied by good health. This study tested whether higher optimism was associated with increased likelihood of healthy aging. METHODS: Prospective data analyzed in 2018 from the Nurses' Health Study included 33,326 women with no major chronic diseases at baseline. Poisson regression models evaluated if optimism was associated with healthy aging 8 years later, considering potential confounders (sociodemographic variables, depression) and intermediate variables (health behaviors). Optimism was assessed in 2004 by validated self-report using mailed questionnaires and healthy aging was assessed in 2012, defined as (1) remaining free of major chronic diseases; (2) having no subjective memory impairment; (3) having intact physical function; and (4) surviving through follow-up. RESULTS: Overall, 20.5% of women (n=6,823) fulfilled the definition of healthy aging in 2012. After adjusting for sociodemographic factors and depression, the most (top quartile) versus least (bottom quartile) optimistic women had a 23% greater likelihood of healthy aging (95% CI=1.16, 1.30). Associations were similar in white and black participants, although the sample of black women was small (n=354). CONCLUSIONS: Higher optimism was associated with increased likelihood of healthy aging, suggesting that optimism, a potentially modifiable health asset, merits further research for its potential to improve health in aging. | Optimism |
BACKGROUND: Transitional hypothermia (TH) is associated with increased morbidity and mortality in very low birth weight (VLBW) infants worldwide. OBJECTIVES: To assess the effect of a quality improvement project (QIP) on outborn TH and the associated mortality/morbidity among VLBW neonates. METHODS: We conducted a multi-intervention QIP to reduce TH (<36 degrees C) among outborn VLBW neonates. This cohort study compared a historical group (group I, n = 86) to a prospective group (group II, established after QIP implementation, n = 86). The primary outcome was axillary temperature measured in the delivery room (DR) and upon admission to the neonatal intensive care unit (NICU). RESULTS: The baseline characteristics of the two groups were similar. After introducing the QIP, the mean DR and NICU admission temperatures of the patients rose from 35.5 to 36.1 degrees C and from 34.6 to 36.2 degrees C, respectively (p < 0.01), and the percentage of patients with temperatures <36 degrees C in the DR and NICU decreased from 80 to 40% and from 81 to 42% (p < 0.01), respectively. Meanwhile, the percentage of patients with a normal temperature in the DR and NICU rose from 20 to 58% and from 19 to 56% (p < 0.01), respectively, which was accompanied by significantly decreased mortality (p < 0.02) and other improvements. CONCLUSION: Implementation of a QIP resulted in a decrease in the number of moderately hypothermic VLBW neonates and a sustained improvement in normothermia rates during DR stabilization and transfer to the NICU in outborn VLBW neonates. | Delivery Rooms |
Most studies of clinical decision making in nursing have been guided by analytic theories, such as information-processing and decision-analysis theories. Recently, some investigators have used naturalistic methods and have identified knowing the patient" as relevant to clinical judgment. The author discusses two lines of inquiry and offers possible explanations for differences between the two conceptualizations of clinical decision making. Insights for future research are proposed." | Models, Nursing |
PURPOSE: We aimed to determine myopia control efficacy with novel contact lenses (CL) that (1) reduced both central and peripheral defocus, and (2) provided extended depth of focus with better global retinal image quality for points on, and anterior to, the retina and degraded for points posterior to the retina. METHODS: Children (n = 508, 8-13 years) with cycloplegic spherical equivalent (SE) -0.75 to -3.50D were enrolled in a prospective, double blind trial and randomised to one of five groups: (1) single vision, silicone hydrogel (SH) CL; (2) two groups wearing SH CL that imposed myopic defocus across peripheral and central retina (test CL I and II; +1.00D centrally and +2.50 and +1.50 for CL I and II at 3 mm semi-chord respectively); and (3) two groups wearing extended depth of focus (EDOF) hydrogel CL incorporating higher order aberrations to modulate retinal image quality (test CL III and IV; extended depth of focus of up to +1.75D and +2.50D respectively). Cycloplegic autorefraction and axial length (AL) measurements were conducted at six monthly intervals. Compliance to lens wear was assessed with a diary and collected at each visit. Additionally, subjective responses to various aspects of lens wear were assessed. The trial commenced in February 2014 and was terminated in January 2017 due to site closure. Myopia progression over time between groups was compared using linear mixed models and where needed post hoc analysis with Bonferroni corrections conducted. RESULTS: Myopia progressed with control CL -1.12 +/- 0.51D/0.58 +/- 0.27 mm for SE/AL at 24 months. In comparison, all test CL had reduced progression with SE/AL ranging from -0.78D to -0.87D/0.41-0.46 mm at 24 months (AL: p < 0.05 for all test CL; SE p < 0.05 for test CL III and IV) and represented a reduction in axial length elongation of about 22% to 32% and reduction in spherical equivalent of 24% to 32%. With test CL, a greater slowing ranging from 26% to 43% was observed in compliant wearers (>/=6 days per week; Control CL: -0.64D/0.30 mm and -1.14D/0.58 mm vs test CL: -0.42D to -0.47D/0.12-0.18 mm and -0.70 to -0.81D/0.19-0.25 mm at 12 and 24 months respectively). CONCLUSIONS: Contact lenses that either imposed myopic defocus at the retina or modulated retinal image quality resulted in a slower progression of myopia with greater efficacy seen in compliant wearers. Importantly, there was no difference in the myopia control provided by either of these strategies. | Myopia, Degenerative |
The occurrence of members of the Pasteurellaceae and Neisseriaceae families was studied in dogs and cats. A total of 110 nasal and pharyngeal swab samples from 47 dogs and 8 cats were collected. Most of the strains were identified by 16S rDNA sequencing, except Frederiksenia canicola and Pasteurella multocida where species-specific polymerase chain reactions were applied. The most frequently isolated species was F. canicola, which occurred only in dogs, mainly in the pharyngeal cavity. The second commonest bacterium, P. multocida was found in both types of samples and in both hosts. Other species from the family Pasteurellaceae, such as Haemophilus haemoglobinophilus, Pasteurella canis and P. dagmatis, were detected only in dogs. All isolated species belonging to the family Neisseriaceae, mainly representing Neisseria weaveri, were found only in the pharyngeal cavity. Neisseria weaveri and N. zoodegmatis could be detected in both hosts. Neisseria dumasiana and N. canis were isolated from dogs, while N. shayeganii only from a cat. For phylogenetic analysis, rpoB gene sequencing was performed, where the strains were on monophyletic branches and clearly separated from each other. In this study, recently described species such as F. canicola, N. shayeganii and N. dumasiana were detected that had never been isolated in Hungary before. | Pasteurellaceae Infections |
The late (L) domain sequence used by mouse mammary tumor virus (MMTV) remains undefined. Similar to other L domain-containing proteins, MMTV p8 and p14(NC) proteins are monoubiquitinated, suggesting L domain function. Site-directed mutagenesis of p8, PLPPV, and p14(NC), PLPPL, sequences in MMTV Gag revealed a requirement only for the PLPPV sequence in virion release in a position-dependent manner. Electron microscopy of a defective Gag mutant confirmed an L domain budding defect morphology. The equine infectious anemia virus (EIAV) YPDL core L domain sequence and PLPPV provided L domain function in reciprocal MMTV and EIAV Gag exchange mutants, respectively. Alanine scanning of the PLPPV sequence revealed a strict requirement for the valine residue but only minor requirements for any one of the other residues. Thus, PLPPV provides MMTV L domain function, representing a fourth type of retroviral L domain that enables MMTV Gag proteins to co-opt cellular budding pathways for release. | Mammary Tumor Virus, Mouse |
Evaluations of new graduated licensing systems (GLS) commonly examine pre-post young driver crash rates relative to another driver group. This comparison approach is important to account for other influences on crashes over time, but has limited ability to determine which GLS components are most effective and at what stage during the licensing process. We previously identified declines in young driver crashes in Queensland, Australia, following introduction of a new GLS in 2007. The objective of the current research was to conduct complementary modelling to identify at what points through the licensing process had particular GLS policies contributed to reductions. Crash trends were explored for learner and provisional drivers under the new GLS versus previous system for three time periods relative to the month of acquiring a provisional licence: the preceding learner period, the first month of provisional licensure (when crashes typically peak), and the overall provisional period. Interrupted time series analyses were conducted for the log ratio of crashes per 10,000 licensed (learner and provisional) drivers with the total number of licensed drivers as an offset. The greatest declines were found in the first month of licensure, with indications that a longer learner period, higher supervised driving hours, and a new provisional night-passenger restriction were key contributors to provisional crash reductions. There was also some indication that a restriction on all phone use reduced crashes during the learner period. We conclude that time series analysis focusing on licensing stage, rather than calendar time only, offers a complementary approach to analysing GLS effectiveness by better identifying where and how changes impact crashes. | Licensure |
Iodoacetate and iodoacetamide were compared as to their capacity to block islet glycolysis and interfere with glucose inhibition of glucagon release and glucose stimulation of insulin release. Glycolysis was measured in isolated rat islet by the rate of lactate formation from 27 mM glucose. Hormone release was investigated by perfusing isolated rat pancreas with a 10 mM mixture of 19 amino acids, with and without 5 mM glucose. In perfusion experiments, lactate (2.5 mM) and pyruvate (0.5 mM) were present to provide alternate source of energy independent of glycolysis. Iodoacetate was about twice as potent as iodoacetamide in blocking glycolysis in islets, 0.2 and 0.5 mM, respectively being needed for complete inhibition of lactate production. Levels of either agent lower than 0.05 mM did not affect lactate accumulation. Iodoacetate, at the level which completely inhibited glycolysis did not interfere with the permissive action of glucose for insulin release. In contrast, iodoacetamide at a level (0.05 mM) which had no effect on lactate production, changed the response of the beta-cell dramatically: amino acids now released insulin even in the absence of glucose and insulin release by 5 mM glucose alone was greatly augmented. Both thiol reagents at 0.025 mM concentration completely prevented glucose from suppressing amino acid stimulated glucagon release, iodoacetamide being more potent than iodoacetate. These data indicate that the opposite physiological actions of glucose in alpha and beta-cells are in each case dissociable from the fuel function of the sugar molecule, and the results best support the concept that glucose and thiol reagents effect insulin and glucagon secretion by acting on sulfhydryl groups related to receptor sites in the alpha-and beta-cell membrane. | Iodoacetamide |
The two putative proteins RGV-63R and RGV-91R encoded by Rana grylio virus (RGV) are DNA polymerase and proliferating cell nuclear antigen (PCNA) respectively, and are core proteins of iridoviruses. Here, the interaction between RGV-63R and RGV-91R was detected by a yeast two-hybrid (Y2H) assay and further confirmed by co-immunoprecipitation (co-IP) assays. Subsequently, RGV-63R or RGV-91R were expressed alone or co-expressed in two kinds of aquatic animal cells including amphibian Chinese giant salamander thymus cells (GSTCs) and fish Epithelioma papulosum cyprinid cells (EPCs) to investigate their localizations and effects on RGV genome replication. The results showed that their localizations in the two kinds of cells are consistent. RGV-63R localized in the cytoplasm, while RGV-91R localized in the nucleus. However, when co-expressed, RGV-63R localized in both the cytoplasm and the nucleus, and colocalized with RGV-91R in the nucleus. 91R big up tri, openNLS represents the RGV-91R deleting nuclear localization signal, which is localized in the cytoplasm and colocalized with RGV-63R in the cytoplasm. qPCR analysis revealed that sole expression and co-expression of the two proteins in the cells of two species significantly promoted RGV genome replication, while varying degrees of viral genome replication levels may be linked to the cell types. This study provides novel molecular evidence for ranavirus cross-species infection and replication. | Viral Core Proteins |
INTRODUCTION: The saphenous nerve has great importance on the sensitivity of the lower limb. In its normal course, it enters the adductor canal and travels under the sartorius muscle, on the medial side of the thigh. METHODS: The anatomical variation was found accidentally during routine cadaveric dissection of the thigh at the Human Anatomy Laboratory of the Department of Morphophysiology of the Faculty of Medical Sciences of Minas Gerais (FCMMG). RESULTS: A different pattern of path of the saphenous nerve was found, which appears to perforate the sartorius muscle. DISCUSSION: Complaints of pain in the lower limbs are highly prevalent in the adult population. Saphenous neuropathy is a pathological entity that is associated with such a clinic and may have compression or trauma as its etiology. In the context of compression, it can be caused due to the unusual nerve path, as described in the present study. In trauma, knowledge of this variation is important to prevent iatrogenic damage to nervous tissue during surgical procedures. CONCLUSION: The anatomic variation presented may be related to the symptom of pain in the lower limbs and is also relevant in the surgical context, in order to prevent complications. | Anatomic Variation |
The independent effects of hydrodynamic stress (assessed as the Energy Dissipation/Circulation Function, EDCF) and dissolved oxygen tension (DOT) on the growth, morphology and laccase production by Pleurotus ostreatus CP50 were studied using a 3(2) factorial design in a 10L reactor. A bell-shape function for fungus growth between 8 and 22% DOT was observed, as well as a significant negative effect on laccase production and the expression of poxc, the gene encoding for the most abundant laccase produced by P. ostreatus CP50. Increasing EDCF from 1 to 21 kW/m(3)s, had a positive effect on fungus growth, whereas no effect on poxc gene expression was observed. However, the increase in EDCF favored the specific laccase production due to the generation of smaller pellets with less diffusional limitations and increased metabolically active biomass. The results show, for the first time, that hydrodynamic effects on growth and laccase production are mainly physical and diffusional, while the influence of the dissolved oxygen is at transcriptional level. | Pleurotus |
OBJECTIVES: To evaluate the long-term clinical and cost outcomes associated with biphasic insulin aspart 30/70 (BIAsp 30/70, premixed 30% soluble and 70% protaminated insulin aspart in one injection) compared to insulin glargine treatment in insulin-naive type 2 diabetes patients failing oral antidiabetic agents in the UK, based on findings recently reported from the INITIATE clinical trial. METHODS: The CORE Diabetes Model, a published, peer-reviewed and validated model of diabetes, was used to evaluate life expectancy, quality-adjusted life expectancy, cumulative incidence of complications and direct medical costs over patient lifetimes. The model simulates the range of diabetic complications and disease progression within a series of sub-models (cardiovascular disease, neuropathy, renal and eye disease) based on published data. Baseline cohort characteristics (54.5% male, mean age 52.45 years, mean diabetes duration 9 years, mean HbA(1c) 9.77%) and treatment effects were based on INITIATE. Costs were derived from published UK sources. The analysis was run over a 35-year time horizon (patient lifetime) from a third party payer perspective. Costs and clinical benefits were discounted at 3.5% per annum. Sensitivity analyses were performed. RESULTS: BIAsp 30/70 was associated with projected improvements in discounted life expectancy (0.19 +/- 0.20 years) and quality-adjusted life expectancy (0.19 +/- 0.14 quality-adjusted life years [QALYs]), as well as a reduced incidence of retinopathy and nephropathy complications, versus glargine. Total lifetime direct costs were 1319 pounds higher with BIAsp 30/70 than with glargine leading to an incremental cost-effectiveness ratio of 6951 pounds per QALY gained. CONCLUSIONS: This study is the first to address the long-term health economic implications of treating type 2 diabetes patients failing oral anti-diabetics with a biphasic insulin mix versus long-acting insulin. Our projections indicate that improved HbA1c levels with BIAsp 30/70 treatment are associated with improvements in life expectancy and quality-adjusted life expectancy, and that BIAsp 30/70 represents excellent value for money compared to insulin glargine in the UK. | Insulins |
Subsets and Splits
No saved queries yet
Save your SQL queries to embed, download, and access them later. Queries will appear here once saved.