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pubmed_408_14866
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Serum immunoglobulins (IgG, IgA, and IgM) have been studied in 70 patients with squamous cell carcinoma of oral cavity and in 40 age-matched normal controls. The results were correlated with clinical stage, tumor size, lymph node status, tumor differentiation, and treatment modalities. There was a significant rise in serum IgM and IgA in oral cancer patients as compared to controls. It was further raised in advanced clinical stage, but tumor size and histological differentiation and treatment modalities (surgery and chemotherapy) do not seem to affect serum immunoglobulin levels. The observations implies that the extension and dissemination of tumor mass is the important factor for the change in serum immunoglobulin level in squamous cell carcinoma of the oral cavity.
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10.1002/jso.2930200111
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pubmed_33_17261
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Paclitaxel/carboplatin chemotherapy for cancer (TC therapy) exhibits neurotoxicity and causes peripheral neuropathy at a high frequency, which is difficult to cope with. In this study, we investigated the efficacy of Goshajinkigan, a traditional Japanese herbal medicine, for TC therapy-induced peripheral neuropathy. The subjects included in our study were patients with ovarian or endometrial cancer who underwent TC therapy and developed peripheral neuropathy. The patients were randomly divided into Group A, comprising of 14 patients (vitamin B12 treatment), and Group B, comprising of 15 patients (vitamin B12 + Goshajinkigan treatment). The observation period was 6 weeks following treatment initiation, and the evaluation items were as follows: i) the current perception threshold (CPT value) of the peripheral nerve, ii) visual analogue scale for numbness, iii) National Cancer Institute Common Terminology Criteria for Adverse Events v3.0 grade of neurotoxicity, and iv) a questionnaire on the subjective symptoms of peripheral neuropathy (functional assessment of cancer therapy-taxane). These were compared between the groups and no significant differences were noted in any item. However, CTCAE grade 3 neurotoxicity developed in 2 patients (14.3%) after 6 weeks of administration in Group A, whereas no neurotoxicity was observed in Group B. When the change in the frequency of abnormal CPT ratio at 6 weeks of administration from that before treatment was compared between the groups, the frequency of abnormal value was significantly lower in Group B than in Group A (p<0.05). This suggests that Goshajinkigan inhibits the progression of peripheral neuropathy.
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10.3892/etm.2011.375
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pubmed_202_9700
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Pancreatic carboxylester lipase catalyzes the exchange of 18O between water and 13,16-cis,cis-doco-sadienoic acid (DA) in monolayers at the argon-buffer interface (Muderhwa, J.M., Schmid, P.C., and Brockman, H.L. (1992) Biochemistry 31, 141). In mixed monolayers of 18O, 18O-DA and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), both the extent and mechanism of 18O exchange show characteristics of a critical transition in the range of 0.5-0.6 mol fraction of DA (Muderhwa, J.M., and Brockman, H. L. (1992) Biochemistry 31, 149). To determine if the regulatory behavior exhibited on this type of surface is limited to members of the carboxylester lipase gene family (cholinesterases), comparable experiments were performed with a genetically and functionally unrelated lipase, pancreatic colipase-dependent lipase (PL). PL readily catalyzed the exchange of 18O between water and the carboxyl group of DA with enzyme at either monolayer or catalytic levels in the fatty acid-buffer interface. The oxygen exchange reaction obeyed a random, sequential mechanism, indicating that the dissociation of the enzyme.DA complex is much faster than the rate-limiting step in the overall exchange process. Kinetic analysis of oxygen exchange in pure DA monolayers showed a first-order dependence on interfacial PL and DA concentrations from which kcat/Km values were calculated. The oxygen exchange reaction proceeded with a rate constant of 16 x 10(-2) cm2 pmol-1 s-1, a value comparable to that for hydrolysis of the ester substrate, 1,3-dioleoylglycerol. With a monolayer of PL adsorbed to the interfacial phase, kcat/Km for oxygen exchange was about 600-fold lower than the value obtained with catalytic levels of adsorbed enzyme, indicating a possible restriction of substrate diffusion in the protein-covered fatty acid monolayer. With constant bulk PL concentration and mixed lipid monolayers containing DA and the non-substrate lipid, POPC, the extent of oxygen exchange increased abruptly as the abundance of DA in the interface was increased from 0.5 to 0.6 mol fraction. Concomitant with this critical transition was a change in the apparent mechanism of oxygen exchange from coupled to random, sequential. For both the extent of oxygen exchange and its mechanism shift, the critical transition was independent of the lipid packing density, i.e. surface pressure, of the interface. These results show that PL responds similarly to carboxylester lipase with respect to changes in interfacial lipid mole fraction in DA-POPC surfaces.(ABSTRACT TRUNCATED AT 400 WORDS)
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pubmed_202_9700
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pubmed_159_11549
|
BACKGROUND
There is limited research quantifying the direct and indirect economic costs associated with intellectual disability (ID) in Australia. Costs incurred by families, governments and broader society include time spent providing care, absenteeism and increased healthcare utilisation. The purpose of this research is to quantify the costs associated with ID in childhood using a range of methods to collect cost data.
METHODS
Costs included healthcare service utilisation, pharmaceutical use, caregiver productivity losses and time spent providing care because of the child's disability. The sample comprised caregivers with a child with ID aged between 2 and 10 years old recruited in Australia. Healthcare service utilisation and pharmaceutical use were obtained from routinely collected administrative claims data. Healthcare utilisation not captured in the routinely collected administrative data and absenteeism data were obtained from a retrospective recall-based questionnaire. Time spent providing care because of the child's disability was obtained using a time-use diary.
RESULTS
The total cost of ID in Australia was estimated to be AUD 72 027 per year per child, and the total cost of ID in childhood was estimated to be AUD 12.5 billion per year. The cost to governments of ID in childhood was estimated to be AUD 6385 per child per year, resulting in a total cost to government of AUD 1.1 billion per year.
CONCLUSIONS
This is the first study to estimate the direct and indirect costs associated with ID in childhood. The results of this research demonstrate the considerable economic impact of ID in childhood on families, governments and broader society in terms of both direct and indirect costs. An understanding of the cost implications of any intervention are critical in assisting policymakers in planning and prioritising of health services.
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10.1111/jir.12732
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pubmed_669_19831
|
BACKGROUND
Functional diarrhea (FDr), one of the most common functional gastrointestinal diseases, is a kind of functional bowel disease characterized by repeated paste feces or watery feces. However, no relevant systematic review or meta-analysis has been designed to evaluate the effects of herbal acupoint application (HAA) on FDr. There is also a lack of systematic evaluation and analysis of acupoints and herbs.
METHODS
We will search the following 8 databases from their inception to October 15, 2021, without language restrictions: the Cochrane Central Register of Controlled Trials, PubMed, Embase, the Web of Science, the Chinese Biomedical Literature Database, the Chinese Scientific Journal Database, the Wan-Fang Database, and the China National Knowledge Infrastructure. The primaryoutcome measures will be clinical effective rate, functional outcomes, and quality of life. Data that meets the inclusion criteria will be extracted and analyzed using RevMan V.5.3 software (Available at: https://community.cochrane.org/help/tools-and-software/revman-5). Two reviewers will evaluate the studies using the Cochrane Collaboration risk of bias tool. We will use the Grading of Recommendations Assessment, Development and Evaluation approach to assess the overall quality of evidence supporting the primary outcomes. We will also use SPASS software (Version 19.0 (Available at: https://www.ibm.com/analytics/spss-statistics-software)) for complex network analysis to explore the potential core prescription of acupoint herbal patching for FDr.
RESULTS
This study will analyze the clinical effective rate, bristol stool scale, number of daily bowel movements, clinical symptom scale of diarrhea, and effective prescriptions of HAA for patients with FDr.
CONCLUSION
The conclusion of our findings will provide evidence for the effectiveness and potential treatment prescriptions of HAA for patients with FDr.
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10.1097/MD.0000000000027702
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pubmed_311_20713
|
A 40-year-old man with no history of trauma or previous sinus surgery complained sudden right diplopia after vigorous sneezing. The patient was submitted elsewhere to a MRI study for persisting diplopia, with inconclusive findings. One week later the patient was submitted to a maxillofacial cone beam CT (CBCT) in our Institution. A blowout fracture of the right orbital floor and lateral orbital wall with an intact orbital rim and a ipsilateral maxillary sinus effusion with an air liquid level, were detected at the CBCT study. Our conclusion, confirmed by the clinician, was the patient had a barotraumatic, isolated, pure blowout fracture of the right orbit consequence of the episode of vigorous sneezing. The patient was treated by steroid and antibiotic therapy and diplopia resolved after two weeks. Clinicians and radiologists should be aware that a barotraumatic blowout fracture of the orbit after sneezing should be included among the unusual causes of sudden diplopia.
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10.7417/CT.2018.2089
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pubmed_133_9555
|
The properties of the pore of cyclic-nucleotide-gated channels are thought to depend mostly on the structure of the "P loop" which connects the S5 and S6 transmembrane segments. We applied scanning cysteine mutagenesis to the P loop of the alpha subunit of cGMP-gated channels from bovine rod, i.e. to the amino acid residues K346 to S371 (here named K2-S27). Mutant channels were expressed in Xenopus laevis oocytes and currents recorded from inside-out patches, in symmetrical sodium and in the absence of divalent cations. Cysteine mutations had minor effects on the affinity for cGMP and the selectivity to monovalent alkali cations. However, in mutants within the segment W9-T16, open probability was strongly reduced. It was less than 0.2 in saturating cGMP compared to 0.8 in wild-type channels. Moreover, W9C and L12C mutants were outward rectifiers, while T16C was an inward rectifier. These mutant channels showed a time dependence in the development of the steady-state current. Currents from I17C channels progressively decayed in inside-out patches. This rundown was prevented by 1 mM dithiothreitol on the cytoplasmic side of the plasma membrane, suggesting that I17 is an intracellular residue. On the other hand, mutants within the segment T20-S27 had normal open probabilities, around 0.8 in saturating cGMP, but altered single-channel conductance.
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10.1007/s004249900062
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pubmed_861_24096
|
Clostridia are Gram-positive, spore-forming, obligate anaerobic bacteria that can produce solvents such as acetone, ethanol, and butanol, which can be used as biofuels or building block chemicals. Many successful attempts have been made to improve solvent yield and titer from sugars through metabolic engineering of solventogenic and acidogenic clostridia. More recently, cellulolytic and acetogenic clostridia have also attracted high interests for their ability to utilize low-cost renewable substrates such as cellulose and syngas. Process engineering such as in situ butanol recovery and consolidated bioprocessing (CBP) has been developed for improved solvent titer and productivity. This review focuses on metabolic and process engineering strategies for solvent production from sugars, lignocellulosic biomass, and syngas by various clostridia, including conventional solventogenic Clostridium acetobutylicum, engineered acidogens such as C. tyrobutyricum and C. cellulovorans, and carboxydotrophic acetogens such as C. carboxidivorans and C. ljungdahlii.
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10.1007/s00253-019-09916-7
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pubmed_1012_10303
|
Breast reconstruction has become a routine procedure, being performed in a growing part of the mastectomy patients' population. Proven improvement in body image and in coping with breast cancer encouraged plastic and general surgeons to warmly recommend the procedure. The advances in the genetic evaluation of the breast cancer population cause an increase in prophylactic surgery and subsequent reconstructions. Today, we can offer two types of reconstruction: by using tissue expanders or by using autologous tissues from various sources: abdomen, back and the gluteal region. The advancement in surgical techniques enable us to offer a custom made reconstruction that is performed according to the patient condition and desire. We describe our experience in breast reconstruction using Becker implant-expanders in 229 patients in the last decade. We detail the organization chart of our multidisciplinary breast reconstruction team clinic and we suggest a flow chart for the evaluation and planning of breast reconstruction. Custom made reconstruction, done in the envelope of a multidisciplinary supporting system is the future of this procedure.
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pubmed_1012_10303
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pubmed_664_7006
|
CopA uses ATP to pump Cu(+) across cell membranes. X-ray crystallography has defined atomic structures of several related P-type ATPases. We have determined a structure of CopA at 10 Å resolution by cryo-electron microscopy of a new crystal form and used computational molecular docking to study the interactions between the N-terminal metal-binding domain (NMBD) and other elements of the molecule. We found that the shorter-chain lipids used to produce these crystals are associated with movements of the cytoplasmic domains, with a novel dimer interface and with disordering of the NMBD, thus offering evidence for the transience of its interaction with the other cytoplasmic domains. Docking identified a binding site that matched the location of the NMBD in our previous structure by cryo-electron microscopy, allowing a more detailed view of its binding configuration and further support for its role in autoinhibition.
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10.1016/j.str.2011.05.014
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pubmed_695_25122
|
BACKGROUND
Intrahepatic lithiasis (IHL) is a rare disease in the western world. Complications associated with IHL include acute cholangitis, liver atrophy, secondary biliary cirrhosis, and risk for intrahepatic cholangiocarcinoma. Liver resection is considered the treatment of choice for IHL. The objective of this study was to analyze patients who underwent liver resection for non-Asian hepatolithiasis.
METHODS
127 patients with symptomatic non-Asian hepatolithiasis underwent resection in six institutions. Demographic data, clinical presentation, diagnosis, classification according to stone location, presence of atrophy, bile duct stricture, biliary cirrhosis, incidence of cholangiocarcinoma, treatment and postoperative course were evaluated.
RESULTS
52 patients (40.9%) were male and the mean age was 46.1 years. Sixty-six patients (51.9%) presented with history of cholangitis. Stones were located in the left lobe in 63 (49.6%), and right lobe in 28 patients (22.0%). Atrophy was observed in 31 patients (24.4%) and biliary stenosis in 18 patients (14.1%). The most common procedure performed was left lateral sectionectomy in 63 (49.6%) patients, followed by left hepatectomy in 36 (28.3%), right hepatectomy in 19 (15.0%), and associated hepaticojejunostomy in 28 (22.0%). Forty-two patients (33.0%) presented postoperative complications and the most common were biliary fistula (13.3%) and surgical site infection (7.0%). Postoperative mortality was 0.7%. Intrahepatic cholangiocarcinoma was observed in 2 patients (1.5%). Recurrence was identified in 10 patients (7.8%), mostly with bilateral stones and/or hepaticojejunostomy.
CONCLUSION
Liver resection is the standard treatment for symptomatic unilateral or complicated IHL with good operative results. Risk of cholangiocarcinoma was low in non-Asian patients.
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10.1016/j.asjsur.2020.11.011
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pubmed_749_18231
|
OBJECTIVE
Transfusions represent one of the main progresses of modern medicine. However, accumulating evidence supports that transfusions correlate with worse survival outcomes in patients affected by solid cancers. In the present study, we aimed to investigate the effects of perioperative blood transfusion in locally advanced cervical cancer.
METHODS
Data of consecutive patients affected by locally advanced cervical cancer scheduled to undergo neoadjuvant chemotherapy plus radical surgery were retrospectively searched to test the impact of perioperative transfusions on survival outcomes. Five-year survival outcomes were evaluated using Kaplan-Meier and Cox models.
RESULTS
The study included 275 patients. Overall, 170 (62%) patients had blood transfusion. Via univariate analysis, we observed that transfusion correlated with an increased risk of developing recurrence (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.09-4.40; P = 0.02). Other factors associated with 5-year disease-free survival were noncomplete clinical response after neoadjuvant chemotherapy (HR, 2.99; 95% CI, 0.92-9.63; P = 0.06) and pathological (P = 0.03) response at neoadjuvant chemotherapy as well as parametrial (P = 0.004), vaginal (P < 0.001), and lymph node (P = 0.002) involvements. However, via multivariate analysis, only vaginal (HR, 3.07; 95% CI, 1.20-7.85; P = 0.01) and lymph node involvements (HR, 2.4; 95% CI, 1.00-6.06; P = 0.05) correlate with worse disease-free survival. No association with worse outcomes was observed for patients undergoing blood transfusion (HR, 2.71; 95% CI, 0.91-8.03; P = 0.07). Looking at factors influencing overall survival, we observed that lymph node status (P = 0.01) and vaginal involvement (P = 0.06) were independently associated with survival.
CONCLUSIONS
The role of blood transfusions in increasing the risk of developing recurrence in LAAC patients treated by neoadjuvant chemotherapy plus radical surgery remains unclear; further prospective studies are warranted.
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10.1097/IGC.0000000000000902
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pubmed_1019_19519
|
Several hepatobiliary abnormalities have been described in association with inflammatory bowel disease (IBD), including primary sclerosing cholangitis (PSC), small duct PSC, chronic hepatitis, cryptogenic cirrhosis, cholangiocarcinoma, and cholelithiasis. PSC is the most common biliary condition in patients with IBD, with an incidence ranging from 2.5% to 7.5%. PSC usually progresses insidiously and eventually leads to cirrhosis independent of inflammatory bowel disease activity. There is a very high incidence of cholangiocarcinoma and an elevated risk for developing colon cancer in patients with PSC. Medical therapy has not proven successful in slowing disease progression or prolonging survival. Treatment of symptoms due to cholestasis, such as pruritis and steatorrhea, is an important aspect of the medical care of patients with PSC. Our preferred treatment of pruritis due to cholestasis is with bile acid binding exchange resins, such as cholestyramine or colestipol. Endoscopic manipulation is recommended for treating complications of recurrent cholangitis or worsening jaundice in the setting of a dominant stricture, but endoscopic approaches have not been conclusively demonstrated to improve survival or decrease the need for liver transplantation. Liver transplantation remains the only effective treatment of advanced PSC, and should be considered in patients with complications of cirrhosis or intractable pruritis or fatigue.
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10.1007/s11894-011-0213-9
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pubmed_4_11446
|
Background: The incidence and characteristics of gastric cancer have been shown to vary widely across Western and Eastern countries. Our study had two aims: to evaluate long-term trends in gastric adenocarcinoma in Japan over a period of 70 years, and to anticipate the future of gastric cancer in Japan, through comparison with data from the United States. Methods: Japanese patient data for 19,306 incident cases of gastric adenocarcinoma from 1946 - 2014 were collected from the Gastric Cancer Database at the Cancer Institute Hospital, Tokyo, Japan (CIH-GCDB). U.S. patient data for 78,625 incident cases of gastric cancer from 1973 - 2012 were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. Changes over time in patient and tumor characteristics were investigated in these two cohorts. Results: There was a marked reduction of cancer incidence in the lower third of the stomach in the CIH-GCDB; over 70% to around 30%. The incidence in the upper third has been increasing steadily over time; 3% to 19%, although the number of cardia tumors has not changed. An increase in elderly and obese patients was also noted. In the U.S. population, there was a significant difference in the primary site across races. A notable overall increase in cardia cancer was evident in the Western population during the study period, with no similar change evident in the Japanese population over the last 15 years. In the East Asian population, the proportional frequency of tumors in the cardia was lower and that of tumors in the pyloric antrum was higher. Conclusion: In Japan, cancer in the antrum or pylorus of the stomach has been declining, whereas cancer in the body has been increasing. Unlike the Western population in the United States, adenocarcinoma of esophago-gastric junction is not increasing in Japan.
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10.7150/jca.19174
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pubmed_247_14966
|
Complete 5S ribosomal RNA sequences were obtained for four acidophilic actinomycetes, seven neutrophilic streptomycetes and a strain of Streptoverticillium baldaccii. All of the organisms contained RNAs belonging to the 120 nucleotide type. An evolutionary tree was generated after combining the test data with results from similar studies on representative Gram-positive bacteria. The acidophilic, neutrotolerant and neutrophilic actinomycetes were recovered in a distinct cluster that was equated with the genus Streptomyces. The sequence data support the view that the genera Chainia, Elytrosporangium, Kitasatoa and Microellobosporia should be considered as synonyms of the genus Streptomyces. The recovery of the Streptoverticillium baldaccii strain on the fringe of the Streptomyces cluster is also consistent with current trends in the taxonomy of these organisms. Further work is needed to determine the taxonomic status of the two streptomycete subgroups that comprised the streptomycete cluster.
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10.1099/00221287-137-9-2265
|
pubmed_874_3306
|
BACKGROUND
Chronic non-cancer pain (CP) is one of the most common complaints that bring patients to the hospital. When pain persists, people move from doctor-to-doctor seeking for help, thus the burden of CP is huge. This study, therefore was aimed at assessing attitude and knowledge of doctors in three teaching hospitals in Nigeria to CP.
MATERIALS AND METHODS
Structured questionnaire was administered to doctors practicing at the University of Ilorin Teaching Hospital, Usmanu Danfodio University Teaching Hospital and University of Maiduguri Teaching Hospital. Responses were graded on maximum scale of five.
RESULTS
Of the 410 doctors who participated in study, 79.7% were men. Their years of practice varied from 1 year to 20 years (mean SD = 4.5 ± 1.7 years). Close to 58% of participants were resident doctors, 36.4% medical officers and 8.6% consultants. Only 23.3% of participants had basic medical or postgraduate training on pain management. The physicians' mean goal of treating CP in patients was 3.7 ± 1.1, compared to 4.0 ± 1.1 in close relative and 4.1 ± 0.9 for doctors'-self pain. Only 9.5% of doctors use opioids for CP compared to 73% who use Nonsteroidal anti-inflammatory drugs (NSAIDs). Few doctors (23%) use ≥2 drugs to treat CP. Doctors were indifferent on the appropriateness of patients with CP to request for additional analgesics (mean score = 3.1 + 1.4). Doctors' self-rated knowledge of CP was 1.8 ± 0.7 compared to 4.1 ± 0.9 for acute and 0.8 ± 0.3 for cancer pains (P = 0. 003).
CONCLUSION
Incorporation of pain management into continuing medical education could help improve observed deficiency in doctors' knowledge of pain treatment which resulted from lack of basic medical education on pain.
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10.4103/0300-1652.129635
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pubmed_1103_19795
|
Previous research has suggested that infants are unable to make a corrective eye movement in response to a small base-out prism placed in front of one eye before 14-16 weeks [1]. Three hypotheses have been proposed to explain this early inability, and each of these makes different predictions for the time of onset of a response to a larger prism. The first proposes that infants have a 'degraded sensory capacity' and so require a larger retinal disparity (difference in the position of the image on the retina of each eye) to stimulate disparity detectors [2]. This predicts that infants might respond at an earlier age than previously reported [1] when tested using a larger prism. The second hypothesis proposes that infants learn to respond to larger retinal disparities through practice with small disparities [3]. According to this theory, using a larger prism will not result in developmentally earlier responses, and may even delay the response. The third hypothesis proposes that the ability to respond to prismatic deviation depends on maturational factors indicated by the onset of stereopsis (the ability to detect depth in an image on the basis of retinal disparity cues only) [4] [5], predicting that the size of the prism is irrelevant. To differentiate between these hypotheses, we tested 192 infants ranging from 2 to 52 weeks of age using a larger prism. Results showed that 63% of infants of 5-8 weeks of age produced a corrective eye movement in response to placement of a prism in front of the eye when in the dark. Both the percentage of infants who produced a response, and the speed of the response, increased with age. These results suggest that infants can make corrective eye movements in response to large prismatic deviations before 14-16 weeks of age. This, in combination with other recent results [6], discounts previous hypotheses.
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10.1016/s0960-9822(99)80456-4
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pubmed_524_16662
|
With Black and Hispanic communities across the USA experiencing more detrimental negative effects from the COVID-19 pandemic as compared with other demographic groups, the virus has exposed the racial and ethnic disparities in treatment and care that public health experts have been grappling with for years. This paper explains how the systematic collection of racial and ethnic data gleaned from COVID-19 testing in underserved communities can be used to better understand this pandemic and inform measures within our control to prevent the spread of disease in the future.
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10.1007/s40615-021-00989-7
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pubmed_23_3799
|
The aim of this study was to characterise the morphological and histochemical features of equine nasopharyngeal tonsillar tissue. Nasal and oropharyngeal tonsillar tissue has been described as the gatekeeper to mucosal immunity because of its strategic location at the entrance to the respiratory and alimentary tracts. A combination of light, scanning and transmission electron microscopy has revealed the presence of follicle-associated epithelium (FAE) overlying lymphoid tissue of the equine nasopharyngeal tonsil caudal to the pharyngeal opening of the guttural pouch. Membranous microvillus (M) cells were identified in the FAE on the basis of short microvilli, an intimate association with lymphocytes, cytoplasmic vimentin filaments and epitopes on the apical surface reactive with lectin GS I-B4 specific for alpha-linked galactose. CD4-positive lymphocytes were scattered throughout the lamina propria mucosae as well as forming dense aggregates in the subepithelial part. The central follicular area was heavily populated with B lymphocytes and the dome and parafollicular areas contained both CD4- and CD8-positive lymphocytes. CD8-positive lymphocytes were also present in the epithelium and, together with B lymphocytes, in small numbers in the lamina propria mucosae. These observations indicate that the nasopharyngeal tonsil is potentially an important mucosal immune induction site in the horse and an appropriate target for intranasally administered vaccines.
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10.2746/042516401776249697
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pubmed_117_16949
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Clinical assessment of drug-drug interactions (DDIs) in children is not a common practice in drug development. Therefore, physiologically-based pharmacokinetic (PBPK) modeling can be beneficial for informing drug labeling. Using ivabradine and its metabolite (both cytochrome P450 3A4 enzyme (CYP3A4) substrates), the objectives were (i) to scale ivabradine-metabolite adult PBPK/PD to pediatrics, (ii) to predict the DDIs with a strong CYP3A4 inhibitor, and (iii) to compare the sensitivity of children to DDIs using two CYP3A4 hepatic ontogeny functions: Salem and Upreti. A scaled parent-metabolite PBPK/PD model from adults to children satisfactorily predicted pharmacokinetics (PK) and pharmacodynamics (PD) in 74 children (0.5-18 years) regardless of CYP3A4 hepatic ontogeny function applied. However, using the Salem ontogeny, mean predicted parent and metabolite area under the concentration-time curve over 12 hours (AUC12h ) and heart rate change from baseline were 2-fold, 1.5-fold, and 1.4-fold higher in young children (0.5-3 years old) compared with Upreti ontogeny, respectively. Despite these differences, choice of appropriate hepatic CYP3A4 ontogeny was challenging due to sparse PK and PD data. Different sensitivity to ivabradine-ketoconazole DDIs was simulated in young children relative to adults depending on the choice of hepatic CYP3A4 ontogeny. Predicted ivabradine and metabolite AUCDDI /AUCcontrol were 2-fold lower in the youngest children (0.5-1 year old) compared with adults (Salem function). In contrast, the Upreti function predicted comparable ivabradine DDIs across all age groups, although predicted metabolite AUCDDI/ AUCcontrol was 1.3-fold higher between the youngest children and adults. In the case of PD, differences in predicted DDIs were minor across age groups and between both functions. Current work highlights the importance of careful consideration of hepatic CYP3A4 ontogeny function and implications on labeling recommendations in the pediatric population.
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10.1002/cpt.2134
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pubmed_177_13187
|
Preview Because the pathoanatomy of shoulder problems in athletes is becoming better understood, a straightforward approach to diagnosis and treatment based on careful history taking and physical examination is feasible. Imaging techniques are greatly improved, but the clinical examination remains the keystone of management. Most shoulder problems are treated nonoperatively, and athletes are usually able to return to sports quickly and safely.
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10.1080/00325481.1995.11945959
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pubmed_337_25051
|
Epidemiological data of methicillin resistant Staphylococcus aureus (MRSA) carriage in Indonesian hospitals are still scarce. These data are required for health management of infectious diseases in order to control hospital MRSA. The carriage rate of MRSA in nose and throat of patients on admission to Dr Soetomo Hospital Surabaya, Indonesia was 8.1% of 643 patients, 5.4% from throat, 3.9% from nose and 1.2% from both sites. Prevalence of MRSA among patients admitted to surgical and non-surgical ward was not different (8.2% and 8.0%, respectively). Although MRSA prevalence in Indonesian hospitals is low compared to many other countries worldwide, appropriate health strategies will be needed to be implemented if this infection is to be controlled.
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pubmed_337_25051
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pubmed_598_16644
|
The increasing importance of integrated care necessitates that education and training experiences prepare clinical neuropsychologists for competent practice in integrated care settings, which includes (a) general competence related to an integrated/interdisciplinary approach and (b) competence specific to the setting. Formal neuropsychology training prepares neuropsychologists with a wide range of knowledge and skills in assessment, intervention, teaching/supervision, and research that are relevant to such settings. However, less attention has been paid to the knowledge and skills that directly address functioning within integrated teams, such as the ability to develop, maintain, and expand collaboration across disciplines, bidirectional clinical-research translation and implementation in integrated team settings, and how such collaboration contributes to clinical and research activities. Foundational knowledge and skills relevant to interdisciplinary systems have been articulated as part of competencies for entry into clinical neuropsychology, but their emphasis in education and training programs is unclear. Recommendations and resources are provided regarding how competencies relevant to integrated care can be provided across the continuum of education and training (i.e., doctoral, internship, postdoctoral, and post-licensure).
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10.1093/arclin/acx141
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pubmed_372_23158
|
OBJECTIVE
Surgical treatment of severe infectious spondylodiskitis remains challenging. Although minimally invasive percutaneous endoscopic drainage and debridement (PEDD) may yield good results in complicated cases, outcomes of patients with extensive structural damage and mechanical instability may be unsatisfactory. To address severe infectious spondylodiskitis, we have developed a surgical technique called percutaneous endoscopic interbody debridement and fusion (PEIDF), which comprises endoscopic debridement, bonegraft interbody fusion, and percutaneous posterior instrumentation.
METHODS
Outcomes of PEIDF in 12 patients and PEDD in 15 patients with infectious spondylodiskitis from April 2014 to July 2018 were reviewed retrospectively. Outcome were compared between 2 kinds of surgical procedures.
RESULTS
Patients in PEIDF group had significantly lower rate of revision surgery (8.3% vs. 58.3%), better kyphosis angle (-5.73° ± 8.74 vs. 1.07° ± 2.70 in postoperative; 7.09° ± 7.23 vs. 0.79° ± 4.08 in kyphosis correction at 1 year), and higher fusion rate (83.3% vs. 46.7%) than those who received PEDD.
CONCLUSION
PEIDF is an effective approach for treating infectious spondylodiskitis, especially in patients with spinal instability and multiple medical comorbidities.
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10.14245/ns.2142640.320
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pubmed_315_13241
|
Recent findings have revealed very slow (<0.5 Hz) oscillatory phenomena in the structures of the brain visual system. It has been proposed that very slow brain potentials in an extremely slow domain, less than 0.1 Hz, recorded from the lateral geniculate complex and primary visual cortex are associated with periodic influences originating from the locus coeruleus and dorsal raphe nucleus. The present study was performed to test the hypothesis that extremely slow brain potential oscillatory patterns in the locus coeruleus and dorsal raphe nucleus during several types of visual stimulation--light exposure, darkness, and photostimulation--are similar to those in the primary visual cortex and lateral geniculate complex under the same conditions of illumination. The results support this hypothesis. Specifically, spectral patterns of multisecond oscillations in the range of 0.02-0.04 Hz and fluctuations in the domain of minutes (below 0.002 Hz) were present in both the locus coeruleus and dorsal raphe nucleus and were similar to those found in the primary visual cortex and lateral geniculate complex. Additionally, we detected significant increases in the power spectra of multisecond oscillations in both nuclei in response to photostimulation (P<0.05). Our tentative conclusion is that extremely slow potentials in the locus coeruleus and dorsal raphe nucleus contribute to the regulation of extremely slow activity in the brain visual system.
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10.1016/j.neulet.2004.03.048
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pubmed_984_8741
|
A new pyrene-dihydrophenazine dyad was prepared. Oxidation of the neutral species produced a bis(radical cation) species, which was characterized by the absorptions of their component radical cations in the visible region. A thermally accessible triplet state was observed in the ESR measurement in frozen n-PrCN. The energy gap between the singlet and triplet states was determined to be 2J/k(B) = -36 +/- 3 K.
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10.1021/ol9009927
|
pubmed_330_21174
|
OBJECTIVE
To evaluate the ability of magnetic resonance imaging (MRI) quantitation of disc prolapse and dural sac to identify those who would benefit from discectomy.
METHODS
Thirty consecutive patients with disc herniation and leg pain who had MRI of lumbar spine and subsequently underwent discectomy were prospectively enrolled and compared with 30 controls. The anteroposterior (AP) diameter and the cross-sectional area of disc prolapse and of dural sac were measured. The ratios of AP diameters and cross-sectional areas were calculated. The measurements were correlated with the relief of symptoms based on a visual analogue scale assessment preoperatively and 1 week postoperatively.
RESULTS
All patients preoperatively had a pain score of seven or higher (mean +/- SD = 7.9 +/- 0.3) and postoperatively a score of < or = 2(mean +/- SD = 1.1 +/- 0.2). The AP diameter of disc prolapse and the ratio of AP diameters demonstrated the highest sensitivity and specificity: an AP diameter of 3.3 mm was 99% sensitive and specific and a ratio of the AP diameters of 0.37 was 100% sensitive and 99% specific.
CONCLUSION
Quantitative measurements of MRI can improve significantly the ability to identify the patients who would benefit from discectomy.
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10.1111/j.1742-1241.2008.01862.x
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pubmed_447_2868
|
Materials to enhance cell adhesion were synthesized by surface integration of peptide, Arg-Gly-Asp-Ser(RGDS), which is an active-site sequence of cell-adhesive proteins. Polystyrene film was glow-discharged and graft-copolymerized with acrylic acid. Then the peptide was immobilized to the poly(acrylic acid) grafts by using water-soluble carbodiimide. The cell-adhesive activity of the RGDS-immobilized film increased with increasing amount of immobilized peptide, and approached the activity of fibronectin(FN)-immobilized film. The RGDS-immobilized film was more stable against heat treatment and pH variation than the FN-immobilized film. In addition, the RGDS-immobilized film enhanced cell growth more strongly than the FN-immobilized film.
|
10.1002/jbm.820251102
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pubmed_27_20342
|
1. This study investigates the signal transduction mechanisms leading to the enhanced formation of nitric oxide (NO) due to the induction of NO synthase (iNOS) in murine J774.2 macrophages in culture activated with lipoteichoic acid (LTA), a cell wall component of the gram-positive bacterium Staphylococcus aureus. 2. LTA (10 microgram ml-1) caused within 24 h an enhanced accumulation of nitrite (an indicator of NO biosynthesis) in the supernatant of J774.2 macrophages which was prevented by the non-selective NOS inhibitor NG-monomethyl-L-arginine (L-NMMA; IC50: 35 microM) or by the iNOS-selective NOS inhibitor, aminoethyl-isothiourea (AE-ITU; IC50: 6 microM). The inhibition of nitrite formation afforded by these agents was prevented by excess L-arginine (3-30 mM), but not by D-arginine (3-30 mM). Furthermore, the degree of iNOS inhibition was similar when these NOS inhibitors were added to the macrophages 10 h after LTA. 3. Pretreatment of J774.2 macrophages with cyclohexamide or dexamethasone prevented the enhanced formation of nitrite caused by LTA. This inhibition did not occur when dexamethasone or cyclohexamide were added to the cells 10 h after LTA. The increase in nitrite formation stimulated by LTA (10 micrograms ml-1) was not affected by polymyxin B (0.05-0.5 microgram ml-1), an agent which binds and inactivates endotoxin. 4. A specific inhibitor of phosphatidylcholine-phospholipase C (PC-PLC), D609, prevented the increase in nitrite formation (IC50 = 20 micrograms ml-1) caused by LTA. The inhibition afforded by D609 was significantly smaller when this agent was added to the cells 10 h after LTA. 5. The structurally distinct tyrosine kinase inhibitors, erbstatin, genistein, and tyrphostin AG126 prevented the formation of nitrite caused by LTA. The inhibition afforded by these compounds was significantly attenuated when they were added to the cells 10 h after LTA. In contrast, daidzein or tyrphostin A-1, which are inactive analogues of genistein and tyrphostin (up to a concentration of 10 microM) did not affect the nitrite formation caused by LTA. 6. Inhibitors of the activation of the nuclear transcription factor NF-kappa B such as pyrrolidine dithiocarbamate (PDTC; an antioxidant and a metal chelator), butylated hydroxyanisole (BHA; an antioxidant), L-1-tosylamido-2-phenylethyl chloromethyl ketone (TPCK), calpain inhibitor I (both I kappa B-protease inhibitors), or rotenone (an antioxidant which inhibits electron transport) prevented the nitrite formation stimulated by LTA. The inhibition afforded by these agents was significantly smaller when they were added to the macrophages 10 h after LTA. 7. Incubation of J774.2 cells with LTA over 24 h resulted in the expression of iNOS protein (130 kDa) as identified by Western blot analysis. The expression of iNOS protein by LTA was significantly attenuated by cyclohexamide, D609, tyrphostin AG126, PDTC or by TPCK. 8. Thus, the signal transduction leading to the expression of iNOS protein and activity caused by LTA in murine J774.2 macrophages involves (i) the activation of PC-PLC, (ii) phosphorylation of tyrosine kinase, and (iii) the activation of the transcription factor NF-kappa B.
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10.1111/j.1476-5381.1996.tb16711.x
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pubmed_447_18124
|
At the detection threshold, a line orientation is identified by the accuracy of 15-20 deg. Deviations from this rule are observed for short lines presented on a dim background. We checked up for one possible source of deviation: the substitution for foveal cone vision by peripheral rod vision. Long wavelength (red) light was used for the test line. In a control experiment such light did not stimulate rods. The test line was 4 min of arc long. It was presented for 20 ms on a white background of 1 or 1000 trolands and was viewed foveally. In a 2-alternative forced-choice experiment the psychometric functions for detection and orientation identification (vertical v. horizontal) were compared. In another experiment, the line was presented randomly in one of 18 orientations in the range 0-180 deg and the subject was asked to determine the orientation. In both experiments orientation perception was impaired at the dim background in comparison with the results at the bright background. This suggests that light-adaptational changes of the mechanisms responsible for orientation perception exist within the photopic vision.
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pubmed_447_18124
|
pubmed_248_15065
|
PURPOSE
To review the current limits on the efficacy of radiotherapy (RT) due to technical factors and to assess the potential for major improvements in technology.
METHODS AND MATERIALS
The method of this review was to assess the efficacy of current RT in general terms; strategies for improving RT; historical record of technological advances; rationale for further reductions of treatment volume; and importance of defining and excluding nontarget tissues from the target volume. The basis for the interest in proton beam RT is developed, and the relative dose distributions of intensity-modulated radiotherapy (IMRT) and intensity-modulated proton RT (IMPT) are discussed. The discovery of the proton and the first proposal that protons be used in RT is described. This is followed by a brief mention of the clinical outcome studies of proton RT. Likely technical advances to be integrated into advanced proton RT are considered, specifically, four-dimensional treatment planning and delivery. Finally, the increment in cost of some of these developments is presented.
RESULTS
For definitive RT, dose limits are set by the tolerance of normal tissues/structures adjacent or near to the target. Using imaging fusion of CT, MRI, positron emission tomography, magnetic resonance spectroscopic imaging, and other studies will result in improved definition of the target margins. Proton beams are likely to replace photon beams because of their physical characteristics. Namely, for each beam path, the dose deep to the target is zero, across the target it is uniform, and proximal to the target it is less. Proton therapy can use as many beams, beam angles, noncoplanar, and dynamic, as well as static, intensity modulation, as can photon plans. The ability for much greater accuracy in defining the target position in space and then maintaining the target in a constant position in the radiation beam despite target movement between and during dose fractions will be possible. The cost of proton RT will be modestly higher than comparable high technology photon therapy.
CONCLUSION
The technology of RT is clearly experiencing intense and rapid technical developments as pertains to treatment planning and dose delivery. It is predicted that radical dose RT will move to proton beam technology and that the treatment will be four dimensional (the fourth dimension is time). The impact will be higher tumor control probability and reduced frequency and severity of treatment-related morbidity.
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10.1078/0939-3889-00281
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pubmed_160_1985
|
Periconceptional undernutrition and twin conception alter intrauterine growth and metabolism and are associated with later adverse metabolic outcomes. The contribution of postnatal growth to these outcomes is less well defined. We investigated whether maternal periconceptional undernutrition or twin conception altered postnatal growth regulation in ways that could lead to metabolic disease. Single and twin offspring of ewes undernourished (UN) from 61 d before until 30 d after mating, fed to achieve and maintain 10-15% weight loss (UN), were compared with offspring of maintenance-fed controls (N). At 2 h and 1, 6, and 12 wk after birth, lambs were weighed and plasma hormone and metabolite concentrations analyzed. Milk intake, measured by deuterium oxide dilution, was inversely related to birth weight only in N singles, although twins had the greatest postnatal growth velocity. Positive associations were seen between milk intake, growth velocity, and leptin concentrations in N, but not UN, offspring. We conclude that periconceptional undernutrition alters the relationships between regulators of postnatal growth, including nutrient intake and key hormonal axes, in both singles and twins without affecting size at birth or postnatal growth velocity. Dissociation of growth from its key regulators is one possible mechanism underlying adverse metabolic outcomes after periconceptional undernutrition.
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10.1203/PDR.0b013e3182242deb
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pubmed_880_21097
|
In the title compound, [Cu(C(14)H(13)N(2)O(2))(NCS)(C(3)H(7)NO)], the Cu(2+) ion is coordinated by an N,N',O-tridentate 2-meth-oxy-6-(2-pyridylmethyl-imino-meth-yl)phenolate ligand, an N-bonded thio-cyanate ion and an O-bonded dimethyl-formamide (DMF) mol-ecule, resulting in a distorted CuN(3)O(2) square-based pyramidal geometry for the metal ion, with the DMF O atom in the apical site. The dihedral angle between the aromatic rings in the ligand is 8.70 (16)°. The S atom is disordered over two positions in a 0.901 (6):0.099 (6) ratio. In the crystal, mol-ecules inter-act by way of π-π stacking inter-actions [centroid-centroid separation = 3.720 (2) Å].
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10.1107/S1600536810014212
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pubmed_931_20355
|
Surgical hand antisepsis is routinely carried out prior to undertaking invasive procedures in an attempt to reduce surgical site infection. There are a number of components within hand antisepsis which include the choice of antiseptic agent, the method of application and the duration of the process. This article presents the findings of a postal survey of 1,471 (out of 8,000) perioperative practitioners identifying their surgical hand antisepsis practices. While a traditional scrub using chlorhexidine gluconate remains the preferred method of antisepsis, 20% of practitioners use alcohol rubs for repeated cases. Compliance with recommended guidelines is patchy (for example, only 3% of practitioners scrub for the recommended time of two minutes) and guidelines need to address more issues.
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10.1177/175045890701700103
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pubmed_126_13385
|
OBJECTIVE
To study the relationship between breast-feeding cessation and the onset of postpartum depression.
METHOD
The association between breast-feeding and depression was retrospectively examined in an obstetrical outpatient sample of 51 postpartum women who were suffering from major depression and who had stopped breast-feeding. Self-report questionnaire data were obtained from the subjects; the severity of the illness and the clinical course of each subject were evaluated.
RESULTS
The majority (39 out of 51; 83%) of the women reported that their depression began the cessation of breast-feeding, while only 8 patients (17%) stated that their depression was subsequent to breast-feeding cessation.
CONCLUSIONS
In an outpatient sample of depressed postpartum women, the onset of depression preceded the cessation of breast-feeding. The severity of the illness did not appear to influence breast-feeding persistence significantly.
|
10.1177/070674379704201007
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pubmed_868_24067
|
In the implant procedure there are 3 factors: a) The height and width of the bone. b) The implant length and diameter. c) The implant system drills and technique. As factors (a) and (b) are constants, the only variable factor is the drilling technique(c). Since the quality of the bone varies (type D1-4), the clinician would like to have the ability to influence the amount of drilled bone. In addition, the clinician wants absolute accuracy & control in location and direction of the drill--in the minimizing of error and the ability to see it and correct it. These elements can be achieved by a system which includes trephine drills and leading pins. This article suggests a drilling technique developed for the purpose of placing dental implants. Its target is to simplify the process of implants placement while effectively using the available bone.
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pubmed_868_24067
|
pubmed_281_20641
|
Exposure to stress is one of the greatest contributing factors to developing a psychiatric disorder, particularly in susceptible populations. Enhancing resilience to stress could be a powerful intervention to reduce the incidence of psychiatric disease and reveal insight into the pathophysiology of psychiatric disorders. (R,S)-ketamine and its metabolites have recently been shown to exert protective effects when administered before or after a variety of stressors and may be effective, tractable prophylactic compounds against psychiatric disease. Drug dosing, sex, age, and strain in preclinical rodent studies, significantly influence the prophylactic effects of (R,S)-ketamine and related compounds. Due to the broad neurobiological actions of (R,S)-ketamine, a variety of mechanisms have been proposed to contribute to the resilience-enhancing effects of this drug, including altering various transcription factors across the genome, enhancing inhibitory connections from the prefrontal cortex, and increasing synaptic plasticity in the hippocampus. Promisingly, select data have shown that (R,S)-ketamine may be an effective prophylactic against psychiatric disorders, such as postpartum depression (PPD). Overall, this review will highlight a brief history of the prophylactic effects of (R,S)-ketamine, the potential mechanisms underlying its protective actions, and possible future directions for translating prophylactic compounds to the clinic.
|
10.1016/j.neuropharm.2022.109345
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pubmed_452_4169
|
A man in his early 70s visited a previous hospital because of pancytopenia and was diagnosed with acute myeloid leukemia based on a bone marrowexamination. The karyotype was 46,XY, t(9;22)(q34;q11.2)[2/20], and real-time polymerase chain reaction(PCR)revealed minor bcr-abl chimeric mRNA. Finally, the patient was judged as having Philadelphia chromosome- positive acute myeloid leukemia, and remission induction chemotherapy with the JALSG AML 201 protocol was initiated in combination with dasatinib to achieve complete remission. After 3 courses of consolidation chemotherapy, the anticancer drugs were discontinued because of deterioration of his general condition and renal insufficiency. Six months after the initial treatment, he was referred to our department, and no evidence of recurrence was confirmed on bone marrow examination. However, 2 months later, right massive pleural effusion was detected, and he was admitted to the department of pneumology at our hospital. Thoracoscopic pleural biopsy was performed at the time of chest tube insertion, and he was diagnosed with acute myeloid leukemia extramedullary recurrence. Peripheral myeloblasts appeared and increased rapidly, accompanied by further exacerbation of renal function; thus, he received palliative care at the department of hematology and oncology.
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pubmed_452_4169
|
pubmed_743_22297
|
The role of multi-heavy metal tolerant bacteria isolated from the rhizosphere of Eichhornia crassipes in the phytoremediation of Cu and Pb under laboratory conditions was investigated. The heavy metal tolerant rhizosphere bacteria were identified as Bacillus cereus, Paenibacillus alvei, Aeromonas caviae, Paenibacillus taiwanensis, and Achromobacter spanius. Results showed a significant variation in wet weight, Heterotrophic Plate Count (HPC) of the rhizosphere, HPC of water, removal and uptake of Cu and Pb by E. crassipes, either alone or in association with the rhizosphere bacteria. The removal of Cu by E. crassipes in different experimental conditions showed that OTC (Oxytetracycline) untreated E. crassipes with rhizosphere bacteria has maximum removal with 95%, followed by E. crassipes alone with 84%. The OTC treated E. crassipes with rhizosphere bacteria could remove 81% of Cu. The maximum Pb removal efficiency of 93.4% was shown by OTC untreated E. crassipes with rhizosphere bacteria, followed by E. crassipes alone with 86.8%. The OTC treated E. crassipes with rhizosphere bacteria showed the least removal efficiency with 82.32%. The translocation factor (TF) values for Cu and Pb were lower than 1 indicated that the absorption was mainly accomplished in the roots of E. crassipes. The order of accumulation of Cu and Pb in E. crassipes was noted as root > leaf > petiole.
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10.1080/15226514.2021.2007215
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pubmed_106_12417
|
In 1991, routine biotoxin monitoring of bivalve molluscs at aquaculture sites along the eastern shore of Nova Scotia, Canada revealed a group of novel seafood toxins called spirolides, whose origin was the dinoflagellate Alexandrium ostenfeldii. Result from this preliminary study in rodents demonstrates a highly toxic lethal response in rats and mice after intraperitoneal injections of lipophilic extracts. To elucidate the modes of action and toxicologic pathology, brain and internal organs were examined by histology and various biomarkers of neural injury were monitored by immunohistochemistry (IH) and/or transcriptional analysis. The histological and transcriptional data showed that the effects of spirolides are species dependent for mice and rats. Histopathology showed that in the mouse brain, the hippocampus and brain stem appeared to be the major target regions but no histological changes were observed in the rat. Transcriptional analysis in the mouse brain showed no alterations in the biomarkers whereas in the rat brain there were major changes in the markers of neuronal injury. These biomarkers included the early injury markers HSP-72, c-jun and c-fos which are essential for converting stimuli into intracellular changes within neurons. The potential effects of spirolides were also evaluated with respect to different subtypes of the acetylcholine receptors (AChRs) since earlier reports showed these as putative targets. Both the muscarinic and nicotinic AChRs were found to be upregulated. Hence, transcriptional and immunohistochemical analysis does provide insight to the molecular mechanisms of this novel group of shellfish toxins. No histological changes were observed in other tissues.
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10.1016/S0161-813X(03)00014-7
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pubmed_34_11811
|
BACKGROUND AND OBJECTIVES
Dent disease is a hereditary form of progressive renal failure characterized by hypercalciuria and proximal tubular dysfunction. The clinical presentation is often insidious with the majority of patients remaining asymptomatic throughout childhood. Despite the seemingly mild, early course, more than 20% of 32 asymptomatic patients in one study had biopsy evidence of focal glomerulosclerosis. Furthermore, end-stage renal disease often occurs in men in early to middle adulthood.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS
This article describes two male patients who presented with asymptomatic proteinuria and were found to have focal glomerulosclerosis. Despite the absence of nephrocalcinosis on renal ultrasound, the diagnosis of Dent disease was considered because of unexplained proteinuria. Subsequent history revealed renal calculi in each maternal family.
RESULTS
The clinical diagnosis of Dent disease was established by intermittent hypercalciuria and low molecular weight proteinuria and confirmed through mutational analysis.
CONCLUSIONS
It is hypothesized that a diagnosis of Dent disease may be unrecognized in patients with unexplained proteinuria and idiopathic focal glomerulosclerosis.
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10.2215/CJN.00900207
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pubmed_234_15253
|
The control of progenitor cell proliferation in concert with terminal differentiation during embryonic development is poorly understood. The present paper examines this issue in the different cell lineages of the fetal mouse pituitary. Mouse fetuses were pulse-exposed to 3H-thymidine (3H-T) on a single day between embryonic day (E) 10 and E16 (prior to the onset of hormone phenotype expression) and the 3H-T labeling index of each cell type determined 3 or 4 days later (E13-19), when hormone phenotypes were detectable. In the pars tuberalis primordium, TSHbeta appeared from E13. Of these cells 75.5% were labeled when 3H-T had been administered on E10. Label decreased to 40.8% when it had been incorporated on E11 and was negligible (4.2%) when it had been taken up on E12. In the pars distalis, ACTH appeared on E13, TSHbeta, and PRL on E14, LHbeta/FSHbeta on E15 and GH on E16. When examined on E16, all these cell types were labeled for 50-60% if 3H-T had been injected on E12, but this number dropped to about 15% when 3H-T had been given on E13. Only 5-10% of the hormonal cells had taken up label when E14, 15, and 16 were the days of 3H-T administration. The decline in overall labeling index (LI) within both parts of the pituitary was significantly smaller than that in the hormone expressing cells. It is concluded that an outspoken decline in proliferation of the cells destined to become hormone-expressing cell types occurs one to several days before these hormones come to expression. In the pars distalis, this decline occurs at a common time point i.e. between E12 and E13 for each cell type. Pars tuberalis and pars distalis TSHbeta cells show distinct 3H-T labeling profiles, suggesting distinct cell lineage sources for each.
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10.1016/s0303-7207(99)00028-3
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pubmed_634_21502
|
Unusual 1,2-migration reactions of N-heterocyclic carbene (NHC) on transition metals were investigated using density functional theory calculations. Our results reveal that the electronic properties, ring strain of the four-membered ring, and aromaticity of NHC play crucial roles in the thermodynamics of such a 1,2-migration. Further studies show that changing the methylene on the metal center in the reactant with a more electronegative group (NH or O) will lead to the formation of products with nitrogen coordinating to the metal center, whereas other groups (BH, CF2 , and SiH2 ) will make such a 1,2-migration reverse. In addition, the reversed rearrangement of 1,2-boron, silyl migration could be thermodynamically and kinetically favorable.
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10.1002/asia.201900895
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pubmed_605_17640
|
OBJECTIVE
To compare counts of Aggregatibacter actinomycetemcomitans, Prevotella intermedia, Porphyromonas gingivalis and Fusobacterium nucleatum between crack users and non-users.
MATERIALS AND METHODS
A cross-sectional study was conducted involving seventy-four crack cocaine users and eighty-one non-users matched for age, gender and tobacco use. Demographic and clinical variables were analysed. Subgingival bacterial samples were collected from four sites with the greatest probing depths and were analysed using real-time polymerase chain reaction.
RESULTS
No significant difference was found in the prevalence of total counts for each bacterial species analysed between groups. However, crack users had a 1.85 (95% CI: 1.03-3.31), 2.19 (95% CI 1.24-3.88), 2.53 (95% CI 1.27-5.04) and 2.40 (95% CI 1.22-4.75) greater probability of having the higher counts (≥75th percentile) for Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum, respectively.
CONCLUSION
Although some crack users had higher (>75th percentile) bacterial counts for Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia and Fusobacterium nucleatum, total counts did not differ between crack users and non-users, leading to the hypothesis that the higher occurrence of periodontitis on crack users may be related to other non-bacterial factors.
|
10.1111/odi.12609
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pubmed_293_2849
|
BACKGROUND
The World Health Organization (WHO) International Classification of Diseases and Related Health Problems (ICD) is used globally by 194 WHO member nations. It is used for assigning clinical diagnoses, providing the framework for reporting public health data, and to inform the organization and reimbursement of health services. Guided by overarching principles of increasing clinical utility and global applicability, the 11th revision of the ICD proposes major changes that incorporate empirical advances since the previous revision in 1992. To test recommended changes in the Mental, Behavioral, and Neurodevelopmental Disorders chapter, multiple vignette-based case-controlled field studies have been conducted which examine clinicians' ability to accurately and consistently use the new guidelines and assess their overall clinical utility. This manuscript reports on the results from the study of the proposed ICD-11 guidelines for feeding and eating disorders (FEDs).
METHOD
Participants were 2288 mental health professionals registered with WHO's Global Clinical Practice Network. The study was conducted in Chinese, English, French, Japanese, and Spanish. Clinicians were randomly assigned to apply either the ICD-11 or ICD-10 diagnostic guidelines for FEDs to a pair of case vignettes designed to test specific clinical questions. Clinicians selected the diagnosis they thought was correct for each vignette, evaluated the presence of each essential feature of the selected diagnosis, and the clinical utility of the diagnostic guidelines.
RESULTS
The proposed ICD-11 diagnostic guidelines significantly improved accuracy for all FEDs tested relative to ICD-10 and attained higher clinical utility ratings; similar results were obtained across all five languages. The inclusion of binge eating disorder and avoidant-restrictive food intake disorder reduced the use of residual diagnoses. Areas needing further refinement were identified.
CONCLUSIONS
The proposed ICD-11 diagnostic guidelines consistently outperformed ICD-10 in distinguishing cases of eating disorders and showed global applicability and appropriate clinical utility. These results suggest that the proposed ICD-11 guidelines for FEDs will help increase accuracy of public health data, improve clinical diagnosis, and enhance health service organization and provision. This is the first time in the revision of the ICD that data from large-scale, empirical research examining proposed guidelines is completed in time to inform the final diagnostic guidelines.
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10.1186/s12916-019-1327-4
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pubmed_499_20756
|
Carposina sasakii Matsumura (Lepidoptera: Carposinidae) is an important pest of fruit trees in a large area of Asia. The adults mainly depend on olfaction to communicate with the environment, but the olfactory mechanism has not been well known. Odorant degrading enzymes (ODEs) are important olfactory proteins, which inactivate and degrade odorants to free odorant receptors for maintaining olfactory sensitivity. Carboxylesterases (CXEs) are considered to be a major group of moth ODEs. In this study, four candidate CXEs (CsasCXE1 ~ CsasCXE4) were identified by using head transcriptomic data from C. sasakii adult females and males. Sequence alignment showed conserved amino acid residues and their variations in C. sasakii CXEs. Phylogenetic analysis indicated the CXEs with the variations cluster well, and each C. sasakii CXE clusters in a clade with some of the other lepidopteran CXEs, with a high enough bootstrap value. Gene expression analysis revealed that CsasCXE2 and CsasCXE3 have similar tissue and sex expression patterns in C. sasakii adults. The two CXEs have relatively high expression levels in the heads and are expressed more abundantly in the female heads than male heads. CsasCXE1 and CsasCXE4 are expressed at higher levels in the male heads than female heads, but not dominantly expressed in the heads among the different tissues. Whether these CXEs function as ODEs remains to be further researched. This study laid the foundation for exploring functions of C. sasakii CXEs.
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10.1017/S0007485322000244
|
pubmed_206_8209
|
BACKGROUND
Mortality risk in Danish dairy cows has more than doubled since 1990 (from 2% in 1990 to 5% in 2005). Until now, registrations about dead cows in the Danish Cattle Database have not included information about whether the cow died unassisted or was euthanized.
METHODS
We interviewed a random sample of 196 Danish dairy farmers that had reported a dead cow to the Danish Cattle Database in 2002 and 196 dairy farmers that had reported a dead cow in 2006. Our objectives were to evaluate the proportion of euthanized cows, changes in the behaviour of farmers regarding euthanasia of cows over the years and possible reasons for these changes.
RESULTS
It seems that the threshold for euthanasia of cows among farmers has changed. Farmers generally reported a lower threshold for euthanasia compared to 5-10 years ago.
CONCLUSION
The threshold for euthanasia of cows has, according to the dairy farmers, become lower. This might have positive impacts on animal welfare as more seriously ill cows are euthanized in the herds and not put through a period of suffering associated with disease and treatment or transported to a slaughterhouse in poor condition.
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10.1186/1751-0147-50-33
|
pubmed_48_8480
|
Hypoxia is a prominent characteristic of many acute or chronic inflammatory diseases, and exerts significant influence on their progression. Macrophages and neutrophils are major cellular components of innate immunity and contribute not only to O2 deprivation at the site of inflammation, but also alter many of their functions in response to hypoxia to either facilitate or suppress inflammation. Hypoxia stabilizes HIF-αs in macrophages and neutrophils, and these O2-sensitive transcription factors are key regulators of inflammatory responses in myeloid cells. In this review, we will summarize our current understanding of the role of HIF-αs in shaping macrophage and neutrophil functions in the pathogenesis and progression of multiple inflammatory diseases.
|
10.1172/JCI84426
|
pubmed_691_15154
|
Nasopharyngeal swabs were taken from four groups of veal calves at intervals throughout their growth and the aerobic bacteria cultivated from the swabs counted. The calves were kept under three different husbandry systems; naturally ventilated straw-yards, fan-ventilated crates and crates with a controlled climate. The numbers of bacteria isolated varied in a complex manner; however, in one group of calves a significant proportion (P less than 0.01) of the variation in weekly bacterial counts was associated with the changes in vapour pressure and temperature which took place between two and four days previously. In calves kept at a constant temperature of 16 degrees C, the bacterial populations in the nasopharynx were at a minimum between 65 and 75 per cent relative humidity and tended to rise at humidities outside this range. There was a temporal relationship between nasopharyngeal bacteria and lung lesions. In three groups the numbers of bacteria in calves at nine weeks old were positively correlated (P less than 0.05) with lung damage observable at 16 to 18 weeks old.
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pubmed_691_15154
|
pubmed_564_13978
|
Inability to cross the site of occlusion with a guidewire is the most common cause of failed angioplasty. The Glidewire, a kink-resistant, flexible wire with a hydrophilic coating, was applied to 71 (59 total, 12 subtotal) refractory occlusions, resulting in an overall angioplasty success rate of 45%. The Glidewire may improve the success rate for PTCA of total and subtotal occlusions that cannot be crossed with conventional guidewires.
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10.1002/ccd.1810300304
|
pubmed_78_21903
|
The speed of the initial 30 m of an all-out run from a stationary start on a flat track was determined for 12 medium level male sprinters by means of a radar device. The peak speed of 9.46+/-0.19 m s(-1) (mean +/- s.d.) was attained after about 5 s, the highest forward acceleration (a(f)), attained immediately after the start, amounting to 6.42+/-0.61 m s(-2). During acceleration, the runner's body (assumed to coincide with the segment joining the centre of mass and the point of contact foot terrain) must lean forward, as compared to constant speed running, by an angle alpha = arctang/a(f) (g = acceleration of gravity). The complement (90-alpha) is the angle, with respect to the horizontal, by which the terrain should be tilted upwards to bring the runner's body to a position identical to that of constant speed running. Therefore, accelerated running is similar to running at constant speed up an ;equivalent slope' ES = tan(90-alpha). Maximum ES was 0.643+/-0.059. Knowledge of ES allowed us to estimate the energy cost of sprint running (C(sr), J kg(-1) m(-1)) from literature data on the energy cost measured during uphill running at constant speed. Peak Csr was 43.8+/-10.4 J kg(-1) m(-1); its average over the acceleration phase (30 m) was 10.7+/-0.59 J kg(-1) m(-1), as compared with 3.8 for running at constant speed on flat terrain. The corresponding metabolic powers (in W kg(-1)) amounted to 91.9+/-20.5 (peak) and 61.0+/-4.7 (mean).
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10.1242/jeb.01700
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pubmed_1110_9527
|
Ketamine, principally an antagonist of N-methyl-ᴅ-aspartate receptors, induces schizophrenia-like symptoms in adult humans, warranting its use in the investigation of psychosis-related phenotypes in animal models. Genomic studies further implicate N-methyl-ᴅ-aspartate receptor-mediated processes in schizophrenia pathology, together with more broadly-defined synaptic plasticity and associative learning processes. Strong pathophysiological links have been demonstrated between fear learning and psychiatric disorders such as schizophrenia. To further investigate the impact of ketamine on associative fear learning, we studied the effects of pre- and post-training ketamine on the consolidation and extinction of contextual fear memory in rats. Administration of 25 mg/kg ketamine prior to fear conditioning did not affect consolidation when potentially confounding effects of state dependency were controlled for. Pre-training ketamine (25 mg/kg) impaired the extinction of the conditioned fear response, which was mirrored with the use of a lower dose (8 mg/kg). Post-training ketamine (25 mg/kg) had no effect on the consolidation or extinction of conditioned fear. These observations implicate processes relating to the extinction of contextual fear memory in the manifestation of ketamine-induced phenotypes, and are consistent with existing hypotheses surrounding abnormal associative learning in schizophrenia.
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10.1177/0269881117748903
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pubmed_101_4788
|
CONTEXT
Women's concerns about contraceptive-induced menstrual changes can lead to method discontinuation and nonuse, contributing to unmet need for contraception. Research on women's perceptions of amenorrhea related to longer acting methods and in low-income countries is limited.
METHODS
Data were from nationally representative household surveys and focus group discussions with women of reproductive age conducted in Burkina Faso and Uganda in 2016-2017. Bivariate cross-tabulations and multivariate logistic regression analyses were used to examine sociodemographic and reproductive characteristics associated with women's attitudes about contraceptive-induced amenorrhea (n=2,673 for Burkina Faso and 2,281 for Uganda); menstrual health determinants were also examined for Burkina Faso. Qualitative data from focus group discussions were analyzed to understand reasons behind women's attitudes and how they influence contraceptive decision making.
RESULTS
Sixty-five percent of women in Burkina Faso and 40% in Uganda reported they would choose a method that caused amenorrhea during use. In Burkina Faso, the predicted probability of accepting amenorrhea was higher for women aged 15-19 (compared with older women), living in rural areas, married and cohabiting (compared with never married), currently using a contraceptive method (compared with never users) and from Mossi households (compared with Gourmantché); menstrual health practices were not associated with amenorrhea acceptability. In Uganda, the least wealthy women had the highest predicted probability of accepting amenorrhea (51%). Qualitative analysis revealed a variety of reasons for women's attitudes about amenorrhea and differences by country, but the relationship between these attitudes and contraceptive decision making was similar across countries.
CONCLUSIONS
Addressing misconceptions about contraception and menstruation may result in more informed method decision making.
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10.1363/46e1520
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pubmed_89_6453
|
OBJECTIVE
People with HIV (PWH) co-infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are at higher odds of severe diseases. Whereas the immunogenicity of mRNA vaccine and adenovirus-vectored vaccine was similar between PWH in stable condition and healthy adults, the effects of inactivated vaccines are not known.
DESIGN
Prospective longitudinal observational study in real-world setting.
METHODS
Adult PWH in care and planning to receive either inactivated (day 0 and day 28) or mRNA-based (day 0 and day 21) vaccine against SARS-CoV-2 were recruited, with blood samples collected over 6 months for surrogate virus neutralization test (sVNT). Demographic and clinical data including age, sex, CD4 + cell count, and suppressed viral load (SVL) status were transcribed for analyses, by simple and multivariable linear regression models, and multivariable linear generalized estimating equations (GEE).
RESULTS
A total of 611 HIV patients, 91% male patients, were recruited, of whom 423 and 184 have received mRNA-based and inactivated vaccine, respectively. The seroconversion rate was 99% for mRNA-based vs, 86% for inactivated vaccine [odds ratio (OR) = 21.56, P = 0.004]. At 6 months, mRNA-based vaccine continued to give a higher response (94 vs. 57%, P < 0.001). The temporal pattern varied between the two vaccines. By GEE, mRNA-based vaccine ( B = 40.59, P < 0.001) and latest SVL status ( B = 10.76, P = 0.01) were positively associated with sVNT level, but not latest CD4 + cell count.
CONCLUSION
In HIV patients, inactivated vaccine gave a lower peak and shorter duration of sVNT responses compared with mRNA vaccine. The results suggested that different strategies may be needed in boosting the immunity in anticipation of the emergence of variants in the community.
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10.1097/QAD.0000000000003237
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pubmed_192_5245
|
A chemoenzymatic synthesis of the title compound has been developed using an efficient and highly enantioselective lipase-catalyzed acylation in a hydrophobic ionic liquid, [bmim][PF6], followed by a diastereoselective asymmetric dihydroxylation as the key steps for incorporating the stereogenic centers. The further conversion to the appropriate intermediates and subsequent acylation with lauric acid furnished the target compound.
|
10.3762/bjoc.15.42
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pubmed_259_22518
|
Relative hydrophobicity and lipophilicity of 63 compounds with known permeability through the blood-brain barrier (BBB) was examined by partitioning in aqueous dextran-poly(ethylene glycol) two-phase system and octanol-buffer system, and by gradient RP-HPLC at pH 7.4. Combination of the relative hydrophobicity estimates, N(CH(2)) obtained by aqueous two-phase partitioning and the lipophilicity (logD(exp) or logD(HPLC)) values obtained by the shake-flask technique or HPLC technique allows one to differentiate between compounds capable of crossing the BBB and those that cannot. A simple model for predicting blood-brain distribution is proposed.
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10.1016/s0223-5234(03)00044-8
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pubmed_1073_15023
|
Anaerobic ammonium oxidation (anammox) couples the oxidation of ammonium with the reduction of nitrite, producing N2. The presence and activity of anammox bacteria in groundwater were investigated at multiple locations in an aquifer variably affected by a large, wastewater-derived contaminant plume. Anammox bacteria were detected at all locations tested using 16S rRNA gene sequencing and quantification of hydrazine oxidoreductase (hzo) gene transcripts. Anammox and denitrification activities were quantified by in situ (15)NO2(-) tracer tests along anoxic flow paths in areas of varying ammonium, nitrate, and organic carbon abundances. Rates of denitrification and anammox were determined by quantifying changes in (28)N2, (29)N2, (30)N2, (15)NO3(-), (15)NO2(-), and (15)NH4(+) with groundwater travel time. Anammox was present and active in all areas tested, including where ammonium and dissolved organic carbon concentrations were low, but decreased in proportion to denitrification when acetate was added to increase available electron supply. Anammox contributed 39-90% of potential N2 production in this aquifer, with rates on the order of 10 nmol N2-N L(-1) day(-1). Although rates of both anammox and denitrification during the tracer tests were low, they were sufficient to reduce inorganic nitrogen concentrations substantially during the overall groundwater residence times in the aquifer. These results demonstrate that anammox activity in groundwater can rival that of denitrification and may need to be considered when assessing nitrogen mass transport and permanent loss of fixed nitrogen in aquifers.
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10.1021/acs.est.5b02488
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pubmed_942_6310
|
Zeatin metabolites were isolated from seedcoats and pod tissues of Phaseolus vulgaris and P. lunatus. The differences observed previously between P. vulgaris and P. lunatus embryos, i.e. the formation of O-ribosyl derivatives in the former and O-glucosyl derivatives in the latter, could also be detected in seedcoats, although the levels of these metabolites were much lower and there was a concomitant increase of breakdown products (adenine, adenosine and AMP). Inner pod wall tissues of both genotypes metabolized zeatin at a slow rate and the major metabolite was the mononucleotide of zeatin. The array of metabolites recovered was not influenced by the extraction method (cold ethanol or modified Bieleski solution).
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10.1104/pp.79.1.321
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pubmed_380_1837
|
We evaluated the use of tele-education to provide an induction programme for accident and emergency senior house officers (SHOs) in three remote locations, and compared their performance with that of SHOs receiving the same induction programme in the conventional manner. Both groups of doctors performed similarly in a pre-course multiple-choice question (MCQ) paper, and showed comparable improvement following the induction programme lectures. Sound quality and levels of interactivity were identified as areas for improvement in the tele-education programme. Tele-education might allow doctors based in peripheral units similar access to high-quality teaching to that enjoyed by those in larger hospitals. Further experience and evaluation are required to optimize this method of education delivery.
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10.1258/135763303322196268
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pubmed_1082_11429
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D0870 is a novel azole antifungal compound. It was compared with conventional amphotericin B and itraconazole therapy in two murine models of invasive aspergillosis, one a systemic nonimmunocompromised mouse model and the other a temporarily neutropenic mouse respiratory model. D0870 was given orally and achieved measurable concentrations in serum approximately proportional to the daily dose with accumulation over time if it was given twice daily. Amphotericin B at 3.3 mg/kg of body weight was given intraperitoneally for four to six doses, and itraconazole was given orally in a cyclodextrin suspension at 5 to 50 mg/kg daily or twice daily (BID). The duration of therapy varied from 7 to 14 days. In the nonimmunocompromised mouse model, D0870 at 25 mg/kg BID was slightly inferior to amphotericin B and itraconazole with regard to mortality, with a median survival of 20 days for the three groups (P = 0.03 compared with amphotericin B). However, D0870 at 25 mg/kg BID was inferior to amphotericin B (but not itraconazole) with respect to renal culture (P = 0.01) and brain culture (P = 0.0001) results. Only amphotericin B was statistically superior to controls with regard to mortality. In the neutropenic mouse respiratory model, D0870 at 50 mg/kg/day was superior to amphotericin B, itraconazole, and controls with regard to mortality. D0870 at both 25 and 50 mg/kg/day was statistically superior to controls with regard to lung culture results (P = 0.004 to 0.04). A second experiment with a higher inoculum showed that no drug regimen was effective in that model. In all models low doses and concentrations of D0870 in serum were ineffective. D0870 has some efficacy for the treatment of invasive aspergillosis when it is given at modest doses.
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10.1128/AAC.39.8.1809
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pubmed_684_1846
|
We report on clinicopathological and whole body MRI analyses of the index patient of a large nonconsanguineous German-Ukraine family with homozygous and heterozygous AGL gene mutations at position p.W1327X (c.3980G > A). There are only limited reports on this phenotype with a homozygous genotype. The index patient, a 49-year-old woman presented with hepatomegaly, cardiomyopathy and moderate progressive proximal limb myopathy. Skeletal muscle showed severe vacuolar myopathy with storage of PAS-positive non-membrane-limited glycogen. An increase in glycogen content and completely decrease of debranching enzyme activity was measured in erythrocytes. Mutational analysis of the AGL gene showed a homozygous p.W1327X mutation. In the family, two brothers had been affected by severe infantile onset hepatomegaly and died within their first years of life by fatal liver cirrhosis. Furthermore, another sister severely affected by hepatomegaly, cardiomyopathy and proximal skeletal myopathy died at age 33. Three younger heterozygous sisters and a brother noticed exercise-induced myalgia and weakness since their teens. In sum, a homozygous p.W1327X mutation leads to a severe generalized glycogenosis types 3a and 3b within the same family. Even heterozygous p.W1327X mutation carriers may present with mild non-progressive neuromuscular symptoms, such as exercise-induced myalgia and fatigue.
|
10.1002/ajmg.a.32529
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pubmed_332_19769
|
OBJECTIVE
Cushing's disease (CD) is a rare endocrine disorder characterized by excess secretion of ACTH due to a pituitary adenoma. Current treatment options are limited and may pose additional risks. A literature review was conducted to assess the holistic burden of CD.
DESIGN
Studies published in English were evaluated to address questions regarding the epidemiology of CD, time to diagnosis, health-related quality of life (HRQoL), treatment outcomes, mortality, prevalence of comorbidities at diagnosis, and reversibility of comorbidities following the treatment.
METHODS
a two-stage literature search was performed in Medline, EMBASE, and Science Citation Index, using keywords related to the epidemiology, treatment, and outcomes of CD: i) articles published from 2000 to 2012 were identified and ii) an additional hand search (all years) was conducted on the basis of bibliography of identified articles.
RESULTS
At the time of diagnosis, 58-85% of patients have hypertension, 32-41% are obese, 20-47% have diabetes mellitus, 50-81% have major depression, 31-50% have osteoporosis, and 38-71% have dyslipidemia. Remission rates following transsphenoidal surgery (TSS) are high when performed by expert pituitary surgeons (rates of 65-90%), but the potential for relapse remains (rates of 5-36%). Although some complications can be partially reversed, time to reversal can take years. The HRQoL of patients with CD also remains severely compromised after remission.
CONCLUSIONS
These findings highlight the significant burden associated with CD. As current treatment options may not fully reverse the burden of chronic hypercortisolism, there is a need for both improved diagnostic tools to reduce the time to diagnosis and effective therapy, particularly a targeted medical therapy.
|
10.1530/EJE-11-1095
|
pubmed_444_13523
|
BACKGROUND
Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency and has a broad spectrum of clinical manifestations. Among non-infectious complications, an increased incidence of malignancies may have a special relevance for survival, but little is known about treatment efficacy on malignant complications.
METHODS
This was a monocenter retrospective study on CVID patients, designed to provide preliminary data for the investigation of the possible link between therapeutic delay and tumor incidence.
RESULTS
A total of 67 CVID subjects were included. The median diagnostic delay was 7.5 years (range: 0-63 years), and the median therapeutic delay was 8.5 years (range: 0-67 years). Malignancies were diagnosed in 18 (27%) patients. Eight out of 18 (44%) patients with a malignancy had lymphoma. Patients who developed a malignancy showed a longer therapeutic delay in comparison to patients with no malignancy, although no statistical significance was achieved (11 years vs 8 years, respectively, p = 0.424). We observed a lower frequency of malignancy in CVID patients with reduced therapeutic delay compared with patients with therapeutic delay ≥ 10 years. With a therapeutic delay of > 1 year, 74% had no tumor, and 25% had a tumor; with a therapeutic delay of > 10 years, 65% had no tumor and 35% had a malignancy. Among patients who had no malignancy, 64% had a therapeutic delay of < 10 years, and 36% had a therapeutic delay of ≥ 10 years. Among patients with malignancy, 47% of subjects had a therapeutic delay < 10 years, and 53% a therapeutic delay ≥ 10 years.
CONCLUSIONS
The observation of clinical characteristics of our patients with CVID may suggest that an early institution of IgG replacement therapy could be of benefit for the prevention of malignant complications.Name of the registry: Comitato Etico Regionale delle Marche. Trial registration number: 1505. Date of registration: 27/10/2016, Retrospectively registered URL of trial registry record: http://www.ospedaliriuniti.marche.it/portale/archivio13_cerm-ancona_0_446_1.html. The trial was not registered before the first participant was enrolled.
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10.1186/s13223-020-00451-z
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pubmed_148_7531
|
Two critically ill newborn babies with severe infection associated with sclerema were successfully treated with appropriate antibiotics and repeated exchange transfusions.
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10.1136/adc.50.11.901
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pubmed_756_4175
|
The immortal HeLa cells case is an intriguing example of bio-objectification processes with great scientific, social, and symbolic impacts. These cells generate questions about representation, significance, and value of the exceptional, variety, individuality, and property. Of frightening (a lethal cancer) and emarginated (a black, poor woman) origins, with their ability to "contaminate" cultures and to "spread" into spaces for becoming of extraordinary value for human knowledge, well-being, and economy advancements, HeLa cells have represented humanity, and emphasized the importance of individual as a core concept of the personalized medicine. Starting from the process leading from HeLa "cells" to HeLa "bio-objects," we focus on their importance as high quality bio-specimen. We discuss the tension between phenomenological characteristic of fundamental biological research and the variety of material and methodologies in epidemiology and personalized medicine. The emerging methodologies and societal changes reflect present EU policies and lead toward a new paradigm of science.
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10.3325/cmj.2013.54.397
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pubmed_572_2574
|
Klebsiella pneumoniae is responsible for nosocomial infections causing significant morbidity and mortality. Treatment of newly emerging multi-drug resistant strains is hampered due to severely limited antibiotic choices. Passive immunization targeting LPS O-antigens has been proposed as an alternative therapeutic option, given the limited variability of Klebsiella O-antigens. Here we report that the O3 serogroup, previously considered to have uniform O-antigen built of mannan, represents three different subtypes differing in the number of mannose residues within the O-antigen repeating units. Genetic analysis of the genes encoding mannose polymerization revealed differences that underline the observed structural alterations. The O3 variants represent antigenically different types based on the different reactivity pattern of murine monoclonal antibodies raised against a K. pneumoniae O3 strain. Typing of a collection of K. pneumoniae O3 clinical isolates showed that strains expressing the novel O3b antigen, the tri-mannose form, were more prevalent than those having the penta-mannose form, traditionally called O3, while the tetra-mannose variant, termed here O3a, seems to be rare. A monoclonal antibody cross-reacting with all three O3 sub-serogroups was also selected and shown to bind to the surface of various K. pneumoniae strains expressing different O3 subtypes and capsular antigens.
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10.1038/s41598-017-06682-2
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pubmed_596_15625
|
Near infrared spectroscopy technique combined with chemometrics methods was applied to predict crystallinity of Neosinocalamus affinins. Three improved partial least squares (PLS) methods, including interval partial least squares (iPLS), synergy interval partial least squares (siPLS) and backward interval partial least squares (biPLS), were used to find the most informative ranges and build models with better predictive quality based on multiplicative scatter correction spectra. And then the models were compared with PLS model which was developed on the whole wavelength range 350-2 500 nm. The results showed that the models built by the three improved PLS methods had higher predictive ability than that of PLS model, and the optimal model was obtained by siPLS method that separated the whole spectra into 30 intervals and combined three intervals. The siPLS model had correlation coefficient (R) of 0.88 and root mean standard error of prediction (RMSEP) of 0.011 7. Therefore, through selecting the effective wavelength range, siPLS method could accurately and rapidly predict crystallinity in Neosinocalamus affinins.
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pubmed_596_15625
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pubmed_1114_1176
|
Asthma as a chronic inflammatory airway disease is considered to be the most common chronic disease that is involving genetic and environmental factors. Toll like receptors (TLRs) and other inflammatory mediators are important in modulation of inflammation. In this study, we evaluated the role of TLR2 Arg753Gln and TLR4 Asp299Gly polymorphisms in the asthma susceptibility, progress, control levels and lung functions in Iranian patients. On 99 asthmatic patients and 120 normal subjects, TLR2 Arg753Gln and TLR4 Asp299Gly polymorphisms were evaluated by PCR-RFLP method recruiting Msp1 and Nco1 restriction enzymes, respectively. IgE serum levels by ELISA technique were determined and asthma diagnosis, treatment and control levels were considered using standard schemes and criteria. Our results indicated that the genotype and allele frequencies of the TLR2 Arg753Gln and TLR4 Asp299Gly polymorphisms were not significantly different between control subjects and asthmatics and were not related to in asthma features such as IgE levels, asthma history and pulmonary factors. Wherease some previous studies indicated TLRs and their polymorphisms might have some role in asthma incidence and features, our data demonstrated that TLR2 Arg753Gln and TLR4 Asp299Gly gene variants were not risk factors for asthma or its features in Iranian patients. Genetic complexity, ethnicity, influence of other genes or polymorphisms may overcome these polymorphisms in our asthmatics.
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pubmed_1114_1176
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pubmed_804_5631
|
Thymic stromal lymphopoietin (TSLP) is an IL-7-like cytokine, which is secreted by epithelial cells under the stimulation of Toll-like receptor (TLR) ligands. Dendritic cells (DCs) which express the thymic stromal lymphopoietin receptor (TSLPR) can be activated by TSLP. Mature DCs can express the OX40 ligand, which has the ability to combine with OX40 on the surface of T cells to stimulate T cell proliferation. TSLP secreted by corneal epithelial cells can engage in the process of T helper type 2 (Th2) inflammation in Aspergillus fumigatus keratitis, but the mechanism remains unclear. We demonstrated that in A. fumigatus-infected corneas, DCs aggregated, matured, and gradually migrated not only from the basement membrane to the corneal epithelium, but also from the corneal limbus to the central cornea. Mature DCs secreted Th2-attracting chemokines, the thymus and activation-regulated chemokine (TARC), and the macrophage-derived chemokine (MDC), encouraging the secretion of TNF-α and Th2 cytokine Interleukin (IL) -4, IL-5, and IL-13. The above processes were all restricted with subconjunctivally injection of TSLP siRNA, while they were strengthened with the injection of rTSLP. We demonstrated that in A. fumigatus keratitis, TSLP, through combination with TSLPR on the surface of DCs, induced DC aggregation, maturation, and migration, and then the mature DCs secreted Th2-attracting chemokines, promoting the secretion of proinflammatory cytokine TNF-α and Th2 cytokines, which finally induced Th2 inflammation.
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10.1016/j.exer.2018.03.014
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pubmed_152_21086
|
BACKGROUND
Gastro-oesophageal reflux (GOR) is common in newborn infants. A common first line management is the use of feed thickeners.
OBJECTIVES
In newborn infants with GOR, to evaluate the use of feed thickeners in reducing signs and symptoms of GOR, acid episodes on pH monitoring and histological evidence of oesophagitis.
SEARCH STRATEGY
We searched MEDLINE from 1966 to December 2001, the Cochrane Controlled Trials Register, The Cochrane Library, Issue 1, 2002. CINAHL from 1982 to December 2001, and conference and symposia proceedings published in Pediatric Research 1990 to 1994. We also searched conference proceedings for the European Society for Paediatric Gastroenterology and Nutrition (ESPGAN) and the North American Society for Pediatric Gastroenterology and Nutrition (NASPGAN) from 1994 to December 2001. We did not restrict the searches to the English language.
SELECTION CRITERIA
All randomised controlled trials that examine the effects of thickening formulas on treating gastro-oesophageal reflux in neonates. The eligible studies were to compare thickened feeds to no intervention (unthickened feeds).
DATA COLLECTION AND ANALYSIS
Two independent reviewers identified potential studies from the literature search. Quality was independently assessed by two independent reviewers.
MAIN RESULTS
No studies fulfilled the requirements for inclusion in the systematic review.
REVIEWER'S CONCLUSIONS
There is no evidence from randomised controlled trials to support or refute the efficacy of feed thickeners in newborn infants with GOR. Given the absence of evidence, we cannot recommend using thickening agents for management of GOR in newborn infants.
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10.1002/14651858.CD003211
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pubmed_856_2295
|
We report here the complete genome sequence of the Rhizobium rhizogenes (formerly Agrobacterium rhizogenes) strain LBA9402 (NCPPB1855rifR), a pathogenic strain causing hairy root disease. To assemble a complete genome, we obtained short reads from Illumina sequencing and long reads from Oxford Nanopore Technology sequencing. The genome consists of a 3,958,212 bp chromosome, a 2,005,144 bp chromid (secondary chromosome) and a 252,168 bp Ri plasmid (pRi1855), respectively. The primary chromosome was very similar to that of the avirulent biocontrol strain K84, but the chromid showed a 724 kbp deletion accompanied by a large 1.8 Mbp inversion revealing the dynamic nature of these secondary chromosomes. The sequence of the agropine Ri plasmid was compared to other types of Ri and Ti plasmids. Thus, we identified the genes responsible for agropine catabolism, but also a unique segment adjacent to the TL region that has the signature of a new opine catabolic gene cluster including the three genes that encode the three subunits of an opine dehydrogenase. Our sequence analysis also revealed a novel gene at the very right end of the TL-DNA, which is unique for the agropine Ri plasmid. The protein encoded by this gene was most related to the succinamopine synthases of chrysopine and agropine Ti plasmids and thus may be involved in the synthesis of the unknown opine that can be degraded by the adjacent catabolic cluster. The available sequence will facilitate the use of R. rhizogenes and especially LBA9402 in both the laboratory and for biotechnological purposes.
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10.1002/mbo3.1180
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pubmed_295_11083
|
Fibroblast-like synoviocytes (FLSs) have been introduced in recent years as a key player in the pathogenesis of rheumatoid arthritis (RA), but the exact mechanisms of their transformation and intracellular pathways have not yet been determined. This study aimed to investigate the role of fibroblast activation protein-alpha (FAP-α) in the regulation of genes involved in the transformation and pathogenic activity of RA FLSs. Synovial FLSs were isolated from RA patients and non-arthritic individuals (n=10 in both groups) and characterized; using immunocytochemistry and flow cytometry analysis. FLSs were divided into un-treated and Talabostat-treated groups to evaluate the FAP-α effect on the selected genes involved in cell cycle regulation (p21, p53, CCND1), apoptosis (Bcl-2, PUMA), and inflammatory and destructive behavior of FLSs (IL-6, TGF-β1, MMP-2, MMP-9, P2RX7). Gene expression analysis was performed by quantitative real-time polymerase chain reaction (qRT-PCR), and immunoblotting was carried out to evaluate FAP-α protein levels. The basal level of FAP-α protein in RA patients was significantly higher than non-arthritic control individuals. However, no differences were observed between RA and non-arthritic FLSs, at the baseline mRNA levels of all the genes. Talabostat treatment significantly reduced FAP-α protein levels in both RA and non-arthritic FLSs, however, had no effect on mRNA expressions except an upregulated TGF-β1 expression in non-arthritic FLSs. A significantly higher protein level of FAP-α in FLSs of RA patients compared with that of healthy individuals may point to the pathogenic role of this protein in RA FLSs. However, more investigations are necessary to address the mechanisms mediating the FAP-α pathogenic role in RA FLSs.
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10.18502/ijaai.v20i3.6335
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pubmed_200_3469
|
The medicinal mushroom Ganoderma lucidum is well recognized for its effective cancer-preventative and therapeutic properties, while specific components responsible for these anticancer effects are not well studied. Six triterpenoids that are ganolucidic acid E, lucidumol A, ganodermanontriol, 7-oxo-ganoderic acid Z, 15-hydroxy-ganoderic acid S, and ganoderic acid DM were isolated and identified from an extract of the mushroom. All compounds reduced cell growth in three human carcinoma cells (Caco-2, HepG2, and HeLa cells) dose dependently with LC50s from 20.87 to 84.36 μM. Moreover, the six compounds induced apoptosis in HeLa cells with a maximum increase (22%) of sub-G1 accumulations and 43.03% apoptotic cells in terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay (15-hydroxy-ganoderic acid S treatment). Apoptosis was further confirmed by annexin-V staining. Four of the compounds also caused apoptosis in Caco-2 cells with maximum 9.5% increase of sub-G1 accumulations (7-oxo-ganoderic acid Z treatment) and maximum 29.84% apoptotic cells in TUNEL assay (ganoderic acid DM treatment). Contrarily, none of the compounds induced apoptosis in HepG2 cells. The different responses of the three cell lines following these treatments indicated that the bioactive properties of these compounds may vary from cells of different sites of origin and are likely acting under diverse regulatory mechanisms.
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10.1002/ptr.5426
|
pubmed_789_2744
|
Episodic memory events occur within multidimensional contexts; however, the electrophysiological manifestations associated with processing of more than one context have been rarely investigated. The effect of the amount of context on the ERPs was studied using two single and one double source memory tasks and by comparing full and partial context retrieval within a double source task. The single source tasks elicited waveforms with a larger amplitude during successful encoding and retrieval than the double source task. Compared with the waveforms elicited with a full source response, a partial source response elicited waveforms with a smaller amplitude, probably because the retrieval success for one context was combined with the retrieval attempt processes for the missing source. Comparing the tasks revealed that the larger the amount of contextual information processed, the smaller the amplitude of the ERPs, indicating that greater effort or further control processes were required during double source retrieval.
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10.1016/j.bbr.2012.04.012
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pubmed_880_19116
|
OBJECTIVE
To develop an Arabic version of the Chronic Respiratory Disease Questionnaire (CRQ) to be known as ArabiCRQ.
MATERIALS AND METHODS
We conducted a linguistic validation of the CRQ in the Arabic language. The validation process involved 4 phases, including forward and backward translations, pilot testing, and revision to produce a final version of the ArabiCRQ. Five native Arabic-speaking patients with chronic obstructive pulmonary disease completed the ArabiCRQ both in initial and follow-up visits. Wording was modified according to feedback the participants provided.
RESULTS
Two of the patients' scores changed appreciably, despite ensuring their clinical stability.
CONCLUSION
The ArabiCRQ may be a valuable tool to assess the health-related quality of life in patients with chronic respiratory diseases.
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10.1159/000324874
|
pubmed_758_6150
|
Bovine interferon (bIFN) tau, which plays a key role in maternal-fetal recognition of pregnancy, was expressed by an Autographa californica nuclear polyhedrosis virus expression system. cDNA coding bIFNtau was derived from cultured trophoblast cells. The recombinant (r) bIFNtau had high antiviral activity (1 x 10 (8) IU/mg) and the molecular weight of rbIFNtau was estimated to be 23 kDa by Western blotting analysis. We investigated the biological effect of rbIFNtau on prostaglandin (PG) F(2alpha) synthesis in cultured bovine endometrial epithelial cells in the presence or absence of oxytocin (OT, 100 nM). rbIFNtau suppressed basal and OT-induced PGF(2alpha) production in a dose-dependent manner (1-1,000 ng/ml). These results showed that biologically active rbIFNtau was produced in the baculovirus expression system, and that rbIFNtau had the ability to suppress the synthesis of PGF(2alpha) from bovine endometrial epithelial cells.
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10.1262/jrd.49.433
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pubmed_397_7084
|
Ammonium production in the presence of specific inhibitors of sulfate reduction and methanogenesis was investigated in six marine sediments which differed in bulk properties and organic matter input. In all cases, little effect of the inhibitors on ammonium production was observed, although sulfate reduction was suppressed by molybdate. This gives evidence that the processes of fermentation and hydrolysis are of primary importance in ammonium generation at the sites studied. Although sulfate reduction rates may appear to be coupled to ammonium production rates, sulfate reduction does not necessarily contribute directly to generation of ammonium in marine environments.
|
10.1128/aem.53.10.2435-2439.1987
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pubmed_443_4625
|
The test organism was Escherichia coli 1810 which was highly resistant to trimethoprim (TMP). Electron microscopy (EM) of cells grown in the presence of subinhibitory concentrations of 300 micrograms/ml sulphadiazine (SD) and/or 300 micrograms/ml TMP indicated marked structural damage. No effect on the outer membrane (OM) or ultrastructure of E. coli 1810 was observed with 7.68 micrograms/ml TMP and/or 16.9 micrograms/ml SD. Concentrations of antibacterials affecting the ultrastructure of the bacterial cells of resistant and sensitive E. coli as determined by EM, were shown by a permeability probe (Triton X-100) to alter the OM permeability and to partially inhibit growth of E. coli 1810 cultures. It was concluded that, since the action of SD and TMP, singly and in combination, on the cell structure of E. coli 1810 took place only at concentrations approaching the respective MICs, then this was a part of their normal mechanisms of antibacterial action.
|
pubmed_443_4625
|
pubmed_485_4139
|
When rats are subjected to chemical hepatocarcinogenesis according to the protocol of D. Solt and E. Farber ((1976) Nature (London) 263, 701-703), the liver exhibits elevated levels of tyrosine protein kinase activity as early as 3 weeks after the injection of diethylnitrosoamine. A more striking elevation in tyrosine protein kinase activity is noted in rat hepatomas induced by administration of chemical carcinogens, in particular that of 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB). Tyrosine protein kinase solubilized from the particulate fraction of 3'-Me-DAB-induced hepatoma has a molecular weight identical to that of p60v-src, cross-reacts with p60v-src immunologically, phosphorylates the heavy chain of anti-p60v-src IgG, and probably belongs to a family of p60c-src. The tyrosine protein kinase from the particulate fraction of normal rat liver is indistinguishable from the hepatoma kinase in these properties; thus it apparently differs only in the level of activity. Whether the liver and hepatoma kinases differ merely quantitatively or whether they differ even qualitatively, however, remains to be elucidated.
|
10.1016/0003-9861(88)90140-3
|
pubmed_770_5056
|
The influence of single and repeated oral administration of ethylenethiourea (ETU) on hematologic parameters of the peripheral blood and the bone marrow was studied in male and female rats. Effects of single treatment on the erythrocytic system were initially indicated by increase in red blood cell count, hemoglobin concentration and hematocrit of the peripheral blood. The initial polyglobulia was followed by a decrease in the blood hemoglobin concentration and the number of erythroblasts of the bone marrow. Continuous administration of ETU resulted in hyporegenerative anemia. The white blood picture showed leukopenia after single and continuous administration of the substance. This effect resulted from a decline in lymphocyte numbers which occurred both in the peripheral blood and in the bone marrow. The hematologic changes were induced with 50 mg ETU/kg body weight and more using single treatment and 600 ppm (= 70 mg ETU/kg body weight) and more under dietary administration.
|
10.1002/food.19880320316
|
pubmed_347_7613
|
Lactic acid bacteria play a pivotal role in many food fermentations and sometimes represent a health threat due to the ability of some strains to produce biogenic amines that accumulate in foods and cause trouble following ingestion. These strains carry specific enzymatic systems catalyzing the uptake of amino acid precursors (e.g., ornithine and lysine), the decarboxylation inside the cell, and the release of the resulting biogenic amines (e.g., putrescine and cadaverine). This study aimed to identify the system involved in production of cadaverine from lysine, which has not been described to date for lactic acid bacteria. Strain Lactobacillus saerimneri 30a (formerly called Lactobacillus sp. 30a) produces both putrescine and cadaverine. The sequencing of its genome showed that the previously described ornithine decarboxylase gene was not associated with the gene encoding an ornithine/putrescine exchanger as in other bacteria. A new hypothetical decarboxylation system was detected in the proximity of the ornithine decarboxylase gene. It consisted of two genes encoding a putative decarboxylase sharing sequence similarities with ornithine decarboxylases and a putative amino acid transporter resembling the ornithine/putrescine exchangers. The two decarboxylases were produced in Escherichia coli, purified, and characterized in vitro, whereas the transporter was heterologously expressed in Lactococcus lactis and functionally characterized in vivo. The overall data led to the conclusion that the two decarboxylases and the transporter form a three-component decarboxylation system, with the new decarboxylase being a specific lysine decarboxylase and the transporter catalyzing both lysine/cadaverine and ornithine/putrescine exchange. To our knowledge, this is an unprecedented observation of a bacterial three-component decarboxylation system.
|
10.1128/JB.02070-12
|
pubmed_20_10548
|
Understanding how malaria parasites gain entry into human red blood cells is essential for developing strategies to stop blood stage infection. Plasmodium vivax preferentially invades reticulocytes, which are immature red blood cells. The organism has two erythrocyte-binding protein families: namely, the Duffy-binding protein (PvDBP) and the reticulocyte-binding protein (PvRBP) families. Several members of the PvRBP family bind reticulocytes, specifically suggesting a role in mediating host cell selectivity of P. vivax. Here, we present, to our knowledge, the first high-resolution crystal structure of an erythrocyte-binding domain from PvRBP2a, solved at 2.12 Å resolution. The monomeric molecule consists of 10 α-helices and one short β-hairpin, and, although the structural fold is similar to that of PfRh5--the essential invasion ligand in Plasmodium falciparum--its surface properties are distinct and provide a possible mechanism for recognition of alternate receptors. Sequence alignments of the crystallized fragment of PvRBP2a with other PvRBPs highlight the conserved placement of disulfide bonds. PvRBP2a binds mature red blood cells through recognition of an erythrocyte receptor that is neuraminidase- and chymotrypsin-resistant but trypsin-sensitive. By examining the patterns of sequence diversity within field isolates, we have identified and mapped polymorphic residues to the PvRBP2a structure. Using mutagenesis, we have also defined the critical residues required for erythrocyte binding. Characterization of the structural features that govern functional erythrocyte binding for the PvRBP family provides a framework for generating new tools that block P. vivax blood stage infection.
|
10.1073/pnas.1516512113
|
pubmed_93_19083
|
PURPOSE
We compared mortality rates among state prisoners and other state residents to identify prisoners' health care needs.
METHODS
We linked North Carolina prison records with state death records for 1995-2005 to estimate all-cause and cause-specific death rates among black and white male prisoners ages 20-79 years and used standardized mortality ratios (SMRs) to compare these observed deaths with the expected number on the basis of death rates among state residents.
RESULTS
The all-cause SMR of black prisoners was 0.52 (95% confidence interval, 0.48-0.57), with fewer deaths than expected from accidents, homicides, cardiovascular disease, and cancer. The all-cause SMR of white prisoners was 1.12 (95% confidence interval, 1.01-1.25) with fewer deaths than expected for accidents but more deaths than expected from viral hepatitis, liver disease, cancer, chronic lower respiratory disease, and HIV.
CONCLUSIONS
The mortality of black prisoners was lower than that of black state residents for both traumatic and chronic causes of death. The mortality of white prisoners was lower than that of white state residents for accidents but greater for several chronic causes of death. Future studies should investigate the effect of prisoners' preincarceration and in-prison morbidity, the prison environment, and prison health care on prisoners' patterns of mortality.
|
10.1016/j.annepidem.2011.04.007
|
pubmed_765_16339
|
BACKGROUND
For real-time monitoring of hospital patients, high-quality inference of patients' health status using all information available from clinical covariates and lab test results is essential to enable successful medical interventions and improve patient outcomes. Developing a computational framework that can learn from observational large-scale electronic health records (EHRs) and make accurate real-time predictions is a critical step. In this work, we develop and explore a Bayesian nonparametric model based on multi-output Gaussian process (GP) regression for hospital patient monitoring.
METHODS
We propose MedGP, a statistical framework that incorporates 24 clinical covariates and supports a rich reference data set from which relationships between observed covariates may be inferred and exploited for high-quality inference of patient state over time. To do this, we develop a highly structured sparse GP kernel to enable tractable computation over tens of thousands of time points while estimating correlations among clinical covariates, patients, and periodicity in patient observations. MedGP has a number of benefits over current methods, including (i) not requiring an alignment of the time series data, (ii) quantifying confidence regions in the predictions, (iii) exploiting a vast and rich database of patients, and (iv) inferring interpretable relationships among clinical covariates.
RESULTS
We evaluate and compare results from MedGP on the task of online prediction for three patient subgroups from two medical data sets across 8,043 patients. We find MedGP improves online prediction over baseline and state-of-the-art methods for nearly all covariates across different disease subgroups and hospitals.
CONCLUSIONS
The MedGP framework is robust and efficient in estimating the temporal dependencies from sparse and irregularly sampled medical time series data for online prediction. The publicly available code is at https://github.com/bee-hive/MedGP .
|
10.1186/s12911-020-1069-4
|
pubmed_1039_8688
|
It has been proposed that Ca2+ ions mediate the stimulation by insulin of glucose uptake in muscle (Clausen, T., Cell Calcium 1:311-325, 1980). However, absolute measurements of the concentration of cytosolic free Ca2+, [Ca2+]i, during the course of insulin action have not been made. The stimulation of hexose uptake by insulin was studied in an in vitro model system of muscle cells, the L6 cell line. The following evidence suggests that Ca2+ ions are not likely to fulfill the purported role. 1) Insulin in Ca2+-free media induced stimulation of 2-deoxy-D-glucose uptake. 2) Elevation of [Ca2+]i with the ionophore A23187 did not enhance hexose uptake. 3) Insulin action was not diminished when the hormone was added to Ca2+-depleted cells in Ca2+-free media with A23187. 4) Hexose uptake was not affected by a number of agents thought to modify [Ca2+]i including epinephrine, caffeine, 2,4-dinitrophenol, hyperosmolar mannitol, salicylate, vanadate, veratrine, and trypsin. 5) Direct determinations of [Ca2+]i by fluorescence of the novel indicator Quin-2 did not show differences between basal and insulin-stimulated cells; under identical conditions hexose uptake was stimulated by the hormone. 6) Chelation of [Ca2+]i with Quin-2 in Ca2+-free media did not affect the response to insulin. 7) Low concentrations of trypsin (7.5 micrograms/ml) elevated [Ca2+]i but did not increase the rate of hexose uptake.
|
10.1152/ajpendo.1984.247.3.E297
|
pubmed_155_4405
|
Thyrotropin response to thyrotropin-releasing hormone is impaired during endogenous depression and normalized between the depressive periods. Changes in the thyrotropin response to thyrotropin-releasing hormone were shown to be of predictive value and might be useful in the control of continuation therapy with antidepressants in patients with endogenous depression.
|
10.1017/s0033291700016202
|
pubmed_866_9420
|
Background: There are only a few studies that have assessed awareness and knowledge regarding aerobic type of physical activity (PA) guidelines recommendations, while no previous studies have examined muscular type of activity recommendation guidelines. The aim was to assess knowledge and awareness and study the associations with demographic variables and physical activity and fitness. Methods: Participants were 776 young (age 26 ± 7 years) men. Awareness and knowledge of PA recommendation guidelines were assessed by prompted questionnaires together with demographic variables and physical activity. In addition, physical fitness was measured. Results: Forty percent of the participants reported being aware of the physical activity recommendation. Moreover, 7% correctly identified the recommendations for moderate aerobic physical activity and 25% for muscular type of activity. In addition, 4% correctly identified both aerobic and muscular activity recommendations. Being aware of the PA recommendations was associated with being married or partnered, having higher education level and being more physically active during leisure-time (p < 0.05). Individuals with no awareness of the recommendations had lower results in cardiorespiratory and muscular fitness compared to those being aware (p < 0.05). Being married or partnered was positively associated with the knowledge of the muscular activity recommendations (p < 0.05). Moreover, the individuals with correct knowledge of the PA recommendations had higher levels of muscular fitness (p < 0.05). Conclusion: A low number of individuals are aware or know the physical activity recommendations among young adult men. Therefore, more vigorous attempts to promote physical activity recommendations are needed.
|
10.3389/fpubh.2019.00310
|
pubmed_1134_3025
|
Sexual dysfunction is a common complaint in women across different treatment settings and throughout the lifecycle. Defining normality in sexual response is extremely difficult and little data exists to guide the clinician encountering these complaints. The latest edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) provides a useful classification for sexual dysfunction in both women and men. Female sexual dysfunctions defined in DSM-IV-TR are divided into disorders of desire, arousal, orgasm, and pain. This article defines the scope of the problem of female sexual dysfunction, discusses the diagnosis of various disorders of sexual function, and summarizes available psychological and physiologic treatments.
|
pubmed_1134_3025
|
pubmed_206_7561
|
PURPOSE
The clinical success of fixed restorations is linked to the precise reproduction of the prepared teeth by dental impressions. The hypothesis under examination was that neither clinical parameters nor the impression technique influenced the reproduction of the finishing line during impression making.
MATERIALS AND METHODS
For 48 patients who needed a fixed restoration, a 1-stage putty-wash, 2-stage putty-wash, and monophase impression were made after preparation in a randomized order. Clinical parameters (Plaque Index, probing depth, bleeding on probing, Gingival Index, location of the finishing line, bleeding during impression taking, and blood at the impression) were recorded. Master casts were manufactured and optically digitized. Using the data of the 1-stage putty-wash impression as reference, the reproduction of the finishing line was measured 3-dimensionally. Linear models were used for statistical analysis.
RESULTS
The finishing line was reproduced most precisely by the 1-stage putty-wash technique. Variables with significant influence were the impression technique, blood at the impression, and probing depth. The 2-stage putty-wash impressions showed significantly reduced accuracy compared with the 1-stage impressions.
CONCLUSION
Clinical parameters and the impression techniques determine the reproduction of the finishing line. The benefit of 2-stage putty-wash impressions with regard to a more complete rendering of subgingival finishing lines should be questioned in light of these results.
|
pubmed_206_7561
|
pubmed_764_22440
|
In a prospective, randomized, double-blind clinical study, we have studied 100 children, aged 2-12 yr, to compare halothane and sevoflurane in outpatient dental anaesthesia. All patients were unpremedicated and received inhalation induction using nitrous oxide in oxygen supplemented with either halothane (maximum inspired concentration 5%) or sevoflurane (maximum inspired concentration 8%). Time to loss of the eyelash reflex was more rapid using sevoflurane although time to adequate anaesthesia (to allow insertion of a mouth prop) was slower in the sevoflurane group. The incidence of cardiac arrhythmia was higher during halothane (62%) than during sevoflurane anaesthesia (28%) (P < 0.005) and the arrhythmias were more often ventricular in origin. The two agents were comparable in terms of ease of use and quality of anaesthesia, and times to eye opening and satisfying discharge criteria were similar. We conclude that sevoflurane has qualities that have made halothane the most used inhalation agent for children, and that it is superior to halothane in dental outpatients where cardiac arrhythmias are a particular problem.
|
10.1093/bja/79.3.280
|
pubmed_18_14879
|
Pulse pressure is a well established marker of vascular stiffness and is associated with increased mortality in hemodialysis patients. Here we sought to determine if a decrease in pulse pressure during hemodialysis was associated with improved outcomes using data from 438 hemodialysis patients enrolled in the 6-month Crit-Line Intradialytic Monitoring Benefit Study. The relationship between changes in pulse pressure during dialysis (2-week average) and the primary end point of non-access-related hospitalization and death were adjusted for demographics, comorbidities, medications, and laboratory variables. In the analyses that included both pre- and post-dialysis pulse pressure, higher pre-dialysis and lower post-dialysis pulse pressure were associated with a decreased hazard of the primary end point. Further, every 10 mm Hg decrease in pulse pressure during dialysis was associated with a 20% lower hazard of the primary end point. In separate models that included pulse pressure and the change in pulse pressure during dialysis, neither pre- nor post-dialysis pulse pressure were associated with the primary end point, but each 10 mm Hg decrease in pulse pressure during dialysis was associated with about a 20% lower hazard of the primary end point. Our study found that in prevalent dialysis subjects, a decrease in pulse pressure during dialysis was associated with improved outcomes. Further study is needed to identify how to control pulse pressure to improve outcomes.
|
10.1038/ki.2009.340
|
pubmed_348_11948
|
BACKGROUND
Hawthorn extract (Crataegeus sp.) a botanical complementary and alternative medicine is often used to treat heart failure. The mechanism(s) by which hawthorn extract may treat heart failure is unknown but may include, theoretically, immunological effects. Therefore, the purpose of this study is to determine the effect of hawthorn extract on the immunomodulatory response in a pressure overload model of heart failure.
MATERIAL/METHODS
A total of 62 male Sprague-Dawley rats were randomized to either aortic constriction + vehicle (AC; n=15), aortic constriction + hawthorn 1.3 mg/kg (HL, n=17), aortic constriction + hawthorn 13 mg/kg (HM, n=15), or aortic constriction + hawthorn 130 mg/kg (HH, n=15). Six months after surgical procedure animals were sacrificed and plasma samples obtained for the measurement of the following immunomodulatory markers: interleukin (IL) IL-1ss, IL-2, IL-6, IL-10; and leptin.
RESULTS
The mortality rate following 6 months of aortic constriction was 40% in the AC group compared to 41%, 60%, and 53% for the HL, HM, and HH groups respectively (P>0.05 compared to AC). Aortic constriction produced a similar increase in the left ventricle/body weight ratio for all groups. Hawthorn extract had no effect on the immunomodulatory markers measured in this study, although there appeared to be a trend suggesting suppression of IL-2 plasma concentrations.
CONCLUSIONS
In this animal model of heart failure, hawthorn extract failed to significantly affect the immunomodulatory response characterized after 6 months of pressure overload at a time when approximately 50% mortality was exhibited. Mechanisms other than immunological may better define hawthorn's effect in treating heart failure.
|
pubmed_348_11948
|
pubmed_1070_13137
|
A 51-year-old man with a diagnosis of myelodysplasia and non-Hodgkin's lymphoma underwent an unmatched allogenic bone marrow transplantation and was treated posttransplant with chronic immunosuppressive medication. Eight months following transplantation, he presented with progressive dysarthria, cognitive and visual decline. Evaluation included brain magnetic resonance (MR) imaging demonstrating multifocal areas of increased T2 and FLAIR (fluid attenuated inversion recovery) signals involving the left frontal, parietal, and occipital lobes. The MR lesions demonstrated diffuse increased signal on DWI (diffusion-weighted images) and normal to low signal on ADC (apparent diffusion coefficients). Contrast-enhanced T1 images were unremarkable. Lumbar puncture revealed a mild elevation in cerebrospinal fluid (CSF) protein. CSF PCR assay for viral DNA fragments were negative on two occasions. Serum serology for HIV was negative as well. A brain biopsy was subsequently performed. The clinical and neuroimaging differential diagnoses as well as neuropathologic correlation are presented.
|
10.1111/j.1552-6569.2007.00106.x
|
pubmed_10_7160
|
Aneurysmal Bone Cyst (ABC) is a benign expansile cystic blood filled reactive lesion of the bone, most common in the first 2 decades of life. Though it can involve any bone in the body but tibia, humerus, femur and posterior elements of spine are most commonly affected. They most commonly involve metaphysis or metaphysio-diaphyseal part of the bone. Primary involvement of epiphysis is rarely reported. Here we present a case of 6 year old male child with an epiphyseal ABC of distal ulna. Its diagnosis, surgical management, clinical outcome with review of literature is discussed.
|
10.13107/jocr.2250-0685.356
|
pubmed_141_6667
|
Two fundamental ethical questions involved in all health care decisions: what attitudes and practices enhance human values and what attitudes and practices diminish human values? Specifically, in the area of pain control, the ethical dilemma of balancing therapeutic relief with toxic side-effects is complicated by two salient factors. First is the need for an understanding of ethics that recognizes pain control as a crucial ethical issue. Second is the need to examine myths, attitudes, and behaviors in clinical practice that result in restrictive, insensitive, and inappropriate rationing of pain relief.
|
pubmed_141_6667
|
pubmed_695_23476
|
AIMS
Our objective was to determine the ventricular arrhythmia burden in implantable cardioverter-defibrillator (ICD) patients during COVID-19.
METHODS AND RESULTS
In this multicentre, observational, cohort study over a 100-day period during the COVID-19 pandemic in the USA, we assessed ventricular arrhythmias in ICD patients from 20 centres in 13 states, via remote monitoring. Comparison was via a 100-day control period (late 2019) and seasonal control period (early 2019). The primary outcome was the impact of COVID-19 on ventricular arrhythmia burden. The secondary outcome was correlation with COVID-19 incidence. During the COVID-19 period, 5963 ICD patients underwent remote monitoring, with 16 942 episodes of treated ventricular arrhythmias (2.8 events per 100 patient-days). Ventricular arrhythmia burden progressively declined during COVID-19 (P < 0.001). The proportion of patients with ventricular arrhythmias amongst the high COVID-19 incidence states was significantly reduced compared with those in low incidence states [odds ratio 0.61, 95% confidence interval (CI) 0.54-0.69, P < 0.001]. Comparing patients remotely monitored during both COVID-19 and control periods (n = 2458), significantly fewer ventricular arrhythmias occurred during COVID-19 [incident rate ratio (IRR) 0.68, 95% CI 0.58-0.79, P < 0.001]. This difference persisted when comparing the 1719 patients monitored during both the COVID-19 and seasonal control periods (IRR 0.69, 95% CI 0.56-0.85, P < 0.001).
CONCLUSIONS
During COVID-19, there was a 32% reduction in ventricular arrhythmias needing device therapies, coinciding with measures of social isolation. There was a 39% reduction in the proportion of patients with ventricular arrhythmias in states with higher COVID-19 incidence. These findings highlight the potential role of real-life stressors in ventricular arrhythmia burden in individuals with ICDs.
TRIAL REGISTRATION
Australian New Zealand Clinical Trial Registry; URL: https://www.anzctr.org.au/; Unique Identifier: ACTRN12620000641998.
|
10.1093/eurheartj/ehaa893
|
pubmed_944_3835
|
In the neurosciences digital databases more and more are becoming important tools of data rendering and distributing. This development is due to the growing impact of imaging based trial design in cognitive neuroscience, including morphological as much as functional imaging technologies. As the case of the 'Laboratory of Neuro Imaging' (LONI) is showing, databases are attributed a specific epistemological power: Since the 1990s databasing is seen to foster the integration of neuroscientific data, although local regimes of data production, -manipulation and--interpretation are also challenging this development. Databasing in the neurosciences goes along with the introduction of new structures of integrating local data, hence establishing digital spaces of knowledge (epistemic spaces): At this stage, inherent norms of digital databases are affecting regimes of imaging-based trial design, for example clinical research into Alzheimer's disease.
|
10.1002/bewi.201101502
|
pubmed_516_8715
|
Perimetric sensitivity of patients with glaucoma has traditionally been measured in logarithmic (dB) units, but linear sensitivity correlates better with conventional structural measures of glaucomatous damage. Monte Carlo simulations of perimetric algorithms were used to assess potential effects of logarithmic steps on bias and variability when perimetric sensitivity was represented in linear units, and to assess the potential benefits of algorithms using linear steps. Simulations predicted that linear staircases could reduce the sensitivity-dependence of bias, variability and efficiency. These predictions were supported by a perimetric study of 21 patients with glaucoma and 20 age-similar controls who made repeat visits over several weeks.
|
10.1016/j.visres.2006.03.004
|
pubmed_236_6183
|
Synovium is characterised by an intimal layer of cells, now recognised to be a mixture of bone marrow-derived macrophages and specialised fibroblast-like cells. The fibroblast-like cells, or synoviocytes, differ from other fibroblasts in a number of respects, including high activity of uridine diphosphoglucose dehydrogenase (UDPGD) and constitutive expression of VCAM-1. Experiments have been devised to try to establish the factors that control these specialised features. Both high UDPGD activity and VCAM-1 expression can be seen in adventitious or regenerate connective tissue linings tissue under certain circumstances. Mechanical factors may be implicated in the induction of UDPGD activity and VCAM-1 expression, but there is evidence that they are controlled independently. The factors involved in synoviocyte differentiation both in the embryo and under conditions of regeneration or generation ab initio at adventitious sites in the adult require further investigation.
|
pubmed_236_6183
|
pubmed_658_6269
|
Clinical trials have demonstrated therapeutic benefit in inducing angiogenesis in chronic occlusive arterial disease. The route of application mostly used was the intramuscular injection of high dosages of plasmid. Therefore, a local perivascular application of low amounts of vascular endothelial growth factor (VEGF) plasmid was used in an interventional occlusion model, and the effect of VEGF on coronary and peripheral occlusions compared in the same animal model. Coronary and peripheral arteries were chronically occluded in Pietrain pigs using a non-surgical, interventional approach. Adventitial delivery of the DNA for VEGF was performed with a needle injection catheter. The DNA was applied as lipoplexes using the novel cationic liposomes DOCSPER. Optimized transfer conditions were used. Angiography, polymerase chain reaction (PCR), reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemistry were undertaken within a follow-up period of 6 months. Expression of the transfected VEGF gene was observed at 1 and 3 weeks following application. The DNA was detected up to 5 months following application. Around occluded coronary arteries, there was formation of new collaterals and arterial prolongation, whereas surrounding occluded peripheral arteries there was no collateralization but development of new arterial branches was seen. Results demonstrate that the response to VEGF is also sufficient, when minimal amounts of plasmid encoding for VEGF are applied locally into the perivasculature allowing for more safety of this therapy. Comparison of treatment of chronic coronary and peripheral arterial disease revealed differences in angiogenesis following VEGF application during a total follow-up period of almost 6 months which may be related to their different developmental origins. This may have important implications for developing future therapeutic strategies using VEGF in different vessels.
|
10.1046/j.1365-201X.2002.01018.x
|
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