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pubmed_232_11270
Sixty-one healthy men and women, aged 20 to 75 years, received single 0.25-mg doses of triazolam, a cytochrome P450 (CYP) 3A substrate benzodiazepine, and placebo in a double-blind crossover study. Among women, age had no significant effect on area under the triazolam plasma concentration curve (AUC) (Spearman r=0.14, P=.44) or clearance (r =-0.09, P=.62). Among men, AUC increased (r=0.43, P <.02) and clearance declined (r=-0.42, P <.02) with increasing age. Gender differences in triazolam kinetics were not apparent. Compared with placebo, triazolam impaired digit-symbol substitution test performance, increased observer-rated sedation, impaired delayed recall of information learned at 1.5 hours after dosing, and increased electroencephalographic beta amplitude. Among men, mean values of relative digit-symbol substitution test decrement (P <.002) and observer-rated sedation (P <.05) were significantly greater in elderly subjects compared with young subjects. Age-dependent differences among women reached significance for observer-rated sedation (P <.02). A combination of higher plasma levels and increased intrinsic sensitivity explained the greater pharmacodynamic effects of triazolam in elderly subjects. Although the findings are consistent with reduced clearance of triazolam in elderly men, individual variability was large and was not explained by identifiable demographic or environmental factors.
10.1016/j.clpt.2004.07.009
pubmed_504_22178
In this study, we investigated the clinical value of CC chemokine ligand 2 (CCL2) and CC chemokine ligand 3 (CCL3) in osteoarthritis (OA). A prospective analysis was performed on 126 patients with rheumatoid arthritis of the knee (observation group (OG)) who admitted to Qilu hospital from August 2016 to August 2018 and 135 healthy controls (control group (CG)) who underwent physical examinations during the same period. The concentrations of CCL2 and CCL3 in peripheral blood were compared between the two groups, and the predictive value of the two on the occurrence, efficacy and prognosis of recurrence of OA were analyzed. In addition, an OA rat model was established to detect the relative protein levels of CCL2 and CCL3 in rat knee joint tissues. There were no statistically significant differences between the two groups in baseline data such as age, body mass index (BMI), gender, smoking, drinking, educational level, family medical history and living environment (P > 0.05). CCL2 and CCL3 increased in peripheral blood of patients in the OG (P < 0.05), both of which were positively correlated with rheumatoid factor (RF) (P < 0.001). CCL2 and CCL3 were of good predictive value for the occurrence, efficacy and prognosis of recurrence of OA (P < 0.001). The relative protein levels of CCL2 and CCL3 in bone and joint tissues of OA rats were significantly higher than those of normal rats (P < 0.001). CCL2 and CCL3 are elevated in peripheral blood of OA patients, which have good predictive value for the occurrence, efficacy and prognosis of recurrence of OA, indicating their potential roles as excellent markers for diagnosis and treatment of OA in the future.
10.1016/j.yexmp.2020.104576
pubmed_583_11646
Leishmaniasis has been ignored for many years mainly because it plagues remote and poor areas. However, recently, it has drawn attention of several investigators, and active research is going on for antileishmanial drug discovery. The current available drugs have high failure rates and significant side effects. Recently, liposomal preparations of amphotericin B are available and have proved to be a better drug, but they are very expensive. Miltefosine is one of the few orally administered drugs that are effective against Leishmania. However, it has exhibited teratogenicity, hence, should not be administered to pregnant women. Thus, the search for novel and improved antileishmanial drugs continue. A rational approach to design and develop new antileishmanials can be to identify several metabolic and biochemical differences between host and parasite that can be exploited as drug target. Moreover, many natural products also have significant antileishmanial activity and are yet to be exploited. In the current review, we aim to bring together various drug targets of Leishmania, recent development in the field, future prospects, and hope in the area.
10.1007/s12010-009-8764-z
pubmed_472_19098
Semiconductor nanowires represent powerful building blocks for next generation bioelectronics given their attractive properties, including nanometer-scale footprint comparable to subcellular structures and bio-molecules, configurable in nonstandard device geometries readily interfaced with biological systems, high surface-to-volume ratios, fast signal responses, and minimum consumption of energy. In this review article, we summarize recent progress in the field of nanowire bioelectronics with a focus primarily on silicon nanowire field-effect transistor biosensors. First, the synthesis and assembly of semiconductor nanowires will be described, including the basics of nanowire FETs crucial to their configuration as biosensors. Second, we will introduce and review recent results in nanowire bioelectronics for biomedical applications ranging from label-free sensing of biomolecules, to extracellular and intracellular electrophysiological recording.
10.1088/0034-4885/80/1/016701
pubmed_877_23346
Under-diagnosed pathology. Especially in women under 60 without cardiovascular risk factor. Conventional coronary angiography without lesion. Association with fibrodysplasia being evaluated. Impact of IVUS and OCT. Conservative therapy.
10.1016/j.lpm.2017.11.010
pubmed_345_12576
Nitrogen-doped carbon is coated on lithium titanate (Li4Ti5O12, LTO) via a simple chemical refluxing process, using ethylenediamine (EDA) as the carbon and nitrogen source. The process incorporates a carbon coating doped with a relatively high amount of nitrogen to form a conducting network on the LTO matrix. The introduction of N dopants in the carbon matrix leads to a higher density of C vacancies, resulting in improved lithium-ion diffusion. The uniform coating of nitrogen-doped carbon on Li4Ti5O12 (CN-LTO) enhances the electronic conductivity of a CN-LTO electrode and the corresponding electrochemical properties of the cell employing the electrode. The results of our study demonstrate that the CN-LTO anode exhibits higher rate capability and cycling performance over 100 cycles. From the electrochemical tests performed, the specific capacity of CN-LTO electrode at higher rates of 20 and 50 C are found to be 140.7 and 82.3 mAh g(-1), respectively. In addition, the CN-Li4Ti5O12 anode attained higher capacity retention of 100% at 1 C rate after 100 cycles and 92.9% at 10 C rate after 300 cycles.
10.1021/acsami.5b00776
pubmed_405_13886
We conducted a time-location sampling sero-behavioral surveillance survey of men who have sex with men (MSM) in São Paulo, Brazil, the largest city in Latin America and the Southern Hemisphere (N = 1,217 interviewed with serological results for 771). HIV prevalence was 15.4 % (95 % CI 11.6-20.1), with only 45.8 % previously aware of their infection. HIV prevalence achieved 6.4 % among youth 18-24 years and was higher among MSM with lower socio-economic status. In multivariate analysis, correlates of HIV were older age, gay identity, lower socio-economic status, social networks with HIV-positive MSM, receptive anal sex, and internet sex partners. Policy change towards increasing avenues for HIV testing coupled with antiretroviral treatment regardless of CD4 count or stage of disease stand to benefit the MSM community if scaled up fast enough.
10.1007/s10461-014-0944-3
pubmed_452_3657
Although cattle can synthesize vitamin C (VC) endogenously, stress may increase VC requirements above the biosynthetic threshold and warrant supplementation. This study investigated the effects of a VC injection delivered before or after a long-distance transit event on blood parameters and feedlot performance of beef steers. Fifty-two days prior to trial initiation, 90 newly weaned, Angus-based steers from a single source were transported to Ames, IA, USA. On day 0, 72 steers (356 ± 17 kg) were blocked by BW and randomly assigned to intramuscular injection treatments (24 steers/treatment): saline injection pre- and post-transit (CON), VC (Vet One, Boise, ID, USA; 5 g sodium ascorbate/steer) injection pre-transit and saline injection post-transit (PRE) or saline injection pre-transit and VC injection post-transit (POST). Following pre-transit treatment injections, steers were transported on a commercial livestock trailer for approximately 18 h (1675 km). Post-transit (day 1), steers were sorted into pens with one GrowSafe bunk/pen (4 pens/treatment; 6 steers/pen). Steers were weighed on day 0, 1, 7, 30, 31, 56 and 57. Blood was collected from 3 steers/pen on day 0, 1, 2 and 7; liver biopsies were performed on the same 3 steers/pen on day 2. Data were analyzed as a randomized complete block design (experimental unit = steer; fixed effects = treatment and block) and blood parameters were analyzed as repeated measures. A pre-transit VC injection improved steer average daily gain from day 7 to 31 (P = 0.05) and overall (day 1 to 57; P = 0.02), resulting in greater BW for PRE-steers on day 30/31 (P = 0.03) and a tendency for greater final BW (day 56/57; P = 0.07). Steers that received VC pre- or post-transit had greater DM intake from day 31 to 57 (P = 0.01) and overall (P = 0.02) v. CON-steers. Plasma ascorbate concentrations were greatest for PRE-steers on day 1 and POST-steers on day 2 (treatment × day; P < 0.01). No interaction or treatment effects were observed for other blood parameters (P ≥ 0.21). Plasma ferric-reducing antioxidant potential and malondialdehyde concentrations decreased post-transit (day; P < 0.01), while serum non-esterified fatty acids and haptoglobin concentrations increased post-transit (day; P < 0.01). In general, blood parameters returned to pre-transit values by day 7. Pre-transit administration of injectable VC to beef steers mitigated the decline in plasma ascorbate concentrations and resulted in superior feedlot performance compared to post-transit administration.
10.1017/S1751731120000968
pubmed_1131_10873
We conducted a series of studies on multiple forms of repetitive behavior displayed by four children with autism spectrum disorder. Study 1 showed that each participant's highest probability repetitive behavior persisted in the absence of social consequences, thereby meeting the functional definition of stereotypy. Study 2 showed that preferred, structurally matched stimulation decreased each participant's targeted (highest probability) stereotypy, as well as their non-targeted (lower probability) stereotypy. Study 3 showed that for three participants, non-contingent access to preferred stimulation decreased immediate and, to some extent, subsequent engagement in targeted and non-targeted stereotypy. For the fourth participant, non-contingent access to preferred stimulation decreased immediate engagement in the targeted stereotypy, but increased subsequent engagement in non-targeted stereotypy; this subsequent increase was attenuated by reducing the duration of access to the preferred stimulus. Study 4 showed that a trial-based differential reinforcement of other behavior (DRO) procedure systematically increased the period of time for which the targeted stereotypy was not displayed for three of three participants. In addition, results showed that the participants' non-targeted stereotypy either decreased or was unchanged when DRO was provided for the targeted stereotypy.
10.1177/0145445516652370
pubmed_481_11879
Urgent management of acute biliary pancreatitis has increasingly included early endoscopic intervention. Endoscopic intervention allows effective removal of the offending stone(s) and reestablishment of biliary drainage. Four randomized controlled trials involving more than 800 patients in Western and Asian countries have been completed. This article summarizes the findings of these studies and proposes a preferred approach to the management of acute biliary pancreatitis.
pubmed_481_11879
pubmed_147_1248
PURPOSE OF REVIEW Maintenance of T-cell function and modulation of tolerance are critical issues in organ transplantation. The thymus is the primary organ for T-cell generation, and a preserved thymic function is essential for a self-tolerant diverse T-cell repertoire. Transplant procedures and related immunosuppressive drugs may hinder thymic integrity and function. We review here the recent advances in understanding the regulation of the unique thymic microenvironment with relevance for the field of transplantation. RECENT FINDINGS Recent studies have assigned a role for IL-22 in the regeneration of thymic epithelium, and for microRNAs in the modulation of its survival and function. The interplay of key molecules in the cross-talk between thymic epithelial cells and thymocytes was depicted, opening new perspectives for the in-vitro recapitulation of T-cell development and for thymic transplantation. Additionally, the thymus was shown to be able to sustain thymocyte progenitor renewal. SUMMARY These findings open new venues of research toward therapeutic interventions in the endogenous thymus to modulate or reconstitute the immune system; thymic transplantation; and the future development of artificial thymus, which would represent an important tool to achieve tolerance across the histocompatibility barriers.
10.1097/MOT.0b013e3283615df9
pubmed_419_6911
Cytokine-induced killer (CIK) cells are heterogeneous cells composed mainly of CD3+CD56+ T cells. As an important treatment method of adoptive therapy, it has shown promising efficacy in many clinical trials, especially in combination with multidrug therapy. However, the maximal antitumor efficacy of CIK therapy in the combined administration of multidrug and CIK therapies and which administration scheme can maximize the antitumor efficacy of CIK therapy are still remain unclear. In this study, we observed that pemetrexed administration prior to the injection of CIK cells maximizes the efficacy of CIK therapy. Anti-PD-1 mAbs should be administered prior to CIK cell injection to maximize the efficacy of the therapy. However, administering anti-PD-1 mAbs after CIK cell injection significantly affects the binding rate of anti-PD-1 mAbs to the PD-1 receptor on CIK cells, affecting the efficacy of the antitumor therapy. In conclusion, our study observed that a rational administration sequence of pemetrexed combined with CIK therapy and anti-PD-1 mAbs significantly promotes the efficacy of CIK therapy, providing an experimental basis for the combination therapy mode and regimen of CIK therapy in clinical practice. We hope that this study can provide patients with lung adenocarcinoma with a prolonged survival time.
10.1038/s41417-022-00543-5
pubmed_494_4239
Myocardial cell replacement strategies are emerging as novel therapeutic paradigms for heart failure but are hampered by the paucity of sources for human cardiomyocytes. Human embryonic stem cells (hESC) are pluripotent stem cell lines derived from human blastocysts that can be propagated, in culture, in the undifferentiated state under special conditions and coaxed to differentiate into cell derivatives of all three germ layers, including cardiomyocytes. The current review describes the derivation and properties of the hESC lines and the different cardiomyocyte differentiation system established so far using these cells. Data regarding the structural, molecular, and functional properties of the hESC-derived cardiomyocytes is provided as well as description of the methods used to achieve cardiomyocyte enrichment and purification in this system. The possible applications of this unique differentiation system in several cardiovascular research and applied areas are discussed. Specific emphasis is put on the descriptions of the efforts performed to date to assess the feasibility of this emerging technology in the fields of cardiac cell replacement therapy and tissue engineering. Finally, the obstacles remaining on the road to clinical translation are described as well as the steps required to fully harness the potential of this new technology.
10.1016/j.yjmcc.2008.08.008
pubmed_115_5504
The Epstein-Barr virus (EBV) EBER transcripts are small, highly structured RNAs able to bind to and inhibit activation of the double-stranded RNA-dependent protein kinase PKR in cell-free systems, and within latently infected B-cell lines they inhibit alpha interferon-induced apoptosis that is believed to be mediated through PKR. Here, we address the consequences of EBER expression for PKR activation in vivo in response to alpha interferon. In agreement with published findings, either EBV infection or the EBERs alone protected Burkitt lymphoma cells from alpha-interferon-induced apoptosis. However, utilizing multiple phosphorylation state-specific antibodies to monitor PKR activation within cells in response to interferon, we demonstrate that the EBERs are unable to inhibit phosphorylation of either cytoplasmic or nuclear PKR. Concordantly, a direct substrate of PKR, the alpha subunit of eukaryotic initiation factor 2 (eIF-2alpha), was equally phosphorylated in EBV-positive and EBV-negative cells following interferon treatment. Therefore, EBER inhibition of alpha-interferon-induced apoptosis, and potentially other PKR-mediated events, is unlikely to be mediated through direct inhibition of PKR, as previously thought.
10.1128/JVI.79.23.14562-14569.2005
pubmed_649_34738
We analyzed retrospectively 45 patients who had received silicone oil injection for vitreoretinal problems and divided them into three groups: aphakic patients who had undergone an extracapsular cataract extraction (AEC), aphakic patients who had undergone an intracapsular cataract extraction (AIC) and phakic patients (PHA). Patients were followed up from 4 to 13 months (average: 8.5 months). Irreversible silicone keratopathy was found in 50% of the eyes in the AIC group between 4 and 8 weeks postoperatively. An intact lens or capsule correlated well with the absence of this complication. In phakic eyes, secondary cataract was the most prominent early complication, developing by the end of the eighth week in 60% of eyes. Other early complications were inflammatory surface silicone membranes, rubeosis, iritis, glaucoma and capsular opacification.
pubmed_649_34738
pubmed_448_1893
BACKGROUND Individuals with Tourette syndrome (TS) often report that they express tics as a means of alleviating the experience of unpleasant sensations. These sensations are perceived as an urge to act and are referred to as premonitory urges. Premonitory urges have been the focus of recent efforts to develop interventions to reduce tic expression in those with TS. OBJECTIVE The aim of this study was to examine the contribution of brain γ-aminobutyric acid (GABA) and glutamate levels of the right primary sensorimotor cortex (SM1), supplementary motor area (SMA), and insular cortex (insula) to tic and urge severity in children with TS. METHODS Edited magnetic resonance spectroscopy was used to assess GABA+ (GABA + macromolecules) and Glx (glutamate + glutamine) of the right SM1, SMA, and insula in 68 children with TS (MAge  = 10.59, SDAge  = 1.33) and 41 typically developing control subjects (MAge  = 10.26, SDAge  = 2.21). We first compared GABA+ and Glx levels of these brain regions between groups. We then explored the association between regional GABA+ and Glx levels with urge and tic severity. RESULTS GABA+ and Glx of the right SM1, SMA, and insula were comparable between the children with TS and typically developing control subjects. In children with TS, lower levels of SMA GABA+ were associated with more severe and more frequent premonitory urges. Neither GABA+ nor Glx levels were associated with tic severity. CONCLUSIONS These results broadly support the role of GABAergic neurotransmission within the SMA in the experience of premonitory urges in children with TS. © 2021 International Parkinson and Movement Disorder Society.
10.1002/mds.28868
pubmed_1073_7693
An extremely rare case of anterior mediastinal mature teratoma with almost complete gastrointestinal and bronchial walls is described. A 65-year-old woman presented with left precordial pain. Chest computed tomography showed a huge anterior mediastinal tumor, 15 cm × 21 cm, occupying the left thoracic cavity. Post-resection histopathological examination confirmed the diagnosis of mature teratoma and demonstrated almost complete gastrointestinal and bronchial walls. Although mature teratomas of the ovary and sacrococcygeal area are known to rarely contain organoid structures with various degrees of differentiation, this is the first case of an anterior mediastinal mature teratoma that contained well-developed organoid structures.
10.1002/rcr2.109
pubmed_660_11277
Clinical trials, systematic reviews and guidelines compare beneficial and non-beneficial outcomes following interventions. Often, however, various studies on a particular topic do not address the same outcomes, making it difficult to draw clinically useful conclusions when a group of studies is looked at as a whole. This problem was recently thrown into sharp focus by a systematic review of interventions for preterm birth prevention, which found that among 103 randomised trials, no fewer than 72 different outcomes were reported. There is a growing recognition among clinical researchers that this variability undermines consistent synthesis of the evidence, and that what is needed is an agreed standardised collection of outcomes - a "core outcomes set" - for all trials in a specific clinical area. Recognising that the current inconsistency is a serious hindrance to progress in our specialty, the editors of over 50 journals related to women's health have come together to support The CROWN (CoRe Outcomes in WomeN's health) Initiative.
10.1186/1472-6874-14-75
pubmed_340_18516
In most studies comparing trace and delay conditioning, CS duration is kept constant across training conditions but the interstimulus interval (ISI), the time from CS onset to US onset, is confounded. In the infrequently used long-delay condition, however, ISI is kept constant across the trace and delay conditions but CS duration varies. A recent study reported that trace and long-delay fear conditioning have the same developmental trajectory, with both emerging later in development than standard-delay conditioning (). Past studies have shown that trace conditioning is mediated by the cholinergic system; given the parallel developmental emergence of trace and long-delay conditioning, the present study examined whether the cholinergic system also mediates long-delay conditioning. Two experiments, both involving Sprague-Dawley-derived rats and using freezing as a measure of learned fear, showed that the cholinergic system is critically involved in trace conditioning but is not involved in long-delay conditioning. Specifically, pre-training injections of the muscarinic receptor antagonist scopolamine impaired acquisition of a CS-US association in 32-day-old rats trained with a trace procedure but had no effect on rats this age trained with a long-delay procedure (Experiment 1). Similarly, pre-training injections of physostigmine, a cholinesterase inhibitor, enhanced acquisition of trace conditioning in 25-day-old rats but had no effect on long-delay conditioning in rats this age (Experiment 2). Taken together, the results indicate that despite the similarities between trace and long-delay conditioning in terms of developmental emergence and level of conditioned responding, they are mediated by different physiological systems.
10.1016/j.nlm.2006.06.003
pubmed_575_9666
Peach latent mosaic viroid (PLMVd) represents a continuing threat to peach tree production worldwide. In this study, a sensitive and accurate quantification of PLMVd in peach leaves was established using a reverse transcription droplet digital polymerase chain reaction (RT-ddPCR) assay. The quantitative linearity, accuracy, and sensitivity of RT-ddPCR for the detection of PLMVd were comparatively assessed to those of reverse-transcription real-time quantitative polymerase chain reaction (RT-qPCR) assay. The specificity assay shows no amplification in major peach viruses, apple chlorotic leaf spot virus and prunus necrotic ring spot virus and negative control. Furthermore, the levels of PLMVd transcripts determined using RT-ddPCR and RT-qPCR showed a high degree of linearity and quantitative correlation. Our results also indicated that the RT-ddPCR assay is at least two-fold more sensitive than qPCR and could therefore, be used to detect PLMVd in field samples. Moreover, optimization of RT-ddPCR was found to enhance the sensitivity of PLMVd detection in the peach leaf samples with low viral loads. In summary, the established RT-ddPCR assay represents a promising alternative method for the precise quantitative detection of PLMVd; it would be particularly applicable for diagnosing PLMVd infections in plant quarantine inspection and PLMVd-free certification program.
10.1016/j.mcp.2021.101746
pubmed_90_10555
An ascitic form of tumor was obtained in thymus-free BALB/c mice from a solid strain of human mammary carcinoma. It passed 32 serial transplantations. The paper describes the kinetics of the tumor growth. Cytological and biochemical examinations of the ascitic form of mammary carcinoma demonstrated its appurtenance to human malignant tumors of the mammary gland.
pubmed_90_10555
pubmed_906_1740
The development of new low molecular weight drugs against human immunodeficiency virus Type 1 (HIV-1) targets other than reverse transcriptase (RT) and protease, such as the integrase and the envelope glycoprotein, is likely to take many years. Macromolecular drugs, including antisense oligonucleotides, ribozymes, RNA decoys and transdominant mutant proteins, may be able to interfere with a relatively large number of viral targets, thereby decreasing the likelihood of the emergence of drug-resistant strains. It may also be relatively easy to alter the sequence of some of the macromolecular drugs to counter emerging drug-resistant viruses. The delivery of antisense oligonucleotides and ribozymes to HIV-1 infected or potentially infectable cells by antibody-targeted liposomes, certain cationic lipid formulations and pH-sensitive liposomes results in significant anti-HIV-1 activity. These carriers not only facilitate cytoplasmic delivery but also protect the drugs from nuclease digestion. Delivery of therapeutic genes (another form of macromolecular drug) to target cells is an important challenge of gene therapy. Following delivery by a viral vector, sufficient levels of gene expression must be maintained over an extended period of time to have therapeutic activity. Robust expression of therapeutically useful ribozymes, antisense, decoys and aptamers can be achieved by the use of Pol III expression systems. Moloney murine leukaemia virus- (MoMuLV), adeno-associated virus (AAV)-, or HIV-derived vectors expressing a variety of therapeutic genes have been used successfully to inhibit HIV-1 replication in cultured cells.
10.1517/14712598.1.6.949
pubmed_14_9679
Violence against women is a significant health issue in Canada and around the globe, yet the health-care response has been inadequate. While various reasons for this inadequacy have been suggested, little systematic research has been undertaken. This ethnographic study of 2 hospital emergency units was conducted to describe nursing practice in relation to violence against women. Participant observation and interviews with 25 healthcare providers and 5 patients in the 2 units were complemented by interviews with 5 nurses from other emergency units. The findings illustrate that abuse is obscured and practice shaped by stereotypical thinking and a focus on physical problems and rapid patient processing. Perceptions of patient deservedness influenced care that ranged from "doing nothing" to actively offering the patient choices. This description provides a basis for designing meaningful education for nurses and systemic changes that will foster more effective practice.
pubmed_14_9679
pubmed_785_5840
Articular cartilage injuries and degenerative joint diseases are responsible for progressive pain and disability in millions of people worldwide, yet there is currently no treatment available to restore full joint functionality. As the tissue functions under mechanical load, an understanding of the physiologic or pathologic effects of biomechanical factors on cartilage physiology is of particular interest. Here, we highlight studies that have measured cartilage deformation at scales ranging from the macroscale to the microscale, as well as the responses of the resident cartilage cells, chondrocytes, to mechanical loading using in vitro and in vivo approaches. From these studies, it is clear that there exists a complex interplay among mechanical, inflammatory, and biochemical factors that can either support or inhibit cartilage matrix homeostasis under normal or pathologic conditions. Understanding these interactions is an important step toward developing tissue engineering approaches and therapeutic interventions for cartilage pathologies, such as osteoarthritis.
10.1007/s11926-014-0451-6
pubmed_781_11486
Binge eating disorder (BED) is the most common of the 6 feeding and eating disorders recognized by the DSM-5 and a significant public health problem that can be successfully managed with appropriate help. Many patients, however, are hesitant to discuss the symptoms of BED with their providers because of embarrassment or because they simply do not recognize the behavior as a problem behavior. Clinicians need to increase their awareness of BED, its warning signs, and how and why patients might try to hide it leading to increased BED recognition and timely diagnosis. Then, given the right tools, clinicians can help patients to not only accept the diagnosis and look into various treatment options but also to move beyond it to recognize if any comorbid disorders are present and in need of treatment.
10.4088/JCP.14060wc1c
pubmed_964_10317
Malnutrition in children is a well known critical factor that determines immunocompetence changes with altered immune response and higher risk to many diseases, especially in developing countries. Moreover, it is related to increased morbi-mortality rates mainly due to infections. For those reasons, 12 undernourished children, age 5 to 24 months were studied along 8 weeks at the Nutritional Recovery Center of Chiquinquira Hospital in Maracaibo, Venezuela. There were 5 cases of kwashiorkor, 5 marasmatics, 1 mixed marasmus/kwashiorkor and 1 case with moderate malnutrition. After a control blood sample was taken and cutaneous tests were done, a nutritional recovery program was began. At regular time intervals and at the end of the study, tests were done again by measuring seric immunoglobulins (IgG, IgA, IgM), secretory IgA (IgAs), C3 and C4 complement, lymphocytic sub-populations, and auto antibodies; cutaneous hipersensitivity tests were also done. As a control group, 10 apparently healthy children of matching age and sex were also studied with the same parameters. Results show that basal seric Igs did not differ significantly from the control group and did not change along the recovery program period, but there was a significant decrease in IgAs at all times of the study. C4 did not change and C3 was lower than control (p < 0.05) but returned to normal value at the end of the recovery period. CD3 and CD4 lymphocytes showed the same pattern. Only two patients showed positive skin tests and auto antibodies were not detected. It is concluded that there is indeed an altered immune competence with low levels of C3, IgAs, and CD3-CD4 lymphocytes that is reversible after nutritional recovery.
pubmed_964_10317
pubmed_377_10222
The patients suffering from acidosis usually sign psychological deficits. The cerebral dysfunction is reportedly caused by an acid-induced functional impairment of GABAergic neurons; however, the role of pyramidal neurons in this process remains unclear. By using electrophysiological method and changing extracellular pH, we investigated the influence of acidic environment on pyramidal neurons in the cortical slices, such as their ability of firing spikes and response to synaptic inputs. A low pH of artificial cerebral spinal fluid elevates the responses of pyramidal neurons to excitatory synaptic inputs and their ability of encoding digital spikes, as well as reduces the signal transmission at GABAergic synapses. The elevated ability of neuronal spiking is associated with the decreases of refractory periods and threshold potentials. Therefore, acidosis deteriorates brain functions through making the activities between cortical pyramidal neurons and GABAergic neurons imbalanced toward the overexcitation of neural networks, a process similar to neural excitotoxicity.
10.1016/j.bbrc.2011.08.008
pubmed_511_20677
OBJECTIVES To evaluate the reported amount of 14 vitamins and 10 minerals in over-the-counter (OTC) and prescription (Rx) prenatal multivitamins and minerals (PMVMs) and compare them with the Health and Medicine Division (HMD) of the National Academies recommended dietary allowances (RDAs) and tolerable upper intake levels for intake. DESIGN Observational convenience sample of supplemental facts labels on OTC and Rx PMVMs identified and evaluated from online retailers, grocery stores, and pharmacies. SETTING AND PARTICIPANTS Not applicable. OUTCOME MEASURES Reported vitamin and mineral amounts in PMVMs were compared with HMD RDAs to determine whether PMVMs could correct RDA deficiencies in the average pregnant woman's diet. Reported vitamin and mineral amounts were compared in OTC and Rx PMVMs and to HMD upper intake levels. RESULTS One hundred sixty-three OTC and 88 Rx PMVMs were evaluated. The average pregnant woman in the United States is deficient in many vitamins and minerals from food intake alone. Over 80% of OTC and Rx PMVMs would correct the RDA deficit for vitamin B6, folic acid, vitamin C, vitamin E, and iron. Over 90% of OTC products would correct the deficit for vitamin A and zinc; however, 47% and 74% of Rx products would correct for those deficits, respectively. Approximately 73% of OTC and 60% of Rx PMVMs corrected calcium deficit, and 33% of OTC and 24% of Rx PMVMs corrected vitamin D deficit. A minority of PMVMs corrected deficits for magnesium and choline. OTC products have significantly more of each vitamin compared with Rx, with several exceptions including: iron, folic acid, copper, and vitamin B6. CONCLUSION Most pregnant women take PMVMs. If pregnant women are not consuming enough essential micronutrients from diet, it is possible that PMVMs will provide adequate amounts; however, this depends on the specific vitamin or mineral. There is notable variation between Rx and OTC PMVM options.
10.1016/j.japh.2018.02.006
pubmed_787_11839
Among high-risk human papillomaviruses (HPV), HPV-16 infection is the most prevalent causative factor for cervical cancer. Beside other mucosal targets, HPV-16 was reported to infect the placenta and to replicate in trophoblastic cells. Since these cells share invasive properties of tumoral cells, they represent an ideal model to investigate several oncogenic processes. In the present work, we analyzed the impacts of HPV-16 E5, E6 and E7 oncoproteins on the trophoblastic model. Our results showed that E5 impaired the viability of trophoblastic and cervical cell lines but E6 and E7, favoring cell growth, neutralized the E5 cytotoxic effect. In addition, E5 decreased the adhesiveness of trophoblastic cells to the tissue culture plastic and to endometrial cells similarly as described previously for E6 and E7. E5 and E6 plus E7 increased also their migration and their invasive properties. Cells expressing HPV-16 early proteins under the control of the long control region endogenous promoter displayed growth advantage and were also more motile and invasive compared with control cells. Interestingly, the E-cadherin was downregulated in trophoblastic cells expressing E5, E6 and E7. Nuclear factor-kappaB and activator protein-1 activities were also enhanced. In conclusion, HPV-16 early proteins enhanced trophoblastic growth and intensify the malignant phenotype by impairing cell adhesion leading to increased cellular motile and invasive properties. HPV-16 E5 participated, with E6 and E7, in these changes by impairing E-cadherin expression, a hallmark of malignant progression.
10.1093/carcin/bgp281
pubmed_780_6574
To determine the impact of dietary patterns on the control of hypertension we studied the subgroup of 133 participants with systolic blood pressure (BP) of 140 to 159 mm Hg and/or diastolic BP of 90 to 95 mm Hg enrolled in the Dietary Approaches to Stop Hypertension (DASH) study. Participants were fed a control diet for a 3-week period and were then randomized to receive for 8 weeks either the control diet; a diet rich in fruits and vegetables, but otherwise similar to control; or a combination diet rich in fruits, vegetables, and low-fat dairy products, including whole grains, fish, poultry, and nuts, and reduced in fats, red meats, sweets, and sugar-containing beverages. Sodium intake and body weight were held constant throughout the study. The combination diet significantly reduced systolic BP (-11.4 mm Hg, P < .001) and diastolic BP (-5.5 mm Hg, P < .001). The fruits-and-vegetables diet also significantly reduced systolic BP (-7.2 mm Hg, P < .001) and diastolic BP (-2.8 mm Hg, P = .013). The combination diet produced significantly greater BP effects (P < .05) than the fruits-and-vegetables diet. Blood pressure changes were evident within 2 weeks of starting the intervention feeding. After the 8-week intervention period, 70% of participants eating the combination diet had a normal BP (systolic BP < 140 and diastolic BP < 90 mm Hg) compared with 45% on the fruits-and-vegetables diet and 23% on the control diet. In patients with hypertension, the DASH combination diet effectively lowers BP and may be useful in achieving control of Stage 1 hypertension.
10.1016/s0895-7061(99)00284-8
pubmed_282_12030
BACKGROUND Accelerated step-up or anti-tumor necrosis factor (TNF) before first remission is currently not recommended in pediatric Crohn's disease. METHODS Five-year follow-up data from a prospective observational cohort of children diagnosed with Crohn's disease in Belgium were analyzed. Disease severity was scored as inactive, mild, or moderate to severe. Remission or inactive disease was defined as sustained if lasting ≥2 years. Univariate analyses were performed between anti-TNF-exposed versus naive patients and anti-TNF before versus after first remission and correlations assessed with primary outcomes average disease severity and sustained remission. RESULTS A total of 91 patients (median [IQR] age 12.7 [10.9-14.8] yrs, 53% male) were included. Disease location was 12% L1, 23% L2, and 64% L3 with 76% upper gastrointestinal and 30% perianal involvement. Disease severity was 25% mild and 75% moderate to severe. Of 66 (73%) anti-TNF-exposed patients, 34 (52%) had accelerated step-up. Anti-TNF use was associated with age (13.1 [11.5-15.2] versus 11.8 [8.7-13.8] yrs; P < 0.05), L2 (29% versus 8%; P = 0.04), and average disease severity (1.7 [1.4-1.9] versus 1.4 [1.3-1.6]; P < 0.001). Duration of anti-TNF correlated with average disease severity (r = 0.32, P = 0.002). Accelerated step-up was also associated with age (13.3 [12.1-15.9] versus 12.5 [10.2-14.1]; P = 0.02) and average disease severity (1.8 [1.6-1.9] versus 1.6 [1.3-1.8]; P = 0.002). Duration of sustained remission was similar in all patients, and no serious infections, cancer, or deaths were reported. CONCLUSIONS Anti-TNF therapy and accelerated step-up in older patients with more severe disease leads to beneficial long-term outcomes.
10.1097/MIB.0000000000001193
pubmed_820_7035
Parathyroid carcinoma is a rare condition, comprising less than 1% of the cases of primary hyperparathyroidism (PHP). Nonetheless, due to its aggressiveness, and having prognosis dependent on the precocity of diagnosis and radical therapeutic approach, it is paramount that the clinical suspicion be made before surgery. Clinical presentation is typical of severe PHP, with a parathyroid tumor >1.5 cm, usually palpable. The pathologic features sometimes are difficult to characterize. Our experience with this condition (from 1983 to 2004) includes 7 cases, all symptomatic, hypercalcemic syndrome and bone disease present in most of them. In 6/7 the tumor was palpable, and in all the biochemical profile was compatible with severe PHP. Three patients died of complications of hypercalcemia. Recent findings point to a mutation on the gene HRPT2 as the molecular base for the development of this kind of tumor. The therapeutic approach is surgical and should include ipsilateral thyroidectomy and cervical exploration in order to find possible local metastasis. Post-surgical complications (mainly hypocalcemia) are proportional to the pre-existing metabolic alterations. The long-term prognosis depends upon the precocity of diagnosis, surgical success and control of hypercalcemia. New therapeutic approaches, based on bisphosphonates and calcimimetic drugs, as well as the possibility of genetic diagnosis, tend to ameliorate the prognosis of this severe affection.
10.1590/s0004-27302005000500023
pubmed_1135_21848
Infectious bursal disease virus (IBDV) is an important poultry pathogen. The VP2 protein of IBDV is the major host-protective immunogen. Although the functions of the VP2 protein have been well studied, the factors shaping synonymous codon usage bias and nucleotide composition in the VP2 gene have not yet been reported. In the present study, we have analyzed the relative synonymous codon usage and effective number of codons (ENC) using 69 IBDV VP2 genes. The major trend in codon usage variation was studied using correspondence analysis. The plot of ENC values and GC3s as well as the correlation between base composition and codon usage bias suggests that mutational pressure rather than natural selection is the main factor that determines the codon usage bias in the VP2 gene. In addition, other factors, such as the aromaticity, hydrophobicity and aliphatic index also influence the codon usage variation of the VP2 gene. This study represents a comprehensive analysis of IBDV VP2 gene codon usage patterns and provides a basic understanding of the codon usage bias.
10.1007/s00705-015-2505-0
pubmed_345_17131
Combined with the research in an organic farm in the past 10 years, differences of soil aggregates composition, distribution and organic carbon fractions between organic and conventional cultivation were studied by simultaneous sampling analysis. The results showed that the percentages of aggregates (> 1 mm, 1-0.5 mm, 0.5-0.25 mm and < 0.25 mm) in the conventional cultivation were 23.75%, 15.15%, 19.98% and 38.09%, while those in organic cultivation were 9.73%, 18.41%, 24.46% and 43.90%, respectively. The percentage of < 0.25 mm micro-aggregates was significantly higher in organic cultivation than that in conventional cultivation. Organic cultivation increased soil organic carbon (average of 17.95 g x kg(-1)) and total nitrogen contents (average of 1.51 g x kg(-1)). Among the same aggregates in organic cultivation, the average content of heavy organic carbon fraction was significantly higher than that in conventional cultivation. This fraction accumulated in < 0. 25 mm micro-aggregates, which were main storage sites of stable organic carbon. In organic cultivation, the content of labile organic carbon in > 1 mm macro-aggregates was significantly higher than that in conventional cultivation, while no significant difference was found among the other aggregates, indicating that the labile organic carbon was enriched in > 1 mm macro-aggregates. Organic cultivation increased the amounts of organic carbon and its fractions, reduced tillage damage to aggregates, and enhanced the stability of organic carbon. Organic cultivation was therefore beneficial for soil carbon sequestration. The findings of this research may provide theoretical basis for further acceleration of the organic agriculture development.
pubmed_345_17131
pubmed_21_15778
As IL36RN mutations are a cause of generalized pustular psoriasis (GPP), three recent investigations attempted to correlate the IL36RN genotype with GPP clinical presentations. These studies found that IL36RN mutations account for only a fraction of GPP cases presenting with concomitant psoriasis vulgaris (PV; common or typical psoriasis). Pathogenic alleles were also found in control populations, indicating that environmental triggers and/or modifier genes may contribute to the disease.
10.1038/jid.2013.361
pubmed_659_5755
Online learning has received extensive attention in the field of education in the recent decade, especially after COVID-19 swept the globe in 2020. Online learning satisfaction (OLS) has become the focal point of the research, since it is of vital significance to enhance online learning efficiency. This paper reviews the research on OLS from the dimensions of online learners, online instructors, online platforms and online instructional design to have a clear picture of factors affecting OLS. Based on the review of previous studies, this mini review presents the prospect of future research on OLS and believes that breakthroughs on OLS research can be achieved by innovating research methods, expanding research subjects, and enriching research topics. OLS is a complicated dynamic system influenced by a diversity of factors, and it is worth more in-depth research by scholars and educators in future.
10.3389/fpsyg.2022.852360
pubmed_864_18274
LKB1 is a Ser/Thr kinase that plays an important role in controlling both energy metabolism and cell polarity in metazoan organisms. LKB1 is also a tumor suppressor, and homozygous, inactivating mutations are found in a wide range of human cancers. In lung cancer, inactivating mutations are found in 10 to 50% of cases, but the consequences of functional loss in this context are poorly understood. We report here that LKB1 is required for the maturation of apical junctions in the human bronchial epithelial cell line 16HBE14o- (16HBE). This activity is dependent on an interaction with the Rho guanine nucleotide exchange factor p114RhoGEF but is independent of LKB1 kinase activity. Together, LKB1 and p114RhoGEF control RhoA activity in these cells to promote apical junction assembly.
10.1128/MCB.00154-13
pubmed_902_9671
OBJECTIVE The aim of this study was to test the efficacy of brief physician advice in reducing alcohol use and related harm in college students. METHOD The College Health Intervention Projects (CHIPs) is a randomized, controlled clinical trial with 12-month follow-up conducted in five college health clinics in Wisconsin; Washington state; and Vancouver, Canada. Of the 12,900 students screened for high-risk drinking, 484 men and 502 women met inclusion criteria and were randomized into a control (n = 493) or intervention (n = 493) group. Ninety-six percent of students participated in the follow-up procedures. The intervention consisted of two 15-minute counseling visits and two follow-up phone calls, and used motivational interviewing, contracting, diary cards, and take-home exercises. RESULTS No significant differences were found between groups at baseline on alcohol use, age, socioeconomic or smoking status, rates of depression, or measures of alcohol-related harm. At 12 months, the experimental subjects reduced their 28-day drinking totals by 27.2%, and the control group reduced their totals by 21%. A mixed effects repeated measures model found a statistical difference in favor of the brief-intervention group (beta = 4.7, SE = 2.0, p = .018) in 28-day drinking totals. The total Rutgers Alcohol Problem Index score was also significantly different during the 12-month follow-up period (beta = 0.8, SE = 0.4, p = .033). There was no difference on the other outcome measures of interest, such as frequency of excessive heavy drinking, health care utilization, injuries, drunk driving, depression, or tobacco use. CONCLUSIONS The study supports resource allocation and implementation of alcohol screening and brief physician advice in primary care-based college health clinics.
10.15288/jsad.2010.71.23
pubmed_953_21089
The present investigation focuses in investigating the effect of osmotic pressure, gelling on the mean droplet diameter, polydispersity index, droplet size stability of the developed novel Aspirin containing water-in-oil-in-water (W/O/W) nano multiple emulsion. The aspirin-loaded nano multiple emulsion formulation was successfully generated using two-stage ultrasonic cavitational emulsification which had been reported in author's previous study. The osmotic behavior of ultrasonically prepared nano multiple emulsions were also examined with different glucose concentrations both in the inner and outer aqueous phases. In addition, introducing gelatin into the formulation also observed to play an important role in preventing the interdroplet coalescence via the formation of interfacial rigid film. Detailed studies were also made on the possible mechanisms of water migration under osmotic gradient which primarily caused by the permeation of glucose. Besides, the experimental results have shown that the interfacial tension between the two immiscible phases decreases with varying the composition of organic phase. Although the W/O/W emulsion prepared with the inner/outer glucose weight ratio of 1-0.5% (w/w) showed an excellent droplet stability, the formulation containing 0.5% (w/w) glucose in the inner aqueous phase appeared to be the most stable with minimum change in the mean droplet size upon one-week storage period. Based on the optimization, nano multiple emulsion droplets with the mean droplet diameter of around 400 nm were produced using 1.25% (w/w) Span 80 and 0.5% Cremophore EL. Overall, our investigation makes a pathway in proving that the use of ultrasound cavitation is an efficient yet promising approach in the generation of stable and uniform nano multiple emulsions and could be used in the encapsulation of various active pharmaceutical ingredients in the near future.
pubmed_953_21089
pubmed_205_1518
INTRODUCTION Before the HIV infection era, plasmocyte tumor rarely occurred in patients younger than 40 years of age. Less frequent than lymphomas, the incidence of these blood diseases has however substantially increased in HIV-infected patients. In these patients, in addition to onset at earlier age, their clinical presentation is quite different and extramedullary plasmocytomas in unexpected locations are more common. EXEGESIS We report the case of a 29-year-old HIV-infected female patient in whom were diagnosed occipital, parotidal, sphenoidal, epidural, and uterine plasmocytomas for which chemotherapy and subsequent radiotherapy were successful. The increase in the incidence of plasmocyte tumors in HIV-infected patients might be facilitated by Epstein Barr Virus (EBV) co-infection, HIV-related chronic antigenic stimulation, and secretion of interleukin 6 by infected lymphocytes. CONCLUSION Plasmocyte tumors belong to neoplasia whose incidence is increased in HIV infection. Their currently poor diagnosis should be improved by highly active antiretroviral therapies allowing enhanced chemotherapy with possibility of autograft.
10.1016/s0248-8663(00)80008-9
pubmed_952_1923
The authors establish the optimal conditions (protein concentration, temperature) for the coupling of purified mycoplasma antigen to sheep red blood cells, in order to obtain an antigenic complex stable for at least 1 year. This comples allows specific determination by passive hemagglutination--a simple and rapid technique--of anti-mycoplasma antibodies in the sera of men or animals suspected of mycoplasma infections. Under the stated experimental conditions, antibody titers equal to or higher than 1/128 indicate an infection with M. pneumoniae.
pubmed_952_1923
pubmed_439_15946
Prior meta-analyses have provided important information regarding which brain areas are structurally compromised in individuals with mild cognitive impairment (MCI). These studies have not however separated volume, density, and thickness, controlled for important demographic influences, considered null findings, or recognized studies indicating increased brain volumes in MCI individuals. Furthermore, there is a question as to whether deficits extend into cortical regions, and also into the thalamus. This study aims to address these issues using activation likelihood estimation (ALE) analyses with a sample size more than twice that of prior meta-analyses. A total of 71 studies were identified and entered into the ALE analysis which consisted of 2262 with MCI and 1902 healthy controls. Three major clusters were identified showing decreased gray matter volume in the MCI group compared to controls, with the most salient decreases being in the hippocampus, parahippocampal gyrus, and the amygdala. Reduced thalamic volume was also observed, but to a lesser extent. Density was reduced in the left hippocampus, while thickness was reduced in the uncus. No significant cluster emerged from an ALE meta-analysis of studies finding volume increases in MCI individuals. While the MCI group was significantly older and less educated than controls, controlling for these factors still resulted in significant, albeit attenuated findings. These results support hippocampal and parahippocampal deficits in MCI, and further highlight the amygdala, thalamus, and uncus as other areas to be considered in future MCI studies.
10.1007/s11682-022-00659-0
pubmed_31_10474
Medicare's first step in reining in the skyrocketing cost of specialty drugs deserves support--something it has not received from hospitals, doctors, politicians or, of course, the pharmaceutical industry, which benefits the most from the status quo.
pubmed_31_10474
pubmed_585_4404
The resolution of chromosomes during anaphase is a key step in mitosis. Failure to disjoin chromatids compromises the fidelity of chromosome inheritance and generates aneuploidy and chromosome rearrangements, conditions linked to cancer development. Inactivation of topoisomerase II, condensin, or separase leads to gross chromosome nondisjunction. However, the fate of cells when one or a few chromosomes fail to separate has not been determined. Here, we describe a genetic system to induce mitotic progression in the presence of nondisjunction in yeast chromosome XII right arm (cXIIr), which allows the characterisation of the cellular fate of the progeny. Surprisingly, we find that the execution of karyokinesis and cytokinesis is timely and produces severing of cXIIr on or near the repetitive ribosomal gene array. Consequently, one end of the broken chromatid finishes up in each of the new daughter cells, generating a novel type of one-ended double-strand break. Importantly, both daughter cells enter a new cycle and the damage is not detected until the next G2, when cells arrest in a Rad9-dependent manner. Cytologically, we observed the accumulation of damage foci containing RPA/Rad52 proteins but failed to detect Mre11, indicating that cells attempt to repair both chromosome arms through a MRX-independent recombinational pathway. Finally, we analysed several surviving colonies arising after just one cell cycle with cXIIr nondisjunction. We found that aberrant forms of the chromosome were recovered, especially when RAD52 was deleted. Our results demonstrate that, in yeast cells, the Rad9-DNA damage checkpoint plays an important role responding to compromised genome integrity caused by mitotic nondisjunction.
10.1371/journal.pgen.1002509
pubmed_92_9583
OBJECTIVE To compare the influence of archwire material (NiTi, beta-Ti and stainless steel) and brackets design (self-ligating and conventional) on the frictional force resistance. MATERIAL AND METHODS Two types of brackets (self-ligating brackets - Smartclip, 3M/Unitek - and conventional brackets - Gemini, 3M/Unitek) with three (0, 5, and 10 degrees) slot angulation attached with elastomeric ligatures (TP Orthodontics) were tested. All brackets were tested with archwire 0.019"x0.025" nickel-titanium, beta-titanium, and stainless steel (Unitek/3M). The mechanical testing was performed with a universal testing machine eMIC DL 10000 (eMIC Co, Brazil). The wires were pulled from the bracket slots at a cross-head speed of 3 mm/min until 2 mm displacement. RESULTS Self-ligating brackets produced significantly lower friction values compared with those of conventional brackets. Frictional force resistance values were directly proportional to the increase in the bracket/ wire angulation. With regard to conventional brackets, stainless steel wires had the lowest friction force values, followed by nickel-titanium and beta-titanium ones. With regard to self-ligating brackets, the nickel-titanium wires had the lowest friction values, significantly lower than those of other materials. CONCLUSION even at different angulations, the self-ligating brackets showed significantly lower friction force values than the conventional brackets. Combined with nickel-titanium wires, the self-ligating brackets exhibit much lower friction, possibly due to the contact between nickel-titanium clips and wires of the same material.
pubmed_92_9583
pubmed_485_12304
Fusidic acid viscous eye drops, Fucithalmic (R), is a new eye antibiotic preparation which shows sustained-release properties. The long-lasting antibiotic concentrations in tear fluid can be ascribed to the carbomer used in the vehicle. Fusidic acid viscous eye drops was found to give significantly higher tear fluid concentrations than chloramphenicol viscous eye drops, the latter based on methylcellulose when investigated in rabbit eyes and dog eyes. In volunteers the excretion half-life of fusidic acid from tears was found to be 1.9 h. From a pharmacokinetic point of view and from already available clinical data, fusidic acid viscous eye drops would seem to be effective when given only twice daily.
10.1007/BF03189900
pubmed_559_15829
Cystinosis is a rare metabolic disorder characterized by lysosomal cystine accumulation leading to multi-organ damage, with kidneys being clinically first affected. Longer survival of cystinosis patients due to successful renal replacement therapy, revealed previously unknown extra-renal symptoms of cystinosis, generally appearing after the first decade. Respiratory insufficiency caused by overall respiratory muscle myopathy is a severely invalidating and sometimes a life-threatening complication of cystinosis. We report a successful treatment of hypoventilation, due to diaphragm myopathy in a cystinosis patient, by nocturnal non-invasive positive pressure ventilation (NIPPV). After initiation of NIPPV the clinical condition of the patient improved and blood-gasses normalized, indicating that this treatment modality should be considered in cystinosis patients with severe respiratory insufficiency.
10.5414/cnp66306
pubmed_646_22191
In the genomic era DNA sequencing is increasing our knowledge of the molecular structure of genetic codes from bacteria to man at a hyperbolic rate. Billions of nucleotides and millions of aminoacids are already filling the electronic files of the data bases presently available, which contain a tremendous amount of information on the most biologically relevant macromolecules, such as DNA, RNA and proteins. The most urgent problem originates from the need to single out the relevant information amidst a wealth of general features. Intelligent tools are therefore needed to optimise the search. Data mining for sequence analysis in biotechnology has been substantially aided by the development of new powerful methods borrowed from the machine learning approach. In this paper we discuss the application of artificial feedforward neural networks to deal with some fundamental problems tied with the folding process and the structure-function relationship in proteins.
10.1080/10629360008039120
pubmed_534_5887
OBJECTIVE To develop a chart for risk of small-for-gestational-age (SGA) at birth depending on deviations in symphysis-fundus (SF) height values for gestational age during pregnancy weeks 24-42. DESIGN Registry-based population cohort study. SETTING Antenatal clinics, Västra Götaland County, Sweden, 2005-2010. POPULATION The study included 42 018 women with ultrasound-dated singleton pregnancies who delivered at Sahlgrenska University Hospital. Data (including 282 713 SF height measurements) were extracted from the hospital's computerised obstetric database. METHODS Linear and binary regression analyses were used to derive prediction models with deviations in birthweight (BW) and SF height by gestational age as dependent and independent variables, respectively. Receiver operating characteristic curves were generated to evaluate the predictive value of the model in detecting SGA. MAIN OUTCOME MEASURES Birthweight and small-for-gestational-age. RESULTS Symphysis-fundus height accounted for 3% of individual BW variance at 24 weeks, increasing gradually to 20% at 40 weeks. Maternal factors explained an additional 10 percentage points of BW variance. Receiver operating characteristic curves confirmed that SF height was a stronger SGA predictor in late than in early pregnancy. Using an SGA relative risk cut-off limit of ≥2-fold, the overall sensitivity was 50% and the overall specificity 80%. Only the most recent SF measurement was useful in predicting BW deviation; previous measurements added nothing to the predictive value. CONCLUSIONS The ability of SF measurements to detect SGA status at birth increases with gestational age. Only the most recent SF measurement has predictive value; a static or falling pattern of SF values did not increase SGA likelihood. TWEETABLE ABSTRACT New SF curves predict SGA best in late pregnancy; only the most recent SF measurement has predictive value.
10.1111/1471-0528.13727
pubmed_365_15892
OBJECTIVE To examine the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) together with CCAAT/enhancer binding protein alpha (C/EBPalpha), lipoprotein lipase (LPL) and glucose transporter (GLUT4) mRNA in adipose tissue of rhesus monkeys in relation to obesity. DESIGN Cloning of the PPARgamma1 and gamma2 cDNAs and analysis of PPARgamma, C/EBPalpha, LPL and GLUT4 mRNA levels in the adipose tissue of lean and obese monkeys. SUBJECTS 28 rhesus monkeys (Macaca mulatta) with a wide range of body weights (9.2-22.6 kg) and with or without type 2 diabetes. MEASUREMENTS Sequence of PPARgamma1 and gamma2. Tissue distribution of PPARgamma1 and gamma2. The mRNA levels of PPARgamma, C/EBPalpha, LPL and GLUT4 in adipose tissue. The ratio of PPARgamma2 mRNA to total PPARgamma mRNA. RESULTS The monkey PPARgamma2 protein showed 99% identity with the human protein. PPARgamma1 mRNA was shown to be expressed in various tissues and most abundantly in adipose tissue. PPARgamma2 existed mainly in adipose tissue. A significant correlation between the ratio of PPARgamma2 mRNA to total PPARgamma mRNA and obesity was observed, whereas total PPARgamma mRNA levels showed no significant relationships to obesity. There was also a significant relationship between the ratio of PPARgamma2 mRNA to total PPARgamma mRNA and fasting plasma insulin concentration. The mRNA levels of C/EBPalpha, LPL and GLUT4 were highly correlated to that of total PPARgamma mRNA. They were also significantly correlated to the mRNA levels of PPARgamma1 and PPARgamma2. CONCLUSIONS The ratio of PPARgamma2 mRNA to total PPARgamma mRNA is related to obesity in the rhesus monkey and mRNA expression of PPARgamma1, PPARgamma2, C/EBPalpha, LPL and GLUT4 appear to be coordinated in vivo.
10.1038/sj.ijo.0800718
pubmed_879_18149
Both polyesters and polycarbonates have been proposed as alternatives to polyethers as host materials for future polymer electrolytes for solid-state lithium-ion batteries. While being comparatively similar functional groups, the electron density on the coordinating carbonyl oxygen is different, thereby rendering different coordinating strength towards lithium ions. In this study, the transport properties of poly(ε-caprolactone) and poly(trimethylene carbonate) as well as random copolymers of systematically varied composition of the two have been investigated, in order to better elucidate the role of the coordination strength. The cationic transference number, a property well-connected with the complexing ability of the polymer, was shown to depend almost linearly on the ester content of the copolymer, increasing from 0.49 for the pure poly(ε-caprolactone) to 0.83 for pure poly(trimethylene carbonate). Contradictory to the transference number measurements that suggest a stronger lithium-to-ester coordination, DFT calculations showed that the carbonyl oxygen in the carbonate coordinates more strongly to the lithium ion than that of the ester. FT-IR measurements showed the coordination number to be higher in the polyester system, resulting in a higher total coordination strength and thereby resolving the paradox. This likely originates in properties that are specific of polymeric solvent systems, e.g. steric properties and chain dynamics, which influence the coordination chemistry. These results highlight the complexity in polymeric systems and their ion transport properties in comparison to low-molecular-weight analogues, and how polymer structure and steric effects together affect the coordination strength and transport properties.
10.1039/d1cp03929f
pubmed_1025_2990
Intracellular bacterial pathogens exploit host cells as a part of their lifecycle, and they do so by manipulating host cell signaling events. Many such bacteria are known to produce effector proteins that promote cell invasion, alter membrane trafficking, and disrupt signaling cascades. This review highlights recent advances in our understanding of signaling pathways involved in host cell responses to Francisella tularensis, a facultative Gram-negative intracellular pathogen that causes tularemia. We highlight several key pathways that are targeted by Francisella, with a focus on the phosphatidylinositol 3-kinase/Akt pathway. Lastly, we discuss the emerging role of microRNAs (miRs), specifically miR-155, as a key regulator of host signaling and defense.
10.3389/fmicb.2011.00013
pubmed_43_4786
BACKGROUND Emphysema and exercise induced desaturation (EID) are both related to poorer COPD prognosis. More knowledge of associations between emphysema and desaturation is needed for more efficient disease management. RESEARCH QUESTION Is emphysema a risk factor for both new and repeated desaturation, and is emphysema of more or less importance than other known risk factors? METHODS 283 COPD patients completed a 6-min walk test (6MWT) at baseline and one year later in the Bergen COPD cohort study 2006-2011. Degree of emphysema was assessed as percent of low attenuation areas (%LAA) under -950 Hounsfield units using high-resolution computed tomography at baseline. We performed multinomial logistic regression analysis, receiver operating curves (ROC) and area under the curve (AUC) estimations. Dominance analysis was used to rank emphysema and risk factors in terms of importance. RESULTS A one percent increase in %LAA increases the relative risk (RR) of new desaturation by 10 % (RR 1.1 (95%CI 1.1, 1.2)) and for repeated desaturation by 20 % (RR 1.2 (95%CI 1.1, 1.3)). Compared with other important desaturation risk factors, %LAA ranked as number one in the dominance analysis, accounting for 50 % and 37 % of the predicted variance for new and repeated desaturators, respectively. FEV1% predicted accounted for 9 % and 24 %, and resting SpO2 accounted for 22 % and 21 % for new and repeated desaturation. CONCLUSION Emphysema increases the risk of developing and repeatedly experiencing EID. Emphysema seems to be a more important risk factor for desaturation than FEV1% predicted and resting saturation.
10.1016/j.rmed.2021.106542
pubmed_871_14279
The Ku70/80 heterodimer is a critical component of the non-homologous end-joining (NHEJ) pathway and of the telomere cap in yeast and mammals. We report the molecular characterization of the KU70 and KU80 genes in Arabidopsis and describe the consequences of a Ku70 deficiency. Arabidopsis KU70/80 genes are ubiquitously expressed and their products form stable heterodimers in vitro. Plants harboring a T-DNA insertion in KU70 exhibit no growth or developmental defects under standard growth conditions. However, mutant seedlings are hypersensitive to gamma-irradiation-induced double-strand breaks. Unexpectedly, we found that mutants are hypersensitive to methyl methanosulfonate during seed germination, but lose this sensitivity in seedlings, implying that the requirement for NHEJ varies during plant development. Lack of Ku70 results in a dramatic deregulation of telomere length control, with mutant telomeres expanding to more than twice the size of wild type by the second generation. Furthermore, in contrast to the situation in mammals, chromosome fusions are not associated with a Ku deficiency in Arabidopsis. These findings imply that Ku may play a different role in capping plant and animal telomeres.
10.1093/emboj/21.11.2819
pubmed_281_16577
Recycling waste plastics is one of the important ways to save petroleum resources and reduce carbon emissions. However, the current recycling rate of waste plastics is still low. Material flow analysis can help determine the flow of waste plastics, and life cycle assessment (LCA) can be used to quantify environmental impacts. The present study integrates these two methods into the model construction of the residents' waste plastics recycling decision-support system. This model construction is followed by sensitivity analysis of the relevant parameters affecting the performance of the waste plastics recycling system. Finally, the present study forecasts the recycling system's performance and environmental impacts by setting four optimization scenarios based on sensitivity analysis. The results show that in 2019, a total of 8.39 million tons of high-end applications were recovered, carbon emissions during the recycling process were 34.9 million tons, and dioxin emissions were 316.11 g TEQ, with a total emission reduction of 24.47 million tons of CO2 compared to the original production. Sensitivity analysis shows that the selection rate of waste plastic recycling, the re-sorting rate of waste plastic recycling plant, and the classification recovery rate of mixed waste had relatively high effects on the recovery performance and environmental benefits of the recycling system. In the scenario of comprehensive improvement, in 2035, the recycling volume of high-end applications will rise to 33.96 million tons, the carbon emissions will rise to 64.73 million tons, the dioxin emissions will drop to 165.98 g TEQ, and the carbon emission reduction will rise to 99.06 million tons. This study has a certain guiding role for policy-makers to formulate industry norms and related policies for waste plastic recycling.
10.1007/s11356-022-24076-4
pubmed_561_22144
The data on the interaction of bacteria of the genus Bdellovibrio with the representatives of pathogenic Salmonella typhimurium are presented. Different types of such interaction are demonstrated: in a two-component system, in fluid media, in an agar layer and on the surface of a solid carrier. As shown for the first time, Bdellovibrio cells are capable of interacting not only with actively growing bacteria, but also with their noncultivable forms. The data obtained may serve as the basis for the study of possible practical use of such bacteria for controlling Gram-negative organisms, the causative agents of sapronotic infections.
pubmed_561_22144
pubmed_646_12707
INTRODUCTION Effective preventive services are needed most in underserved, inner-city settings that suffer disproportionately from morbidity and mortality. Primary care physicians can play an important role in the provision of efficacious cancer prevention and screening services to patients in these communities. METHOD We surveyed 122 primary care physicians about their cancer prevention and screening knowledge, attitudes, and practices. RESULTS Relative to the findings from national and local surveys, sample physicians were not as knowledgeable about national guidelines for preventive care, were less likely to counsel on smoking cessation, and were less likely to advise diet modification. Although physician practices reflected national cancer prevention and screening guidelines in general, a significant proportion of physicians suggested lung and prostate cancer screening tests that were inconsistent with national recommendations. CONCLUSIONS Systematic efforts are needed to increase the knowledge and practices of inner-city physicians concerning cancer prevention and screening.
10.1016/s0749-3797(00)00152-5
pubmed_877_10607
The molecular mechanisms underlying resistance to radiotherapy in breast cancer cells remain elusive. Previously, we reported that elevated β1-integrin is associated with enhanced breast cancer cell survival postirradiation, but how β1-integrin conferred radioresistance was unclear. Ionizing radiation (IR) induced cell killing correlates with the efficiency of DNA double-strand break (DSB) repair, and we found that nonmalignant breast epithelial (S1) cells with low β1-integrin expression have a higher frequency of S-phase-specific IR-induced chromosomal aberrations than the derivative malignant breast (T4-2) cells with high β1-integrin expression. In addition, there was an increased frequency of IR-induced homologous recombination (HR) repairosome focus formation in T4-2 cells compared with that of S1 cells. Cellular levels of Rad51 in T4-2 cells, a critical factor in HR-mediated DSB repair, were significantly higher. Blocking or depleting β1-integrin activity in T4-2 cells reduced Rad51 levels, while ectopic expression of β1-integrin in S1 cells correspondingly increased Rad51 levels, suggesting that Rad51 is regulated by β1-integrin. The low level of Rad51 protein in S1 cells was found to be due to rapid degradation by the ubiquitin proteasome pathway (UPP). Furthermore, the E3 ubiquitin ligase RING1 was highly upregulated in S1 cells compared to T4-2 cells. Ectopic β1-integrin expression in S1 cells reduced RING1 levels and increased Rad51 accumulation. In contrast, β1-integrin depletion in T4-2 cells significantly increased RING1 protein levels and potentiated Rad51 ubiquitination. These data suggest for the first time that elevated levels of the extracellular matrix receptor β1-integrin can increase tumor cell radioresistance by decreasing Rad51 degradation through a RING1-mediated proteasomal pathway.
10.1128/MCB.00672-17
pubmed_1064_17039
Nicotiana attenuata plants growing in close proximity to damaged sagebrush (Artemisia tridentata ssp. tridentata) suffer less herbivory than plants near undamaged sagebrush. Sagebrush constitutively releases methyl jasmonate (MeJA), a compound that when applied directly to N. attenuata, elicits herbivore resistance and the direct defense traits [protease inhibitors (PIs), nicotine]. Damage increases the release of volatile MeJA, primarily in the cis epimer, suggesting that cis-MeJA may mediate this apparent interplant signaling. We characterized sagebrush's MeJA plume before and after damage in nature and in the laboratory, and compared the activity of trans- and cis-MeJA in inducing PIs, nicotine, and Manduca sexta resistance in N. attenuata. We used both lanolin applications and aqueous sprays that mimic natural exposures, and we determined the amount of volatilized MeJA required to elicit a nicotine response in open-grown plants. Wounding rapidly and transiently increased cis-MeJA emissions from damaged parts (but not systemically), and the released plume did not rapidly dissipate in nature. cis-MeJA was not consistently more active than trans-MeJA, and the order of exposure (trans- then cis-) did not influence activity. We conclude that volatile MeJA, either trans- or cis-, when applied at levels consistent with those released by sagebrush does not elicit direct defenses in N. attenuata.
10.1023/b:joec.0000048783.64264.2a
pubmed_890_18221
Genetic interventions, which include transgenic engineering, gene editing, and other forms of genome modification aimed at altering the information "in" the genetic code, are rapidly increasing in power and scale. Biosemiotics offers unique tools for understanding the nature, risks, scope, and prospects of such technologies, though few in the community have turned their attention specifically in this direction. Bruni (2003, 2008) is an important exception. In this paper, I examine how we frame the concept of "side effects" that result from genetic interventions and how the concept stands up to current perspectives of the role of organism activity in development. I propose that once the role of living systems in constructing and modifying the informational value of their various developmental resources is taken into account, the concept of a "side effect" will need to be significantly revised. Far from merely a disturbance brought about in a senseless albeit complex system, a biosemiotic view would take "side effects" as at least sometimes the organism's active re-organization in order to accommodate or make use of novelty. This insight is nascent in the work of developmental plasticity and niche construction theory (West-Eberhard 2003; Odling-Smee et al. 2003), but it is brought into sharper focus by the explicitly interpretive perspective offered by biosemiotics. Understanding the "side effects" of genetic interventions depends in part on being able to articulate when and where unexpected consequences are a result of semiotic activity at various levels within the system. While a semiotic interpretation of "side effects" puts into question the naive attitude that would see all unintended side effects as indications of disturbance in system functionality, it certainly does not imply that such side effects are of no concern for the viability of the organisms in the system. As we shall see, the fact that such interventions do not respect the translation of information that occurs in multi-level biological systems ensures that disruption is still likely. But it does unprivilege the human agent as the sole generator of meaning and information in the products of biotechnology, with important consequences on how we understand our relationship with other species.
10.1007/s12304-016-9274-3
pubmed_621_10208
The aim of the present study was to determine whether the levels of reactive oxygen species (ROS) substances production and the levels of lipid peroxidation of the sperm membrane were related to the quality that the ejaculates exhibited after cryopreservation in boars. Ejaculates from 42 healthy boars were used in this study and they were cryopreserved with the lactose-egg yolk extender (LEY). Several sperm quality parameters were assessed by flow cytometry in samples incubated for 30 and 150 min at 37 °C after thawing: the percentage of sperm with intact plasma membrane (SIPM), intracellular reactive oxygen substances production through mean of DCF fluorescence intensity of total sperm (mean-DCF) and the percentage of viable and non-viable sperm containing oxidized BODIPY (VSOB and NVSOB). In addition, the percentages of total motile (TMS) and progressively motile sperm (PMS) were assessed at the same incubation times with a computer-assisted sperm analysis system. The classification of the ejaculates into good or bad freezers was performed through hierarchical cluster analysis from SIPM and TMS at 150 min post-thawing. The ejaculates of those males classified as good freezers exhibited higher (p < 0.05) SPIM, TMS and PMS than the bad freezers, although both groups presented similar (p > 0.05) VSOB, NVSOB and mean-DCF. Therefore, these results show that lipid peroxidation and the amount of reactive oxygen substances in the sperm after cryopreservation are similar between boars classified as good or bad freezers.
10.1111/j.1439-0531.2012.02126.x
pubmed_878_11465
Rrp6 is a conserved catalytic subunit of the eukaryotic nuclear exosome ribonuclease complex that functions in the productive 3' end maturation of stable RNAs, the degradation of transiently expressed noncoding transcripts and in discard pathways that eradicate the cell of incorrectly processed or assembled RNAs. The function of Rrp6 in these pathways is at least partially dependent upon its interaction with a small nuclear protein called Rrp47/Lrp1, but the underlying mechanism(s) by which Rrp47 functions in concert with Rrp6 are not established. Previous work on yeast grown in rich medium has suggested that Rrp6 expression is not markedly reduced in strains lacking Rrp47. Here we show that Rrp6 expression in rrp47∆ mutants is substantially reduced during growth in minimal medium through effects on both transcript levels and protein stability. Exogenous expression of Rrp6 enables normal levels to be attained in rrp47∆ mutants. Strikingly, exogenous expression of Rrp6 suppresses many, but not all, of the RNA processing and maturation defects observed in an rrp47∆ mutant and complements the synthetic lethality of rrp47∆ mpp6∆ and rrp47∆ rex1∆ double mutants. Increased Rrp6 expression in the resultant rrp47∆ rex1∆ double mutant suppresses the defect in the 3' maturation of box C/D snoRNAs. In contrast, increased Rrp6 expression in the rrp47∆ mpp6∆ double mutant diminishes the block in the turnover of CUTs and in the degradation of the substrates of RNA discard pathways. These results demonstrate that a principal function of Rrp47 is to facilitate appropriate expression levels of Rrp6 and support the conclusion that the Rrp6/Rrp47 complex and Rex1 provide redundant exonuclease activities for the 3' end maturation of box C/D snoRNAs.
10.1371/journal.pone.0080752
pubmed_143_25338
BACKGROUND The present protocol was designed for a systematic review and meta-analysis aimed at determining the association of telomere length with substance use disorders with the exclusion of nicotine addiction, and to identify potential moderators of the effect of telomere length. Such methodological information may provide guidance to improve the quality of future research on this important topic. METHODS Potential studies will be identified through electronic databases (PubMed/MEDLINE, EMBASE, PsycINFO, and Web of Science) up from inception onwards. The inclusion criteria will include published or unpublished observational studies (cohort, case-control, and cross-sectional studies) reporting telomere length in adult patients with substance use disorder compared with a control group. Non-human studies or other study designs such as reviews, case-only, family-based, and/or population studies with only healthy participants will be excluded, as well as those focused solely on nicotine addiction. The main outcome will be telomere length in adults with substance use disorder (primary) and, specifically, in those with alcohol use disorder (secondary). Two investigators will independently evaluate the preselected studies for possible inclusion and will extract data following a standardized protocol. Disagreements will be resolved by consensus. The risk of bias of all included studies will be assessed using the Newcastle-Ottawa Quality Assessment Scale for non-randomized studies. Data will be converted into standardized mean differences as effect size index, and random-effects models will be used for the meta-analysis. Cochran's Q statistic, I2 index, and visual inspection of the forest plot will be used to verify study heterogeneity. Subgroup analyses and meta-regressions will be conducted to ascertain heterogeneity. Several sensitivity analyses will be conducted to address the influence of potential confounding factors. Publication bias will be examined using the "funnel plot" method with Duval and Tweedie's trim-and-fill method and Egger test. DISCUSSION This systematic review will assess the association of telomere length with substance use disorders aside from nicotine addiction. SYSTEMATIC REVIEW REGISTRATION PROSPERO registration number CRD42019119785.
10.1186/s13643-019-1199-x
pubmed_480_11998
The driving force behind food adulteration is monetary profit and this has remained unchanged for at least the last hundred years. Food adulterations were and still are difficult to uncover because they occur mostly in an unpredictable and unexpected way. Very often food falsifiers take advantage of modern technology in such a way that food adulterations are difficult or sometimes even impossible to detect. Targets for food adulteration were and still are highly priced food items such as spirits, meat, seafood and olive oil. Although difficult to detect, food adulterations were in the past strong driving forces for the development of adequate detection methods in the official food control laboratories and for the enforcement of the food law. A very prominent example in this context is the 'Ravioli scandal' in Switzerland in the late 1970s which showed that cheap second-class meat could be processed into products without being discovered for long time. As a consequence the official food control laboratories in Switzerland were reinforced with more laboratory equipment and technical staff. With the introduction of new detection principles such as DNA-based analytical methods new kinds of food adulteration could and can be uncovered. Analytical methods have their limits and in some cases of food fraud there are no analytical means to detect them. In such cases the examination of trade by checking of accounts is the method of choice.
10.2533/chimia.2016.334
pubmed_41_9781
This study follows previous research showing how green space quantity and contact with nature (via access to gardens/allotments) helps mitigate stress in people living in deprived urban environments (Ward Thompson et al., 2016). However, little is known about how these environments aid stress mitigation nor how stress levels vary in a population experiencing higher than average stress. This study used Latent Class Analysis (LCA) to, first, identify latent health clusters in the same population (n = 406) and, second, to relate health cluster membership to variables of interest, including four hypothetical stress coping scenarios. Results showed a three-cluster model best fit the data, with membership to health clusters differentiated by age, perceived stress, general health, and subjective well-being. The clusters were labeled by the primary health outcome (i.e., perceived stress) and age group (1) Low-stress Youth characterized by ages 16-24; (2) Low-stress Seniors characterized by ages 65+ and (3) High-stress Mid-Age characterized by ages 25-44. Next, LCA identified that health membership was significantly related to four hypothetical stress coping scenarios set in people's current residential context: "staying at home" and three scenarios set outwith the home, "seeking peace and quiet," "going for a walk" or "seeking company." Stress coping in Low stress Youth is characterized by "seeking company" and "going for a walk"; stress coping in Low-stress Seniors and High stress Mid-Age is characterized by "staying at home." Finally, LCA identified significant relationships between health cluster membership and a range of demographic, other individual and environmental variables including access to, use of and perceptions of local green space. Our study found that the opportunities in the immediate neighborhood for stress reduction vary by age. Stress coping in youth is likely supported by being social and keeping physically active outdoors, including local green space visits. By contrast, local green space appears not to support stress regulation in young-middle aged and older adults, who choose to stay at home. We conclude that it is important to understand the complexities of stress management and the opportunities offered by local green space for stress mitigation by age and other demographic variables, such as gender.
10.3389/fpsyg.2017.01760
pubmed_727_1549
The immunogenicity of three DNP-LE conjugates possessing different numbers of haptenic determinants per molecule of carrier (DNP 3-LE, DNP6-LE, DNP 13-LE) has been tested in mice. All conjugates induce only 19S anti-DNP antibodies, but the lowest conjugate is more immunogenic. Lack of response to DNP-LE is observed in guinea-pigs and in rabbits, animals in which native LE is not immunogenic. The immune response is not affected in mice tolerant to LE, when immunization is performed intravenously. These results are discussed with a view to determine the role played by a T-independent carrier in the antibody synthesis against a hapten.
pubmed_727_1549
pubmed_341_428
BACKGROUND AND AIMS Duodenal-jejunal bypass (DJB) shows great effects on weight loss and diabetes improvement. Previously, we reported that the bilio-pancreatic (BP) limb plays an important role in glycemic improvement and in serum bile acid (BA) level increase as reported by Miyachi et al. (Surgery 159(5):1360-71, 2016). This study aimed to investigate the mechanism of BA elevation after DJB and the relationship between these effects and BP-limb length. METHODS Otsuka Long-Evans Tokushima Fatty rats with diabetes were randomly assigned into four groups: one sham group and three DJB groups. Three DJB groups were defined according to the BP-limb length: 0 cm, 15 cm, and 30 cm. The lengths of the alimentary limb and common channel were set equally in each DJB groups. Body weight, glucose tolerance, and BA levels in the liver, bile juice, portal vein, and intestinal contents were assessed postoperatively. Changes in enterohepatic circulation of BAs were assessed using labeled BA. RESULTS BA elevation after DJB was higher with longer BP-limb. In the 30-cm group, the serum total BA level and BA levels in the portal vein, liver, and bile juice were greater than those in other groups. The enterohepatic circulation was shortened in the 15-cm and 30-cm groups. CONCLUSIONS Shortening of the "enterohepatic circulation" by early reabsorption of BAs in the BP-limb, not by the early influx of bile juice into the ileum, was the main cause of BA elevation after DJB. Thus, glycemic improvement and elevation of BA concentration after DJB depend on the BP-limb length.
10.1007/s11695-019-03790-y
pubmed_543_20799
The release of mannoprotein (MP) antigen from Candida albicans grown at 28 degrees C (yeast form) or 37 degrees C (mycelial form), and the ability of each released material to stimulate a cell-mediated immune (CMI) response by human lymphocytes in vitro, were studied. Overall, the mycelial cells released more MP per unit of dry mass increase and the released material was relatively enriched with MP constituents of lower molecular mass with respect to the material released from yeast cells. Moreover, the mycelial MP contained a 65 kDa component (MP65) which was the largely predominant MP recognized by a rabbit anti-mycelium antiserum. When peripheral blood mononuclear cells from normal human subjects were stimulated in vitro with graded amounts of yeast or mycelial MP, the latter was about one order of magnitude more potent than the former in inducing lymphocyte proliferation. Following MP separation by gel permeation chromatography, an appreciable CMI response was stimulated only by the MP65-containing MP fractions, and to a degree apparently related to the amount of MP65 itself. Altogether, these data confirm our previous findings about the MP65 antigen as a major target of CMI response to C. albicans, and demonstrate that this antigen is released predominantly by the mycelial cells of the fungus in vitro.
10.1080/02681219480000601
pubmed_140_4571
This article explores some rare sides of twin research. The focus of this article is the sad plight of the Dionne quintuplets, born in Canada in 1934. However, several other studies belong in this category, such as Dr Josef Mengele's horrifying twin research conducted at the Auschwitz concentration camp, Dr John Money's misguided attempt to turn an accidentally castrated male twin into a female, Russian scientists' cruel medical study of conjoined female twins and Dr Peter Neubauer's secret project that tracked the development of separated twins. Reviews of current twin research span twins' representation of self-image, twins with Kleine-Levin Syndrome, heteropaternal twinning in lemurs and factors affecting risk of dental caries. Media coverage includes a pair of high-society models, a book about the 'Winkelevii' twins, Super Bowl twin teammates, a family with three sets of fraternal twins, a twin sister surrogate and a near presidential twin.
10.1017/thg.2019.84
pubmed_106_22541
4-methyl-5-hydroxy-ethyl isothiazole stearic ester (HISE) was synthesized and characterized by FTIR spectroscopy, 1H NMR and MS. The monolayer-forming ability of HISE was studied in subphases with different pH values using isotherms of surface pressure-area per molecule (pi-A). It was observed that the collapse pressure and the film-forming ability of the monolayers of HISE increased gradually as pH values ascended. Research of differentiated pi-A curves (d pi(/dA-A) indicated that there were one or two phase change points during the compressing process, and the incompressibility and the stability of HISE monolayers on alkalescent subphases were better than on acid subphases.
pubmed_106_22541
pubmed_216_246
Cancer anorexia-cachexia syndrome( CACS) occurs in 30-80% of patients with cancer. CACS is connected with poor prognosis and higher risk of treatment complications. CACS belongs to the common cause of death in cancer patients. Main role in the development of this syndrome play cytokines like TNF, interleukin 1 and 6 and interferon alpha and gamma. The importance of a lot of other substances is still unknown. VEGF promotes new vessels development,enhance vascular permeability and plays a role in inflammatory reaction. The aim of this study was comparison of VEGF levels in patients with lung cancer with and without CACS and in control group. The serum levels of VEGF were measured by ELISA method. The VEGF was significatly higher in patients with lung cancer then in control group (p = 0.004). There were no correlations between VEGF and weight lost, histological type and stage of disease. This suggest that VEGF doesnt play a role in development of CACS.
pubmed_216_246
pubmed_20_9699
BACKGROUND Budding yeast, S. cerevisiae, has been used extensively as a model organism for studying cellular processes in evolutionarily distant species, including humans. However, different human tissues, while inheriting a similar genetic code, exhibit distinct anatomical and physiological properties. Specific biochemical processes and associated biomolecules that differentiate various tissues are not completely understood, neither is the extent to which a unicellular organism, such as yeast, can be used to model these processes within each tissue. RESULTS We present a novel framework to systematically quantify the suitability of yeast as a model organism for different human tissues. To this end, we develop a computational method for dissecting the global human interactome into tissue-specific cellular networks. By individually aligning these networks with the yeast interactome, we simultaneously partition the functional space of human genes, and their corresponding pathways, based on their conservation both across species and among different tissues. Finally, we couple our framework with a novel statistical model to assess the conservation of tissue-specific pathways and infer the overall similarity of each tissue with yeast. We further study each of these subspaces in detail, and shed light on their unique biological roles in the human tissues. CONCLUSIONS Our framework provides a novel tool that can be used to assess the suitability of the yeast model for studying tissue-specific physiology and pathophysiology in humans. Many complex disorders are driven by a coupling of housekeeping (universally expressed in all tissues) and tissue-selective (expressed only in specific tissues) dysregulated pathways. While tissue-selective genes are significantly associated with the onset and development of a number of tissue-specific pathologies, we show that the human-specific subset has even higher association. Consequently, they provide excellent candidates as drug targets for therapeutic interventions.
10.1186/s12918-015-0253-0
pubmed_137_2171
BACKGROUND Systemic lupus erythematosus (SLE) often has a profound negative impact on health-related quality of life (HRQoL). In the absence of any qualitative studies in sub-Saharan Africa, we undertook a study to explore living experiences, perceptions and unmet needs of South African patients with SLE. METHODS Twenty-five women with SLE consented to participate in the study. They underwent individual in-depth interviews exploring their physical concerns, emotional health, sexual well-being and fertility. NVivo software was used for analysis. RESULTS Participants were either of black ancestry or mixed racial ancestry, mainly indigent with only a quarter gainfully employed. Living with pain was the most common complaint, negatively impacting on activities of daily living (ADL), family expectations, social life, sleep and intimacy. Most participants expressed challenges of living with fatigue, and many felt their fatigue was misconstrued as being 'simply lazy'. This pernicious fatigue had negative consequences on many facets of ADL, including caring for dependants, job sustainability and sexual well-being. All participants experienced low emotional states, often associated with suicidal ideations. Many experienced difficulties with fertility and childbearing and these were exacerbated in many instances by the pessimism of health care providers, resulting in confusion and depression. Physical disfigurements resulting from lupus-associated alopecia and rashes and corticosteroid-induced weight fluctuations were a major concern. These changes often affected self-image and libido, leading to strained personal relationships. Coping mechanisms that participants adopted included intense spiritual beliefs, 'pushing through the difficult times' and use of alternative therapies to relief symptoms was common. A poor understanding of SLE on the part of participant's family and the community, coupled with the unpredictable course of the disease, exacerbated frustration and social exclusion. For most, limited income, lack of basic services, family dependencies, and comorbid diseases, such as human immune deficiency virus (HIV), exacerbated the daily negative SLE experiences. CONCLUSION In this study of mainly indigent South African women, SLE is associated with complex, chronic and challenging life experiences. The chronic relapsing and unpredictable nature of the disease, poor understanding and acceptance of SLE, compounded by a background of poverty, inadequate social support structures, negatively impact on a range of personal, social and vocational daily life experiences. Improved access to psychosocial services and SLE education might result in better outcomes. TRIAL REGISTRATION (Ethics Project identification code: 275/2016 and M160633 registered 10 & 29 August 2016).
10.1186/s12955-019-1132-y
pubmed_784_18259
The present survey was carried out in two villages of the same malaria endemicity but different levels of transmission in Lamae District, Chumphon Province, southern Thailand with the aim to study whether behavior of people to malaria was similar or not. The total populations in low (village 11) and high (village 13) transmission areas were surveyed twice during low (February 1990) and high (June 1990) transmission periods. All subjects were interviewed by trained interviewers using a structured interview form. Among 410 and 614 people in villages 11 and 13, respectively, it was revealed that during the low transmission period behavior related to chemoprophylaxis and use of bed nets was similar in both villages, whereas risk behavior of night work was significantly higher in village 11 than village 13. This was likely due to their different principal occupations: farming of rubber plantation in village 11 and of coffee plantation in village 13. Concerning pattern of seeking malaria treatment, the malaria clinic and the district hospital were the common places attended by people in both villages. During the second survey in high transmission period, a cohort of 277 in village 11 and 430 in village 13 were available for follow up to study changes in their behavior between low and high transmission seasons. There were significant decrements related to night work and significant increments related to bed net use in both villages.
pubmed_784_18259
pubmed_955_8277
Enteropathogenic Escherichia coli (EPEC) express rope-like bundles of filaments, termed bundle-forming pili (BFP) (J. A. Girón, A. S. Y. Ho, and G. K. Schoolnik, Science 254:710-713, 1991). Expression of BFP is associated with localized adherence to HEp-2 cells and the presence of the EPEC adherence factor plasmid. In this study, we describe the identification of rod-like fimbriae and fibrillae expressed simultaneously on the bacterial surface of three prototype EPEC strains. Upon fimbrial extraction from EPEC B171 (O111:NM), three fimbrial subunits with masses of 16.5, 15.5, and 14.7 kDa were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Their N-terminal amino acid sequence showed homology with F9 and F7(2) fimbriae of uropathogenic E. coli and F1845 of diffuse-adhering E. coli, respectively. The mixture of fimbrial subunits (called FB171) exhibited mannose-resistant agglutination of human erythrocytes only, and this activity was not inhibited by alpha-D-Gal(1-4)-beta-Gal disaccharide or any other described receptor analogs for P, S, F, M, G, and Dr hemagglutinins of uropathogenic E. coli, which suggests a different receptor specificity. Hemagglutination was inhibited by extracellular matrix glycoproteins, i.e., collagen type IV, laminin, and fibronectin, and to a lesser extent by gangliosides, fetuin, and asialofetuin. Scanning electron microscopic studies performed on clusters of bacteria adhering to HEp-2 cells revealed the presence of structures resembling BFP and rod-like fimbriae linking bacteria to bacteria and bacteria to the eukaryotic cell membrane. We suggest a role of these surface appendages in the interaction of EPEC with eukaryotic cells as well as in the overall pathogenesis of intestinal disease caused by EPEC.
10.1128/jb.175.22.7391-7403.1993
pubmed_163_25045
The potential translation of bio-inert polymer scaffolds as bone substitutes is limited by the lack of neovascularization upon implantation and subsequently diminished ingrowth of host bone, most likely resulted from the inability to replicate appropriate endogenous crosstalk between cells. Human umbilical vein endothelial cell-derived decellularized extracellular matrix (HdECM), which contains a collection of angiocrine biomolecules, has recently been demonstrated to mediate endothelial cells(ECs) - osteoprogenitors(OPs) crosstalk. We employed the HdECM to create a PCL (polycaprolactone)/fibrin/HdECM (PFE) hybrid scaffold. We hypothesized PFE scaffold could reconstitute a bio-instructive microenvironment that reintroduces the crosstalk, resulting in vascularized bone regeneration. Following implantation in a rat femoral bone defect, the PFE scaffold demonstrated early vascular infiltration and enhanced bone regeneration by microangiography (μ-AG) and micro-computational tomography (μ-CT). Based on the immunofluorescence studies, PFE mediated the endogenous angiogenesis and osteogenesis with a substantial number of type H vessels and osteoprogenitors. In addition, superior osseointegration was observed by a direct host bone-PCL interface, which was likely attributed to the formation of type H vessels. The bio-instructive microenvironment created by our innovative PFE scaffold made possible superior osseointegration and type H vessel-related bone regeneration. It could become an alternative solution of improving the osseointegration of bone substitutes with the help of induced type H vessels, which could compensate for the inherent biological inertness of synthetic polymers.
10.1016/j.bioactmat.2021.07.030
pubmed_189_23363
Though much progress has been made to understand feature integration, debate remains regarding how objects are represented in mind based on their constituent features. Here, we advance this debate by introducing a novel shape-color "conjunction task" to reconstruct memory resolution for multiple object features simultaneously. In a first experiment, we replicate and extend a classic paradigm originally tested using a change detection task. Replicating previous work, memory resolution for individual features was reduced when the number of objects increased, regardless of the number of to-be-remembered features. Extending previous work, we found that high resolution memory near perfect in resemblance to the target was selectively impacted by the number of to-be-remembered features. Applying a data-driven statistical model of stochastic dependence, we found robust evidence of integration for lower-resolution feature memories, but less evidence for integration of high-resolution feature memories. These results suggest that memory resolution for individual features can be higher than memory resolution for their integration. In a second experiment which manipulated the nature of distracting information, we examined whether object features were directly bound to each other or by virtue of shared spatial location. Feature integration was disrupted by distractors sharing visual features of target objects but not when distractors shared spatial location - suggesting that feature integration can be driven by direct binding between shape and color features in memory. Our results constrain theoretical models of object representation, providing empirical support for hierarchical representations of both integrated and independent features.
10.1016/j.cognition.2022.105024
pubmed_33_19962
The skeletal muscles play an essential role in life, providing the mechanical basis for respiration and movement. Skeletal muscle dysfunction is prevalent in all stages of chronic obstructive pulmonary disease (COPD), and significantly influences symptoms, functional capacity, health related quality of life, health resource usage and even mortality. Furthermore, in contrast to the lungs, the skeletal muscles are potentially remedial with existing therapy, namely exercise-training. This review summarizes clinical and laboratory observations of the respiratory and peripheral skeletal muscles (in particular the diaphragm and quadriceps), and current understanding of the underlying etiological processes. As further progress is made in the elucidation of the molecular mechanisms of skeletal muscle dysfunction, new pharmacological therapies are likely to emerge to treat this important extra-pulmonary manifestation of COPD.
10.2147/COPD.S28247
pubmed_482_21520
BACKGROUND Human muscle progenitor cell (hMPC) function facilitates skeletal muscle regeneration and is influenced by circulating factors. Yet it is unknown whether dietary interventions impact hMPC function. Blueberry consumption was examined due to the pro-proliferative and antioxidant effects of blueberries and blueberry-derived compounds. OBJECTIVES This study measured indicators of hMPC function in young and old cultures treated with serum collected from a blueberry-enriched diet (BED) intervention. METHODS Younger (21-40 y, n = 12) and older (60-79 y, n = 10) women consumed a 6-wk BED (38 g of freeze-dried blueberries daily). Fasting serum was collected at 0, 4, and 6 wk, and a fed serum sample at 1.5 h (acute) after starting the BED intervention. Young and old hMPCs, derived from 3-5 distinct donors (biological replicates), were individually cultured in media containing pooled, age-group-matched serum from each time point. Determinants of hMPC function (e.g., hMPC number, oxidative stress resistance, and upregulation of metabolic pathways) were measured and compared within age groups. RESULTS Culturing young hMPCs in acute (compared with 0 wk) BED serum did not alter hMPC number or oxidative stress-induced cell death, but increased cellular oxygen consumption (29%, P = 0.026). Culturing young hMPCs in 6-wk (compared with 0-wk) BED serum increased hMPC number (40%, P = 0.0024), conferred minor resistance to oxidative stress-induced cell death (12.6 percentage point decrease, P = 0.10), and modestly increased oxygen consumption (36%, P = 0.09). No beneficial effect of the acute or long-term BED serum was observed in old hMPCs. CONCLUSIONS In younger women, dietary interventions could be a feasible strategy to improve hMPC function and thus muscle regeneration, through altering the serum environment.This study was registered at clinicaltrials.gov (NCT04262258).
10.1093/jn/nxaa190
pubmed_575_8085
To investigate the relationship between intestinal microbiota and SARS-CoV-2-mediated pathogenicity in a United States, majority African American cohort. We prospectively collected fecal samples from 50 SARS-CoV-2 infected patients, 9 SARS-CoV-2 recovered patients, and 34 uninfected subjects seen by the hospital with unrelated respiratory medical conditions (controls). 16S rRNA sequencing and qPCR analysis was performed on fecal DNA/RNA. The fecal microbial composition was found to be significantly different between SARS-CoV-2 patients and controls (PERMANOVA FDR-P = .004), independent of antibiotic exposure. Peptoniphilus, Corynebacterium and Campylobacter were identified as the three most significantly enriched genera in COVID-19 patients compared to controls. Actively infected patients were also found to have a different gut microbiota than recovered patients (PERMANOVA FDR-P = .003), and the most enriched genus in infected patients was Campylobacter, with Agathobacter and Faecalibacterium being enriched in the recovered patients. No difference in microbial community structure between recovered patients and uninfected controls was observed, nor a difference in alpha diversity between the three groups. 24 of the 50 COVID-19 patients (48%) tested positive via RT-qPCR for fecal SARS-CoV-2 RNA. A significant difference in gut microbial composition between SARS-CoV-2 positive and negative samples was observed, with Klebsiella and Agathobacter being enriched in the positive cohort. No significant associations between microbiome composition and disease severity was found. The intestinal microbiota is sensitive to the presence of SARS-CoV-2, with increased relative abundance of genera (Campylobacter, Klebsiella) associated with gastrointestinal (GI) disease. Further studies are needed to investigate the functional impact of SARS-CoV-2 on GI health.
10.1080/19490976.2021.1926840
pubmed_926_20092
Clavibacter michiganensis is the most economically important gram-positive bacterial plant pathogen, with subspecies that cause serious diseases of maize, wheat, tomato, potato, and alfalfa. Much less is known about pathogenesis involving gram-positive plant pathogens than is known for gram-negative bacteria. Comparative genome analyses of C. michiganensis subspecies affecting tomato, potato, and maize have provided insights on pathogenicity. In this study, we identified strains of C. michiganensis subsp. insidiosus with contrasting pathogenicity on three accessions of the model legume Medicago truncatula. We generated complete genome sequences for two strains and compared these to a previously sequenced strain and genome sequences of four other subspecies. The three C. michiganensis subsp. insidiosus strains varied in gene content due to genome rearrangements, most likely facilitated by insertion elements, and plasmid number, which varied from one to three depending on strain. The core C. michiganensis genome consisted of 1,917 genes, with 379 genes unique to C. michiganensis subsp. insidiosus. An operon for synthesis of the extracellular blue pigment indigoidine, enzymes for pectin degradation, and an operon for inositol metabolism are among the unique features. Secreted serine proteases belonging to both the pat-1 and ppa families were present but highly diverged from those in other subspecies.
10.1094/PHYTO-05-17-0171-R
pubmed_891_25102
Monoclonal antibody (mAb) based therapies may provide a valuable new treatment modality for acute and chronic lung diseases, including asthma, respiratory infections, and lung cancer. Currently mAbs are delivered via systemic administration routes, but direct delivery to the lungs via the inhaled route could provide higher concentrations at the site of disease and reduced off-target effects. Though lyophilized mAbs may be reconstituted and delivered to the lungs using nebulizers, dry powder inhalers provide a more patient-friendly delivery method based upon their fast administration time and portability. However, particle engineering processes required to prepare respirable dried powders for DPI delivery involve multiple potential stressors for mAbs, which have not been fully explored. In this study, a systematic examination of various aspects of the particle engineering process (atomization, freezing, drying, and storage) was performed to further understand their impact on mAb structure and aggregation. Using anti-streptavidin IgG1 as a model mAb, atomization settings were optimized using a design of experiments approach to elucidate the relationship between feed flow rate, formulation solid content, and atomization airflow rate and protein structural changes and aggregation. The optimized atomization conditions were then applied to spray drying and spray freezing drying particle engineering processes to determine the effects of freezing and drying on IgG1 stability and aerosol performance of the powders. IgG1 was found to be particularly susceptible to degradation induced by the expansive air-ice interface generated by spray freeze drying and this process also produced powders that exhibited decreased storage stability. This study further delineates the design space for manufacturing of respirable biologic therapies and is intended to serve as a roadmap for future development work.
10.1016/j.xphs.2021.08.022
pubmed_128_126
Lumbar puncture (LP) is a procedure for obtaining spinal fluid from spinal meningeal spaces this can be done as a diagnostic or therapeutic procedure which can result in to a typical positional headache named as post lumbar puncture headache .This can cause a lot of discomforts for patients and makes fear from the procedure. This study designed to evaluate the effect of resting position after LP on post lumbar puncture headache (PLPH). Patients who had a diagnostic lumbar puncture were divided randomly in two groups .Group A patients had one hour rest in the supine position while group B patients had one hour rest in the prone position. Both groups followed for appearance of symptoms of PLPH for 5 days. 119 patients completed the study, 57 (48%) male patients and 62 (52%) female .PLPH totally appeared in 38 (31.9%) patients .In the group A PLPH was present in 20 patients whereas in group B it was present in 18 patients. Statistical analysis showed no significant differences between two groups (P>0.07). Position of rest after LP has no significant effect on reducing post lumbar puncture headache and there is no need to emphasize on position of rest after LP.
pubmed_128_126
pubmed_757_17589
Background  Less invasive surfactant administration (LISA) is the preferred mode of surfactant administration for spontaneously breathing preterm babies supported by noninvasive ventilation (NIV). Objective  The aim of this study was to determine whether LISA on the neonatal unit or in the delivery suite was associated with reduced rates of bronchopulmonary dysplasia (BPD) or the need for intubation, or lower durations of invasive ventilation and length of hospital stay (LOS). Methods  A historical comparison was undertaken. Each "LISA" infant was matched with two infants (controls) who did not receive LISA. Results  The 25 LISA infants had similar gestational ages and birth weights to the 50 controls (28 [25.6-31.7] weeks vs. 28.5 [25.4-31.9] weeks, p  = 0.732; 1,120 (580-1,810) g vs. 1,070 [540-1,869] g, p  = 0.928), respectively. LISA infants had lower requirement for intubation (52 vs. 90%, p  < 0.001), shorter duration of invasive ventilation (median 1 [0-35] days vs. 6 [0-62] days p  = 0.001) and a lower incidence of BPD (36 vs. 64%, p  = 0.022). There were no significant differences in duration of NIV (median 26 [3-225] vs. 23 [2-85] days, p  = 0.831) or the total LOS (median 76 [24-259] vs. 85 [27-221], p  = 0.238). Conclusion  LISA on the neonatal unit or the delivery suite was associated with a lower BPD incidence, need for intubation, and duration of invasive ventilation.
10.1055/s-0041-1735632
pubmed_1136_13860
In the spring of 2009, a novel swine-origin H1N1 virus, whose antigenicity is quite different from those of seasonal human H1N1 strains, emerged in Mexico and readily transmitted and spread among humans, resulting in the first influenza pandemic in the 21st century. Molecular analyses of the pandemic H1N1 2009 viruses indicate low-pathogenic features for humans, although worldwide transmission of the virus and a considerable numbers of lethal cases with acute pneumonia have been observed in the first wave of the current pandemic. Here, we review our current molecular knowledge of transmissibility and pathogenicity of influenza viruses and discuss the future aspects of the pandemic virus.
pubmed_1136_13860
pubmed_540_8631
AIM Traumatic brain injury (TBI) is a severe disease with very high mortality, and most TBI patients are young adults. In the present study, we aimed to explore whether the combination regimen of dexmedetomidine (Dex) and butorphanol (But) could benefit patients with TBI. MATERIAL AND METHODS A total of 208 TBI patients admitted from February 2018 to January 2020 were randomly divided into four groups as follows: control group (A), Dex group (B), But group (C), and combination of Dex and But group (D). Statistical analysis was performed to assess the changes in vital signs, oxygen saturation, serum neuroendocrine data, pain, and agitation scores. RESULTS The statistical data of vital signs and blood oxygen saturation of the four groups were compared, and the differences between group A and group D were statistically significant (P 0.05), indicating that a combination of sedative and analgesic agents at low doses could improve the vital signs of TBI patients, and the safety was relatively good. The scores of pain and agitation in the combination group were significantly improved on days 3 and 5, suggesting that the combination group was better compared with the control group. CONCLUSION The combination of Dex and But was more suitable for the treatment of vital signs. Compared with the individual treatment groups, the patients in the combination group had a rapid improvement. Collectively, the combination of Dex and But could significantly benefit the prognosis of TBI.
10.5137/1019-5149.JTN.36585-21.2
pubmed_110_11023
The Cheesman air dilution olfactometer, although designed for group threshold measurements, was modified to allow individual testing of subjects. However, adaptation effects of olfactory stimuli precluded use of interstimulus intervals of less than 30 sec. so that 3-hr. testing sessions were necessary to obtain a single measurement of sensitivity. Four subjects were tested intensively with isopropyl alcohol (CH3CH(OH)CH3) at concentration levels determined by previous group threshold studies. In the first condition, one concentration only was presented in testing sessions, while in the second condition, six concentrations were presented and the limits of concentrations adjusted to allow subthreshold presentations. Signal detectability indices (dc') were calculated more frequently and more reliably in the second condition than in the first.
10.2466/pms.1988.67.3.827
pubmed_992_18671
The in-situ stress state in the Tarim Basin, Northwest China, down to 7 km depth is constrained using the anelastic strain recovery (ASR) method and wellbore failure analysis. Results are consistent between the two methods, and indicate that the maximum principal stresses (σ1) are close to vertical and the intermediate and minimum principal stresses (σ2 and σ3) are approximately horizontal. The states of stress at the studied wellbore is in the normal faulting stress regime within the Tarim Basin rather than in the compressional tectonic stress regime as in the periphery of the Tarim Basin, which explains the presence of the normal faults interpreted in 3-D seismic profiles collected from adjacent areas. Our results demonstrate that the ASR method can be used for rocks recovered from depths as deep as 7 km to recover reliable stress state information. The in-situ stress measurement results revealed in this paper will help future development of the petroleum resources and kinematics study in the Tarim Basin.
10.1038/s41598-017-04516-9
pubmed_933_4864
Recording the state and dynamics of intracellular signaling networks in clinical specimens can help identify and validate biomarkers, but may also prove useful in developing and monitoring targeted therapies. Studying cell signaling on a system-wide level in solid tissue, however, is often not feasible using mass spectrometry, because this technique generally requires relatively large sample quantities. A number of promising miniaturized proteomic technologies have emerged, which circumvent these limitations and offer the ability to monitor protein abundances and posttranslational modification states in a multiplexed and quantitative fashion. These technologies have the potential to accelerate molecular diagnostics and therapeutics, and may ultimately facilitate the broad adoption of personalized approaches to patient management and treatment.
10.1126/scisignal.293pe64
pubmed_1075_2260
Calcium dependent protein kinases (CDPKs) are found only in plants and alveolates and are distinguished from other kinases by an activation domain that binds calcium directly. Plants contain families of these kinases and their functions are modulated by post translational modifications as well as calcium activation. Apicomplexan parasites also contain CDPK families and this review is focused on CDPK1 in Plasmodium spp. This enzyme has been implicated in parasite motility and host cell invasion and at least two substrates associated with the actomyosin motor complex have been identified. By analogy with the plant CDPKs we propose that its activity is modulated both by post translational modifications and by its subcellular location in a compartment within the parasite's pellicle, which may regulate the calcium concentration required for activation.
10.1016/j.micinf.2012.04.006
pubmed_1086_959
Commercially important edible nut seeds were analyzed for chemical composition and moisture sorption. Moisture (1.47-9.51%), protein (7.50-21.56%), lipid (42.88-66.71%), ash (1.16-3.28%), total soluble sugars (0.55-3.96%), tannins (0.01-0.88%), and phytate (0.15-0.35%) contents varied considerably. Regardless of the seed type, lipids were mainly composed of mono- and polyunsaturated fatty acids (>75% of the total lipids). Fatty acid composition analysis indicated that oleic acid (C18:1) was the main constituent of monounsaturated lipids in all seed samples. With the exception of macadamia, linoleic acid (C18:2) was the major polyunsaturated fatty acid. In the case of walnuts, in addition to linoleic acid (59.79%) linolenic acid (C18:3) also significantly contributed toward the total polyunsaturated lipids. Amino acid composition analyses indicated lysine (Brazil nut, cashew nut, hazelnut, pine nut, and walnut), sulfur amino acids methionine and cysteine (almond), tryptophan (macadamia, pecan), and threonine (peanut) to be the first limiting amino acid as compared to human (2-5 year old) amino acid requirements. The amino acid composition of the seeds was characterized by the dominance of hydrophobic (range = 37.16-44.54%) and acidic (27.95-33.17%) amino acids followed by basic (16.16-21.17%) and hydrophilic (8.48-11.74%) amino acids. Trypsin inhibitory activity, hemagglutinating activity, and proteolytic activity were not detected in the nut seed samples analyzed. Sorption isotherms (Aw range = 0.08-0.97) indicated a narrow range for monolayer water content (11-29 mg/g of dry matter). No visible mold growth was evident on any of the samples stored at Aw < 0.53 and 25 degrees C for 6 months.
10.1021/jf0606959
pubmed_475_1219
BACKGROUND The Spinal Instability Neoplastic Score (SINS) categorizes tumor related spinal instability. It has the potential to streamline the referral of patients with established or potential spinal instability to a spine surgeon. This study aims to define the inter- and intra-observer reliability and validity of SINS among radiation oncologists. METHODS Thirty-three radiation oncologists, across ten international sites, rated 30 neoplastic spinal disease cases. For each case, the total SINS (0-18 points), three clinical categories (stable: 0-6 points, potentially unstable: 7-12 points, and unstable: 13-18 points), and a binary scale ('stable': 0-6 points and 'current or possible instability'; surgical consultation recommended: 7-18 points) were recorded. Evaluation was repeated 6-8 weeks later. Inter-observer agreement and intra-observer reproducibility were calculated by means of the kappa statistic and translated into levels of agreement (slight, fair, moderate, substantial, and excellent). Validity was determined by comparing the ratings against a spinal surgeon's consensus standard. RESULTS Radiation oncologists demonstrated substantial (κ=0.76) inter-observer and excellent (κ=0.80) intra-observer reliability when using the SINS binary scale ('stable' versus 'current or possible instability'). Validity of the binary scale was also excellent (κ=0.85) compared with the gold standard. None of the unstable cases was rated as stable by the radiation oncologists ensuring all were appropriately recommended for surgical consultation. CONCLUSIONS Among radiation oncologists SINS is a highly reliable, reproducible, and valid assessment tool to address a key question in tumor related spinal disease: Is the spine 'stable' or is there 'current or possible instability' that warrants surgical assessment?
10.1186/1748-717X-9-69
pubmed_825_13953
1. The horizontal eye movements induced by acceleration along the interaural axis were recorded from five monkeys (Macaca mulatta) by the use of the electromagnetic search-coil technique. Animals sat on a sled that was moved briefly in darkness along a linear track (bell-shaped acceleration profile: peak, 400 mm/s2; duration, 200 ms). Immediately before acceleration, animals fixated one of five target lights located at distances ranging from 16 to 150 cm. During fixation, the horizontal positions of both eyes were used to check vergence, while accommodation was monitored with an infrared optometer. 2. Sled motion induced eye movements that were generally smooth and compensatory, e.g., rightward sled motion elicited leftward eye movement. We attribute these responses to a translational vestibuloocular reflex (TVOR) that senses the sled motion through the otolith organs. However, in three animals, these responses were preceded by weak anticompensatory movements (duration, less than 40 ms; amplitude, less than 10% of the maximum compensatory response). 3. Geometry indicates that, during brief sled motion, the eye movements required to keep gaze aligned on a particular location ("full" compensation) are inversely proportional to the viewing distance. Response measures based on the computed eye velocity profiles, such as the velocity achieved at specific times ("time slices") or the peak values of the estimated covariance functions, all indicated that compensatory responses were a linear function of the inverse of the prior viewing distance. Cross-correlation analyses indicated that the effect of the prior viewing distance was to scale responses, although detailed spectral analyses revealed that high-frequency components (greater than 10 Hz) tended to scale less vigorously than lower ones. 4. The adequacy of the compensatory eye movements was assessed by calculating the gain (response recorded/response required for full compensation). Regardless of the response measure used, gains varied considerably from one animal to another and, in some particular animals, from one direction to another but showed a general tendency to increase with viewing distance. For example, on the basis of the peak eye velocity achieved within 250 ms of the onset of sled motion, mean gain at 16 cm was 0.74 (range, 0.48-1.01), whereas at 150 cm it was 1.25 (range, 0.67-1.73). 5. Using wedge prisms to dissociate vergence and accommodation indicated that ocular responses to sled motion were sensitive to selective increases in either vergence (base-out prism with the most distant target) or accommodation (base-in prism with the nearest target). However, the magnitude of the effects showed considerable variability from one animal to another and, in some particular animals, from one direction to another.(ABSTRACT TRUNCATED AT 400 WORDS)
10.1152/jn.1991.66.3.851
pubmed_576_10866
A total of 76 premature newborn infants with gestational age of 34 weeks or less were enrolled in a randomized controlled study to determine whether intravenously administrated immunoglobulin (IVIG) is able to prevent nosocomial sepsis. Forty infants were given 0.5 g/kg IVIG on the first day of life and 36 infants with similar gestational age and birth weight were selected as controls and did not receive IVIG. The frequency of proven sepsis, with a positive blood and/or cerebrospinal fluid culture, was significantly lower in infants who received IVIG as compared to controls (42.5 vs 80.0%) (p < 0.01). The mortality rate attributable to infection was not different in IVIG recipients and in controls (41 vs 48%) (p > 0.05). The overall mortality rates in the two groups were not different either (35.0 vs 44.4%) (p > 0.05). The majority of micro-organisms isolated from the blood culture of the patients were gram negative microorganisms (Klebsiella, Enterobacter). IVIG therapy was believed to be effective for prophylaxis of nosocomial infection, but such therapy was not able to reduce overall mortality rate or mortality rate due to systemic infection in prematurely born infants in our intensive care unit where the causative pathogens are usually gram negative microorganisms.
10.1007/BF02905726
pubmed_301_16917
OBJECTIVE To analyze paraoxonase2 (PON2) expression in human monocyte-derived macrophages (HMDM) from patients with hypercholesterolemia in relation to cellular cholesterol and oxidative stress. METHODS AND RESULTS Ten healthy subjects (controls) and 10 patients with hypercholesterolema who received 20-mg/d atorvastatin participated in the study. The patients' versus controls' HMDM demonstrated increased cholesterol content (270%) and oxidative stress (30% to 45%). Atorvastatin therapy reduced these parameters (59% and 25%, respectively). The patients' versus controls' macrophage-PON2 mRNA expression and PON2 activity were lower (100% and 40%, respectively), and atorvastatin therapy increased these parameters (76% and 200%, respectively). Untreated patient HMDM incubation with atorvastatin (0 to 10 micromol/L) resulted in a dose-dependent reduction in cellular cholesterol content and in cell-mediated low-density lipoprotein (LDL) oxidation up to 79% and 66%, respectively. In parallel, PON2 mRNA expression and PON2 activity increased dose-dependently up to 3.6- and 2.1-fold, respectively. On incubation of control HMDM with acetylated-LDL or aggregated-LDL, cellular cholesterol content increased (77% and 100%), and macrophage-PON2 activity decreased (49% and 22%), respectively. In contrast, oxidized LDL increased both cellular oxidative stress and PON2 expression. CONCLUSIONS HMDM-PON2 expression is reduced in patients with hypercholesterolemia as a result of their increased cellular cholesterol content. Atorvastatin therapy reduced both macrophage oxidative stress and cholesterol content, and upregulated PON2 expression, thus contributing to attenuation of foam cells formation.
10.1161/01.ATV.0000104011.88939.06
pubmed_556_18150
The effects of COVID-19 have gone undocumented in nomadic pastoralist communities across Africa, which are largely invisible to health surveillance systems despite the fact that they are of key significance in the setting of emerging infectious disease. We expose these landscapes as a "blind spot" in global health surveillance, elaborate on the ways in which current health surveillance infrastructure is ill-equipped to capture pastoralist populations and the animals with which they coexist, and highlight the consequential risks of inadequate surveillance among pastoralists and their livestock to global health. As a platform for further dialogue, we present concrete solutions to address this gap.
10.4269/ajtmh.20-1004
pubmed_51_21461
Sunitinib is an oral multitarget tyrosine kinase inhibitor with potent antiangiogenic properties. Preclinical data have demonstrated that pancreatic neuroendocrine tumors depend on vascular endothelial growth factor receptors and platelet growth factor receptors-signaling pathways for tumor angiogenesis. Sunitinib has recently been approved for the treatment of patients with advanced, progressive pancreatic neuroendocrine tumors. Sunitinib has demonstrated clinically meaningful improvements in progression-free survival in a double-blinded randomized trial against placebo, setting progression-free survival as a valid endpoint for the evaluation of novel agents in patients with pancreatic neuroendocrine tumors. Although patients who progressed in this phase III trial were allowed to cross-over, a trend toward improvement in overall survival was also observed. In this trial, side effects reported with sunitinib were those previously reported in other tumor types, including hand-foot syndrome, diarrhea, and hypertension. This trial also investigated patient-reported outcome and showed that treatment with sunitinib did not affect quality of life of patient. Interestingly, this trial showed that sunitinib could be combined with somatostatin analogues without affecting the safety profile of either sunitinib or somatostatin analogues. Since the overall survival of patients with well-differentiated neuroendocrine tumors remains sufficiently long, it is worth considering using alternate sequences of targeted therapy (such as everolimus) and chemotherapy to optimize the care of patients with advanced diseases. The optimal sequence for using chemotherapy, everolimus, and sunitinib will remain to be established in clinical trials.
10.1007/s11523-012-0220-2
pubmed_103_16376
Prevotella is part of the oral bacterial community implicated in periodontitis. Pan genome analyses of eight oral Prevotella species, P. dentalis, P. enoeca, P. fusca, P. melaninogenica, P. denticola, P. intermedia 17, P. intermedia 17-2 and P. sp. oral taxon 299 are presented in this study. Analysis of the Prevotella pan genome revealed features such as secretion systems, resistance to oxidative stress and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas systems that enable the bacteria to adapt to the oral environment. We identified the presence of type VI secretion system (T6SS) in P. fusca and P. intermedia strains. For some VgrG and Hcp proteins which were not part of the core T6SS loci, we used gene neighborhood analysis and identified putative effector proteins and putative polyimmunity loci in P. fusca and polymorphic toxin systems in P. intermedia strains. Earlier studies have identified the presence of Por secretion system (PorSS) in P. gingivalis, P. melaninogenica and P. intermedia. We noted the presence of their homologs in six other oral Prevotella studied here. We suggest that in Prevotella, PorSS is used to secrete cysteine proteases such as interpain and C-terminal domain containing proteins with a "Por_secre_tail" domain. We identified subtype I-B CRISPR-Cas system in P. enoeca. Putative CRISPR-Cas system subtypes for 37 oral Prevotella and 30 non-oral Prevotella species were also predicted. Further, we performed a BLASTp search of the Prevotella proteins which are also conserved in the red-complex pathogens, against the human proteome to identify potential broad-spectrum drug targets. In summary, the use of a pan genome approach enabled identification of secretion systems and defense mechanisms in Prevotella that confer adaptation to the oral cavity.
10.1007/s10142-017-0550-3
pubmed_169_7504
A patient with a benign condroblastoma of the talus bone is described. A review of the pathogenesis and more common sites of predilection of this unusual tumor is presented. This is the first case, to our knowlege, shown by labeled phosphate scanning.
10.1097/00003072-197802000-00008
pubmed_472_9425
INTRODUCTION Suicide is defined as an individual taking action towards themselves with the intention of terminating their own life. According to the World Health Organisation (WHO), 800,000 deaths per year worldwide are due to suicide. In 2012, suicide cases constituted 1.4% of all the deaths worldwide. In most countries throughout the world, the suicide rates of the elderly are higher than those of other age groups. Epidemiological studies have concluded that suicide rates increase with advancing age in all societies, this increase accelerates after the age of 65 years and the highest rates are reached after the age of 75 years. The aim of this study was to evaluate the demographic features, suicide methods and reasons for suicide in geriatric suicide cases between 2009 and 2013 using the data of the Turkish Statistics Institute (TUIK). MATERIAL AND METHODS A retrospective evaluation was made of the TUIK data related to proven suicide cases aged 65 years and older in the 5-year period of 2009-2013. RESULTS A total of 1723 geriatric suicides were determined in Turkey between 2009 and 2013. These comprised 1284 (74.5%) males and 439 (25.5%) females, showing a rate of males approximately 3 times higher than that of females. An increase of approximately 10% was seen in the deaths by suicide in 2013 compared to 2009. The highest rate of geriatric suicides within total geriatric deaths was observed to be in 2012 (15.2%) and the lowest rate was in 2010 (12.4%). The most common method of suicide in both genders was hanging. In the majority of cases of geriatric suicide of both genders, the reason could not be determined. In those cases where the reason was known, the most common reason was illness. CONCLUSION It has been reported that the most significant factors in suicide prevention are friends and family. As there continues to be an extensive family structure and family connections are strong in Turkey, this can be considered to be one of the reasons for lower rates of geriatric suicide compared to other countries. As there is a strong adherence to Islam in Turkey, another significant reason for the low rate could be the effect of the belief that suicide is a sin in the Islamic religion.
10.1016/j.jflm.2016.10.016