Changes in the secretory activity of the glandular lobe of the corpus cardiacum of Locusta migratoria induced by flight. A quantitative electron microscopic study.
The glandular lobe of the corpus cardiacum of Locusta migratoria is characterized by the presence of one type of secretory cells containing secretory granules with a diameter of 2000-3000 A, and of axons with small granules (diameter 950 A). The axons form synaptic contacts with the cells. The secretory products of the glandular cell are released by exocytosis in the gland proper. In the axon terminals, release is indicated by the presence of synaptic vesicles and omega-shaped indentations. In order to study possible changes in the secretory activity of the gland during flight, three groups of locusts were studied with quantitative electron microscopical methods, i.e., resting insects, having flown for 5 min (short flight, SF), and insects after prolonged flight (PF, 60 min). After flight, greater secretory activity of the glandular cells is indicated by a marked increase in the number of exocytotic pits in SF and PF insects, by an enlarged nuclear volume as well as an increased amount of secretory products in the Golgi cisterns of PF animals. Flight also causes greater release activity in the axon terminals. From these results it is concluded that an intrinsic hormone, apparently the adipokinetic hormone, is released from the glandular lobe and regulates the substrate supply from the fat body during flight. It is suggested that the secretory activity of the glandular cells is controlled by the axon terminals on these cells.


Emergency Neurology Oral Cases for Trainee Assessment and Education.
Neurological emergencies comprise much of neurology residency, but there may be a lack of clinical experience. For our program, oral examinations have been used to assess resident readiness for additional clinical independence. In this study, we examined the perceptions of learners and examiners of oral case examinations. Six attending physicians administered case-based oral examinations to 8 trainees. Each case involved a chief complaint and progressed through a clinical encounter. Following the examination, each attending physician and trainee completed an online 5-point Likert scale survey of content and educational value. Statistical analysis of point assignment based on Likert scale responses was performed. Six attendings (100% response) and 7 trainees (87.5% response) completed the assessment. The trainees assessed all 6 cases. Residents had negative responses for 3 cases with specific concern in "feedback" and "learning experience." Residents responded with less positive response than attendings for "The case is easy to understand and progressed in a logical fashion" (3.90 for residents vs. 4.83 attendings; P=0.015) and "The case complexity is appropriate for level of training" (4.14 vs. 4.83; P=0.033). Attendings noted better understanding of trainees thought processes following oral examinations. Trainees noted feedback as the most useful component of case-based assessments. Case-based assessment in neurology training allows for rapid evaluation of trainees' abilities to critically think. There is general agreement from attendings and trainees that case-based assessment is a useful and positive learning tool. The responses from this survey are being used to modify the cases for future examinations.


[Measurement of spontaneous platelet aggregation. Platelet aggregation test III (author's transl)].
A new measuring device for the estimation of the "spontaneous" aggregating activity of thrombocytes has been developed. In this photometric platelet aggregation test (PAT III) a small amount (0.6 ml) of platelet-rich plasma (PRP) is being rotated in a disc-shaped cuvette at 20 rpm, at 37% C. Changes in optical density of PRP which are induced by the formation of platelet aggregates are continuously registered using a chart recorder. The decisive trigger mechanism for aggregation is an increase of plasma pH in the rotating sample which is caused by evaporation of CO2. The results of the test depend on the platelet count in PRP. Aggregation curves are misrepresented by admixture of erythrocytes and lipid turbidity. The tendency of platelets to aggregate increases within 60-90 min following blood sampling. During this period the time interval to the onset of aggregation(Tr) is shortening, and the maximum aggregation speed (alpha2) is increasing. The spontaneously enhanced aggregation tendency of thrombocytes may be reliably measured from 60 min after drawing the blood. The reason for these time-dependent changes which are also demonstrable in ADP-collagen-or epinephrine-induced aggregation is probably the primary shape change of platelets, which occurs after blood drawing and makes them "stickly" and aggregable. PAT III was developed for the detection of enhanced platelet aggregation, indicating a risk of thrombosis and thromboembolic omplications. The new measuring device has been designed as "universal" aggregometer. Additional equipment is available for the registration of ADP-collagen-or epinephrine-induced aggregation similar to Born's and O'Brien's methods. The device may be mounted easily on an Eppendorf photometer without further modifications.


Unintentional Fusion in Preserved Facet Joints without Bone Grafting after Percutaneous Endoscopic Transforaminal Lumbar Interbody Fusion.
A percutaneous endoscopic transforaminal lumbar interbody fusion (PETLIF) procedure has been previously developed. During postoperative follow-up, in some patients, bone fusion occurred between opened facet joints, despite not having bone grafting in the facet joints. Here, we investigated facet fusion's frequency and tendencies following PETLIF. A retrospective analysis was conducted on a prospectively collected, nonrandomized series of patients. Forty-two patients (6 males and 36 females, average age: 69.9 years) who underwent single-level PETLIF at our hospital from February 2016 to March 2019 were included in this study. Patients were assessed with lumbar X-ray images and computed tomography (CT) prior to, immediately after, and 1 year after surgery. Pseudarthrosis was not observed in any patients, and facet fusion was observed in 26 of 42 post-PETLIF patients (61.9%) by CT 1 year postoperatively. The average interfacet distance increased from 1.3 mm preoperatively to 4.5 mm postoperatively, and facet fusion was observed under the opened conditions of 3.8 mm at 1 year. Segmental lordotic angle of the fusion segment in the lumbar X-ray images was significantly larger in the facet fusion subgroup prior to surgery, immediately following surgery, and 1 year after surgery compared to the facet non-fusion group (p=0.02, p<0.01, p=0.01, respectively). There were no significant differences in patient background, correction loss of segmental lordosis, interfacet distance, or clinical score between the facet fusion and facet non-fusion subgroups. Facet fusion was achieved over time within the facet joints that were opened through indirect decompression after PETLIF. We hypothesized that the preserved facet joints potentially became the base bed for spontaneous bone fusion due to the preserved facet joint capsule and surrounding soft tissue, which maintained cranio-caudal facet traffic and blood circulation in the facet joints. The complete preservation of the facet joints was a key advantage of minimally invasive lumbar interbody fusion procedures. Level III.


The vitreous after C3F8 gas instillation: long-term histologic findings after spontaneous reabsorption of the gas in rabbit eyes.
Perfluoropropane gas (C3F8) was injected intravitreally into rabbit eyes to displace the vitreous. Histologic examination by light and scanning electron microscopy revealed the vitreous material slowly expanded up to a nearly normal configuration during a follow-up of 6 months. Neither posterior vitreous detachment nor liquefaction of the vitreous could be observed.


Influence of internal climate variability on Indian Ocean Dipole properties.
The Indian Ocean Dipole (IOD) is the dominant mode of interannual variability over the tropical Indian Ocean (IO) and its future changes are projected to impact the climate and weather of Australia, East Africa, and Indonesia. Understanding the response of the IOD to a warmer climate has been largely limited to studies of individual coupled general circulation models or multi-model ensembles. This has provided valuable insight into the IOD's projected response to increasing greenhouse gases but has limitations in accounting for the role of internal climate variability. Using the Community Earth System Model Large Ensemble (CESM-LE), the IOD is examined in thirty-five present-day and future simulations to determine how internal variability influences properties of the IOD and their response to a warmer climate. Despite small perturbations in the initial conditions as the only difference between ensemble members, significant relationships between the mean state of the IO and the IOD arise, leading to a spread in the projected IOD responses to increasing greenhouse gases. This is driven by the positive Bjerknes feedback, where small differences in mean thermocline depth, which are caused by internal climate variability, generate significant variations in IOD amplitude, skewness, and the climatological zonal sea surface temperature gradient.


Modelling the Cost Effectiveness of Treatments for Parkinson's Disease: An Updated Methodological Review.
This article systematically reviewed the methodological quality of modelling approaches for economic evaluations of the treatment of motor symptoms in Parkinson's disease in studies published after 2010. A systematic literature search was undertaken using PubMed, EconLit, the Cochrane Database of Systematic Reviews, National Health Service Economic Evaluation Database and Health Technology Assessment databases of the UK National Health Service Centre for Review and Dissemination (March 2010 to July 2022). Quality was assessed using a checklist from the German Scientific Working Group. A total of 20 studies were evaluated, with the majority based on Markov models (n = 18). Studies assessed the cost effectiveness of medical (n = 12) or surgical (n = 8) treatment, and included costs from a payer or healthcare provider's perspective (n = 17). Furthermore, all studies included quality-adjusted life-years as an effect measure. In the quality assessment of the literature, a mean score of 42.1 points (out of 56 points) on the checklist of the German Scientific Working Group was achieved. Seventeen studies concluded the intervention under study was (likely) cost effective. No intervention was classified as cost ineffective. The quality of economic evaluation models in Parkinson's disease has improved in terms of calculating cost and transition parameters, as well as carrying out probabilistic sensitivity analyses, compared with the published literature of previous systematic reviews up to 2010. However, there is still potential for further development in terms of the integration of non-motor complications and treatment changes, the transparent presentation of parameter estimates, as well as conducting sensitivity analyses and validations to support the interpretation of results.


Structural mechanisms for gating and ion selectivity of the human polyamine transporter ATP13A2.
Mutations in ATP13A2, also known as PARK9, cause a rare monogenic form of juvenile-onset Parkinson's disease named Kufor-Rakeb syndrome and other neurodegenerative diseases. ATP13A2 encodes a neuroprotective P5B P-type ATPase highly enriched in the brain that mediates selective import of spermine ions from lysosomes into the cytosol via an unknown mechanism. Here we present three structures of human ATP13A2 bound to an ATP analog or to spermine in the presence of phosphomimetics determined by cryoelectron microscopy. ATP13A2 autophosphorylation opens a lysosome luminal gate to reveal a narrow lumen access channel that holds a spermine ion in its entrance. ATP13A2's architecture suggests physical principles underlying selective polyamine transport and anticipates a "pump-channel" intermediate that could function as a counter-cation conduit to facilitate lysosome acidification. Our findings establish a firm foundation to understand ATP13A2 mutations associated with disease and bring us closer to realizing ATP13A2's potential in neuroprotective therapy.


Under Pressure: Living with Diabetes in Cairo.
This article is based on 9 months of ethnographic fieldwork carried out in Cairo, Egypt during the years of 2015 and 2017 as part of a research project on the topic of type-2 diabetes. The article examines different understandings of the onset and treatment of type-2 diabetes across people in Cairo living with the condition and their healthcare providers. The article argues that those who are diagnosed with type-2 diabetes primarily relate their condition to experiences of ḍaghṭ (stress or pressure), above any other risk factors. This understanding clashes with healthcare providers who instead link type-2 diabetes primarily to obesity. The article exemplifies these different understandings of type-2 diabetes by drawing on the topic of food specifically, showing how the intake of food is not perceived by those diagnosed with type-2 diabetes as related to their condition in similar ways as is the case among their healthcare providers. As opposed to relating type-2 diabetes to matters of abundance and an excess consumption of food and calories, those in Cairo who are diagnosed with type-2 diabetes instead relate their condition to matters of deprivation and scarcity-as well as the experiences of ḍaghṭ brought on by such potential deprivation and scarcity.


Serum non-coding RNAs for diagnosis and stage of liver fibrosis.
All chronic liver diseases could lead to liver fibrosis. Accurate diagnosis and stage of fibrosis were important for the medical determination, management, and therapy. Liver biopsy was considered to be the gold criteria of fibrosis diagnosis. However, liver biopsy was an invasive method with some drawbacks. Non-invasive tests for liver fibrosis included radiologic method and serum-based test. Radiologic examination was influenced by obesity, cost, and availability. Serum-based test was widely used in the screening and diagnostic of liver fibrosis. However, the accuracy was still needed to be improved. Recent studies showed serum non-coding RNAs: microRNA, long non-coding RNA(lncRNA), and circular RNA(circRNA), which have the potentiality to be non-invasive markers for liver fibrosis. The recent progress was summarized in this review. These studies showed serum non-coding RNAs exerted a good diagnostic performance for liver fibrosis. A panel that included several non-coding RNAs could increase the accuracy of single marker. Serum microRNAs, lncRNAs, and circRNAs could be potential non-invasive markers for diagnosis and stage of liver fibrosis. More high-quality clinical study is needed for further research.


Urinary tract injuries during pelvic surgery: incidence rates and predisposing factors.
To review the cases of urinary tract injury following major pelvic surgery that were treated in our hospital over the last 12 years, in relation to possible predisposing factors and incidence rates of injury arising in various surgical procedures. From 8,824 major gynecological operations performed in our department, 29 cases of intraoperative urinary tract injury were found. Thirty eight patients visited the urology department during the same period for the management of urogenital fistula following pelvic surgery. Parameters that were examined included type of urinary tract injury, indication for surgery, type of operation, coexisting pathological conditions, past history of pelvic surgery or pelvic irradiation, and the delay in the recognition and management of the urinary tract injury. The overall incidence of urinary tract injury in pelvic surgery was 0.33%. The incidence of urinary tract injury in radical hysterectomy was higher than that of total abdominal hysterectomy(0.76 vs 0.26%). Of the intraoperative urinary tract injuries, 48.4% coexisted pelvic pathologies. Of all the cases with urinary tract injury, the most common type of operation was total abdominal hysterectomy (n = 45, 67.2%), and the most common indication was uterine myoma (n = 25, 36.9%). The most common type of urinary tract injury was bladder injury, including bladder laceration and vesicovaginal fistula(n = 57, 76.1%). The frequency of reoperation was found to be lower in patients with a shorter delay in the recognition of the injury (p < 0.05). Possible predisposing factors for urinary tract injury are coexisting pelvic adhesion, distortion of normal pelvic configuration, previous irradiation history, previous operation history, and the extent of surgery. In high-risk patients, proper evaluation is needed to avoid urology complications before operation.


Construction of high-density genetic linkage map and mapping quantitative trait loci (QTL) for flowering time in autotetraploid alfalfa (Medicago sativa L.) using genotyping by sequencing.
Flowering time is an important agronomic trait of alfalfa (Medicago sativa L.). Managing flowering time can produce economic benefits for farmers. To understand the genetic basis of this trait, quantitative trait loci (QTL) mapping was conducted in a full-sib population that consisted of 392 individuals segregating based on flowering time. High density linkage maps were constructed using single nucleotide polymorphism (SNP) markers generated by genotyping-by-sequencing (GBS). The linkage maps contained 3,818 SNP markers on 64 linkage groups in two parents. The average marker density was 4.33 cM for Parent 1 (P1) and 1.47 cM for Parent 2 (P2). Phenotypic data for flowering time was collected for three years at one location. Twenty-eight QTLs were identified associated with flowering time. Eleven QTLs explained more than 10% of the phenotypic variation. Among them, five main effect QTLs located on linkage group (LG) 7D of P1 and five main effect QTLs located on LG 6D of P2 were identified. Three QTLs were co-located with other QTLs. The identified linked markers to QTLs could be used for marker-assisted selection in breeding programs to develop new alfalfa varieties to modulate flowering time.


[Synovial tumors and tumor-like lesions].
Synovial tumors comprise a variety of lesions, including those with benign and aggressive neoplastic changes as well as inflammatory causes. In this article we focus on neoplastic tumors. Synovial tumors with other etiologies, such as sarcoidosis, granuloma, synovitis, or gouty arthritis, are not dealt with here. Through a precise differentiation between these disease entities can an optimization of treatment be achieved.


[Clinical results after implantation of a new segmental refractive multifocal intraocular lens].
The aim of the study was a clinical evaluation of an intraocular lens (IOL) with a segmental multifocal optic design and near addition of + 3.0 D as part of a CE approval study. In a multicenter study the LENTIS Mplus LS-312 MF IOL (Oculentis) was implanted in 134 eyes of 79 patients with a mean age of 68 ± 12 years. The multifocality is achieved by implementation of a distance part and a segmented near sector. Three months after surgery, uncorrected and best corrected distance visual acuity (UCDVA and BCDVA, respectively), near visual acuity (UCNVA and BCNVA, respectively), contrast vision and patient satisfaction (questionnaire) were evaluated. The IOLs were implanted uneventfully either unilaterally or bilaterally and 3 months postoperatively (n = 86 eyes) the following mean visual acuities were obtained (logMAR): UCDVA = 0.05, BCDVA = - 0.01, UCNVA = 0.09 and BCNVA = 0.02. Contrast sensitivity (n = 25 eyes) was within normal limits. Of the 66 questioned patients 10.6% spontaneously reported halos and 3% glare. This new innovative multifocal IOL concept showed very good functional results as well as high patient satisfaction.


Chloral hydrate sedation in radiology: retrospective audit of reduced dose.
Chloral hydrate (CH) is safe and effective for sedation of suitable children. The purpose of this study was to assess whether adequate sedation is achieved with reduced CH doses. We retrospectively recorded outpatient CH sedations over 1 year. We defined standard doses of CH as 50 mg/kg (infants) and 75 mg/kg (children >1 year). A reduced dose was defined as at least 20% lower than the standard dose. In total, 653 children received CH sedation (age, 1 month-3 years 10 months), 42% were given a reduced initial dose. Augmentation dose was required in 10.9% of all children, and in a higher proportion of children >1 year (15.7%) compared to infants (5.7%; P < 0.001). Sedation was successful in 96.7%, and more frequently successful in infants (98.3%) than children >1 year (95.3%; P = 0.03). A reduced initial dose had no negative effect on outcome (P = 0.19) or time to sedation. No significant complications were seen. We advocate sedation with reduced CH doses (40 mg/kg for infants; 60 mg/kg for children >1 year of age) for outpatient imaging procedures when the child is judged to be quiet or sleepy on arrival.


A system for ambulatory monitoring and computerised analysis of oesophageal motility and luminal pH.
It is often desirable to monitor physiological events from subjects free to participate in their normal daily activities. This is especially so where clinical symptoms are elusive or precipitated by specific activities. Through ambulatory monitoring, evidence of a causal relationship between recorded parameters and the spontaneous onset of symptoms may be revealed. We describe an ambulatory monitoring system which permits continuous 24-hour recording of oesophageal motility from three levels within the oesophagus together with luminal pH. Computerised analysis of the recorded data addresses many of the problems associated with processing the information accrued through long-term monitoring by providing an automatic comparison of patient data against either preselected values or those of the program's algorithm. Motility is quantified in terms of wave frequency, amplitude, duration and temporal relationship together with an integration of the wave area and mean pressure baseline. The corresponding pH data is quantified as frequency, duration and integrated area of pH excursions throughout a range of pH1-8. This system provides access to the entire patient record which may either be viewed on screen, analysed or output to a printer. Analysis yields a tabulated breakdown of motility and pH events from any section of the patient's record. Selective analysis readily permits statistical comparison of discrete time-matched samples corresponding to different patient circumstances.


Performance of oyster mushroom (Pleurotus ostreatus) on paddy straw, water hyacinth and their combinations.
This study aimed to investigate the performance of oyster mushrooms on different substrate combinations, including rice straw alone, rice straw and water hyacinth (1:1), rice straw and water hyacinth (1:2), and rice straw and water hyacinth (2:1), in Pokhara, Kaski from April to June in 2022. A Completely Randomized Design with four replications was used to analyze the growth and yield parameters of the four different substrate combinations. The data were analyzed using R-Studio. Highly significant results (P > 0.001) were found in all growth and yield parameters. The best response in terms of days to colonization, pinhead formation, and total crop duration was observed with rice straw alone (11.5, 13.25, and 54.00 days, respectively). The stipe length, pileus diameter, and fruiting body per bunch had their highest values (3.44 cm, 5.21 cm, and 34.50 cm, respectively) with rice straw alone, followed by rice straw and water hyacinth in a 2:1 ratio (3.05 cm, 4.63 cm, and 34.25 cm, respectively). The maximum total fresh yield of mushrooms (1.53 kg with 153.16% BE) was observed for rice straw alone, followed by rice straw and water hyacinth in a 2:1 ratio (1.17 kg with 116.5% BE), while the poorest yield (0.76 kg with 76.38% BE) was observed in the case of rice straw and water hyacinth in a 1:2 ratio. The highest profitability was observed for mushroom production using rice straw alone with a B:C ratio of 1.24, followed by using rice straw and water hyacinth in a 2:1 ratio (1.03), while the lowest B:C ratio was observed for rice straw and water hyacinth in a 1:2 ratio (0.74). Overall, the best treatment was found to be rice straw alone, followed by rice straw and water hyacinth in a 2:1 ratio. These results suggest that using rice straw alone or in combination with water hyacinth in a 2:1 ratio can be an effective strategy for oyster mushroom cultivation.


Spectrofluorimetric analysis of certain macrolide antibiotics in bulk and pharmaceutical formulations.
The macrolides (erythromycin, erythromycin esters, azithromycin dihydrate, clarithromycin and roxithromycin) can be analyzed by a simple spectrofluorimetric method based on the oxidation by cerium(VI) in the presence of sulphuric acid and monitoring the fluorescence of cerium(III) formed at lambda(ex) 255 nm and lambda(em) 348 nm. All variables affecting the reaction conditions as cerium(VI), sulphuric acid concentrations, heating time, temperature and dilution solvents were carefully studied. Linear calibration graphs were obtained in the range of 42.6-1200 ng ml(-1) with a percentage relative standard deviation in the range of 0.014-0.058%. Quantitation and detection limits were calculated. The method was applied successfully for the assay of the studied drugs in pure and pharmaceutical dosage forms as tablets, capsules and suspension. Recovery experiments revealed recovery of 98.3-100.8%. The effect of potential interference due to common ingredients as glucose, sucrose, lactose, citric acid, and propylene glycol was investigated. Applying standard addition method shows a recovery of 97.7-100.9% macrolide antibiotics from their corresponding dosage forms.


Macromolecular crowding amplifies allosteric regulation of T-cell protein tyrosine phosphatase.
T-cell protein tyrosine phosphatase (TC-PTP) is a negative regulator of T-cell receptor and oncogenic receptor tyrosine kinase signaling and implicated in cancer and autoimmune disease. TC-PTP activity is modulated by an intrinsically disordered C-terminal region (IDR) and suppressed in cells under basal conditions. In vitro structural studies have shown that the dynamic reorganization of IDR around the catalytic domain, driven by electrostatic interactions, can lead to TC-PTP activity inhibition; however, the process has not been studied in cells. Here, by assessing a mutant (378KRKRPR383 mutated into 378EAAAPE383, called TC45E/A) with impaired tail-PTP domain interaction, we obtained evidence that the downmodulation of TC-PTP enzymatic activity by the IDR occurs in cells. However, we found that the regulation of TC-PTP by the IDR is only recapitulated in vitro when crowding polymers that mimic the intracellular environment are present in kinetic assays using a physiological phosphopeptide. Our FRET-based assays in vitro and in cells confirmed that the effect of the mutant correlates with an impairment of the intramolecular inhibitory remodeling of TC-PTP by the IDR. This work presents an early example of the allosteric regulation of a protein tyrosine phosphatase being controlled by the cellular environment and provides a framework for future studies and targeting of TC-PTP function.


New Graduate Nurses' Perceptions of Patient Safety: Describing and Comparing Responses With Experienced Nurses.
A significant proportion of the acute health system workforce is composed of new graduate nurses, yet there is a limited understanding of patient safety perceptions among new graduate nurses and how they compare with nurses who have more experience. This study used a descriptive approach to complete secondary analysis on two sources of data containing new graduate nurses' (n = 1,613) and experienced nurses' (n = 64,906) responses to the Hospital Survey on Patient Safety Culture. New graduate nurses had a more positive perception of safety culture than more experienced nurses. The greatest differences were observed in perceptions of how nurse managers respond to mistakes. Similarities in perceptions were observed on items associated with communication. Educational systems and transitional programs must prepare new graduate nurses for patient care. There is an opportunity for academic and practice partners to collaborate on programs that facilitate the transition of new graduate nurses to the workforce. [J Contin Educ Nurs. 2020;51(7):309-315.].


Evaluation of structural and secretory glycoconjugates in normal human jejunum by means of lectin histochemistry.
The labelling pattern of eight lectins was studied in jejunal samples from ten normal subjects, in order to define the normal distribution of structural and secretory glycoconjugates in the small bowel. The following lectins were studied by means of a peroxidase technique on formalin-fixed samples: Arachis hypogaea, Ricinus communis, Canavalia ensiformis, Lens culinaris, Phaseolus vulgaris, Triticum vulgaris, Ulex europaeus, Dolichos biflorus. Phaseolus vulgaris reacted with goblet cell mucus throughout the villus-crypt axis. Conversely Ulex europaeus, Dolichos biflorus and Triticum vulgaris lectin labelling of goblet cells appeared to be confined to the upper part of the villi. This finding suggests that during cell migration from crypt to villus tip, the continuing maturation of goblet cells is associated with the differentiation of secretory carbohydrates, which probably parallels the cell maturation cycle. Lectin histochemistry appears to be a reliable tool for the study of structural and secretory glycoconjugates in the jejunal mucosa, and might be of value in the study of diseases in which the cell-maturation cycle in the small bowel is altered.


The Caco-2 cell culture model enables sensitive detection of enhanced protein permeability in the presence of N-decyl-β-d-maltopyranoside.
Appropriate assessment of transepithelial permeability in vitro is needed to estimate and model trans-mucosal bioavailability to achieve oral delivery of protein biopharmaceuticals. The Caco-2 cell-based intestinal epithelium model is widely used for this purpose for low molecular mass drugs. The aim of this study was to test the suitability of the Caco-2 model for assessing enhanced transepithelial permeability to proteins. Four unrelated proteins were chosen to test the permeability of Caco-2 monolayers. It was found that proteins could cross the epithelium model, in spite of their size. All tested proteins had similar very low apparent permeability coefficients (Papp) of around 4×10(-10)cm/s. Protein stability over three-hour exposure to Caco-2 was also confirmed. Their crossing rate in a cell-free setup was also measured, to determine the upper limit of permeability to proteins. An epithelium permeability enhancer N-decyl-β-d-maltopyranoside (MP C10) was used to demonstrate accelerated permeability conditions. Papp values could be increased dose dependently up to about 1×10(-7)cm/s, close to the level in the cell-free setup, indicating distinctive potential of the model. This along with enhancing effect of known specific route permeators suggests involvement of the paracellular route in protein transport. Our results thus indicate that the Caco-2 model is a suitable tool for in vitro assessment of enhanced permeability to proteins.


Properties of asparagine synthetase in asparagine-independent variants of Jensen rat sarcoma cells induced by 5-azacytidine.
Jensen rat sarcoma cells in culture require L-asparagine for growth and lack detectable levels of asparagine synthetase. Cultures exposed for 24 h to graded concentrations of 5-azacytidine give rise to asparagine-independent variants in high frequency. These prototrophs are stable phenotypically whether maintained in the presence or absence of L-asparagine. Asparagine synthetase activity in several variant clones was uniform in thermolability and several kinetic parameters, as well as in immunological properties. Parental Jensen rat sarcoma cells contained no detectable immunologically cross-reacting material. Our data suggest that transitions between asparagine dependence and independence in these cells are mediated by stable shifts in gene expression rather than by structural gene mutations.


Influence of oral moisturizing jelly as a saliva substitute for the relief of xerostomia in elderly patients with hypertension and diabetes mellitus.
Dry mouth is common in elderly patients. However, the use of saliva substitute has been limited due to its inedibility. This study investigated the efficacy of oral moisturizing jelly (OMJ), a novel edible saliva substitute. A pre-post design was conducted in 118 elderly patients diagnosed with hypertension and/or diabetes mellitus. After using OMJ, signs and symptoms of dry mouth were compared with baseline data. The properties of saliva were compared between the OMJ use and non-use periods. The use of OMJ for 2 weeks significantly reduced symptoms of dry mouth, while the use for 1 month reduced the signs of xerostomia, prevented the decline of salivary pH(s) and improved buffering capacities. OMJ was equally effective in patients taking 1 to 2 and 3 to 7 medications. Furthermore, 65% of patients preferred OMJ over a commercial product. OMJ could be new edible saliva substitute for elderly patients suffering from dry mouth. Clinicaltrials.gov ID: NCT02317172.


Climate and vectorborne diseases.
Climate change could significantly affect vectorborne disease in humans. Temperature, precipitation, humidity, and other climatic factors are known to affect the reproduction, development, behavior, and population dynamics of the arthropod vectors of these diseases. Climate also can affect the development of pathogens in vectors, as well as the population dynamics and ranges of the nonhuman vertebrate reservoirs of many vectorborne diseases. Whether climate changes increase or decrease the incidence of vectorborne diseases in humans will depend not only on the actual climatic conditions but also on local nonclimatic epidemiologic and ecologic factors. Predicting the relative impact of sustained climate change on vectorborne diseases is difficult and will require long-term studies that look not only at the effects of climate change but also at the contributions of other agents of global change such as increased trade and travel, demographic shifts, civil unrest, changes in land use, water availability, and other issues. Adapting to the effects of climate change will require the development of adequate response plans, enhancement of surveillance systems, and development of effective and locally appropriate strategies to control and prevent vectorborne diseases.


Feeding behaviour after injection of α-adrenergic receptor agonists into the median raphe nucleus of food-deprived rats.
This study investigated the participation of median raphe nucleus (MnR) α1-adrenergic receptors in the control of feeding behaviour. The α1-adrenergic agonist phenylephrine (PHE) and α2-adrenergic agonist clonidine (CLON) (at equimolar doses of 0, 6 and 20 nmol) were injected into the MnR of: a) rats submitted to overnight fasting (18 h); or b) rats maintained with 15 g of lab chow/day for 7 days. Immediately after the drug injections, the animals were placed in the feeding chamber and feeding and non-ingestive behaviours such as grooming, rearing, resting, sniffing and locomotion were recorded for 30 min. The results showed that both doses of PHE injected into the MnR of overnight fasted animals decreased food intake accompanied by an increase in the latency to start feeding. A reduction in feeding duration was observed only after treatment of the MnR with the 20 nmol dose of PHE. Both locomotion duration and sniffing frequency increased after injection with the highest dose PHE into the MnR. Feeding frequency and the other non-ingestive behaviours remained unchanged after PHE treatment in the MnR. Both doses of PHE injected into the MnR of food-restricted rats decreased food intake. This hypophagic response was accompanied by a decrease in feeding duration only after treatment of the MnR with the highest dose of PHE. The latency to start feeding and feeding frequency were not affected by injection of either dose of PHE into the MnR. While both doses of PHE increased sniffing duration, the highest dose of PHE increased resting duration and resting frequency. Treatment with CLON into the MnR did not affect feeding behaviour in either of the food deprivation conditions. The present results indicate the inhibitory functional role of α1-adrenergic receptors within the MnR on feeding behaviour.


Insulin producing cells derived from embryonic stem cells: are we there yet?
Derivation of insulin producing cells (IPCs) from embryonic stem (ES) cells provides a potentially innovative form of treatment for type 1 diabetes. Here, we discuss the current state of the art, unique challenges, and future directions on generating IPCs.


Higher plasma transforming growth factor (TGF)-β is associated with kidney disease in older community dwelling adults.
TGF-β is induced in the vasculature with aging suggesting that high plasma TGF-β levels may be a risk factor for chronic kidney disease (CKD) in older adults. We conducted a cross-sectional analysis of the association between plasma TGF-β levels and CKD including data for 1722 older adults who had participated in the 1996/97 visit of the Cardiovascular Health Study (CHS). Prevalent CKD was defined as eGFR < 60 mL/min/1.73 m2 or urinary albumin/creatinine ratio (ACR) ≥30 mg/g. We also evaluated whether baseline TGF-β levels predicted change in eGFR, cardiovascular (CV) events, or mortality in longitudinal analysis. Plasma TGF-β levels were significantly and independently associated with lower eGFR in cross-sectional analysis. Doubling of TGF-β was significantly associated with lower eGFR (β estimate after adjusting for CV risk factors = -1.18, 95% CI -2.03, -0.32). We observed no association with albuminuria. There was no association between baseline TGF-β and change in eGFR, but each doubling of TGF-β at baseline was associated with increased risk of a composite outcome of CV events and mortality, adjusted HR 1.10 (95% C.I. 1.02- 1.20, p = 0.006). In this large cohort of community-dwelling older individuals, high plasma TGF-β levels are modestly, but independently associated with lower eGFR but not with albuminuria in cross-sectional analysis. In addition, TGF-β levels are associated with increased risk of CV events and mortality. Further research is needed to determine the direction of association between plasma TGF-β and the risk of CKD and CKD-associated morbidities in older adults.


Loss of liposome binding of NADH dehydrogenase from alkalophilic Bacillus on subtilisin digestion.
Alkalophile NADH dehydrogenase consisting of two 65-kDa subunits was changed by subtilisin into an enzyme species consisting of two 38-kDa subunits. The amino acid composition and enzyme activity per molecule of the subtilisin-treated enzyme were almost the same as those of the native enzyme, respectively. On mixing with phospholipid liposome, the conformation of the native enzyme was changed, as suggested by the changes in the type of Arrhenius plot and of CD spectrum and enzyme activity. These conformational properties of the subtilisin-treated enzyme, on the other hand, were not affected by liposome. Gel filtration of the subtilisin-treated enzyme mixed with the liposome showed no binding of the protein to liposome.


A quantitative ultrastructural evaluation of the cell organelle specificity of the uranaffin reaction in normal human platelets.
The purpose of this study was to determine the normal variation in the number of uranaffin-positive organelles in normal human platelets and to study the effect of pH and fixation on the uranaffin reaction. The normal variation in uranaffin organelles was determined by studying platelets from nine normal subjects. At pH 3.9, the mean number of reactive sites/platelet profile was 0.43 +/- 0.10 when platelets were fixed with lower glutaraldehyde concentrations and 0.56 +/- 0.24 with higher glutaraldehyde concentrations. Fixed platelets were reacted at pH 2.8, 3.9, 5.0, and 7.0 with four different uranaffin procedures that varied in the extent of fixation and rinse steps (isotonic saline vs. cacodylate buffer). The number of uranaffin-positive sites in 200 platelet profiles was scored under the electron microscope. There was a progressive increase in the number of reactive sites/platelet profile as the pH increased from 2.8 to 7.0. In general, higher pH favored granule matrix and core staining, whereas low pH favored both the staining of granule membranes and their contents. The uranaffin reaction showed organelle specificity when run under certain experimental conditions. At low pH and using isotonic saline in the rinse steps, only the dense bodies and ribosomes stained. The biochemical content of the dense body responsible for uranaffin reactivity is discussed.


Persistent modulatory actions and task switching in the feeding network of Aplysia.
The activity of multifunctional networks is configured by neuromodulators that exert persistent effects. This raises a question, does this impact the ability of a network to switch from one type of activity to another? We review studies that have addressed this question in the Aplysia feeding circuit. Task switching in this system occurs "asymmetrically." When there is a switch from egestion to ingestion neuromodulation impedes switching (creates a "negative bias"). When there is a switch from ingestion to egestion the biasing is "positive." Ingestion promotes subsequent egestion. We contrast mechanisms responsible for the two types of biasing and show that the observed asymmetry is a consequence of the fact that there is more than one set of egestive circuit parameters.


The effect of fine particulate matter exposure on allergic rhinitis of adolescents aged 10-13 years: A cross-sectional study from Chongqing, China.
Allergic rhinitis (AR) has become a tremendous disease burden worldwide. Only a few studies have explored the effects of environmental exposure on the prevalence of AR in children in China. In the present study, we investigated the associations of environmental exposure (including fine particulate matter (PM2.5), air humidity, temperature, and passive smoking) with AR in adolescents aged 10-13 years in Chongqing. Data from 4,146 participants in urban and rural areas between March 2019 and May 2019 were collected. The overall prevalence of AR was 17.50% in adolescents. After adjusting for other covariates, AR was positively correlated with the annual mean PM2.5 concentration, monthly mean PM2.5 concentration and air temperature, and negatively related to air humidity. Furthermore, the annual mean PM2.5 was positively associated with the risk of AR after adjusting for air temperature and humidity. Passive smoking (PS) was marginally associated with a high risk of AR. High PM2.5 exposure, high air temperature, and low air humidity were associated with a high risk of AR in adolescents. Our findings have potential implications for public health strategies and interventions aimed at reducing the burden of AR in adolescents.


Changes in gastro-intestinal serotonin content associated with fasting and satiation.
Rats fasted for 24 h were fed for 3 h, after which time food was removed. Food intake decreased serotonin levels in the stomach and duodenum by 30 and 40%, respectively. These changes persisted for about 3 h. Food intake did not change tryptophan content in the stomach, while, in the duodenum, tryptophan level rose by 100% at the end of the feeding period and remained elevated for about 9 h.


Relationships of hippocampal theta cycles with bar pressing during self-stimulation.
Previous reports have demonstrated a relationship between hippocampal rhythmical slow activity (theta) and movement, and have suggested that rhythmical movements tend to occur during certain phase of theta. Therefore, the relationships between theta cycles and voluntary motor activity were investigated. Bar pressing for electrical brain stimulation provided the reference to relate hippocampal activity. Ongoing theta increased in amplitude and frequency before and after pressing. Periodic waves preceding and following pressing. These waves only appear if the presses occur at particular phases of the theta cycles. They gradually disappeared during sessions lasting 4 to 8 hr. Light weights ( less than 90 g) added to the lever did not alter theta, but heavier weights (greater than 90 g) produced averages without periodic waves and with movement-related potentials. Introduction of a delay between pressing and electrical stimulation delayed evoked potentials, while averaging indicated that periodical waves persisted before and after bar pressing. Total lesions of the septum or superior fornix abolished theta and increased the frequency of self stimulation. In animals with partial lesions, theta reappeared during pressing. The above results indicating that the rats tended to lever press during particular phases of theta, suggest that phase-locked theta may be a corollary of motor mechanisms, and perhaps of the timing of motor responses.


Increasing prevalence of methicillin resistance in serious ocular infections caused by Staphylococcus aureus in the United States: 2000 to 2005.
To report the nationwide prevalence of methicillin resistance in serious ocular infections involving Staphylococcus aureus and profile in vitro antimicrobial susceptibility of S aureus from ocular isolates over time. Mount Sinai School of Medicine, New York, New York, USA. Data on S aureus submitted to The Surveillance Network (TSN) by more than 200 laboratories in the United States from January 2000 to December 2005 were reviewed. The prevalence of methicillin resistance in S aureus ocular infections and in vitro susceptibility to antibiotic agents commonly used to treat or prevent ocular infections were determined. The proportion of S aureus infections culture-positive for methicillin-resistant S aureus (MRSA) increased from 29.5% in 2000 to 41.6% in 2005. The MRSA ocular isolates were multidrug resistant; that is, in vitro resistance to 3 antibiotic agents or more, including all fluoroquinolones tested. Multidrug-resistant MRSA is increasing in serious ocular infections. Based on the rate of increase in the TSN database, MRSA cultures from serious ocular infections could be more common than methicillin-susceptible S aureus within 2 to 3 years. Large-scale national surveillance programs are needed to monitor in vitro antimicrobial resistance trends in ocular isolates.


Carbohydrate-Binding Modules of Potential Resources: Occurrence in Nature, Function, and Application in Fiber Recognition and Treatment.
Great interests have recently been aroused in the independent associative domain of glycoside hydrolases that utilize insoluble polysaccharides-carbohydrate-binding module (CBM), which responds to binding while the catalytic domain reacts with the substrate. In this mini-review, we first provide a brief introduction on CBM and its subtypes including the classifications, potential sources, structures, and functions. Afterward, the applications of CBMs in substrate recognition based on different types of CBMs have been reviewed. Additionally, the progress of CBMs in paper industry as a new type of environmentally friendly auxiliary agent for fiber treatment is summarized. At last, other applications of CBMs and the future outlook have prospected. Due to the specificity in substrate recognition and diversity in structures, CBM can be a prosperous and promising 'tool' for wood and fiber processing in the future.


The Wheat Snn7 Gene Confers Susceptibility on Recognition of the Parastagonospora nodorum Necrotrophic Effector SnTox7.
Parastagonospora (syn. ana, Stagonospora; teleo, Phaeosphaeria) nodorum (Berk.) Quaedvleig, Verkley & Crous is a necrotrophic fungal pathogen that causes the disease Septoria nodorum blotch (SNB) on wheat (Triticum aestivum L. subsp. aestivum). The fungus produces necrotrophic effectors (NEs) that cause cell death when recognized by corresponding host genes, which ultimately leads to disease. To date, eight host gene-NE interactions have been described in the wheat-P. nodorum system. Here, we report the identification and partial characterization of a ninth interaction involving a P. nodorum-produced NE designated SnTox7 and a wheat gene designated Snn7. SnTox7 is a small protein with an estimated size less than 30 kDa and largely resistant to heat and chemical treatment. The Snn7 gene governs sensitivity to SnTox7 and was delineated to a 2.7-cM interval on the long arm of wheat chromosome 2D. The Snn7-SnTox7 interaction explained 33% of the variation in disease among a segregating population, indicating that the interaction plays a prominent role in the development of SNB. The Snn7 sensitivity allele was identified in the hexaploid wheat cultivar Timstein, but evaluation of a set of 52 hexaploid lines of diverse origin indicated that few genotypes harbored a functional Snn7 allele, thus indicating that Snn7 is relatively rare. The identification of the Snn7-SnTox7 interaction adds to our knowledge of the wheat-P. nodorum pathosystem, which has become a model for necrotrophic specialist fungal pathogens and their interactions with plants leading to necrotrophic effector-triggered susceptibility.


Immunoinformatics design of a novel multi-epitope peptide vaccine to combat multi-drug resistant infections caused by Vibrio vulnificus.
Multi-drug resistant Vibrio vulnificus is a Gram-negative bacillus responsible for diseases, such as: sepsis, septicemia, gastroenteritis, and fatal necrotizing fasciitis in humans. The treatment and prevention of V. vulnificus infections are challenging because of resistance to antibiotics and the non-availability of a licensed vaccine. Considering this, an in-silico based approach comprising subtractive proteomics, immunoinformatics, molecular docking, and dynamics simulation studies is applied herein to identify potential epitope vaccine candidates for the mentioned pathogen. Two potential vaccine candidates: vibC and flgL are filtered based on essentiality, outer membrane localization, virulence, antigenic, pathway mapping, and cellular protein-protein network analysis. Using immunoinformatic tools, 9-mer B-cell derived T-cell antigenic epitopes are predicted for the said shortlisted two proteins that are demonstrating excellent affinity for predominant HLA allele (DRB1*0101) in human population. Screened peptides are used further in multi-epitope peptide designing and linked to an adjuvant to enhance the immunogenic properties of the designed construct. Furthermore, the construct was docked blindly to TLR4 immune receptor, and analyzed in conformational dynamics simulation to decipher the complex affinity and understand time dependent behavior, respectively. We expect this designed in silico construct to be useful for vaccinologists to evaluate its immune protective efficacy in in vivo animal models.


[Not Available].
Mycotoxin analyses in the state of Vorarlberg were concentrated on the aflatoxins B1, B2, G1, G2 and occasionally M1, on Ochratoxin A (OTA) and Patulin. The analyses were carried out on high performance liquid chromatography. For fast screening a radio immuno affinity technique (CHARM II) was introduced and employed lately.The results prove that only very few food samples are not contaminated by mycotoxins. In some samples the mycotoxin content exceeded the limit several times. The actual average mycotoxin content of food was very low but with regards to the precautionary principle the intake of these mould-toxins should be further minimised.


Resistance to mental health consultation directed at change in public institutions.
Mental health consultants need to be aware that institutions in a community are frequently resistant to change. Official agreement that change is necessary may still evoke resistance by those individuals most threatened in the agency. The consultant's awareness of how such resistance is manifest and used permits some educative counterefforts which may be effective. There is a brief review of the literature, and case examples are given of effective and noneffective consultation.


"They're trying to bribe you and taking away your freedoms": COVID-19 vaccine hesitancy in communities with traditionally low vaccination rates.
Vaccination is an essential public health intervention to control the COVID-19 pandemic. A minority of Canadians, however, remain hesitant about COVID-19 vaccines, while others outright refuse them. We conducted focus groups to gauge perceptions and attitudes towards COVID-19 vaccines in people who live in a region with historically low rates of childhood vaccination. Participants discussed their perception of COVID-19 vaccines and their intention to get vaccinated, and the low rate of COVID-19 vaccine uptake in Manitoba's Southern Health Region compared to other regions in Canada. We identified three drivers of vaccine hesitancy: (1) risk perceptions about COVID-19 and the vaccines developed to protect against it, (2) religious and conservative views; and (3) distrust in government and science. Participant proposed recommendations for improving communication and uptake of the COVID-19 vaccines included: public health messages emphasising the benefits of vaccination; addressing the community's specific concerns and dispelling misinformation; highlighting vaccine safety; and emphasising vaccination as a desirable behaviour from a religious perspective. Understanding the specific anxieties elicited by COVID-19 vaccines in areas with low childhood immunization rates can inform risk communication strategies tailored to increase vaccination in these specific regions. This study adds important information on potential reasons for vaccine hesitancy in areas with historically low rates of childhood vaccination, and provides important lessons learned for future emergencies in terms of vaccine hesitancy drivers and effective risk communication to increase vaccine uptake.


Secretion into and elimination from blood circulation of prostate specific acid phosphatase, measured by radioimmunoassay.
The concentration of prostate specific acid phosphatase (PAP) was significantly higher in serum specimens from prostatic venous plexus blood than from peripheral venous blood in 6 patients operated upon because of benign prostatic hypertrophy. This suggests that normally circulating PAP is secreted via the prostatic venous plexus. We also investigated the disappearance of PAP from the circulation after total prostatectomy and staging pelvic lymphadenectomies in 5 patients with nonmetastazing prostatic cancer and in 1 patient with bladder cancer. During the postmaximum period, serum PAP concentrations declined, following 2-exponential curves, the 1st mean half life of elimination being 1.2 hours (range 0.5--2.5 hours). It is possible that PAP released from the prostate during the operation was eliminated during the 1st period. The 2nd half life was found to be remarkably long (mean = 281 hours), and it may represent PAP bound by serum protein(s).


In vitro synthesis of biologically active beet necrotic yellow vein virus RNA.
Beet necrotic yellow vein virus (BNYVV) has a quadripartite plus-strand RNA genome in which the two smallest genome components, RNA 3 and 4, are not necessary for virus multiplication in leaves. Infectious transcripts of BNYVV RNA 3 and 4 have already been described (V. Ziegler-Graff, S. Bouzoubaa, I. Jupin, H. Guilley, G. Jonard, and K. Richards (1988) J. Gen. Virol. 69, 2347-2357). In this paper we describe synthesis of a full-length RNA-1 transcript by bacteriophage T7 RNA polymerase-directed run-off transcription of cloned viral cDNA. A recombinant plasmid containing a full-length cDNA insert of RNA 2 could not be maintained in Escherichia coli. Therefore full-length transcript of RNA 2 was produced by transcription of cDNA ligation products without amplification in bacteria. When inoculated together to leaves of Chenopodium quinoa or Tetragonia expansa the RNA 1 and 2 transcripts were infectious; they also supported multiplication of the BNYVV RNA 3 and 4 transcripts, providing a totally synthetic inoculum of the virus. In one recombinant clone of RNA 2 a point mutation causing an arginine to serine substitution at position 119 of the viral coat protein was discovered. The mutation was detected because the resulting coat protein had altered electrophoretic mobility. RNA 2 transcripts containing this mutation were infectious but viral RNA was not encapsidated. The mutation also interfered with long distance movement of the virus in spinach, presumably as a consequence of the packaging deficiency.


Ring-Expansion Approach to Medium-Sized Lactams and Analysis of Their Medicinal Lead-Like Properties.
Medium-sized rings are widely considered to be under-represented in biological screening libraries for lead identification in medicinal chemistry. To help address this, a library of medium-sized lactams has been generated by using a simple, scalable and versatile ring-expansion protocol. Analysis of the library by using open-access computational tool LLAMA suggested that these lactams and their derivatives have highly promising physicochemical and 3D spatial properties and thus have much potential in drug discovery.


Soluble CD40 ligand and outcome in patients with coronary artery disease undergoing percutaneous coronary intervention.
CD40 ligand (CD40L), a transmembrane glycoprotein belonging to the tumor necrosis factor family and expressed by a variety of cells, is involved in the basic mechanisms of inflammation, atherosclerosis and thrombosis. Some studies suggest that the soluble form of CD40L (sCD40L) is a predictor of major cardiovascular events and mortality in a variety of clinical settings, but data from literature are conflicting. We studied consecutive patients with acute (ACS) or chronic (CCS) coronary syndrome who underwent percutaneous coronary artery intervention (PCI). Blood samples for sCD40L dosage were taken at baseline immediately before PCI. We tested the relation between sCD40L and pre-specified outcome measures consisting of new ACS, clinical restenosis and all-cause mortality. We recruited 3,841 patients (mean age 64 ± 11 years, 79% men) with ACS (n=2,383) or CCS (n=1,458). During a mean follow-up of two years (±0.6 years), 642 patients developed ACS, 409 developed restenosis (≥70% of at least one of the previously treated coronary segments) and 175 died. For each 1-standard deviation increase in sCD40L (0.80 ng/mL), the hazard ratios (HRs) for ACS, restenosis, and mortality were 1.11 (95% confidence interval [CI]: 1.05 to 1.18, p<0.0001), 1.10 (95% CI: 1.02 to 1.19, p=0.010), and 1.00 (95% CI: 0.86 to 1.16, p=0.983), respectively. In multivariable Cox regression models with adjustment for several potential confounders including age, acute or chronic coronary syndrome, multi-vessel disease, stent placement, diabetes, previous coronary events and dyslipidemia, sCD40L remained an independent predictor of ACS and coronary restenosis. There were no interactions between sCD40L and acute or chronic coronary syndrome or stent placement. Among patients with ACS or CCS who undergo PCI, higher levels of sCD40L predict an increased risk of acute coronary events and coronary restenosis, but not of mortality.


Neopterin concentrations in synovial fluid may reflect disease severity in patients with osteoarthritis.
We aimed to detect neopterin concentrations in serum and synovial fluid (SF) of knee osteoarthritis (OA) patients and to clarify their relationship with clinical severity of the disease. We cross-sectionally enrolled 176 knee OA patients and 63 age- and sex-matched controls. We measured neopterin concentrations by enzyme-linked immunosorbent assay (ELISA) and investigated the correlation between serum/SF neopterin concentrations and Kellgren-Lawrence (KL) grades as well as Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores in OA patients. Our results demonstrated that increased SF neopterin concentrations were independently correlated with greater symptomatic and radiographic severity in OA patients. These results suggested a crucial role of neopterin activation in the development and progression of knee OA. Assessment of neopterin levels in SF is a potential biomarker to evaluate disease severity in OA patients.


Liver volumetry plug and play: do it yourself with ImageJ.
A small remnant liver volume is an important risk factor for posthepatectomy liver failure and can be predicted accurately by computed tomography (CT) volumetry using radiologic image analysis software. Unfortunately, this software is expensive and usually requires support by a radiologist. ImageJ is a freely downloadable image analysis software package developed by the National Institute of Health (NIH) and brings liver volumetry to the surgeon's desktop. We aimed to assess the accuracy of ImageJ for hepatic CT volumetry. ImageJ was downloaded from http://www.rsb.info.nih.gov/ij/ . Preoperative CT scans of 15 patients who underwent liver resection for colorectal cancer liver metastases were retrospectively analyzed. Scans were opened in ImageJ; and the liver, all metastases, and the intended parenchymal transection line were manually outlined on each slice. The area of each selected region, metastasis, resection specimen, and remnant liver was multiplied by the slice thickness to calculate volume. Volumes of virtual liver resection specimens measured with ImageJ were compared with specimen weights and calculated volumes obtained during pathology examination after resection. There was an excellent correlation between the volumes calculated with ImageJ and the actual measured weights of the resection specimens (r(2) = 0.98, p < 0.0001). The weight/volume ratio amounted to 0.88 +/- 0.04 (standard error) and was in agreement with our earlier findings using CT-linked radiologic software. ImageJ can be used for accurate hepatic CT volumetry on a personal computer. This application brings CT volumetry to the surgeon's desktop at no expense and is particularly useful in cases of tertiary referred patients, who already have a proper CT scan on CD-ROM from the referring institution. Most likely the discrepancy between volume and weight results from exsanguination of the liver after resection.


Amyloid β-peptide neurotoxicity assay using cultured rat cortical neurons.
Neurons cultured from rodent central nervous system tissues represent an important tool in the study of neurodegenerative disease mechanisms and neuroregenerative processes, including the survival- and axon growth-promoting properties of neurotrophic factors. This chapter presents a detailed protocol for the preparation of rat and mouse cortical and hippocampal neuron cell cultures, using either embryonic or postnatal tissue.


Pentoxifylline inhibits liver expression of tumor necrosis factor alpha mRNA following normothermic ischemia-reperfusion.
Pentoxifylline (PTX) has been shown to reduce hepatic injury after normothermic ischemia and reperfusion (I-R) in rat liver. The aim of this study was to evaluate the effects of PTX on liver expression of tumor necrosis factor alpha (TNFalpha) mRNA following normothermic liver I-R. A segmental normothermic ischemia of the liver was induced in male Lewis rats by occluding the blood vessels including the bile duct to the median and left lateral lobes for 90 min. At the end of ischemia the nonischemic liver lobes were resected. Rats were divided into three groups: group 1, control Ringer lactate administration; group 2, PTX treatment; group 3, sham-operated control rats. PTX (50 mg/kg) was injected intravenously 30 min before and 60 min after induction of ischemia. Survival rates were compared and the serum activities of TNFalpha, serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) were measured. Histology of the liver was assessed 6 h after reperfusion. Liver TNFalpha mRNA was assessed by PCR amplification at 0, 60, 120, and 210 min after reperfusion. PTX treatment significantly increased 7 day survival (93.3%) compared with nontreated control rats (46.6%, p<0.007). The extent of liver necrosis and the release of liver enzymes were significantly decreased after PTX treatment. Serum activities of TNFalpha were significantly decreased and liver expression of TNFalpha mRNA was inhibited after PTX treatment. PTX protects the liver from ischemic injury and inhibits liver expression of TNFalpha mRNA.


Recurrence pattern for superficial bladder cancer.
Patients with superficial bladder tumors sometimes have long recurrence-free intervals. We evaluated whether patients with long recurrence-free periods had subsequent recurrences. We also clarified how these patients should be followed. We enrolled 244 patients with superficial bladder cancer (62 pTa and 182 pT1) treated by transurethral resection of bladder tumor (TURBT) and adjuvant chemotherapy with pirarubicin. Median follow up was 75.5 months. Patients were stratified by the length of their recurrence-free interval. Recurrences occurred in 124 patients (50.8%). Of 185 patients who did not have a recurrence for the first 3 years, subsequent recurrences occurred in 65 patients; in more than half the first recurrence developed after 5 years or more. Ta tumors had a low recurrence rate (14.5%) with the first recurrence often developing after a long recurrence-free period. Of 40 patients who remained recurrence-free for 3 years or more after at least one recurrence occurred, 16 patients (40%) had subsequent recurrences. Furthermore, most of these patients who remained free of recurrence for more than 5 years eventually had a recurrence. The overall progression rate was 15.6%, and this did not relate to the length of the recurrence-free interval. When patients did not have a recurrence for the first 3 years, tumors subsequently often recurred, even in pTa tumors. In patients with at least once recurrence, subsequent recurrences appear to occur irrespective of the length of the recurrence-free period. Thus, we recommend that all patients with superficial bladder tumors be followed for as long as possible.


Involvement of the endothelin and nitric oxide systems in the pathogenesis of renal ischemic damage in an experimental diabetic model.
Ischemic acute kidney injury (iAKI) in experimental diabetes mellitus (DM) is associated with a rapid kidney dysfunction more than in non-diabetic rats. We hypothesize that this vulnerability is due to excessive endothelin-1 (ET-1) expression along with dysregulation of nitric oxide synthase (NOS) isoforms. The aim of the present study was to assess the impact of ischemia on renal function in diabetic rats as compared with non-diabetic rats, and to investigate the involvement of ET-1 and NO systems in the susceptibility of diabetic kidney to ischemic damage. DM was induced by Streptozotocin. iAKI was induced by clamping of left renal artery for 30 min. Right intact kidney served as control. 48 h following ischemia, clearance protocols were applied to assess glomerular filtration rate (GFR), urinary flow (V) and sodium excretion (U(Na)V) in both kidneys. The renal effects of ABT-627, ET(A) antagonist; A192621.1, ET(B) antagonist; L-NAME, NOS non-selective inhibitor; 1400 W, inducible NOS (iNOS) inhibitor; and NPLA, neuronal NOS (nNOS) inhibitor, were assessed following ischemic renal injury in diabetic rats. Induction of iAKI in diabetic and non-diabetic rats caused significant reductions in GFR, V, and U(Na)V, which were greater in diabetic than non-diabetic rats. While, treatment with ABT-627 decreased V and U(Na)V, and increased GFR, A192621.1 decreased all these parameters. L-NAME, 1400 W, and NPLA improved GFR in the ischemic diabetic kidney. Excessive vasoconstrictive effects of ET-1 via ET(A) and upregulation of iNOS, are partly responsible for the impaired recovery of renal function following ischemia in diabetic rats.


Coats disease in female population: A comparison of clinical presentation and outcomes.
To compare clinical characteristics at presentation and outcomes of Coats disease between females and males. In this retrospective, consecutive case series we included all children diagnosed with Coats disease in a single tertiary referral center. Initial clinical presentation, treatment and outcomes were collected. A total of 158 children were included, of whom 29 (18.3%) were females and 11 (6.9%) had bilateral involvement. Age at diagnosis and disease stage were similar between females and males. Females had more bilateral involvement (p < 0.001) and tended to have a worse visual acuity at diagnosis (p = 0.05). At last follow-up, visual acuity and anatomical outcome after treatment were similar between genders. Female patients with Coats disease had more bilateral involvement and tended to have worse visual acuity at presentation. Clinical presentation and outcomes seemed to be similar between genders.


Long-Term Opioid Prescriptions After Spine Surgery: A Meta-Analysis of Prevalence and Risk Factors.
Opioids are frequently prescribed for back pain, but the prevalence of and risk factors for long-term opioid use after spine surgery were not clearly reported. We conducted a systematic review and meta-analysis to summarize the evidence for long-term opioid use (>90 days) among adults who underwent spine surgery. PubMed, EMBASE, and Cochrane indexing databases were searched until November 9, 2018 for studies reporting the prevalence of and risk factors for long-term opioid use after spine surgery. Separate meta-analyses were conducted for commercial claims databases or registries (claims/registries) and nonclaims observational studies using the random-effects model to estimate the pooled odds ratio (OR). Prevalence meta-analysis was performed in a clinically homogeneous subset of these patients who underwent lumbar spine surgery. Eight claims and 5 nonclaims were meta-analyzed to avoid double-counting participants. The meta-analysis showed that preoperative opioid users (OR, 5.59; 95% confidence interval [CI], 3.37-9.27 vs. OR 4.21; 95% CI, 2.72-6.51) and participants with preexisting depression and/or anxiety (OR, 1.86, 95% CI, 1.43-2.42 and OR, 1.20; 95% CI, 0.83-1.74, respectively) had a statistically significantly higher odds of long-term postoperative opioids, compared with their peers. Males showed lower odds of long-term postoperative opioid use in the claims group (OR, 0.85; 95% CI, 0.79-0.92), but not in the nonclaims group (OR, 0.99; 95% CI, 0.71-1.39). The pooled prevalence of post-lumbar spine surgery long-term opioid use was 63% (95% CI, 50%-74%) in claims and 47% (95% CI, 38%-56%) in nonclaims. Patients undergoing spine surgery represent a high-risk surgical population requiring special attention and targeted interventions, with the strongest evidence for those treated with opioids before surgery and those with psychiatric comorbidities.


Respective healthcare system performances taking into account environmental quality: what are the re-rankings for OECD countries?
Efficiency analyses have been widely used in the literature to rank countries regarding their health system performances. However, little place has been given to the environmental aspect: two countries with the same characteristics could experience completely different healthcare system outcomes just because they do not face the same environmental quality situation, which is a major determinant of the health of inhabitants. Using a stochastic frontier model, this paper analyses the effect of environmental quality on health system outcomes in OECD countries, measured by life expectancy at birth. We show that the healthcare system performance ranking of OECD countries changes significantly, depending on whether the environmental index is taken into account. These findings, once again, underline the critical importance of the environment when addressing population health issues. In general, our results can be aligned with the messages of the One Health approach literature.


Functional columns in the primate prefrontal cortex revealed by optical imaging in vitro.
Although the functional column has been implicated in the dorsolateral prefrontal cortex (DLPFC) of primates, its dynamics and even existence are still uncertain. We performed optical recording with a voltage-sensitive dye (RH482) in brain slices obtained from the principal sulcal region (area 46) of macaque monkeys. Columnar activity was evoked by electrical stimulation of the middle layer (lower layer III or layer IV); this activity consisted of two components: probably action potentials and excitatory postsynaptic potentials. The width of the columnar activity was saturated when the current intensity of stimulation exceeded a certain level, that is, approximately 900 microm at the peak with this intensity. The stimulation of different sites within the same slice activated different columnar activities with only slight overlaps. Furthermore, similar columnar activity appeared when a different site within the area with columnar activity was stimulated. These findings suggest that the primate DLPFC consists of functional columns formed by excitatory synaptic connections.


Barriers to access to antiretroviral therapy by people living with HIV in an indonesian remote district during the COVID-19 pandemic: a qualitative study.
Coronavirus disease (COVID-19) pandemic has a significant influence on the access to healthcare services. This study aimed to understand the views and experiences of people living with HIV (PLHIV) about barriers to their access to antiretroviral therapy (ART) service in Belu district, Indonesia, during the COVID-19 pandemic. This qualitative inquiry employed in-depth interviews to collect data from 21 participants who were recruited using a snowball sampling technique. Data analysis was guided by a thematic framework analysis. The findings showed that fear of contracting COVID-19 was a barrier that impeded participants' access to ART service. Such fear was influenced by their awareness of their vulnerability to the infection, the possibility of unavoidable physical contact in public transport during a travelling to HIV clinic and the widespread COVID-19 infection in healthcare facilities. Lockdowns, COVID-19 restrictions and lack of information about the provision of ART service during the pandemic were also barriers that impeded their access to the service. Other barriers included the mandatory regulation for travellers to provide their COVID-19 vaccine certificate, financial difficulty, and long-distance travel to the HIV clinic. The findings indicate the need for dissemination of information about the provision of ART service during the pandemic and the benefits of COVID-19 vaccination for the health of PLHIV. The findings also indicate the need for new strategies to bring ART service closer to PLHIV during the pandemic such as a community-based delivery system. Future large-scale studies exploring views and experiences of PLHIV about barriers to their access to ART service during the COVID-19 pandemic and new intervention strategies are recommended.


Castration-resistant prostate cancer cells are dependent on the high activity of CDK7.
Prostate cancer (PC) is successfully treated with anti-androgens; however, a significant proportion of patients develop resistance against this therapy. Anti-androgen-resistant disease (castration-resistant prostate cancer; CRPC) is currently incurable. Cyclin-dependent kinase 7 (CDK7) is positioned to positively regulate both cell cycle and transcription, the two features critical for the rapid proliferation of the CRPC cells. Here, we assess if CDK7 is a viable target to halt the proliferation of CRPC cells. We use recently developed clinically relevant compounds targeting CDK7 and multiple cell proliferation assays to probe the importance of this kinase for the proliferation of normal, androgen-dependent, and CRPC cells. PC patient data were used to evaluate expression of CDK7 at different disease-stages. Finally, comprehensive glycoproteome-profiling was performed to evaluate CDK7 inhibitor effects on androgen-dependent and CRPC cells. We show that CDK7 is overexpressed in PC patients with poor prognosis, and that CRPC cells are highly sensitive to compounds targeting CDK7. Inhibition of O-GlcNAc transferase sensitizes the CRPC, but not androgen-dependent PC cells, to CDK7 inhibitors. Glycoproteome-profiling revealed that CDK7 inhibition induces hyper-O-GlcNAcylation of the positive transcription elongation complex (pTEFB: CDK9 and CCNT1) in the CRPC cells. Accordingly, co-targeting of CDK7 and CDK9 synergistically blocks the proliferation of the CRPC cells but does not have anti-proliferative effects in the normal prostate cells. We show that CRPC cells, but not normal prostate cells, are addicted on the high activity of the key transcriptional kinases, CDK7 and CDK9.


Clinical pharmacokinetics of oxaprozin.
Oxaprozin is a nonsteroidal anti-inflammatory drug which reaches peak plasma concentrations 2 to 6 hours after oral administration. Oxaprozin binds extensively, in a concentration-dependent manner, to plasma albumin. The area under the plasma concentration-time curve (AUC) of oxaprozin is linearly proportional to the dose for oral doses up to 1200 mg. At doses greater than 1200 mg there is an increase in the unbound fraction of drug, leading to an increased clearance and volume of distribution (Vd) of total oxaprozin. Accumulation of the drug at steady state is between 40 and 58% lower than predicted by single dose data. After administration of multiple doses, the apparent oral clearance (CL/F) and Vd of total oxaprozin increased while those of the unbound drug decreased significantly. Substantial concentrations of oxaprozin are attained in synovial fluid, which is a proposed site of action for nonsteroidal anti-inflammatory drugs. Relationships between total plasma, unbound plasma and synovial concentrations, and therapeutic and toxicological effects have yet to be established. Oxaprozin is eliminated following biotransformation to glucuroconjugated metabolites which are excreted in urine and bile, with little drug being eliminated unchanged. Two hydroxylated metabolites have been shown to possess anti-inflammatory activity. Hepatic disease and rheumatoid arthritis do not significantly alter the disposition of oxaprozin. Patients with renal impairment demonstrate an increase in unbound plasma concentrations of oxaprozin. A significant drug interaction has been demonstrated between oxaprozin and aspirin (acetylsalicylic acid).


Early Revision Rates of Total Hip Arthroplasty Using the Intellijoint HIP Computer Navigation System: A Study From the Australian National Joint Replacement Registry of 1911 Procedures.
Total hip arthroplasty (THA) is an effective treatment for symptomatic hip osteoarthritis. The aim of this study was to determine the revision outcome of commercially available navigation technologies. Data from the Australian Orthopaedic Association National Joint Replacement Registry from January 2016 to December 2020 included all primary THA procedures performed for osteoarthritis. Procedures using the Intellijoint HIP navigation system were identified and compared to procedures using "other" computer navigation systems and to nonnavigated procedures. The cumulative percent revision (CPR) was compared between the 3 groups using Kaplan-Meier estimates of survivorship and hazard ratios from Cox proportional hazards models, adjusted for age and gender. There were 1911 procedures that used the Intellijoint system, 4081 used "other" computer navigation systems, and 160,661 were nonnavigated procedures. The all-cause 2-year CPR rate for the Intellijoint system was 1.8% (95% confidence interval [CI], 1.2-2.6), compared to 2.2% (95% CI, 1.8-2.8) for other navigated cases and 2.2% (95% CI, 2.1-2.3) for nonnavigated cases. A prosthesis analysis identified the Paragon/Acetabular Shell THAs combined with the Intellijoint system to have a higher (3.4%) rate of revision than nonnavigated THAs (hazard ratio = 2.00 [95% CI, 1.01-4.00], P = .048). When this combination was excluded, the Intellijoint group demonstrated a 2-year CPR of 1.3%. There was no statistical difference in the CPR between the 3 groups before or after excluding the Paragon/Acetabular Shell system. The preliminary data presented demonstrate no statistical difference in all-cause revision rates when comparing the Intellijoint system with "other" navigation systems and "nonnavigated" approaches for primary THAs. III (National registry analysis).


Accurate transcription of a cloned gene from Babesia bovis in Saccharomyces cerevisiae.
Two cloned chromosomal segments of the hemoprotozoan Babesa bovis bearing genes from the polymorphic locus designated BabR were inserted into plasmid vector YCp19, cloned in Escherichia coli and then introduced into Saccharomyces cerevisiae. Both genes were transcribed producing poly(A+) RNAs. In at least one case, the transcript was very similar if not identical to that produced in B. bovis. It is therefore possible that S. cerevisiae can recognize at least some hemoprotozoan promoter and poly(A+)-addition signals.


The diversity and function of soil microbial communities exposed to different disturbances.
To improve understanding of the relationship between the diversity and function of the soil ecosystem, we investigated the effect of two different disturbances on soil bacterial communities -- long-term exposure to the heavy metal mercury and transient exposure to the antibiotic tylosin. In the mercury-contaminated soil the diversity (Shannon index) was reduced as assessed from denaturing gradient gel electrophoresis (DGGE) of amplified 16S rDNA sequences from the soil community DNA and from colony morphology typing of the culturable bacterial population. However, analysis of the substrate utilization profiles did not reveal any differences in diversity. In the tylosin-treated soil, DGGE revealed a small difference in the diversity of 16S rDNA compared to the control soil, whereas analysis of the colony morphology typing or substrate utilization results did not reveal any differences in diversity. Soil function was also affected by mercury contamination. The lag time before soil respiration increased following addition of glucose or alfalfa substrate was longer in the mercury-contaminated soil than in the control soil. Moreover, it was markedly prolonged in mercury-contaminated soil subjected to heat treatment prior to substrate addition, thus indicating reduced resistance to a new disturbance in the mercury-contaminated soil as compared to the control soil. Tylosin treatment did not have any significant effect on any of the respiration parameters measured, either with or without prior heat treatment of the soil.


Preclinical Research on a Mixture of Red Ginseng and Licorice Extracts in the Treatment and Prevention of Obesity.
The anti-obesity effects of RL (a 3:1 mixture of Panax ginseng saponin fractions and Glycyrrhiza glabra L. extracts) on 3T3-L1 adipocytes and C57BL/6J obese mice were evaluated at different concentrations. We investigated the anti-obesity effects of RL through lipid accumulation inhibition rate, serum lipid composition analysis, adipose tissue size, adipogenic transcription factors and AMPK pathway. RL inhibited the lipid accumulation of 3T3-L1 adipocytes in a dose-dependent manner at concentrations of 50-200 μg/mL without cytotoxicity (50-400 μg/mL). Oral administration of RL at the highest concentration (400 mg/kg/day) did not cause significant liver toxicity in high-fat diet-induced obese mice. RL stimulated adiponectin secretion in a dose-dependent manner and primarily mediates the AMPK pathway to inhibit triglyceride synthesis and attenuate adipocyte hypertrophy. RL significantly reduced weight in obese mice, but none of the body weight, adipose tissue weight, serum triglyceride level, and AMPK pathway activation degree showed any difference between dosing concentrations of 200 and 400 mg/kg/day. Therefore, 200 mg/kg/day of RL is the optimal preclinical concentration, which can be a reference concentration for conversion into a human clinical trial dose.


Red pitaya peels-based carbon dots for real-time fluorometric and colorimetric assay of Au3+, cellular imaging, and antioxidant activity.
The synthesis of fascinating multifunctional carbon dots (CDs) attracted immense attention. Here, a facile solvothermal treatment of red pitaya peels in acetic acid produced CDs (designated as ACDs, excitation/emission wavelengths at 357/432 nm). ACDs with high sp2-hybridized carbon and carboxylic group contents can rapidly and selectively reduce Au3+ to Au0, and stabilize produced Au nanoparticles (AuNPs). The synergetic effect of electron transfer from ACDs to Au3+ and inner filter effect (IFE) from ACDs to AuNPs quenches the fluorescence within 30 s. Simultaneously, the resulting AuNPs have a purple color with a maximum absorption at 545 nm for visual detection. Therefore, for the first time, we reported a fluorometric and colorimetric dual-mode sensing system for real-time, highly sensitive and selective detection of Au3+. The fluorescence quenching ratio and absorbance change linearly with the increase of Au3+ concentration in the range of 0.3-8.0 μM and 3.3-60.0 μM with limits of detection (LODs) at 0.072 μM and 2.2 μM, respectively. The assay was applied for Au3+ determination in spiked real water samples with recoveries from 95.5 to 105.0%, and relative standard deviation (RSD) of less than 6.5%. Furthermore, ACDs with good photostability, low cytotoxicity, and excellent biocompatibility were successfully applied for intracellular Au3+ sensing and imaging. In addition, ACDs exhibited an extraordinarily high antioxidant activity, with an IC50 value for DPPH radical scavenging (0.70 μg mL-1) much lower than that of ascorbic acid (4.34 μg mL-1). The proposed strategy demonstrates the outstanding properties of ACDs in chemical and biomedical analysis. Graphical abstract.


Canadian court dismisses Pfizer attempt to prevent approval of generic fluconazole.
On 10 January 2001, Pfizer lost its bid before the Federal Court of Appeal to prohibit the federal Minister of Health from issuing approvals for two generic versions of the drug fluconazole.


Micro-CT visualization of the cricothyroid joint cavity in cadavers.
To directly visualize the cricothyroid joint (CTJ) cavity of the human cadaver and to correlate the appearance of the CTJ cavity to its fibrous capsule. Prospective. Twenty-five cadavers (nine females and 16 males; age range, 67-95 years) were used for gross anatomy, micro-computed tomography (CT) arthrography, histology, E12 sheet plastination, and magnetic resonance imaging examinations. The cadavers were donated for the purposes of teaching and research under the Human Tissues Act. Using micro-CT arthrography with intra-articular filling and sheet plastination technique, this study demonstrated that the dimension of the CTJ cavity was much larger than that of the articular surfaces, particularly at the superior and anterior aspects of the joint. Connective tissue fibers were regularly orientated and significantly strengthened in the posterior and inferior aspects of the CTJ capsule. Such fibrous configuration appeared to enhance the strength of the capsule itself rather than to shorten the distance between the articular surfaces. The size of the direct contact area of the opposing articular surfaces varied significantly between the sides of the same subject and among individuals. This study supports the general view that the cricoid cartilage rotates in a visor-like fashion on the inferior cornu of the thyroid cartilage. However, the pivot for the CTJ rotation appears wobbly. The wobbly pivot may increase the joint mobility as the rotation allows the horizontal and vertical gliding movements of the CTJ.


High cervical spinal cord injury in neonates delivered with forceps: report of 15 cases.
To inform obstetricians of a serious complication of forceps rotations of 90 degrees or more--high cervical spinal cord injury in neonates. We reviewed the obstetric aspects of 15 cases of high cervical spinal cord birth injury diagnosed during 1982-1994 at two tertiary-care children's hospitals in Canada. The common feature in all cases was a forceps cephalic delivery, almost always a rotation of 90 degrees or more from the occipitoposterior or occipitotransverse position. High cervical spinal cord injury in neonates is a rare but specific complication of forceps rotation.


Heparin-released extracellular superoxide dismutase is reduced in patients with coronary artery atherosclerosis.
We studied whether the amount of heparin-released extracellular superoxide dismutase (EC-SOD), which is an antioxidative enzyme, is associated with coronary artery disease (CAD). EC-SOD was measured in plasma at basal and at post-heparin injection in 315 patients. Heparin-released EC-SOD was calculated as the difference between the two values. After exclusion of a mutant EC-SOD group (n = 27:8.6%), 288 patients were divided into three groups by angiographic findings; those with normal coronary (the normal group; n = 63), those with atherosclerosis without significant stenosis (the mild atherosclerosis group; n = 36), and those with significant stenosis (the atherosclerosis group; n = 189). Although the basal values were similar among the three groups, heparin-released EC-SOD levels were significantly lower in the atherosclerosis group (131.0 +/- 42.8 ng/ml, p = 0.0003) than in the normal group (156.9 +/- 66.2 ng/ml). Moreover, logistic analysis revealed that heparin-released EC-SOD independently contributed to CAD. The coronary score showed a significant correlation with heparin-released EC-SOD. As for factors affecting the level of heparin-released EC-SOD, the level of high-density lipoprotein cholesterol and age showed a positive correlation. The results suggest that heparin-released EC-SOD is significantly reduced in CAD and that the tissue-bound location of this enzyme might be important for antioxidative function.


CENP-I is essential for centromere function in vertebrate cells.
We identified a novel essential centromere protein, CENP-I, which shows sequence similarity with fission yeast Mis6 protein, and we showed that CENP-I is a constitutive component of the centromere that colocalizes with CENP-A, -C, and -H throughout the cell cycle in vertebrate cells. To determine the precise function of CENP-I, we examined its role in centromere function by generating a conditional loss-of-function mutant in the chicken DT40 cell line. In the absence of CENP-I, cells arrested at prometaphase with misaligned chromosomes for long periods of time. Eventually, cells exited mitosis without undergoing cytokinesis. Immunocytochemical analysis of CENP-I-deficient cells demonstrated that both CENP-I and CENP-H are necessary for localization of CENP-C but not CENP-A to the centromere.


Renal vasodilating capacity and endothelial function are impaired in patients with obstructive sleep apnea syndrome and no traditional cardiovascular risk factors.
Patients with obstructive sleep apnea syndrome exhibit accelerated vascular aging and renal damage. Aim of the study was to investigate whether vascular dysfunction is a feature of obstructive sleep apnea syndrome per se or instead related to the presence of traditional cardiovascular risk factors. Forty patients with moderate-severe obstructive sleep apnea syndrome (20 with, 20 without traditional risk factors) and 20 matched healthy controls were enrolled. Renal vasodilating capacity, endothelium-dependent vasodilation in the brachial artery, carotid-femoral pulse wave velocity and carotid stiffness were measured. Oxidative stress, endothelial biomarkers and leukocyte adhesion molecule levels were also evaluated. Apneic patients without traditional cardiovascular risk factors presented reduced endothelium-dependent vasodilation (3.7±2.1 versus 6.1±3.0%, P<0.05), increased serum E-selectin (49.8±11.5 versus 38.9±17.9 ng/ml, P<0.05), and impaired renal vasodilating capacity (6.0±4.3 versus 10.4±6.1%, P<0.05), as compared to healthy controls. Endothelial NO synthase expression was reduced (0.0133 versus 0.0221×10 copies/μg RNA, P<0.05), whereas oxidative stress parameters and leukocyte adhesion molecules were similar to controls. Patients with obstructive sleep apnea syndrome and traditional risk factors also exhibit increased aortic and carotid stiffness, increased renal resistive index and intima-media thickness, and reduced expression of the endothelial progenitor cell marker CD34: however, these parameters were similar to those of healthy controls in patients with isolated obstructive sleep apnea syndrome. Obstructive sleep apnea syndrome is characterized by endothelial dysfunction and activation and impaired renal vasodilating capacity even in the absence of traditional cardiovascular risk factors, possibly due to reduced endothelial NO synthase expression.


A water-soluble, monitorable peptide and protein crosslinking agent.
A novel, freely water-soluble, heterobifunctional crosslinking reagent, N-maleimido-6-aminocaproyl ester of 1-hydroxy-2-nitro-4-benzenesulfonic acid (mal-sac-HNSA), was synthesized and used for conjugation of sulfhydryl (cysteine)-containing peptides to carrier proteins. Reaction with amino groups releases the dianion phenolate, HNSA, which allows convenient spectrophotometric quantitation of the reaction in progress. Since mal-sac-HNSA is completely water soluble, its concentration can be adjusted to maximize the rate of amine reaction and to minimize hydrolysis. Conjugates of peptides to appropriate carriers have elicited peptide-specific antibody and did not elicit detectable antibody specific to the crosslink.


Decoding the reaction mechanism of the cyclocondensation of ethyl acetate2-oxo-2-(4-oxo-4H-pyrido [1.2-a] pyrimidin-3-yl) polyazaheterocycle and ethylenediamine using bond evolution theory.
We investigated the flow of electron density along the cyclocondensation reaction between ethyl acetate 2-oxo-2-(4-oxo-4H-pyrido[1.2-a]pyrimidin-3-yl) polyazaheterocycle (1) and ethylenediamine (2) at the ωB97XD/6-311++G(d,p)computational method within of bond evolution theory (BET). The exploration of potential energy surface shows that this reaction has three channels (1-3) with the formation of product 3 via channel-2 (the most favorable one) as the main product and this is in good agreement with experimental observations. The BET analysis allows identifying unambiguously the main chemical events happening along channel-2. The mechanism along first step (TS2-a) is described by a series of four structural stability domains (SSDs), while five SSDs for the last two steps (TS2-b and TS2-c). The first and third steps can be summarized as follows, the formation of N1-C6 bond (SSD-II), then, the restoration of the nitrogen N1 lone pair (SSD-III), and finally, the formation of the last O1-H1 bond (SSD-IV). For the second step, the formation of hydroxide ion is noted, as a result of the disappearance of V(C6,O7) basin and the transformation of C6-N1 single bond into double one (SSD-IV). Finally, the appearance of V(O7,H2) basin lead to the elimination of water molecule within the last domain is observed.


Perioperative change in peripheral blood monocyte count may predict prognosis in patients with colorectal liver metastasis after hepatic resection.
Prognostic value of perioperative change in peripheral blood leukocyte subset count of cancer patients have not been fully investigated. Therefore, we retrospectively investigated the relation between perioperative change in peripheral blood monocyte count and disease-free as well as overall survival after hepatic resection for colorectal liver metastasis (CRLM). The subjects were 64 patients who underwent hepatic resection for CRLM between January 2000 and December 2008. We retrospectively investigated the relation between perioperative change in peripheral blood monocyte count and disease-free as well as overall survival. In multivariate analysis, more than four lymph node metastases (P = 0.0298) and extrahepatic disease (P = 0.0423) were significant predictors of disease-free survival, while significant predictor of overall survival were more than four lymph node metastases (P = 0.0011), bilobar disease (P = 0.0024), and increase in perioperative monocyte less than twice (P = 0.0029). Morover, increase in perioperative monocyte of less than twice positively correlated with intraoperative blood transfusion. Perioperative change in peripheral blood monocyte count is an independent risk factor for overall survival after hepatic resection for CRLM, and may reflect immunosuppressive state.


Use of Prograf (FK 506) as rescue therapy for refractory rejection after liver transplantation. US Multicenter FK 506 Liver Study Group.
This report describes the clinical characteristics and demographics of patients enrolled into this rescue trial for patients experiencing refractory rejection after liver transplantation. Actuarial graft and patient survival at 12 months postconversion was 50% and 72%, respectively. Actual treatment success at 3 months postconversion was 70%. Karnofsky scores and liver function tests were significantly improved for patients continuing on therapy indicating clinical benefit in these patients. The safety profile of FK 506 is acceptable for such a high-risk group of patients. These preliminary clinical results support the conclusion that FK 506 can effectively control and reverse refractory rejection in a majority of liver transplantation patients.