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pubmed_748_1675
In an attempt to gain insight into the dynamics of intron evolution in eukaryotic protein-coding genes, the distributions of old introns, that are conserved between distant phylogenetic lineages, and new, lineage-specific introns along the gene length, were examined. A significant excess of old introns in 5'-regions of genes was detected. New introns, when analyzed in bulk, showed a nearly flat distribution from the 5'- to the 3'-end. However, analysis of new intron distributions in individual genomes revealed notable lineage-specific features. While in intron-poor genomes, particularly yeast Schizosaccharomyces pombe (Sp), the 5'-portions of genes contain a significantly greater number of new introns than the 3'-portions, the intron-rich genomes of humans and Arabidopsis show the opposite trend. These observations seem to be compatible with the view that introns are both lost and inserted in 3'-terminal portions of genes more often than in 5'-portions. Overrepresentation of 3'-terminal sequences among cDNAs that mediate intron loss appears to be the most likely explanation for the apparent preferential loss of introns in the distal parts of genes. Preferential insertion of introns in the 3'-portions suggests that introns might be inserted via a reverse-transcription-mediated pathway similar to that implicated in intron loss. This mechanism could involve duplication of a portion of the coding region during reverse transcription followed by homologous recombination and subsequent rapid sequence divergence in the copy that becomes a new intron.
10.1016/j.gene.2004.05.027
pubmed_703_1817
BACKGROUND C-reactive protein (CRP) is an acute-phase serum protein produced by the liver. High plasma levels of CRP have been associated primarily with infection, but elevated CRP levels have also been found to be associated with more than one hundred conditions and factors, including social and economic factors. MATERIALS AND METHODS To evaluate the possible association between individuals' number of children and plasma levels of C-reactive protein, we studied a representative population of 2,426 adults. CRP was analyzed using the high sensitivity method (hsCRP). Individuals were divided into five groups of zero, one, two, three and four and more children. RESULTS We found that individuals with more children had significantly higher levels of plasma hsCRP than individuals without children or than individuals with a low number of children (p for trend <0.001). This association could reflect the known associations between CRP and higher economic stress, exhaustion, episodic stress and chronic stress. CONCLUSIONS We found significantly elevated levels of plasma CRP in individuals with more children than in individuals without children or with a low number of children.
pubmed_703_1817
pubmed_1039_12730
Arachnoid cyst located near the quadrigeminal cistern has been reported as paracollicular arachnoid cyst, arachnoid cyst of the quadrigeminal cistern, paramesencephalic arachnoid cyst, arachnoid cyst posterior to the third ventricle, cyst of the cisterna ambiens. The purpose of this paper is to present the clinical pictures, diagnostic studies and treatment of 5 cases of the arachnoid cyst of the quadrigeminal cistern. (1) The clinical symptoms and signs result from increased intracranial pressure without lateralizing signs (mid-line syndrome) due to hydrocephalus, precocious puberty and supra-collicular sign due to direct compression of the adjacent structures. (2) Endocrinological study of the pituitary gland shows no abnormal findings, but the patients with precocious puberty shows adult type response in LH and FSH. (3) Metrizamide CT cisternography could be considered as a safe and reliable neurological procedures in evaluating the communication between the cyst and the subarachnoid space as well as CSF dynamics, and subarachnoid space. (4) Patients were treated with ventriculoperitoneal shunt, followed by craniotomy and resection of the cyst wall with good results.
pubmed_1039_12730
pubmed_270_17753
The functions of Myf5 and Myod are well known in trunk myogenesis. However, the roles that Myf5 and Myod play during craniofacial myogenesis are far from well known. We observed that zebrafish myf5 was detected in the primordia of the obliques, lateral rectus, sternohyoideus, and pharyngeal mesoderm cores. In contrast, myod transcripts were expressed in all head muscle precursors at later stages. Knockdown of myf5 revealed that Myf5 was required for the development of the obliques, lateral rectus, sternohyoideus, and all pharyngeal muscles, whereas knockdown of myod proved that Myod was required for the development of superior rectus, medial rectus, inferior rectus, lateral rectus, and the ventral pharyngeal muscles. myod mRNA did not rescue the loss of the cranial muscle caused by injecting myf5-morpholino, or vice versa, suggesting that the functions of Myf5 and Myod were not redundant in head paraxial mesoderm, a finding different from their functions in trunk myogenesis. Myf5, but not Myod, was required for the forward migration of myf5-positive oblique precursors. All evidences reveal that Myf5 and Myod function independently during cranial myogenesis. On the basis of the expression patterns of myf5 and myod, we propose a model to present how Myf5 and Myod are involved in head myogenesis of zebrafish.
10.1016/j.ydbio.2006.08.042
pubmed_1007_13182
Approximately 50 child sarcomas are treated with limb salvage surgery each year in the United Kingdom. These children need an extendable implant that can be lengthened periodically to keep pace with the growth in the opposite limb. Surgically, invasive devices have been used for the past 30 years with intrinsic problems of infection and long-term recurrent trauma to the patient. To eliminate problems associated with the invasive device, a noninvasive extendable prosthesis was developed. The magnetically coupled drive technology used for this prosthesis was a synchronous motor with a gear-driven telescoping shaft. In this design the motor configuration was in two parts: a rotating magnet (rotor) that fitted inside the prosthesis where space was limited and the stator, which was an external device used to extend the prosthesis remotely as the patient grew. This compact external drive produced a focused magnetic flux that required no cooling and operated on a single-phase power supply. The extending mechanism in the implant was able to overcome up to 1300 N force, which is the tension force exerted by the soft tissues during the lengthening procedure. The device has been successfully implanted in 50 patients.
10.1243/09544119JEIM247
pubmed_574_9145
The interaction of mithramycin (MTR) with Ca2+, Cd2+, Tb3+, Gd3+, Li+, Na+ and K+ ions has been studied by circular dichroism and absorption spectroscopy. Mithramycin binds strongly to Ca2+, Cd2+, Tb3+ and Gd3+ forming a 1:4 Ca2+: MTR entities with a left-handed screw conformation. The concentration of Ca2+ present in water currently used being about 10 microM, this leads to the conclusion that, in most of the experiments reported in the literature, about 40 microM mithramycin were actually bound to Ca2+. Mithramycin also binds to Na+, forming entities with left-handed screw conformation, but not to K+ and Li+. None of these cations were able to promote the mithramycin-DNA interaction.
10.1016/0304-4165(93)90097-r
pubmed_880_2620
We have retrospectively investigated 15 nasopharyngeal carcinoma patients treated at our institution between March 2007 and August 2009. We used simultaneous integrated-boost whole field intensity-modulated radiation therapy (SIB WF-IMRT) to treat the entire planning target volume in the head and neck cancer. All of the SIB WF-IMRT plans were replanned by use of the junctioned intensity modulated radiation therapy (J-IMRT) technique for comparison. The effect on target coverage and sparing of organs at risk, including laryngeal sparing in the optimal SIB WF-IMRT plan was compared with that achieved with use of the J-IMRT technique. The mean larynx dose and standard deviation was 25.2 ± 5.8 Gy for SIB WF-IMRT and 19.8 ± 16.8 Gy for J-IMRT. A comparison between SIB WF-IMRT and the J-IMRT technique demonstrated that the larynx dose was increased in SIB WF-IMRT. However, when the strong dose constraint was applied to the larynx and the pseudo-volume was used for a steep dose fall-off immediately outside the target, the SIB WF-IMRT technique would have led to a larynx dose comparable to that achieved with J-IMRT. Therefore, in our current practice we use the SIB WF-IMRT technique, which does not have the problem of setup error at the match line for treatment of nasopharyngeal carcinoma.
10.1007/s12194-011-0119-0
pubmed_946_7832
The proliferative capacity of the presumed pluripotent haematopoietic stem cell (CFUs) was assessed. Repeated (monthly) depletion of this cell population vivo by the alkylating agent TEM was followed by repopulation of the haematopoietic system. The cumulative number of doublings of the CFUs population was estimated to be about 158. It is therefore concluded that either the CFUs do not represent the stem cell population; or, any intrinsic lifespan must be beyond this number of cell doublings.
pubmed_946_7832
pubmed_1121_10623
Hydroquinone (HQ) exposure is common as it is a natural component of plant-based foods and is used in some fingernail polishes, hair dyes, and skin lighteners. Industrially it is used as an antioxidant, polymerization inhibitor, and reducing agent. The current study was undertaken to determine whether HQ may cause DNA damage in an in vivo comet assay in F344 rats. DNA strand breaks were assessed in the duodenum as a direct tissue contact site, the testes, and the liver and kidneys, which were tumor sites in bioassays. Rats were exposed to HQ by gavage at 0, 105, 210, or 420 mg/kg/day. At all dose levels, mean % tail intensity and tail moment values for all tissues in animals given HQ were similar to the control. There were no statistically significant increases in tail intensity in any tissue following HQ treatment of male and female rat and data for all animals fell within the available historical control ranges for each tissue. There was no evidence of induction of DNA damage in cells isolated from duodenum, kidney or liver of male and female rats or in the testes of male rats following exposure to HQ at a dose levels up to 420 mg/kg/day, which caused acute renal necrosis.
10.1016/j.toxrep.2021.01.005
pubmed_436_6565
Sarcomas represent a heterogeneous, challenging, and rare group of tumors that present many management challenges. In this article, the authors concentrate on the radiotherapeutic management of sarcomas occurring in the most common locations: the extremities, the trunk, and the retroperitoneum. An overview of the current radiotherapeutic management of soft tissue sarcoma is presented in addition to a discussion of how surgical management may affect radiotherapeutic management. Finally, the authors describe current controversies surrounding the appropriate management of sarcomas with radiotherapy and describe ongoing studies and future areas of research.
10.1016/j.suc.2008.03.005
pubmed_795_17376
Orlistat (tetrahydrolipostatin) is a lipase inhibitor which is used, in conjunction with appropriate dietary control, for the treatment of obesity. It is generally deemed to be a safe drug, which mainly exerts a topical action on the stomach and small bowel, with negligible systemic absorption and oral bioavailability. Consequently, its adverse effects have largely been limited to relatively mild gastrointestinal disorders. However, there have been recent, published reports of non-fatal acute hepatitis and systemic hypertension associated with its use. The present case concerns a 62-year-old male who died from massive hepatocellular necrosis, consistent with drug-induced, fulminant hepatitis, associated with the use of oral orlistat, presumably administered at the recommended daily dose of 360 mg. It is postulated that this may represent a rare idiosyncratic reaction to the drug.
10.1177/002580240204200405
pubmed_134_11211
Communication in biological systems must deal with noise and metabolic or temporal constraints. We include these constraints into information theory to obtain the distributions of signal usage corresponding to a maximal rate of information transfer given any noise structure and any constraints. Generalized versions of the Boltzmann, Gaussian, or Poisson distributions are obtained for linear, quadratic and temporal constraints, respectively. These distributions are shown to imply that biological transformations must dedicate a larger output range to the more probable inputs and less to the outputs with higher noise and higher participation in the constraint. To show the general theory of reliable communication at work, we apply these results to biochemical and neuronal signaling. Noncooperative enzyme kinetics is shown to be suited for transfer of a high signal quality when the input distribution has a maximum at low concentrations while cooperative kinetics for near-Gaussian input statistics. Neuronal codes based on spike rates, spike times or bursts have to balance signal quality and cost-efficiency and at the network level imply sparseness and uncorrelation within the limits of noise, cost, and processing operations.
10.1103/PhysRevE.70.061910
pubmed_99_1032
The effect of long acting progestational contraceptive injection, norethisterone-oenanthate was studied in twenty six women. The post injection results showed a significant decrease in total lipids, free cholesterol, total cholesterol, triglycerides, phospholipids and free fatty acids.
pubmed_99_1032
pubmed_760_19658
BACKGROUND Influenza is an infectious disease, dangerous for all people, especially for some risk groups such as patients with chronic diseases and health care workers. But most of the people under the risk of influenza, including health care workers are not immunised because of misinformation. In this study, we aimed to determine the knowledge, beliefs and attitudes of patients with allergic rhinitis and asthma and parents of such children related to influenza vaccination. Attitudes and beliefs of physicians treating these patients about influenza vaccination were also investigated. METHODS Two different questionnaires consisting of various items related to influenza vaccine were distributed to physicians and patients and parents of children with asthma and allergic disease. RESULTS The physicians group consisted of 189 physicians from various branches. About one third of physicians from various branches reported that they did not believe the vaccine's effectiveness. Most of the participating physicians did not immunise themselves with influenza vaccination despite the fact that any patient of theirs had died due to influenza infection. Although nearly half of the 183 patients had been vaccinated with influenza vaccine, only 27% of adults and 11.7% of children had been vaccinated annually. CONCLUSIONS Asthmatic patients are not immunised regularly with influenza vaccine due to misperceptions about vaccine effectiveness and fear of adverse effects. Another important reason of this is that most the physicians caring for these patients neither immunise themselves nor recommend the vaccine to their patients.
10.1016/j.aller.2016.08.003
pubmed_324_4405
Painful shoulder is a common painful condition among patients. Apart from acute traumatic lesions such as fractures, dislocations, contusions, sprains and ruptured tendons, 85 to 90% of painful shoulders are due to adhesive capsulitis, acute or chronic calcific tendinitis, bursitis, bicipital tendinitis and lesions of the musculotendinous cuff. Arthritis is the cause of less than 5% of painful shoulders. For evaluating conditions of shoulder joint, X-ray has been regarded as only method of choice for long time. Magnetic resonance imaging (MRI) is an alternative procedure but the cost limits its utilization especially in Bangladesh. Ultrasonography is an effective imaging modality in the evaluation of both rotator and non-rotator cuff disorders. Because of low cost and availability, it can be an alternative procedure for the diagnosis of painful shoulder. The present study was conducted to assess ultrasonography as a useful modality in evaluating cases of shoulder pain and to compare the findings with X-ray findings. Thirty two patients with shoulder pain were evaluated by X-ray and Ultrasonography (USG). Clinical diagnosis was done for correlation. To identify the cause of shoulder pain, 100% patients were found normal in plain X-ray. On Ultrasonography (USG) 12.5% patients had displaced long head of biceps, 21.9% had biceps tendinitis, and 3.1% had bursitis. In the assessment of shoulder pathology, USG had a sensitivity of 73.3%, specificity of 88.2%, Positive predictive value (PPV) of 84.6%, Negative predictive value (NPV) of 78.9% and an accuracy of 81.3%. USG is a useful modality for evaluation the shoulder joint in case of painful shoulder even plain X-ray is non conclusive.
pubmed_324_4405
pubmed_842_25527
PURPOSE OF REVIEW To review and discuss the evidence and arguments to combine enteral nutrition and parenteral nutrition in the ICU, in particular with reference to the Early Parenteral Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients (EPaNIC) study. RECENT FINDINGS The EPaNIC study shows an advantage in terms of discharges alive from the ICU when parenteral nutrition is delayed to day 8 as compared with combining enteral nutrition and parenteral nutrition from day 3 of ICU stay. SUMMARY The difference between the guidelines from the European Society of Enteral and Parenteral Nutrition in Europe and American Society for Parenteral and Enteral Nutrition/Society of Critical Care Medicine in North America concerning the combination of enteral nutrition and parenteral nutrition during the initial week of ICU stay was reviewed. The EPaNIC study clearly demonstrates that early parenteral nutrition in the ICU is not in the best interests of most patients. Exactly at what time point the combination of enteral nutrition and parenteral nutrition should be considered is still an open question.
10.1097/MCO.0b013e32835036a9
pubmed_322_14930
CD4+ helper T cells play key and diverse roles in inducing adaptive immune responses in vertebrates. The CD4 molecule, which is found on the surfaces of CD4+ helper T cells, can be used to distinguish subsets of helper T cells. Teleosts are the oldest living species with bona-fide CD4 coreceptors. Although some components of immune systems of teleosts and mammals appear to be similar, many physiological differences are represented between them. Previous studies have shown that two CD4 paralogs are present in teleosts, whereas only one is present in mammals. Therefore, in this review, the CD4 molecular structure, expression profiles, subpopulations, and biological functions of teleost CD4+ helper T cells were summarized and compared with those of their mammalian counterparts to understand the differences in CD4 molecules between teleosts and mammals. This review provides suggestions for further studies on the CD4 molecular function and regulatory mechanism of CD4+ helper T cells in teleost fish and will help establish therapeutic strategies to control fish diseases in the future.
10.1016/j.vetimm.2021.110316
pubmed_918_2625
BACKGROUND In the United States, patients who have breast cancer experience significant economic burden compared with those who have other types of cancers. Cancer-related economic burden is exacerbated by adverse treatment effects. Strategies to resolve the economic burden caused by breast cancer and its adverse treatment effects have stemmed from the perspectives of health care providers, oncology navigators, and other subject-matter experts. For the current study, patient-driven recommendations were elicited to reduce economic burden after 1) breast cancer and 2) breast cancer-related lymphedema, which is a common, persistent adverse effect of breast cancer. METHODS Qualitative interviews were conducted with 40 long-term breast cancer survivors who were residents of Pennsylvania or New Jersey in 2015 and were enrolled in a 6-month observational study. Purposive sampling ensured equal representation by age, socioeconomic position, and lymphedema diagnosis. Semistructured interviews addressed economic challenges, supports used, and patient recommendations for reducing financial challenges. Interviews were coded, and representative quotes from the patient recommendations were analyzed and reported to illustrate key findings. RESULTS Of 40 interviewees (mean age, 64 years; mean time since diagnosis, 12 years), 27 offered recommendations to reduce the economic burden caused by cancer and its adverse treatment effects. Nine recommendations emerged across 4 major themes: expanding affordable insurance and insurance-covered items, especially for lymphedema treatment (among the 60% who reported lymphedema); supportive domestic help; financial assistance from diagnosis through treatment; and employment-preserving policies. CONCLUSIONS The current study yielded 9 actionable, patient-driven recommendations-changes to insurance, supportive services, financial assistance, and protective policies-to reduce breast cancer-related economic burden. These recommendations should be tested through policy and programmatic interventions.
10.1002/cncr.32012
pubmed_531_9187
The risk of non-A, non-B hepatitis transmission by an intravenous immunoglobulin (IVIG) preparation was assessed in a prospective multicenter trial in 68 patients with primary immunodeficiency disorders (40 children or adolescents and 28 adults). During the 4-week prestudy evaluation period the clinical examinations and liver function tests including alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, alkaline phosphatase, and bilirubin were normal in all patients. The treatment consisted of three infusions of 200 mg IVIG (pH 4; pepsin procedure) per kilogram body weight at 2-week intervals. During the observation period of 24 weeks following the first infusion of the study IVIG, the patients were monitored at regular time intervals. No clinical and laboratory signs of hepatitis or liver dysfunction were noticed. All patients completed the study. In 5 patients, one isolated alanine aminotransferase value and in another patient one gamma-glutamyl transpeptidase value were moderately elevated, but always below 2.5 times the upper limit of the reference range. Similar isolated and transient elevations were observed for aspartate aminotransferase and alkaline phosphatase. It was concluded that the IVIG preparation did not transmit non-A, non-B hepatitis or other viral liver diseases.
10.1111/j.1423-0410.1991.tb00953.x
pubmed_49_4687
Basal cell epithelioma of the lip. An analysis of 42 cases. The authors carried out a histopathological and epidemiological study of 42 basal cell epitheliomas of the lip. Both sexes were equally affected (male to female ratio 0.9:1) but the females were significantly older than the males (mean age: 70.7 years vs 62.3 years respectively). The incidence in the province of Trieste was 1.44%... for males and 1.46%... for females. More than 80% of the lesions (35 cases) consisted in solid forms, but there were also 4 cheratotic basal cell epitheliomas, 1 fibrosing epithelioma and 1 basosquamous epithelioma. In 2 of the males there was a recurrence a year after the surgical exeresis and in 6 cases another epithelioma was synchronous or metachronous to the lip epithelioma. Despite the fact that in 3 cases invasion of the muscular wall was noted and in another case the neoplasm had infiltrated and eroded the left nostril and the lower part of the septum, no patient died from the tumour nor were any metastasis observed.
pubmed_49_4687
pubmed_1047_9111
A recent study of Fe(II).bleomycin-mediated DNA strand scission suggested that the metal binding domain of the drug is also the primary determinant of the observed sequence selectivity of strand scission (Carter, B. J., Murty, V. S., Reddy, K. S., Wang, S.-N., and Hecht, S. M. (1990) J. Biol. Chem. 265, 4193-4196). Although it is well established that the bithiazole moiety+C-terminal substituent of bleomycin are required for DNA binding, the role of the bithiazole in sequence-selective DNA recognition remains unclear. To determine whether the bithiazole moiety exhibits an intrinsic DNA binding selectivity, three synthetic EDTA-conjugated bithiazole derivatives were used to mediate DNA cleavage in the presence of Fe2+ and dithiothreitol. Incubation of these Fe(II).EDTA-bithiazoles in the presence of a 5'-32P end-labeled DNA duplex resulted in strand scission at every position to essentially the same extent. The relative cleavage efficiencies among the bithiazoles were a strong function of their ionic state. These findings imply that the bithiazoles can bind to many sites on the DNA; they support a model of bleomycin-DNA interaction in which the bithiazole moiety+C-terminal substituent are required only for DNA binding, whereas the metal binding domain is responsible for metal ion coordination and oxygen activation as well as being the primary determinant of sequence-selective DNA cleavage.
pubmed_1047_9111
pubmed_370_6602
Patients with severe factor VIII deficiency hemophilia require recurrent factor VIII infusion for complications of their bleeding diathesis, resulting in depletion of peripheral infusion sites. At the University of North Carolina in Chapel Hill, many hemophiliac patients are seen yearly. Therapy for some of these patients requires recurrent administration of factor VIII concentrates. Recent experience with two patients who had exhausted peripheral venous infusion sites necessitated innovative vascular access. Our favorable experience with subcutaneous bovine heterografts prompted use of this technique. An easily cannulated infusion site resulted and facilitated factor VIII concentrate infusion. Patients with bleeding disorders represent a whole new population who may require vascular access. Our experience suggests that it is practical to expand the scope of access to include these patients.
pubmed_370_6602
pubmed_330_21983
Soon after the appearance of West Nile virus (WNV) in North America, a number of public health authorities designated the American Crow (Corvus brachyrhynchos) a sentinel for WNV detection. Although preliminary studies have suggested a positive association between American Crow mortality and increased risk of WNV infection in humans, we still know little about dynamic variation in American Crow mortality, both baseline levels and mortality associated with WNV. We hypothesized that the complex social behavior of American Crows, which is shaped by age and seasonal factors, influences both baseline mortality and WNV mortality in American Crow populations. We examined American Crow mortality data from Quebec for the 2005 WNV surveillance year, which lasted from 5 June to 17 September 2005. The variables of interest were age, gender, body condition index, time of year, and land cover. We used a log-linear model to examine baseline mortality. Logistic regression and general linear regression models were constructed to examine variables associated with mortality due to WNV. We found that both age and time of year were key variables in explaining baseline mortality. These two variables were also risk factors for WNV mortality. The probability that a carcass tested positive for WNV increased with the age of the dead bird and as summer progressed. WNV-positive carcasses also had a lower body condition index than WNV-negative carcasses. We believe that the first major wave of American Crow mortality observed in the early summer of 2005 was the result of natural mortality among young American Crows. Because this mortality was not linked to WNV, it appears that American Crow may not be a good species for early detection of WNV activity. Our data also suggest that second-year American Crows play a major role in propagating WNV during their movements to urban land covers during midsummer.
10.7589/0090-3558-46.1.195
pubmed_637_17753
The edge structure of graphene has a significant influence on its electronic properties. However, control over the edge structure of graphene domains on insulating substrates is still challenging. Here we demonstrate edge control of graphene domains on hexagonal boron nitride (h-BN) by modifying the ratio of working-gases. Edge directions were determined with the help of both moiré patterns and atomic-resolution images obtained via atomic force microscopy measurements. It is believed that the variation of graphene edges is mainly attributed to different growth rates of armchair and zigzag edges. This work demonstrates a potential approach to fabricate smooth-edge graphene ribbons on h-BN.
10.1039/c7nr02578e
pubmed_213_7709
The results of two-step treatment of 62 patients with chronic prostatitis are presented. The first-step treatment was given at the clinic of the Urologic Research Institute of the RSFSR Ministry of Health, and the second step was completed at the Zheleznovodsk Urologic Clinic of the Pyatigorsk Research Institute of Health Resort Treatment and Physiotherapy. In addition to its medical aspect, treatment for chronic prostatitis has significant social implications, as chronic prostatitis mostly affects males of young or middle age, with the inflammation persisting for long periods of time and leading to sexual and reproductive disorders as well as psychoneuroses. Since chronic prostatitis is regarded as an inflammatory disease of infectious-immunologic etiology, with both parenchymal and interstitial tissues of the prostatic gland affected, the patients underwent antibacterial treatment, adjusted to the causative agent's sensitivity to antibacterial drugs, and the availability of physiotherapeutic procedures in hospital as the first stage of treatment. Those to whom further rehabilitation was indicated were referred to the Zheleznovodsc Urologic Clinic where they were given a treatment course making use of the natural factors: oral and external administration of mineral waters of the Smirnovsky and Slavyanovsky springs, mud treatments and physiotherapy where indicated. Treatment was designed to improve microcirculation in prostatic tissues, and used natural factors, capable of normalizing and activating systemic protective potentials. There were good results (considerably improved general condition, both subjectively felt and objectively documented) in 78%.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed_213_7709
pubmed_202_9537
Liposomes are effective carrier systems for prolonged drug release. As all other drug formulations for parenteral use, the safety of liposomal formulations should be established before clinical application. In this study, some safety aspects of intramuscularly injected (single dose) "gel-state" type liposomes and the ability of liposome encapsulation to diminish irritating effects of intramuscularly applied drugs were studied by histopathological analysis over a period of 14 days in mice. Injection of saline solution showed no tissue reaction at the injection site. Intramuscular injection of liposomes alone showed an infiltrative reaction consisting of a population of macrophages. Within this population fat cells were present. In time, the population of macrophages present at the injection site was largely replaced by loose connective tissue. Novaminsulfon (NS) injected intramuscularly in "free" form is a strongly irritating drug, causing hemorrhage, cell necrosis, inflammatory reactions and eventually fibrosis. However, NS being encapsulated in liposomes was hardly more irritating than liposomes alone. The same was true for liposome-encapsulated chloroquine and free chloroquine. When sustained-release of a drug is therapeutically desirable, the parenteral application of a liposome-encapsulated formulation can be considered for drugs, in particular for those drugs causing tissue injury at the injection site.
pubmed_202_9537
pubmed_1015_11877
Plasma levels after single doses of 300 mg and 600 mg fenoprofen were measured in 10 elderly patients with osteoarthritis. Mean peak concentrations occurred at 4 hours. For the 300 mg dose, this was similar to levels obtained in an earlier study with young volunteers but the drug was absorbed more slowly in the elderly, peak levels being achieved approximately 2 hours later. There was no significant difference in the area under the plasma concentration-time curves compared with previous studies, and plasma levels after multiple doses showed no evidence of drug accumulation. Haematological and biochemical values were within acceptable limits for this patient population. It is concluded that fenoprofen is reliably but more slowly absorbed in the elderly, and that normal dosages can be utilized.
pubmed_1015_11877
pubmed_885_782
BACKGROUND Lens epithelium-derived growth factor (LEDGF/p75) is a cellular co-factor of HIV-1 integrase (IN) that tethers the viral pre-integration complex to the host cell chromatin and determines the genome wide integration site distribution pattern of HIV-1. Recently, we demonstrated that HIV-1 replication was reduced in LEDGF/p75 knockout (KO) cells. LEDGF/p75 KO significantly altered the integration site preference of HIV-1, but the pattern remained distinct from a computationally generated matched random control set (MRC), suggesting the presence of an alternative tethering factor. We previously identified Hepatoma-derived growth factor related protein 2 (HRP-2) as a factor mediating LEDGF/p75-independent HIV-1 replication. However, the role of HRP-2 in HIV-1 integration site selection was not addressed. FINDINGS We studied the HIV-1 integration site distribution in the presence and absence of LEDGF/p75 and/or HRP-2, and in LEDGF/p75-depleted cells that overexpress HRP-2. We show that HRP-2 functions as a co-factor of HIV-1 IN in LEDGF/p75-depleted cells. Endogenous HRP-2 only weakly supported HIV-1 replication in LEDGF/p75 depleted cells. However, HRP-2 overexpression rescued HIV-1 replication and restored integration in RefSeq genes to wild-type levels. Additional HRP-2 KD in LEDGF/p75-depleted cells reduces integration frequency in transcription units and shifts the integration distribution towards random. CONCLUSIONS We demonstrate that HRP-2 overexpression can compensate for the absence of LEDGF/p75 and indicate that the residual bias in integration targeting observed in the absence of LEDGF/p75 can be ascribed to HRP-2. Knockdown of HRP-2 upon LEDGF/p75 depletion results in a more random HIV-1 integration pattern. These data therefore reinforce the understanding that LEDGF/p75 is the dominant HIV-1 IN co-factor.
10.1186/1742-4690-9-84
pubmed_1012_15135
The release of acid from the aleurone layer and scutellum of barley (Hordeum vulgare L. cv Himalaya) was investigated. Aleurone layers isolated from mature barley grains acidify the external medium by releasing organic and phosphoric acids. Gibberellic acid and abscisic acid stimulate acid release 2-fold over control tissue incubated in 10 mM CACl2. Gibberellic acid causes medium acidification by stimulating the release of phosphoric and citric acids, whereas abscisic acid stimulates the release of malic acid. The accumulation of these acids in the incubation medium buffers the medium against changes in pH, particularly between pH 4 and 5. The amounts of amino acids that accumulate in the medium are low (2-12 nmol/layer) compared to other organic and phosphoric acids (100-500 nmol/layer). The scutellum does not play a major role in medium acidification but participates in the uptake of organic acids. The organic acid composition of the starchy endosperm changes after 3 d of imbibition; malic, succinic, and lactic acids decrease, whereas citric and phosphoric acids remain unchanged or increase. These results indicate that during postgerminative growth, the acidity of the starchy endosperm is maintained by acid production by the aleurone layer.
10.1104/pp.108.2.769
pubmed_1040_14430
University of California, Davis (UCD) line 140 chickens develop a dysgammaglobulinemia characterized as selective 7S immunoglobulin (Ig) deficiency with elevated serum IgM levels. To study the role of bursal development on the expression of dysgammaglobulinemia in these birds, we examined the effect of bursacyte transfer to line 140 birds and parabiosis between UCD 140 and a control line of chickens on changes in serum IgM and 7S Ig levels. Bursacyte transfer was performed by injecting 18-day UCD 140 embryos (which had been cyclophosphamide treated on Day 15) with bursacytes from major histocompatibility complex B-matched control line (11 X 58) F1 birds. This transfer produced little change in the incidence of dysgammaglobulinemia in UCD 140 transfer birds (56%) compared to unmanipulated line 140 birds (60%). These data reflect a failure of line 140, rather than technique, because successful reconstitution was seen using line 11 X 58 birds injected with 11 X 58 bursacytes. In contrast, the generation of UCD 140/line 11 X 58 chimeras significantly reduced the incidence of dysgammaglobulinemia in line UCD birds. Indeed, fusion of the chorioallantoic vascular system (parabiosis) of UCD 140 and 11 X 58 embryos on Day 15 decreased the frequency of dysgammaglobulinemia of UCD 140 parabionts to 14% compared to 66% in unmanipulated line 140 controls. The success of parabiosis was 83% as determined by demonstrating chimerism with allogeneic blood groups. Moreover, the frequency of dysgammaglobulinemia in the 17% of parabionts that did not reveal chimerism was similar to unmanipulated UCD 140 chickens.
10.1016/0090-1229(85)90033-9
pubmed_707_21216
BACKGROUND The ideal treatment for upper ureteric calculi is still debatable, particularly for patients with large, impacted ureteric calculi. Retroperitoneal laparoscopic ureterolithotomy (RLU) may be a worthwhile alternative to open surgery. In this study, we retrospectively evaluated our clinical experience associated with RLU performed for impacted upper ureteric calculi (>1.5 cm) help urologists in clinical practice and provide a reference for clinical work. METHODS A total of 64 cases (38 males; 26 females) with impacted upper ureteric calculi between April 2018 and January 2020 were analyzed retrospectively. The basic information of the included research subjects are as follows: The mean age was 50.8±25.4 years. The largest stone diameter was 1.8±0.3 cm. The mean stone retention time was 42±11 days. The mean degree of hydronephrosis was 2.8±1.2 cm. RESULTS The mean operative time was 85.4±18.3 minutes. The mean hospital duration was 7.5±1.8 days. The stone-free rate was 98.4%. Two patients required additional intervention. Post-operative fever developed in 3 patients. The decrease in hemoglobin levels was 7.8±3.6 g/L. The increase in procalcitonin (PCT) level was 3.7±1.8 ng/mL. No major complications, for example, sepsis, bleeding, bowel injury, or cardiopulmonary morbidities, were reported. CONCLUSIONS RLU should be regarded as an excellent first line treatment modality for impacted upper ureteric calculi (>1.5 cm) owing to the high success rate, low complication rate, and the short length of operative time and hospital duration.
10.21037/tau-21-1155
pubmed_715_8154
A genetic analysis of a female with a 46,XY genotype and typical symptoms of the complete androgen insensitivity syndrome (CAIS) was conducted. The patient was diagnosed with an abdominal tumor due to the presence of a Sertoli cell adenoma in both gonads. Multiple temperature single-stranded conformational polymorphism (MSSCP) and sequence analyses of the androgen receptor gene revealed a c.C2754 > T mutation in exon 6. This mutation, which has not been previously reported, alters a Gln codon to a termination codon (Q798X). This results in the interruption of the amino acid sequence of the androgen receptor within the ligand-binding domain between helices VII and VIII. The truncated form of the receptor is devoid of 123 amino acids at the carboxyl end, a major part of the ligand-binding domain, and the AT2 sequence responsible for the activation of the transcription. It was concluded that the novel c.C2754 > T transition rendered the androgen receptor incapable of both ligand binding and activating the transcription, and was the cause of CAIS in the patient.
10.1080/09513590400012127
pubmed_1118_15941
Background Although studies have shown that cell pyroptosis is involved in the progression of asthma, a systematic analysis of the clinical significance of pyroptosis-related genes (PRGs) cooperating with immune cells in asthma patients is still lacking. Methods Transcriptome sequencing datasets from patients with different disease courses were used to screen pyroptosis-related differentially expressed genes and perform biological function analysis. Clustering based on K-means unsupervised clustering method is performed to identify pyroptosis-related subtypes in asthma and explore biological functional characteristics of poorly controlled subtypes. Diagnostic markers between subtypes were screened and validated using an asthma mouse model. The infiltration of immune cells in airway epithelium was evaluated based on CIBERSORT, and the correlation between diagnostic markers and immune cells was analyzed. Finally, a risk prediction model was established and experimentally verified using differentially expressed genes between pyroptosis subtypes in combination with asthma control. The cMAP database and molecular docking were utilized to predict potential therapeutic drugs. Results Nineteen differentially expressed PRGs and two subtypes were identified between patients with mild-to-moderate and severe asthma conditions. Significant differences were observed in asthma control and FEV1 reversibility between the two subtypes. Poor control subtypes were closely related to glucocorticoid resistance and airway remodeling. BNIP3 was identified as a diagnostic marker and associated with immune cell infiltration such as, M2 macrophages. The risk prediction model containing four genes has accurate classification efficiency and prediction value. Small molecules obtained from the cMAP database that may have therapeutic effects on asthma are mainly DPP4 inhibitors. Conclusion Pyroptosis and its mediated immune phenotype are crucial in the occurrence, development, and prognosis of asthma. The predictive models and drugs developed on the basis of PRGs may provide new solutions for the management of asthma.
10.3389/fimmu.2022.937832
pubmed_109_1763
Sir Dugald Baird sketches the history of abortion legislation in Great Britain from the beginning of the century. In his views the 1967 Abortion Act has been one of the most important and beneficial pieces of social legislation enacted in Britain in the last 100 years. It has, however, brought problems both of administration in the hospitals and to individual doctors and nurses, particularly when the patients are young single women and even schoolgirls. One of the consequences of the Abortion Act has been a fall in maternal mortality and perinatal mortality rates. Abortion does not seem to be followed by serious emotional sequelae. Nevertheless recent changes in sexual mores have introduced new and serious social problems which are discussed in relation to the role of the doctor in his relationship with patients seeking abortion.
10.1136/jme.1.3.122
pubmed_468_15633
BACKGROUND Education for medical students is crucial to providing pediatric palliative care (PPC). However, few comprehensive curricula of PPC exist in Japan. OBJECTIVE This study aimed to identify and explore the need for education of, as well as the impact of that education on, medical students in Japan. PARTICIPANTS The participants were 5th-year medical students (n = 30) who studied in our hospital from April 2009 to March 2010. DESIGN/METHODS The first survey questionnaire was administered before, during, and after a small group lecture on PPC, followed by a discussion. The lecture discussed and imparted knowledge about general principles of PPC. The second survey questionnaire was administered in September 2010 to determine students understanding and attitudes about PPC. RESULTS In the first survey, none of the students reported any exposure to PPC through textbooks or lectures prior to the lecture. In addition, all of them defined PPC as pain management in end-of-life care for children with cancer. The survey also indicated that after the lecture, they understood the principles of PPC well. Although they scored low in their understanding of PPC in the second survey, their attitude toward the lecture was positive. DISCUSSIONS/CONCLUSIONS This study provided the first opportunity to effectively understand the effect of education on PPC in the short term. However, this effect was inadequate in the long term. Development of organized medical education systems with a primary focus on PPC is urgently needed. Discussion with professionals from multiple disciplines with regard to ethical, legal, and cultural issues, and social consensus are necessary to develop good educational systems.
10.1089/jpm.2010.0475
pubmed_216_18356
Aspergillus carbonarius is an ochratoxin producing fungus that has been considered to be responsible of the ochratoxin A (OTA) contamination in grapes and wine. In order to monitor and quantify A. carbonarius, a specific primer pair Ac12RL_OTAF/Ac12RL_OTAR has been designed from the acyltransferase (AT) domain of the polyketide synthase sequence Ac12RL3 to amplify 141 bp PCR product. Among the mycotoxigenic fungi tested, only A. carbonarius gave a positive result. This specific primer pair was also successfully employed in real-time PCR conjugated with SYBR Green I dye for the direct quantification of this fungus in grape samples. A positive correlation (R(2)=0.81) was found between A. carbonarius DNA content and OTA concentration in 72 grape samples, allowing for the estimation of the potential risk from OTA contamination. Consequently, this work offers a quick alternative to conventional methods of OTA quantification and mycological detection and quantification of A. carbonarius in grapes.
10.1016/j.ijfoodmicro.2006.11.006
pubmed_480_11506
From 6 samples of tropically grown fruits and leaves, 10 lactic acid bacteria belonging Leuconostoc, Weissella, and Lactobacillus species were isolated and identified by 16S rRNA gene sequencing and (GTG)5 fingerprinting. Acidification kinetics determined from BHI broth cultures showed genus-related patterns. In particular, Weissella cibaria appeared to act as a potent acidifier. Tolerance of isolates to acid, oxidative, or salt stress was highly variable and strain dependent. Isolate S14 (Leuconostoc pseudomesenteroides) growth was not affected by the presence of 0.05% H2O2, while Lactobacillus spp. isolates (S17 and S29) were the most tolerant to pH 4.5. The growth of 4 isolates, S5 (Leuconostoc mesenteroides), S14 and S10 (Leuconostoc pseudomesenteroides), and S27 (W. cibaria), was not affected by 5% NaCl. Nutritional beneficial properties were examined through measurement of antioxidant activities of short-term fermented pineapple juice, such as LDL oxidation and polyphenol content, and through exopolysaccharide formation from sucrose. Two isolates, S14 and S27, increased the antioxidant capacity of pineapple juice. The robust capacity of W. cibaria and of Leuconostoc pseudomesenteroides for vegetable lactic fermentation aimed to ameliorate food nutritional and functional quality was highlighted.
10.1139/cjm-2015-0624
pubmed_312_9750
Induction of anesthesia with fentanyl for coronary artery bypass grafting decreased (P less than .05) plasma atrial natriuretic peptide (ANP) concentrations from awake values in twelve patients. During a steady state of anesthesia before surgery, isotonic saline solution (10 mL/kg) was infused simultaneously with the elevation of the lower extremities in six patients, while six subjects served as controls receiving no volume loading and having no leg raising. The ANP levels returned to the awake values in the volume-loaded patients, while plasma ANP remained at anesthetized baseline levels in the control subjects (P less than .01 between the groups). Ten minutes after the end of the loading procedure, plasma ANP had begun to decrease again towards the postinduction level in the loaded group, but a significant (P less than .05) difference was still observed between the groups. These changes in ANP levels paralleled those of cardiac filling pressures. In conclusion, the results suggest that the degree of distention of the atria regulates the secretion of atrial natriuretic peptide into the circulation in patients anesthetized with fentanyl.
10.1016/s0888-6296(87)96814-1
pubmed_663_25173
The occurrence of antimicrobial resistance in Staphylococcus pseudintermedius from skin and ear infections in a representative sample of dogs unexposed to antimicrobial treatment before sampling was examined. The obtained isolates were further examined for genetic polymorphism and genetic background of resistance. A total of 59 isolates of S. pseudintermedius originating from 96 samples of 91 dogs in five different regions in Norway were included in this study. Susceptibility testing was performed using a broth dilution method. Resistant isolates were subjected to polymerase chain reaction for detection of resistance genes. All isolates were subjected to pulsed-field gel electrophoresis to examine the genetic polymorphism. In total, 19% of the isolates were susceptible to all antimicrobial agents included. Resistance to penicillin was most prevalent (70%), followed by resistance to fusidic acid (49%) and oxytetracycline (42%). Resistance to quinolones or cephalosporins was not observed. Resistance to penicillin, tetracycline, and erythromycin was mediated by the blaZ beta-lactamase gene, the tetM gene, and the ermB gene, respectively. One of the fusidic acid-resistant isolates harbored a fusC gene, whereas the mechanisms involved in resistance in the other fusidic acid-resistant isolates remained unknown. Pulsed-field gel electrophoresis showed a high genetic polymorphism of S. pseudintermedius. This study indicates that the occurrence of antimicrobial resistance is common among S. pseudintermedius from dogs unexposed to antimicrobial treatment before sampling, and that there is a high genetic polymorphism among S. pseudintermedius.
10.1089/mdr.2009.0865
pubmed_698_3329
Recent reports suggest that soy protein may reduce the risk of osteoporosis in peri- and postmenopausal women. The objective of this study was to examine whether soy supplementation exerts beneficial effects on serum and urinary biomarkers of bone metabolism in postmenopausal women, regardless of whether or not they are on hormone replacement therapy (HRT). A total of 71 women were randomly assigned to either soy protein (SP) or milk-based protein (MBP), 40 g daily for 3 months, in a double-blind parallel design. Forty-two women completed the study (20 on SP and 22 on MBP). Overall, both protein supplements positively influenced serum IGF-I, known to correlate with bone formation. However, SP had a more pronounced effect on IGF-I than MBP. Urinary deoxypyridinoline (Dpd) excretion, a specific biomarker of bone resorption, was significantly reduced by SP, but not by MBP when all women were included. Furthermore, women on MBP experienced a 33% increase in urinary calcium excretion, whereas SP did not have such an effect. To evaluate whether SP affects women differently on the basis of their HRT status, data from women on HRT (n = 22) and those not on HRT (n = 20) were analyzed separately. The subanalysis of the data indicated that SP had the greatest impact on serum IGF-I (an increase of 97%) in the women not on HRT. The changes in urinary Dpd due to SP were only observed in women not on HRT, indicating that the overall decrease in Dpd occurred with SP in the absence of HRT. These results indicate that soy protein may positively influence bone and calcium homeostasis in postmenopausal women, particularly those not on HRT.
10.1210/jc.2002-020849
pubmed_488_7648
The relative efficacy of potassium-induced ischemic arrest using buffered, isosmotic potassium (25 mEq/liter) was compared with hypothermic arrest in an experimental protocol employing an intact canine heart preparation. Myocardial function (LVSW, dp/dt max), serum creatine phosphokinase levels, myocardial perfusion, and light and electron microscopical examination of the heart were assessed in five groups of 5 dogs each. There was one control group (90 minutes of bypass, no anoxia) and four experimental groups, each subjected to 1 hour of ischemic arrest and 30 minutes of reperfusion, comparing normothermic ischemic arrest (NIA), hypothermic ischemic arrest (myocardial temperature less than 25 degrees C) (HIA), normothermic potassium arrest (NKA), and hypothermic potassium arrest (HKA). Myocardial function decreased significantly following NIA and NKA but remained essentially equal in the control, HIA and HKA groups. Serum creatine phosphokinase analysis documented a significant increase in each group of animals: 2,250 mU after NIA, 1,778 mU after NKA, 1,388 mU after HIA, 1,220 mU after HKA, and 838 mU after control bypass. Left ventricular myocardial perfusion was unmeasurably low after NIA, reduced to 111 m/100 gm of tissue/min after NKA, and increased to 165 to 188 ml/100 gm/min in the control, HIA and HKA groups. Electron microscopical studies showed a range of myocardial changes, from probably irreversible damage after NIA to similar but less diffuse changes after NKA, and to potentially reversible changes after HKA and HIA with the least alteration from control after HIA. The results indicate that potassium arrest alone is not as effective as hypothermia in preventing ischemic injury, and the combination of hypothermia with a single 150 cc administration of potassium (25 mEq/liter) does not appear to provide significant additional protection.
10.1016/s0003-4975(10)64474-8
pubmed_825_5489
The adsorption, at hydroxyapatite surfaces of neutral cystatin SN, acidic cystatin S and the phosphoserine-containing acidic cystatin S1 was compared to that of statherin. The effects of these adsorbed proteins on the constant-composition growth kinetics of hydroxyapatite were also studied. The neutral cystatin SN had a higher adsorption maximum than the acidic cystatins S and S1. Although the affinity of cystatin for hydroxyapatite surfaces was lower than that of statherin, their influence on the growth kinetics of hydroxyapatite was considerably greater, with the acidic cystatin S1 being the most active. At a surface concentration of 7.0 x 10(-8) mol m-2 hydroxyapatite, the cystatins decreased the rate of crystal growth by 80-95% as compared to that in the absence of protein. At this concentration, statherin showed a growth inhibition of 40%.
10.1016/0003-9969(91)90014-l
pubmed_786_19971
A reliable method based on electrochemical measurements for the evaluation of protein interaction with small electroactive coordination compounds is proposed. Protein binding capacity of five different cationic Re(V) complexes was evaluated by means of voltammetric techniques in the absence and the presence of bovine serum albumin. The percentage of interaction between the complex and the protein was estimated from the quantitative decrease of the diffusion coefficient for the sole complex due to the addition of the protein, and therefore the formation of the protein-complex molecular ensemble. The proposed methodology was checked using cisplatin as a molecular complex probe.
10.1016/j.jinorgbio.2003.08.013
pubmed_490_21623
Xylose isomerase from Piromyces sp. E2 (PirXI) can be used to equip Saccharomyces cerevisiae with the capacity to ferment xylose to ethanol. The biochemical properties and structure of the enzyme have not been described even though its metal content, catalytic parameters, and expression level are critical for rapid xylose utilization. We have isolated the enzyme after high-level expression in Escherichia coli, analyzed the metal dependence of its catalytic properties, and determined 12 crystal structures in the presence of different metals, substrates, and substrate analogues. The activity assays revealed that various bivalent metals can activate PirXI for xylose isomerization. Among these metals, Mn2+ is the most favorable for catalytic activity. Furthermore, the enzyme shows the highest affinity for Mn2+, which was established by measuring the activation constants (Kact) for different metals. Metal analysis of the purified enzyme showed that in vivo the enzyme binds a mixture of metals that is determined by metal availability as well as affinity, indicating that the native metal composition can influence activity. The crystal structures show the presence of an active site similar to that of other xylose isomerases, with a d-xylose binding site containing two tryptophans and a catalytic histidine, as well as two metal binding sites that are formed by carboxylate groups of conserved aspartates and glutamates. The binding positions and conformations of the metal-coordinating residues varied slightly for different metals, which is hypothesized to contribute to the observed metal dependence of the isomerase activity.
10.1021/acs.biochem.7b00777
pubmed_460_21947
Depth profiles and cumulative deposition of four fallout radionuclides (7Be, 137Cs, 210Pb and 239,240Pu) were determined in presumably undisturbed soils in Taiwan. Inventories of these radionuclides in different areas correlate significantly with each other (except 7Be) and with mean annual rainfall, providing a necessary condition for the development of soil erosion studies in Taiwan. However, the data show very large spatial variability between and within landscape units, reflecting the steep topographic and meteorological gradients in the island. Thus, the application of fallout radionuclides to study soil conservation in Taiwan is expected to be a demanding task; it will call for dense sampling even at undisturbed reference sites.
10.1016/j.jenvrad.2004.03.002
pubmed_669_27185
Systemic administration of toll-like receptor (TLR) agonists have demonstrated impressive preclinical results as an anti-cancer therapy due to their potent innate immune-stimulatory properties. The clinical advancement has, however, been hindered by severe adverse effects due to systemic activation of the immune system. Liposomal drug delivery systems may modify biodistribution, cellular uptake, and extend blood circulation, and thus, potentially enable systemic administration of TLR agonists at therapeutic doses. In this study, we investigated potential barriers for the administration of TLR agonists formulated in polyethylene glycosylated (PEGylated) liposomes with regards to liposome formulation, TLR agonist, administration route, administration schedule, biodistribution, blood clearance, and anti-PEG antibodies. We found that administration of TLR agonists formulated in PEGylated liposomes led to high anti-PEG antibody titers, which upon multiple intravenous administrations, resulted in accelerated blood clearance and acute hypersensitivity reactions. The latter was found to be associated with anti-PEG IgG antibody and not anti-PEG IgM antibody opsonization. This study highlights the need to carefully design and evaluate nanoparticle delivery systems for immunotherapy as anti-nanoparticle immune responses may challenge the therapeutic application.
10.1016/j.jconrel.2021.12.033
pubmed_235_7209
(1) Objective: to explore and describe the relationship between the occupational balance of university students taking a Degree in Occupational Therapy and the problematic use of the Internet and how these, in turn, favour or not the appearance of phubbing behaviour which involves "a behaviour that happens when an individual looks at his mobile phone during a conversation with other individuals, escaping from interpersonal communication". (2) Methods: this is a quantitative descriptive study of an observational and cross-sectional nature, not experimental. The Spanish version of the Occupational Balance Questionnaire (OBQ-E), the Internet Addiction Test and the Phubbing Scale were used for data collection. 192 university students taking the Degree in Occupational Therapy of the University of Castilla-La Mancha participated (168 women and 24 men). (3) Results: the average score obtained in the OBQ-E was 38.7, indicating a moderate occupational balance; and (4) Conclusions: occupational therapy students from the Faculty of Health Sciences of the University of Castilla-La Mancha have a moderate occupational balance. Furthermore, this is negatively related to both problematic Internet use and phubbing, so a higher occupational balance indicates less Internet addiction and less phubbing.
10.3390/healthcare9020197
pubmed_781_14819
Cytopathological examination through biopsy is very important for carcinoma detection. The embedded relay lens microscopic hyperspectral imaging system (ERL-MHIS) provides a morphological image of a biopsy sample and the spectrum of each pixel in the image simultaneously. Based on the ERL-MHIS, this work develops morphological and spectral methods to diagnose oral carcinoma biopsy. In morphological discrimination, the fractal dimension method is applied to differentiate between normal and abnormal tissues. In spectral identification, normal and cancerous cells are distinguished using five methods. However, the spectra of normal and cancerous cells vary with patient. The diagnostic performances of the five methods are thus not ideal. Hence, the proposed cocktail approach is used to determine the effectiveness of the spectral methods in correlating with the sampling conditions. And then we use a combination of effective spectral methods according to the sample conditions for diagnosing a sample. A total of 68 biopsies from 34 patients are analyzed using the ERL-MHIS. The results demonstrate a sensitivity of 90 ± 4.53 % and a specificity of 87.8 ± 5.21 %. Furthermore, in our survey, this system is the first time utilized to study oral carcinoma biopsies.
10.1007/s40846-015-0052-5
pubmed_158_12888
Oxygen utilisation at the tissue level was investigated by the use of lactate-pyruvate (LP) ratio in forty women; twenty with term twin pregnancy, with a matched controlled group of twenty women with term singleton pregnancy. The lactate-pyruvate ratio in twin pregnancy was significantly higher than in singleton pregnancy at term (p < 0.05). There was also significantly higher LP ratio in advanced labour in twin pregnancy than in singleton pregnancy (p < 0.001). Similarly, the venous cord blood LP ratio of twin II was higher than in twin I. Our findings have thus demonstrated more marked anaerobic metabolism in twin pregnancy than in singleton pregnancy. Secondly, the second twin is more involved in anaerobic metabolism as a result of relative oxygen deficiency, than twin I. This may to some extent account for the higher morbidity and mortality in twin pregnancy, compared to singleton pregnancy, and in twin II compared to twin I.
10.1007/BF02505310
pubmed_748_3928
AP-2 proteins comprise a family of highly related transcription factors, which are expressed during mouse embryogenesis in a variety of ectodermal, neuroectodermal, and mesenchymal tissues. AP-2 transcription factors were shown to be involved in morphogenesis of craniofacial, urogenital, neural crest-derived, and placental tissues. By means of a partial cDNA fragment identified during an expressed sequence tag search for AP-2 genes, we identified a fifth, previously unknown AP-2-related gene, AP-2 epsilon. AP-2 epsilon encodes an open reading frame of 434 amino acids, which reveals the typical modular structure of AP-2 transcription factors with highly conserved C-terminal DNA binding and dimerization domains. Although the N-terminally localized activation domain is less homologous, position and identity of amino acids essential for transcriptional transactivation are conserved. Reverse transcriptase-polymerase chain reaction analyses of murine embryos revealed AP-2 epsilon expression from gestational stage embryonic day 7.5 throughout all later embryonic stages until birth. Whole-mount in situ hybridization using a specific AP-2 epsilon cDNA fragment demonstrated that during embryogenesis, expression of AP-2 epsilon is mainly restricted to neural tissue, especially the midbrain, hindbrain, and olfactory bulb. This expression pattern was confirmed by immunohistochemistry with an AP-2 epsilon-specific antiserum. By using this antiserum, we could further localize AP-2 epsilon expression in a hypothalamic nucleus and the neuroepithelium of the vomeronasal organ, suggesting an important function of AP-2 epsilon for the development of the olfactory system.
10.1002/dvdy.20119
pubmed_394_18113
The present study indicates that activation of dopamine D1-like receptors by administration of SKF 38393 leads to dose-dependent (doses: 5, 10 and 20 mg/kg) increases in the expression of cFos proteins in the rat paraventricular nucleus of the hypothalamus (PVN). This effect was abolished by administration of SCH 23390, a dopamine D1-like receptor antagonist (0.5 and 1 mg/kg, given 30 min before SKF 38393--10 mg/kg), suggesting that the apparent effect is specific for activation of dopamine D1-like receptors. Expression of cFos after SKF 38393 (10 mg/kg) was observed in some, but not all, CRF-immunoreactive neurons, as well as in small portion of oxytocin- but not vasopressin-immunoreactive neurons (double-immunofluorescence experiments). There were also certain populations of nuclei that showed expression of cFos but did not co-localize with the above markers. We also found that both acute and repeated (once daily for 5 consecutive days) exposure to cocaine (25 mg/kg) attenuated the induction of cFos expression triggered by SKF 38393 when administered 24 hours after single or the last dose of cocaine (25 mg/kg). Attenuation was observed at the same level after single and chronic exposure to cocaine, indicating a rapid functional down-regulation of dopamine D1-like receptors that are resistant to subsequent doses of cocaine. These data provide evidence for the functional role of dopamine D1-like receptors in the PVN and indicate a functional adaptation of dopamine D1-like receptors following a single dose of cocaine without further progression of adaptation or resistance of D1-like receptor-mediated genomic function in the course of repeated cocaine intake.
pubmed_394_18113
pubmed_936_25124
Venous air embolism (VAE) is an uncommon event consistent in the entrainment of air from any communication between the environment and the venous vasculature that could occur during central venous catheter (CVC) manipulation, and might trigger circulatory shock within minutes depending on the amount of air embolized. We present a case of a critical care patient who presented sudden clinical hemodynamic deterioration after the removal of central venous catheter. Hemodynamic evaluation with point-of-care ultrasound (POCUS) showed bubbles in both right and left heart cavities wherewith air embolism facilitated by heart septal defect was suspected. Therefore, the patient was reintubated, supported with vasopressors and a new CVC was inserted to proceed with air aspiration. Shortly after, the patient's hemodynamic status improved in terms of vital signs stabilization. 6 h after the event with optimal perfusion markers and diminished sedation, the patient showed left hemiparesis therefore a cerebral magnetic resonance (MRI) was also performed showing hyperintensity in the right precentral gyrus, so ischemic stroke without hemorrhagic transformation diagnosis was made, because of paradoxical embolism. This case report demonstrates the value of POCUS application as a diagnostic tool in the hemodynamically unstable patient.
10.1186/s13089-022-00265-7
pubmed_408_8501
A five year prospective study of equine ovarian problems requiring surgical correction was undertaken at the Ontario Veterinary College. Thirty mares were studied, of which 14 had granulosa cell tumors, six were with anovulatory persistent follicular "structures", five had ovarian hemotoma, two presented ovarian hypoplasia and one each of ovarian dysgerminoma, teratoma and abscessation. The clinical signs manifested by the affected animals were varied. The affected ovaries were removed via flank or midline laparotomy or through colpotomy. Their morphology was studied and representative portions of affected ovaries submitted for laboratory diagnosis. Postsurgical recovery and resumption of reproductive activity were satisfactory.
pubmed_408_8501
pubmed_1055_11170
Toxocara canis, Toxocara cati and Ascaris suum are worldwide-distributed zoonotic roundworms of dogs, cats and pigs, respectively. The epidemiology of these parasites in developed countries is largely unclear. Two countrywide cross-sectional serosurveys were therefore conducted in the Netherlands in 1995/1996 and 2006/2007 to investigate the prevalence, trends and risk factors for human Toxocara and Ascaris infections in the general population. The Netherlands is characterized by high pig production, freedom from stray dogs and virtual absence of autochthonous infections with the human-adapted roundworm Ascaris lumbricoides. Over the 10 years between the two serosurveys, Toxocara seroprevalence decreased significantly from 10.7 % (n = 1159) to 8.0 % (n = 3683), whereas Ascaris seroprevalence increased significantly from 30.4 % (n = 1159) to 41.6 % (n = 3675), possibly reflecting concomitant improvements in pet hygiene management and increased exposure to pig manure-contaminated soil. Increased anti-Toxocara IgGs were associated with increasing age, male gender, contact with soil, ownership of cats, cattle or pigs, hay fever, low education, high income and non-Western ethnic origin. Increased anti-Ascaris IgGs were associated with increasing age, owning pigs, low education, childhood geophagia and non-Dutch ethnic origin. Besides identifying specific groups at highest risk of Toxocara and Ascaris infections, our results suggest that these infections mainly occur through environmental, rather than foodborne, routes, with direct contact with soil or cat and pig ownership being potentially modifiable exposures.
10.1007/s00436-016-5139-6
pubmed_1115_14168
BACKGROUND Excessive proliferation of vascular smooth muscle cells and leukocytes within the artery wall is a major event in the development of atherosclerosis. The growth suppressor p27kip1 associates with several cyclin-dependent kinase/cyclin complexes, thereby abrogating their capacity to induce progression through the cell cycle. Recent studies have implicated p27kip1 in the control of neointimal hyperplasia. For instance, p27kip1 ablation in apolipoprotein-E-null mice enhanced arterial cell proliferation and accelerated atherogenesis induced by dietary cholesterol. Therefore, p27kip1 is a candidate gene to modify the risk of developing atherosclerosis and associated ischaemic events (i.e., myocardial infarction and stroke). RESULTS In this study we found three common single-nucleotide polymorphisms in the human p27kip1 gene (+326T>G [V109G], -79C>T, and -838C>A). The frequency of -838A carriers was significantly increased in myocardial infarction patients compared to healthy controls (odds ratio [OR] = 1.73, 95% confidence interval [95%CI] = 1.12-2.70). In addition, luciferase reporter constructs driven by the human p27kip1 gene promoter containing A at position -838 had decreased basal transcriptional activity when transiently transfected in Jurkat cells, compared with constructs bearing C in -838 (P = 0.04). CONCLUSIONS These data suggest that -838A is associated with reduced p27kip1 promoter activity and increased risk of myocardial infarction.
10.1186/1741-7007-2-5
pubmed_268_912
1. Broiler chickens given diets high in protein, or choice-fed on a high protein balancer, had much lower abdominal fat contents than those reported in many recent experiments. The values for males were 10.8 g/kg liveweight at 56 d at 2.43 kg liveweight in one experiment in Scotland and 16.0 g/kg liveweight at 42 d at 1.93 kg liveweight in another in South Africa. For females the values were 18.8 g/kg liveweight at 56 d at 2.15 kg liveweight in Scotland and 15.7 g/kg liveweight at 42 d at 1.60 kg in South Africa. 2. The content of abdominal fat was, in general, increased by reducing the protein content of the diet or by dilution of the food with oil or starch. It was, in general, reduced by diluting the food with dietary fibre which also reduced liveweight gain. 3. The results are consistent with the idea that chickens attempt to control their food intake so that they achieve a particular fatness. This level of fatness differs between the sexes and between degrees of maturity.
10.1080/00071669008417281
pubmed_316_4811
Treatment of rats with hypoglycaemic doses of hypoglycin has been shown to abolish the relative detritiation of [2-3H,U-14C]glucose [Osmundsen, Billington, Taylor & Sherratt (1978) Biochem. J. 170, 337-342], indicating that both the Cori and the glucose/glucose 6-phosphate cycles were inhibited in vivo. This inhibition was confirmed and, in addition, it was shown that the conversion in vivo of both [14C]lactate and [14C]fructose into glucose was decreased after hypoglycin treatment. These results suggest that hypoglycin poisoning results in the inhibition in vivo of glucose-6-phosphatase activity, which participates in the overall inhibition of gluconeogenesis and hypoglycaemia. Clofibrate feeding apparently protected the rats against the inhibition of the fructose-to-glucose conversion by hypoglycin. However, in isolated hepatocytes prepared from hypoglycin-treated rats, the conversion of [14C]fructose into glucose and the recycling of [2-3H,U-14C]glucose were not different from that in control hepatocytes. This suggests that the inhibition was lost during preparation of the hepatocytes. The direct measurement of glucose-6-phosphatase activity showed that it was inhibited when measured in concentrated, but not dilute, homogenates prepared from hypoglycin-treated rats.
10.1042/bj2400765
pubmed_774_15703
La réduction des médicaments potentiellement inappropriés (MPI) chez les personnes âgées est un enjeu important selon de nombreux cliniciens et chercheurs à travers le monde, car ces médicaments accroissent significativement la morbidité et la mortalité dans la population plus âgée. La prévalence des MPI est un problème répandu malgré l'existence de plusieurs critères explicites et implicites de réduction des MPI chez les personnes âgées, les plus courants étant les critères de Beers, les critères STOPP/START et plusieurs critères nationaux spécifiques. Cette revue non systématique visait à examiner les critères de référence pour la réduction des MPI et à clarifier le rôle de certaines mesures, dont la déprescription, pour optimiser la prescription des médicaments chez les personnes âgées. Des recherches par mots-clés et termes MeSH ont été menées dans des bases de données électroniques. Les nombreux critères disponibles ont chacun leurs avantages et inconvénients. La déprescription, qui vise à réduire l'utilisation des MPI, a considérablement gagné en importance dans les initiatives associées à l'amélioration des pratiques de prescription. La déprescription est une approche méthodique qui implique l'arrêt graduel, éclairé et individualisé des médicaments inappropriés, avec un suivi rigoureux des patients pour assurer la détection d'événements indésirables ou de symptômes de rebond. Une approche combinée centrée sur le patient et le soignant favorise la collaboration entre les prescripteurs et les pharmaciens afin de réduire le nombre de MPI chez les personnes âgées. Reducing potentially inappropriate medications (PIMs) in older adults is an area of sustained interest for many clinicians and researchers across the globe, as PIMs contribute to a significant burden of morbidity and mortality in the aging population. The prevalence of PIMs is a pervasive problem despite the presence of several explicit and implicit criteria for reducing PIMs in older adults, the most common being the Beers criteria, the Screening Tool of Older Persons’ potentially inappropriate Prescriptions/Screening Tool to Alert doctors to the Right Treatment (STOPP/START) criteria, and several country-specific criteria. This narrative review aims to discuss the frequently used published criteria for reducing PIMs, and elucidates the role of certain measures, especially de-prescribing, to optimise medication prescription in older adults. Electronic databases were searched using keywords and MeSH terms. The numerous available criteria have their specific advantages and drawbacks. De-prescribing, an initiative to reduce the use of PIMs, has gained significant importance in improving appropriate prescribing practices. De-prescribing is a methodical approach to gradually stopping inappropriate medications judiciously for each patient and simultaneously monitoring the patient carefully for the onset of adverse events or rebound symptoms. A combined caregiver–patient-centred approach encourages the collaboration between prescribers and pharmacists to reduce PIMs in older adults.
10.1017/S0714980819000084
pubmed_1046_6213
Glioblastoma multiforme (GBM) is the most aggressive malignant brain tumor. Despite new knowledges on the genetic characteristics, conventional therapy for GBM, tumor resection followed by radiotherapy and chemotherapy using temozolomide is limited in efficacy due to high rate of recurrence. GBM is indeed one of the most complex and difficult cancer to treat mainly due to its highly invasive properties and the standard treatments are thus rarely curative. Major challenges in the treatment of GBM are the limitation of irreversible brain damage, the infiltrative part of the tumor which is the ultimate cause of recurrence, the difficulty of identifying tumor margins and disseminated tumor cells, and the transport across the blood-brain barrier in order to obtain a sufficient therapeutic effect for pharmalogical agents. Considering these limitations, this review explores the in vivo potential of metal-based nanoparticles for hyperthermia, radiotherapy and photodynamic therapy. This article describes and clearly outlines the recent in vivo advances using innovative therapeutic metallic nanoparticles such as iron oxide, silver, gadolinium and gold nanoparticles.
10.1016/j.addr.2018.10.013
pubmed_688_11431
The metabolism and the mechanism of action of 5-nitro-2-(2-dimethylaminoethyl)-benzo(de) isoquinoline-1,3-dione (mitonafide), a nitro-containing antitumor drug, have been studied. Incubation of mitonafide under anaerobic conditions with rat liver microsomes and NADPH formed the fully reduced amine metabolite, 5-aminomitonafide. The formation of the amine metabolite was not inhibited by SKF-525A, metyrapone or piperonyl butoxide, indicating that the cytochrome P-450 was not involved in this reduction. Incubation of mitonafide with rat liver microsomes and NADPH under aerobic conditions stimulated oxygen consumption; piperonyl butoxide, SKF-525A, superoxide dismutase and catalase had no effect on this stimulation. Both mitonafide and 5-aminomitonafide were found to bind to DNA in a similar manner. However, in inducing single-stand breaks in the DNA of L1210 cells mitonafide was 10-fold more potent than 5-aminomitonafide. These results suggest that metabolic activation of mitonafide to species other than that of the amine metabolite may play a significant role in the induction of DNA damage and the biological activity of the drug.
10.1016/0006-2952(85)90433-2
pubmed_796_3684
C1300 neuroblastoma cells are nonpermissive for infection with herpes simplex virus but can be rendered permissive by pretreatment with sodium butyrate. This increased permissivity which is specific for HSV is caused by increased transcription of the viral immediate-early genes following infection of butyrate-treated cells and can be observed for at least 24 hr following withdrawal of butyrate. The use of C1300 cells as a model system for studying the regulation of immediate-early gene expression in neuronal cells in vitro and its possible relevance to the study of the processes regulating latent infection in vivo is discussed.
10.1016/0042-6822(89)90631-4
pubmed_21_14880
A dual-probe real time PCR (qPCR) DNA-based analysis was devised for the identification of mandarin in orange juice. A single nucleotide polymorphism at the trnL-trnF intergenic region of the chloroplast chromosome was confirmed in nine orange (Citrus sinensis) and thirteen commercial varieties of mandarin, including Citrus reticulata and Citrus unshiu species and a mandarin × tangelo hybrid. Two short minor-groove binding fluorescent probes targeting the polymorphic sequence were used in the dual-probe qPCR, which allowed the detection of both species in single-tube reactions. The similarity of PCR efficiencies allowed a simple estimation of the ratio mandarin/orange in the juice samples, which correlated to the measured difference of threshold cycle values for both probes. The limit of detection of the assay was 5% of mandarin in orange juice, both when the juice was freshly prepared (not from concentrate) or reconstituted from concentrate, which would allow the detection of fraudulently added mandarin juice. The possible use of the dual-probe system for quantitative measurements was also tested on fruit juice mixtures. qPCR data obtained from samples containing equal amounts of mandarin and orange juice revealed that the mandarin target copy number was approximately 2.6-fold higher than in orange juice. The use of a matrix-adapted control as calibrator to compensate the resulting C(T) bias allowed accurate quantitative measurements to be obtained.
pubmed_21_14880
pubmed_431_11877
STUDY DESIGN A cadaveric study. OBJECTIVE To determine the utility of the nutrient foramen on the lamina in thoracic pedicle screw fixation. SUMMARY OF BACKGROUND DATA Recent studies have examined the portal of entry for pedicle screws. Unfortunately, there is no distinct anatomic marker, and the portal of entry usually depends on the surgeon's preference. METHODS This study investigated the nutrient artery foramen on the lamina from fourth to eighth thoracic vertebrae after partial laminectomy of 7 cadaveric spines. A 2-mm Steinmann pin was inserted as follows: vertical insertion on the right nutrient foramens and a 10-degree caudal on the left nutrient foramens. Radiographs and computed tomography were obtained and the relationship between the Steinmann pin and pedicle were analyzed. RESULTS There were 44 nutrient artery foramens (63%, 44/70). Among them, 31 foramens (70%, 31/44) were on the right. On the lateral radiographs, the right pins were inserted parallel within the upper end plate and the left pins were inserted within the vertebral body in T4 and T5. For T6 to T8, the right pins were inserted below the upper end plate and the left pins were inserted below the center of the vertebral body. On the computed tomography axial scan, 17 degrees of medialization for T4 to T7 and 5 degrees for T8 was possible when the size of pedicle screw for human is considered. CONCLUSIONS The nutrient artery foramen on the lamina of thoracic vertebrae is useful for inserting the thoracic pedicle screw.
10.1097/BSD.0b013e3180ca70ff
pubmed_484_21002
Mutations in the genes encoding fibrillin, an extracellular matrix protein involved in providing elastic properties to the connective tissues, may result in specific craniofacial and oral anomalies. A number of craniofacial (retrognathia, dolichocephaly, high palate) and dental (root deformity, pulp calcification) manifestations are considered pathognomic for the Marfan syndrome (MFS), a condition caused by congenital fibrillin-1 deficiency. Reports on similar features in congenital contractural arachnodactyly (CCA), caused by fibrillin-2 deficiency, support the hypothesis that fibrillin deficiency might result in a number of morphological anomalies by influencing tissue interaction during growth and development. Hence, clinical manifestations can be related to specific aspects of fibrillin deficiency pathogenesis, and may be adopted as diagnostic tools in the outlook for affected individuals.
pubmed_484_21002
pubmed_938_11121
This study was designed to examine the mechanisms causing peripheral insulin resistance in patients with insulin-dependent diabetes mellitus (IDDM) by studying insulin receptor function and glycogen synthase activity in biopsies of skeletal muscle. The results in seven such patients were compared with values obtained in a group of sedentary, age- and sex-matched normal subjects. In addition, since physical training appears to improve insulin sensitivity, the IDDM patients were reexamined after physical training for 6 weeks. The mean maximal glycogen synthase activity was lower in the diabetic than in the normal group [34.5 +/- 10.6 (+/- SD) vs. 45.7 +/- 8.6 nmol/mg protein.min; P less than 0.05], whereas there was no difference in the half-maximal activation constant (A0.5) for glucose-6-phosphate. Likewise, the mean yield of wheat germ agglutinin-purified insulin receptors recovered per mg muscle was 21% lower in the muscle biopsies from the diabetic patients (47 +/- 8 vs. 66 +/- 20 fmol/100 mg; P less than 0.05. However, basal and insulin-stimulated receptor kinase activities, expressed as phosphorylation of the synthetic peptide poly-Glu-Tyr(4:1), were identical in the two groups. After physical training in the diabetic patients the mean maximal oxygen uptake increased from 45.7 +/- 7.4 to 48.9 +/- 9.0 mL O2/kg.min (P less than 0.05), hemoglobin A1c decreased from 7.9 +/- 1.4% to 7.7 +/- 1.5% (P less than 0.05), and insulin requirements decreased from 43 +/- 9 to 38 +/- 8 U/day (P less than 0.05). The number of recovered insulin receptors did not increase, and the receptor kinase activity was similar to the pre-training value. Maximal glycogen synthase activity increased by 15% (P less than 0.02), whereas A0.5 for glucose-6-phosphate did not change. We conclude that insulin binding to muscle-derived insulin receptors is impaired in IDDM patients, whereas receptor kinase function appears to be normal. The capacity for glycogen storage in the diabetic skeletal muscle was reduced. Physical training tended to normalize glycogen synthase activity, but did not improve insulin receptor function significantly.
10.1210/jcem-69-1-158
pubmed_406_8180
The triad of normal-pressure hydrocephalus, parkinsonism, and primary empty sella appeared in a 70-year-old woman. There was dramatic resolution of the extrapyramidal signs and symptoms on treatment with levodopa-carbidopa and ventriculojugular shunt. The syndrome may be the result of several mechanisms, but an alteration of cerebrospinal fluid (CSF) pressure dynamics may be the sole etiology for this triad.
10.1212/wnl.28.11.1191
pubmed_722_22152
The molecular mechanisms driving the conserved metazoan developmental shift referred to as the mid-blastula transition (MBT) remain mysterious. Typically, cleavage divisions give way to longer asynchronous cell cycles with the acquisition of a gap phase. In Drosophila, rapid synchronous nuclear divisions must pause at the MBT to allow the formation of a cellular blastoderm through a special form of cytokinesis termed cellularization. Drosophila Fragile X mental retardation protein (dFMRP; FMR1), a transcript-specific translational regulator, is required for cellularization. The role of FMRP has been most extensively studied in the nervous system because the loss of FMRP activity in neurons causes the misexpression of specific mRNAs required for synaptic plasticity, resulting in mental retardation and autism in humans. Here, we show that in the early embryo dFMRP associates specifically with Caprin, another transcript-specific translational regulator implicated in synaptic plasticity, and with eIF4G, a key regulator of translational initiation. dFMRP and Caprin collaborate to control the cell cycle at the MBT by directly mediating the normal repression of maternal Cyclin B mRNA and the activation of zygotic frühstart mRNA. These findings identify two new targets of dFMRP regulation and implicate conserved translational regulatory mechanisms in processes as diverse as learning, memory and early embryonic development.
10.1242/dev.055046
pubmed_393_9544
Rhizobium meliloti 300hl3 reached the stationary phase of growth very quickly and had an early death when 8.6 muM parathion was added to the growth medium at the start of the culture. Cells also changed their quantitative composition: total carbohydrate content and poly-beta-hydroxybutyrate accumulation diminished, proteins and phospholipids of cellular membranes increased, and some alterations in the proportion of membrane fatty acids were noticed.
10.1007/BF02439934
pubmed_601_5669
Vasoactive arachidonic acid metabolites are postulated to play a role in the pathogenesis of cerebral ischemia. In order to characterize the local generation of cyclooxygenase and lipoxygenase metabolites of arachidonic acid in transient ischemia with reperfusion, Mongolian gerbils were studied for regional cerebral blood flow (CBF), using the hydrogen clearance technique, and for cerebral levels of the thromboxane metabolite TXB2, and prostaglandins 6-keto-PGF1 alpha and PGE2, as well as the leukotriene LTB4. The gerbils were anesthetized with pentobarbital, and half of the animals were pretreated with the cyclooxygenase inhibitor indomethacin. All received 10 or 20 minutes of dense forebrain ischemia followed by reperfusion of 10 minutes, 50 minutes, or 100 minutes. A separate control group received no ischemic lesion. Regional CBF decreased significantly from 23.7 +/- 2.6 to 4.3 +/- 1.7 cc/100 gm/min during ischemia (p less than 0.01). Reperfusion resulted in initially normal flows (22.5 +/- 5.1 cc/100 gm/min) followed by a progressive hypoperfusion (11.3 +/- 2.7 cc/100 gm/min). All metabolites showed parallel significant (p less than 0.05) increases after transient ischemia and reperfusion compared to baseline levels (values (in pg/mg protein) were: TXB2 45.5 +/- 7.1 vs 23.3 +/- 3.6; 6-keto-PGF1 alpha 262.8 +/- 47.9 vs 175.8 +/- 26.8; PGE2 256.5 +/- 35.6 vs 112.5 +/- 11.2; and LTB4 37.8 +/- 4.6 vs 24.6 +/- 6). These levels were all significantly decreased (p less than 0.05) by pretreatment with indomethacin except for the leukotriene LTB4, which was increased. Transient cerebral ischemia results in a reperfusion abnormality and the local generation of cyclooxygenase products, which are reduced by pretreatment with indomethacin; however, cyclooxygenase inhibition may result in increased substrate availability for the lipoxygenase system. Studies of such an interaction may lead to new understandings of the pharmacological modification of detrimental vascular changes after transient cerebral ischemia.
10.3171/jns.1986.64.1.0118
pubmed_292_15518
An efficient and practical method has been developed for the synthesis of trans-4,5-disubstituted 3-carboxy-4,5-dihydropyrroles via an intramolecular iminium ion cyclization reaction of readily accessible Baylis-Hillman derivatives and aldehydes in moderate to high yield. These new dihydropyrroles could be easily converted to pyrroles or pyrrolidines.
10.1021/acs.orglett.5b01787
pubmed_681_13615
Automated methods are described for tracing and analysis of changes in angiogenic vasculature imaged by a multiphoton laser-scanning confocal microscope. Utilizing chronic animal window models, time series of in vivo 3-D images were acquired on approximately the same target volume of the same specimen while undergoing angiogenic change (typically every 24 h for 7 days). Objective, precise, 3-D, rapid, and fully automated vessel morphometry was performed using an adaptive tracing algorithm that is based on a generalized irregular cylinder model of the vasculature. This algorithm was found to be not only adaptive enough for tracing angiogenic vasculature, but also very efficient in its use of computer memory, and fast, taking less than 1 min to trace a 768 x 512 x 32, 8-bit/pixel 3-D image stack on a Dell Pentium III 1-GHz computer. The automatically traced centerlines were manually validated on six image stacks and the average spatial error was measured to be 2 pixels, with an average concordance of 81% between manual and automated traces on a voxel basis. The tracing output includes geometrical statistics of traced vasculature and serves as the basis of statistical change analysis. The computer methods described here are designed to be scalable to much larger hypothesis testing studies involving quantitative measurements of tumor angiogenesis, gene expression relative to known vascular structures, and impact of drug delivery.
10.1016/s0026-2862(03)00039-6
pubmed_139_17033
The role of 24 hour Holter monitoring in the screening of patients complaining of palpitations is reviewed. The term "palpitations", although not always unequivocally used, implies the presence of an arrhythmia. The clinical-instrumental correlation of an intermittent symptom is made possible by continuous electrocardiographic monitoring. Answers to be expected from a 24 hour Holter monitoring in order to achieve an early characterization of the arrhythmia are related to: site of origin, incidence, circadian distribution, prognostic stratification, events aggregation, presence of other asymptomatic abnormalities (rhythm, ST-T).
pubmed_139_17033
pubmed_179_2505
BACKGROUND Hypertensive disorders account for 14% of global maternal deaths. Magnesium sulphate (MgSO4 ) is recommended for prevention and treatment of pre-eclampsia/eclampsia. However, MgSO4 remains underused, particularly in low- and middle-income countries (LMICs). OBJECTIVE This qualitative evidence synthesis explores perceptions and experiences of healthcare providers, administrators and policy-makers regarding factors affecting use of MgSO4 to prevent or treat pre-eclampsia/eclampsia. SEARCH STRATEGY We searched MEDLINE, EMBASE, Emcare, CINAHL, Global Health and Global Index Medicus, and grey literature for studies published between January 1995 and June 2021. SELECTION CRITERIA Primary qualitative and mixed-methods studies on factors affecting use of MgSO4 in healthcare settings, from the perspectives of healthcare providers, administrators and policy-makers, were eligible for inclusion. DATA COLLECTION AND ANALYSIS We applied a thematic synthesis approach to analysis, using COM-B behaviour change theory to map factors affecting appropriate use of MgSO4 . MAIN RESULTS We included 22 studies, predominantly from LMICs. Key themes included provider competence and confidence administering MgSO4 (attitudes and beliefs, complexities of administering, knowledge and experience), capability of health systems to ensure MgSO4 availability at point of use (availability, resourcing and pathways to care) and knowledge translation (dissemination of research and recommendations). Within each COM-B domain, we mapped facilitators and barriers to physical and psychological capability, physical and social opportunity, and how the interplay between these domains influences motivation. CONCLUSIONS These findings can inform policy and guideline development and improve implementation of MgSO4 in clinical care. Such action is needed to ensure this life-saving treatment is widely available and appropriately used. TWEETABLE ABSTRACT Global qualitative review identifies factors affecting underutilisation of MgSO4 for pre-eclampsia and eclampsia.
10.1111/1471-0528.16913
pubmed_831_359
On 14 November 1967 an investigation was begun at the University of South Florida to determine the cause of an increased number of gastrointestinal illnesses on campus. An estimated 300 students suddenly became ill with nausea, vomiting, abdominal pain, and diarrhoea. While at first food poisoning was suspected, no common food, water, or toxic exposure could be found. The data collected were most consistent with Winter Vomiting Disease. This entity is characterized by acute gastrointestinal illnesses which may occur in epidemic form in residential schools between September and March. Most investigators suspect that a viral agent is responsible for the illnesses, though attempts to isolate a virus have been unsuccessful. The incubation period in the University outbreak was estimated at 28 hr., and contact was the most likely mode of transmission. The outbreak illustrated that Winter Vomiting Disease in residential institutions may be an accentuation of the gastrointestinal illnesses occurring simultaneously in the community at large.
10.1017/s0022172400028448
pubmed_97_20111
Subjectively healthy persons were investigated for the presence of Chlamydia pneumoniae (TWAR) with throat cultures using the HL (human lung) cell line. C. pneumoniae was isolated from 11/234 investigated persons.
10.3109/00365549109024328
pubmed_407_14860
Epithelial ovarian cancer is the leading cause of death in the developed world for women with gynecologic carcinomas. Despite the effectiveness of platinum salts and taxanes as primary treatments, approximately 80% of women will recur and for them prognosis with available treatments is poor. Of the novel mechanisms under active investigation, there is ample evidence to indicate that angiogenesis is important to the development, progression and poor prognosis of ovarian cancer. Novel treatments are therefore required. A number of agents are undergoing evaluation, including vascular disrupting agents, angiogenesis inhibitors, tyrosine kinase inhibitors and agents targeting the folate receptor. At present, Phase III data are only available for the VEGF-targeted monoclonal antibody, bevacizumab, and that has demonstrated a progression-free survival benefit when used in combination with first-line paclitaxel/carboplatin and continued as maintenance therapy. The strategy of inhibiting angiogenesis in ovarian cancer remains promising. However, other agents in development may point to other important targets in ovarian cancer.
10.2217/whe.12.26
pubmed_455_11113
Normative data of the Group Embedded Figures Test for a sample of Turkish undergraduate students was provided. Participants were 534 undergraduates from the Departments of Education of two universities in Turkey. Effects of sex and socioeconomic status on the students' cognitive style performance were investigated. Performance and distribution characteristics of the Turkish sample and American adults as reported in the manual of the original test were compared. A Turkish version was developed. Item analyses, reliability, and practice effects were assessed. No sex difference, except in Section 2, was found. Socioeconomic status also was not significantly related to cognitive style performance. Norms reported for American adults in the manual were significantly different from those of the present Turkish adults. These findings suggest that use in different cultures, especially in those other than western cultures, requires caution. Scores obtained from these cultures should be carefully interpreted.
10.2466/pms.2003.96.3.993
pubmed_447_17617
The measurements were made of monovalent cation (K+ + Rb+, Na+) and protein contents, of leucin incorporation into the protein (protein synthesis), and of ouabain-sensitive K+ influx during the growth of the Jurkat culture cells in the presence or in the absence of ouabain. All the data were calculated per cell. The time dependences of these parameters are nonlinear [correction of unline] curves. The results of three independent measurements are not reproduced. The problem was to find out an intracellular "main" parameter, so that the dependences between this and the rest of parameters be of line character. It has been found that it is the protein synthesis rate that may be taken as the main parameter, because between the protein synthesis rate and all the other parameters there is the line connection. Comparative results obtained with or without ouabain showed that K+ and Na+ concentrations in the cell were different, although the constants of the rate of protein synthesis were the same. This points to the same type of change of the protein synthesis process in the cells growing with or without ouabain.
pubmed_447_17617
pubmed_199_14693
In four patients, each of whom displayed overt signs and symptoms of a delirious state, the delirium was overlooked. We describe in detail the features of delirium because this syndrome is protean in its etiology and clinical presentations. It can be life-threatening, and it may not be recognized because the behavioral correlates are often attributed to a functional disorder.
10.1097/00007611-198506000-00014
pubmed_505_9960
The metalloenzyme D-xylose isomerase forms well ordered crystals that diffract X-rays to ultrahigh resolution (<1 A). However, structural analysis using X-ray diffraction data has as yet been unable to differentiate between several postulated mechanisms that describe the catalytic activity of this enzyme. Neutrons, with their greater scattering sensitivity to H atoms, could help to resolve this by determining the protonation states within the active site of the enzyme. As the first step in the process of investigating the mechanism of action of D-xylose isomerase from Streptomyces rubiginosus using neutron diffraction, data to better than 2.0 A were measured from the unliganded protein at the Los Alamos Neutron Science Center Protein Crystallography Station. Measurement of these neutron diffraction data represents several milestones: this is one of the largest biological molecules (a tetramer, MW approximately 160 000 Da, with unit-cell lengths around 100 A) ever studied at high resolution using neutron diffraction. It is also one of the first proteins to be studied using time-of-flight techniques. The success of the initial diffraction experiments with D-xylose isomerase demonstrate the power of spallation neutrons for protein crystallography and should provide further impetus for neutron diffraction studies of biologically active and significant proteins. Further data will be measured from the enzyme with bound substrates and inhibitors in order to provide the specific information needed to clarify the catalytic mechanism of this enzyme.
10.1107/S0907444903025873
pubmed_1110_17236
Single-cell gene expression is inherently stochastic; its emergent behavior can be defined in terms of the chemical master equation describing the evolution of the mRNA and protein copy numbers as the latter tends to infinity. We establish two types of "macroscopic limits": the Kurtz limit is consistent with the classical chemical kinetics, while the Lévy limit provides a theoretical foundation for an empirical equation proposed in N. Friedman et al., Phys. Rev. Lett. 97, 168302 (2006)PRLTAO0031-900710.1103/PhysRevLett.97.168302. Furthermore, we clarify the biochemical implications and ranges of applicability for various macroscopic limits and calculate a comprehensive analytic expression for the protein concentration distribution in autoregulatory gene networks. The relationship between our work and modern population genetics is discussed.
10.1103/PhysRevE.96.040402
pubmed_377_14244
Polyphenols are known to exhibit wide spectrum of benefit for brain health and to protect from several neurodegenerative diseases. The present study was sought to determine the neuroprotective effects of Rosmarinus officinalis' polyphenols (luteolin, carnosic acid, and rosmarinic acid) through the investigation of stress-related proteins. We carried out measurement of the expression of heat-shock protein (Hsp) 47 promoter in heat stressed Chinese hamster ovary transfected cells. We performed proteomic analysis and confirmed gene expression by real time PCR in PC12 cells. Results showed that these compounds modulated significant and different effects on the expression of 4 stress-related proteins: heat shock protein 90 α (Hsp90), Transitional endoplasmic reticulum ATPase (VCP/p97), Nucleoside diphosphate kinase (NDK), and Hypoxia up-regulated protein 1 (HYOU1)) at translational and post translational levels in PC12 cells and they downregulated the expression of Hsp47 activity in Chinese hamster transformed cells. These findings suggest that luteolin, carnosic acid, and rosmarinic acid may modulate the neuroprotective defense system against cellular stress insults and increase neuro-thermotolerance.
10.1007/s10616-011-9352-y
pubmed_472_7345
An intraluminal duodenal diverticulum (IDD) is a rare congenital anomaly that is the result of incomplete recanalization of the embryologic foregut leaving a fenestrated membrane within the lumen of the duodenum. Years of peristalsis acting on the membrane result in the formation of a diverticulum. Most patients are asymptomatic, while some may have abdominal pain, bloating, or fullness. Rare complications include gastrointestinal bleeding, obstruction, pancreatitis, and cholangitis. We present 2 cases with endoscopic findings consistent with partially obstructing symptomatic IDD.
10.14309/crj.2016.108
pubmed_411_9976
The Adirondack Mountain region of New York, a historical hotspot for atmospheric sulfur and nitrogen deposition, features abundant lakes that are experiencing browning associated with recovery from acidification. Yet, much remains unknown about the photoreactivity of Adirondack lake waters. We quantified the apparent quantum yields (Φapp,RI) of photochemically produced reactive intermediates (RIs), such as excited triplet states of dissolved organic matter (3DOM*), singlet oxygen (1O2), and hydroxyl radicals (•OH), for surface waters collected from 16 representative Adirondack lakes. Φapp, and Φapp, for native Adirondack lake waters fell within ranges reported for whole waters and DOM isolates from various sources, while Φapp, were substantially lower than those measured for other aquatic samples. Orthogonal partial least squares and multiple linear regression analyses identified the spectral slope coefficient from 290 to 400 nm (S290-400) as the most effective predictor of Φapp,RI among measured water chemistry parameters and bulk DOM properties. Φapp,RI also exhibited divergent responses to controlled pH adjustment and aluminum or iron addition simulating hypothetical scenarios relevant to past and future water chemistry conditions of Adirondack lakes. This study highlights the need for continued research on changes in photoreactivity of acid-impacted aquatic ecosystems in response to browning and subsequent impacts on photochemical processes.
10.1021/acs.est.0c02811
pubmed_931_13332
Although the role of high dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT) in the treatment of aggressive lymphoma has been established in several large prospective studies, its effectiveness in patients with peripheral T cell lymphoma (PTCL) has not been defined. We aimed to evaluate the efficacy of HDT and ASCT and prognostic factors for survival in patients with PTCL. We retrospectively analyzed the results of 40 PTCL patients treated with HDT and ASCT at Asan Medical Center between January 1995 and December 2005. Twenty patients had PTCL-U (peripheral T cell lymphoma, unspecified), 10 had extranodal natural killer/T cell lymphoma, 5 had anaplastic large cell lymphoma, 3 had angioimmunoblastic T cell lymphoma, 1 had hepatosplenic gammasigma T cell lymphoma, and 1 had disseminated mycosis fungoides. Disease status at transplant was complete response (CR)1 in 3 patients, CR2 or greater in 8, partial remission in 25, and refractory in 4. At a median follow-up of 16 months (range, 5 to 135 months) for surviving patients, the median overall survival (OS) was 11.5 months and the 1-year probability of survival was 46.1%. The median event free survival (EFS) was 3.6 months (95% confidence interval, 2.5 to 4.8 months). Ten patients (25%) remain alive without evidence of disease. The median OS of 11 patients with CR at ASCT was not reached; of these, 7 patients (63.6%) were alive with CR. In multivariate analysis, CR at ASCT was a prognostic factor for EFS (P = 0.025) and OS (P = 0.027) and normal lactate dehydrogenase (LDH) at ASCT was a prognostic factor for improved OS (P = 0.025). Chemosensitive patients with PTCL who achieved CR before ASCT seem to benefit from HDT and ASCT. Pretransplant values of LDH had potential to predict the survival.
10.1007/s00277-007-0254-1
pubmed_71_23448
Patients with thrombocytopenia 5 have an autosomal dominant disorder of decreased platelet number with tendency to bleed, usually presenting in childhood, and have been found to have germline mutations in ETV6, which encodes a master hematopoietic transcription factor. Some patients who present similarly have inherited mutations in RUNX1 or ANKRD26. All three germline syndromes are also associated with a predisposition to myelodysplastic syndrome (MDS) and acute leukemia (AL). Since the first description of germline ETV6 mutations, 18 families have been reported. The common phenotype is mild to moderate thrombocytopenia with a variable predisposition to acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML), and MDS. This review will focus upon the role of ETV6 in hematopoiesis, especially in myeloid differentiation and maturation, and will describe the functional effects of mutant ETV6. The review will also provide an overview of common clinical features as well as recommendations for patient screening and follow-up and will debate whether additional clinical features should be included with the germline ETV6 syndrome.
10.1007/s12185-017-2259-4
pubmed_553_4731
The approximate minimal effective dose of activated charcoal, given to sheep 12 h after the administration of a lethal dose of Moreae polystachya, was found to be 2 g/kg. Serum cation levels remained within normal limits throughout the experiment.
pubmed_553_4731
pubmed_94_5108
The aim of this study was to examine the associations of sedentary behaviour, physical activity, cardiorespiratory fitness (CRF), and body composition parameters with risk of sleep-related breathing disorders (SRBD) in children with overweight/obesity. One-hundred and nine children (10.0 ± 1.1 years old, 45 girls) with overweight (n = 27) and obesity (n = 82) were included. Television viewing time was self-reported by using the Spanish adaptation of the "Youth Activity Profile" (YAP) questionnaire. Sedentary time and physical activity were measured with accelerometry. CRF was assessed with the 20-m shuttle-run test and body composition parameters with Dual-energy X-ray absorptiometry. SRBD were evaluated by using the Spanish version of the Pediatric Sleep Questionnaire. Television viewing time was positively associated with risk of SRBD (r = 0.222, p = 0.021). CRF was negatively correlated with risk of SRBD (r = -0.210, p = 0.030). Body composition parameters were positively associated with risk of SRBD (all p < 0.05), except fat mass index. Stepwise regression analyses showed that body mass index (BMI) explained the largest proportion of the variance in SRBD (r2 = 0.063, p = 0.01) and television viewing time was the only one added after BMI (r2 change = 0.048, p = 0.022). This study supports the notion that higher body weight status negatively influences risk of SRBD and adds that unhealthy behaviours could contribute to worsen SRBD, related to an increased risk of cardiovascular diseases. All the significant association observed in this manuscript were of small magnitude, indicating than other factors in addition to the one hereby studied contribute to explain the variance in SRBD.
10.3390/jcm9051544
pubmed_1007_6843
CNS infections caused by infective agents are rare in immunocompetent hosts, but more frequent in immunocompromised patients. In addition, the spectrum of causative agents is completely different. There are no pathognomonic alterations in radiologic imaging, even in clinically severely ill patients imaging is often non-specific or inconspicious. This article gives a review of the most frequent infective agents and image alterations. Modern radiology is not yet able to replace the gold standard of pathogen detection.
10.1007/s00117-008-1680-3
pubmed_662_213
Oral ethanol (5% v/v) reinforced responding was studied in three rats using a concurrent fixed ratio (FR) schedule with water available at a second lever. First, concurrent (FR8 FR8) responding on both levers for water presentation was established. Then a concurrent (FR8 FR8) water-ethanol presentation schedule was introduced and a food ration was placed in the chamber at the beginning of the session. Within 12 sessions, ethanol responding developed and within-session feeding was discontinued. When stable concurrent water-ethanol performance was achieved, average ethanol responding was 11 times greater than water responding, even when ethanol availability switched from one level to the other. During the one hour session, in some cases, sufficient ethanol was ingested to produce blood ethanol levels between 30 and 50 mg/100 ml. As the ethanol FR requirement was increased for four sessions each to FR10, 12, 14, 16, 18, 20, 40 and 50, rats continued to respond for ethanol, and in some rats, ethanol preference was maintained even when the ethanol FR was 50 while the water FR remained at 8.
10.1016/0091-3057(81)90204-5
pubmed_494_10498
The major focus of care for patients with haemophilia is to ensure health with minimal joint dysfunction. As this population ages, additional coexisting conditions can develop including rare instances of nephrotic syndrome in haemophilia B inhibitor patients undergoing immune tolerance, hypertension, diabetes, and coronary artery disease, all of which can adversely affect the renal system over time. In haemophilia patients, co-infected with HIV and hepatitis C, these conditions can also increase the risk of renal problems resulting in the need for dialysis. This article provides a practical approach for the haemophilia patient who requires dialysis and outlines the decision making process to ensure a positive outcome. The goal of care is to optimize dialysis treatment without increasing the bleeding risk.
10.1111/j.1365-2516.2008.01872.x
pubmed_329_6442
The invasion of pathogens causes a disruption of the gut homeostasis. Innate immune responses and those triggered by endogenous microbiota form the first line of defence in our body. Pathogens often successfully overcome the resistances offered, calling for therapeutic intervention. Conventional strategy involving antibiotics might eradicate pathogens, but often leave the gut uncolonised and susceptible to recurrences. Probiotic supplements are useful alternatives. Bifidobacterium is one of widely studied probiotic genus, effective in restoring gut homeostasis. Mechanisms of probiotic action of bifidobacteria are several, often with strain-specificity. Analysis of streamlined literature reports reveal that although most studies report the probiotic aspect of bifidobacteria, sporadic documented contradictory results exist, challenging its therapeutic application and prompting studies to unambiguously establish the strain-associated probiotic activity and negate adverse effects prior to its clinical administration. Multi-strain/combinatorial therapy possibly relies on a combination of underlying operating mechanisms, each contributing towards enhanced probiotic efficacy, understanding which could help in developing customised formulations against targeted pathogens. Bifidogenic activity is also mediated by surface-associated structural components such as exopolysaccharides, lipoteichoic acids along with metabolites and bifidocins. This highlights scope for developing advanced structural therapeutic strategy which might be pivotal in replacing intact cell probiotics therapy.
10.1016/j.micres.2016.07.001
pubmed_815_6638
Clozapine is an atypical neuroleptic agent given when schizophrenia is resistant to other neuroleptic drugs. Its use is restricted because of the risk of agranulocytosis, which appears in 1% of cases and therefore necessitates frequent WBC counts. We cite the only 2 surveys of the treatment of adolescents with clozapine and report our experience. We treated 7 boys and 6 girls between the ages of 14-17 years (mean 16.6) with clozapine after failure of all other neuroleptic agents tried. Our usual dose was 300 mg/day, for an average of 245 days. In only 2 patients was improvement only partial. In 1 treatment had to be stopped because of symptomatic orthostatic hypotension which appeared 36 hours after the drug was started. In our opinion, clozapine should be considered when severe schizophrenia in adolescents is refractory to other neuroleptic agents, provided the WBC count is monitored.
pubmed_815_6638
pubmed_881_6078
The catalytic site of all dihydrofolate reductases contains an invariant carboxylic acid, equivalent to Asp-27 in Escherichia coli dihydrofolate reductase (ecDHFR). It has been found that various kinetic and ligand binding properties of ecDHFR show a pH profile with a pKa of about 6.5. The group responsible for this pKa is often assumed to be carboxyl group of Asp-27. To determine the ionization state of this carboxyl and its pKa, we have employed a novel method, based on Raman difference spectroscopy, to obtain its vibrational spectrum in situ. The method is general for the study of protein carboxyl groups, which are often significantly implicated in protein function and structure; this study establishes the method's limits and problems. The Raman difference spectrum between wild-type ecDHFR and the Asp-27 to serine mutant (D27S) in the pH range 5.6-9.0 has been taken. No protonation of the carboxyl group was detected, implying that its pKa is probably less than 5.0. We did, however, detect a pH dependence in the intensity of Raman bands in the difference spectrum with a pKa of 6.3, indicating that the apo enzyme undergoes a pH-dependent conformational change. Because the carboxyl group of Asp-27 at the active site is the only ionizable group in the binding site, other groups, away from the catalytic site, must be responsible for the pH behavior of ecDHFR.
10.1016/s0006-3495(97)78727-7
pubmed_720_20407
PURPOSE This matched cohort study aims to determine whether teenagers with a history of childhood sexual abuse (CSA) are at greater risk of consulting for a pregnancy and related complications than teenagers from the general population. It also aims to compare provoked abortion, live births, and fetal losses of participants who were sexually abused in childhood and those of the general population. METHODS A total of 661 girls (aged 13-18 years) with a corroborated by Child Protection Services CSA report between 2001 and 2010 were matched to 661 girls from the general population upon age, biological sex, urban Child Protection Services area, and public drug insurance admissibility at reporting date. Pregnancy consultations and complications during pregnancy and delivery were documented using diagnoses from public health insurance administrative databases from January 1996 to March 2013. Socioeconomic status was controlled. RESULTS Results indicate that compared with participants from the general population, those with a history of CSA were 4.6 times more likely to consult for at least one pregnancy, 5.3 times more likely to consult for at least one complication during pregnancy or delivery, and on average 5.2 and 3.3 times more likely to consult for at least one live birth and provoked abortion, respectively. There were too few observations to compare fetal losses between groups. CONCLUSIONS Medical interventions for teenage pregnancies and related complications should take into consideration a possible history of CSA to reinforce gynecological follow-up and treatment for girls who were sexually abused and to prevent unfavorable outcomes.
10.1016/j.jadohealth.2019.03.001
pubmed_255_9961
Collagen is a typical biological macromolecule having been utilized for a long period of time as a material like cellulose. However, its application is becoming comprehensive, ranging from classical applications such as the leather, gelatine and food industries to the current one, namely, biomaterial and biotechnological uses. The diversification of collagen applications was enhanced by two factors, the accumulation of the scientific knowledge that permitted proper engineering of collagen for a biomaterial use, and the demand for new biomaterials with characteristic biological properties including interaction with cells. The collagen engineering described in this paper is designed for biomaterial use, based on the fundamental chemical and biological properties of collagen; however, it would be useful also for other applications apart from biomaterials.
10.1016/0267-6605(92)90093-9
pubmed_885_24716
BACKGROUND School-based programs to combat childhood obesity often lack resources to incorporate strong evaluation components. This paper describes a collaborative evaluation conducted by partners implementing Active Living by Design (ALbD) programs at one Chicago elementary school. PURPOSE To assess ALbD program outcomes by triangulating various forms of evidence gathered while implementing these programs. METHODS An exploratory, mixed-methods design was used to collect and analyze data from numerous physical activity initiatives implemented at the school from 2004 to 2009. The researchers triangulated quantitative (student BMI data, student standardized test and discipline data, classroom physical activity logs, and student physical activity knowledge surveys) and qualitative (classroom physical activity logs and open-ended teacher surveys questions) findings to assess outcomes. RESULTS Students continuously enrolled at this school from Grades 1 through 4, those most exposed to ALbD activities over time, had significantly lower BMI after 4 years, compared with peers who transferred to the school after Grade 1. Student achievement on standardized tests improved between 2004 (prior to initiating ALbD activities) and 2008. Visits to the Disciplinary Office dropped dramatically over the 4-year period. Teacher interviews and surveys and classroom Take 10! Program activity logs revealed that the program was implemented enthusiastically by all grades. The Physical Activity Knowledge Survey revealed a significant increase in physical activity knowledge after instituting these activities. CONCLUSIONS Collaborative efforts to amass and analyze a variety of data demonstrated the effects of implementing a variety of health promotion activities in one school, documenting the growth of a "culture of health" in that school community.
pubmed_885_24716
pubmed_538_22852
Wilms' tumor (WT) is one of the most common solid tumors of childhood. The genetics of this disorder is complex and few studies have suggested allelic loss of chromosome 22 as a frequent aberration. To assess tumor- and possible germline-specific regions affected with gene copy number variations on this chromosome, we applied a high-resolution genomic clone-based chromosome 22 array to a series of 28 WT samples and the paired blood-derived DNA of the patients. The group of tumors was enriched for cases with metastases, relapse or fatal outcome, criteria that were expected to yield a higher number of alterations on chromosome 22. Overall, the array-based form of comparative genomic hybridization (array-CGH) analysis revealed genomic changes in 53% (15 out of 28) of cases. We identified hemizygous deletion of the whole arm of 22q in 3 tumors (11%). Furthermore, a complex amplifier genotype was detected in 8 samples, presenting regions of gain along the chromosome, which defined 7 distinct minimal overlapping segments. The distribution of aberrations in 4 additional cases displaying regional genomic imbalances delimited 2 tumor suppressor/oncogene candidate loci, 1 in the proximal and the other in the terminal part of 22q. Analysis of these regions revealed the presence of several candidate genes that may play a role in the development of WT. These findings demonstrate the power of array-CGH in the determination of DNA copy number alterations and further strength the notion that WT-associated genes exist on this chromosome.
10.1002/ijc.21868
pubmed_758_6795
The risk of dengue virus infection during pregnancy has increased due to the current rash of frequent and severe dengue epidemics. The effects of dengue virus in the fetus and newborn children have been studied only superficially and with contradictory results. Therefore, a retrospective cohort study was conducted in Medellin, Colombia, to describe the fetal and postnatal effects of dengue virus infection acquired during pregnancy. Twenty-two babies born from mothers who suffered dengue during the epidemics of 1998 were compared with babies from non-infected mothers. In the exposed cohort, three premature births occurred, three children suffered from fetal anomalies and four children were born with low weight. In the non-exposed children, none of these problems were found. Psychomotor development was normal in both groups. Only the low weight subgroup was statistically significant (Fisher test, p = 0.045). These results suggested that the children from women with dengue during pregnancy present low weight, greater frequency of premature birth and increased fetal distress. A larger sample is necessary to confirm these results.
pubmed_758_6795
pubmed_904_6718
The aim of this study was to examine the effect of nurse staffing on both rehospitalizations and emergency department emergency department visits among short-stay nursing home residents in the United States. Data for 11,132 US nursing homes were drawn from the 2016 Nursing Home Compare. We found that the Five-Star Quality Rating System's staffing rating is a significant predictor for the rates of rehospitalization and emergency department visit among short-stay nursing home residents. The results also showed the importance of registered nurse staffing in nursing home caring for short-stay residents. Administrators and policy-makers can employ the findings to formulate management strategies that will reduce rehospitalizations and emergency department visits among nursing home residents.
10.1016/j.gerinurse.2018.09.010