A single, global patient-centered measure from the SF-36 instrument to assess surgical outcomes and quality of life: a pilot study.
Many quality of life (QoL) and patient-reported outcomes (PRO) measures have been developed to assess the effects of disease processes and treatments. Although these instruments are valuable, the process is hampered because of their number and lack of interchangeability. We identified a cohort of patients across a variety of operations within 3-12 months postoperatively. Patients completed the SF-36, measuring eight domains of QoL (physical functioning, role-physical, role-emotional, bodily pain, vitality, mental health, social functioning, and general health), plus a health transition item: Compared to one year ago, how would you rate your health in general now?. (1) Much better now than one year ago. (2) Somewhat better now than one year ago. (3) About the same as one year ago. (4) Somewhat worse than one year ago. (5) Much worse than one year ago. Additional data included improvement of preoperative symptoms, the occurrence of any postoperative symptoms, and the occurrence of any postoperative complications. Of 217 patients, 28 % were much better, 28 % somewhat better, 27 % unchanged, 13 % somewhat worse, and 3 % much worse. The health transition results were associated with all SF-36 domains, preoperative symptom change (p = 0.03) and persistent or new postoperative symptoms (p = 0.001), but not postoperative complications. Patients with persistent or new symptoms postoperatively had worse scores in the role-emotional (p = 0.01), bodily pain (p = 0.05), social functioning (p = 0.02), and mental health (p = 0.009) domains of the SF-36. This single, global assessment of health transition may be a promising practical alternative to assess postoperative patient-centered outcomes. Improved patients had better QoL scores, preoperative symptoms elimination, and no operation-related symptoms, but the occurrence of complications did not affect improvement.


Simultaneous SGLT2 inhibition and caloric restriction improves insulin resistance and kidney function in OLETF rats.
SGLT2 inhibitors (SGLT2i) are emerging as a novel therapy for type 2 diabetes due to their effective hypoglycemic and potential cardio- and nephroprotective effects, while caloric restriction (CR) is a common behavioral modification to improve adiposity and insulin resistance. Therefore, both interventions simultaneously may potentially further improve metabolic syndrome by enhancing carbohydrate metabolism. To test this hypothesis, cohorts of 10-week old, male Long Evans Tokushima Otsuka (LETO) and Otsuka Long Evans Tokushima Fatty (OLETF) rats were treated with SGLT2i (10 mg luseoglifozin/kg/day x 4 wks) (OLETF only) and/or 30% CR (2 wks at 12 weeks of age). CR maintained body mass in both strains while SGLT2i alone did not have any effect on body mass. Simultaneous treatments decreased SBP in OLETF vs SGLT2i alone, decreased insulin resistance index (IRI), and increased creatinine clearance vs OLETF ad lib. Conversely, CR decreased albuminuria independent of SGLT2i. In conclusion, SGLT2i treatment by itself did not elicit significant improvements in insulin resistance, kidney function or blood pressure. However, when combined with CR, these changes where more profound than with CR alone without inducing chronic hypoglycemia.


Social management of LPS-induced inflammation in Formica polyctena ants.
Invertebrates, and especially insects, constitute valuable and convenient models for the study of the evolutionary roots of immune-related behaviors. With stable conditions in the nest, high population densities, and frequent interactions, social insects such as ants provide an excellent system for examining the spread of pathogens. The evolutionary success of these species raises questions about the behavioral responses of social insects to an infected nestmate. In this experiment, we tested the behavioral changes of the red wood ant Formica polyctena toward an immune-stimulated nestmate. We used bacterial endotoxin (lipopolysaccharides, LPS) to active the innate immune system of individual worker ants without biasing our observation with possible cues or host-manipulation from a living pathogen. We show that LPS-induced immune activation in ants triggers behavioral changes in nestmates. Contrary to what would be expected, we did not find removal strategies (e.g. agonistic behaviors) or avoidance of the pathogenic source, but rather a balance between a limitation of pathogen dissemination (i.e. decreased trophallaxis and locomotion of the LPS-treated ant), and what could constitute the behavioral basis for a "social vaccination" (i.e. increased grooming). This supports the importance of social interactions in resistance to disease in social insects, and perhaps social animals in general.


Predator-prey interactions and community structure: chironomids, mosquitoes and copepods in Heliconia imbricata (Musaceae).
Evidence from both field observations and experimental work indicates that predation by larvae of a midge, Pentaneura n. sp. (Chironomidae), causes the low densities of mosquito larvae (Culicidae) found in the water filled bracts of Heliconia imbricata (Musaceae), microhabitats typically colonized by mosquitoes. This predation affects 2 species of mosquitoes, Wyeomyia pseudopecten, a resident species, and Trichoprosopon digitatum, a non-resident species. Predation keeps resident mosquito densities low while completely excluding the nonresident mosquito from the habitat. Both these effects of predation depend on the presence of an abundant alternative prey, an undescribed species of harpacticoid copepod found in the bracts. These copepod prey sustain chironomids when resident mosquito densities are low, permiting predator densities to remain high enough to exclude the non-resident mosquito. I discuss the evolutionary and ecological implications of predation structuring communities.


Genetic basis and molecular profiling in myeloproliferative neoplasms.
BCR::ABL1-negative myeloproliferative neoplasms (MPNs) are clonal diseases originating from a single hematopoietic stem cell that cause excessive production of mature blood cells. The 3 subtypes, that is, polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are diagnosed according to the World Health Organization (WHO) and international consensus classification (ICC) criteria. Acquired gain-of-function mutations in 1 of 3 disease driver genes (JAK2, CALR, and MPL) are the causative events that can alone initiate and promote MPN disease without requiring additional cooperating mutations. JAK2-p.V617F is present in >95% of PV patients, and also in about half of the patients with ET or PMF. ET and PMF are also caused by mutations in CALR or MPL. In ∼10% of MPN patients, those referred to as being "triple negative," none of the known driver gene mutations can be detected. The common theme between the 3 driver gene mutations and triple-negative MPN is that the Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling pathway is constitutively activated. We review the recent advances in our understanding of the early events after the acquisition of a driver gene mutation. The limiting factor that determines the frequency at which MPN disease develops with a long latency is not the acquisition of driver gene mutations, but rather the expansion of the clone. Factors that control the conversion from clonal hematopoiesis to MPN disease include inherited predisposition, presence of additional mutations, and inflammation. The full extent of knowledge of the mutational landscape in individual MPN patients is now increasingly being used to predict outcome and chose the optimal therapy.


Development and characterization of secondary standards for nucleic acid amplification technology (NAAT) assays for detection of hepatitis E virus.
To harmonize assays for detection of HEV RNA, a World Health Organization International Standard (WHO IS) was established. The WHO IS represents the highest order standard for HEV RNA but is limited in quantity. Secondary standards are needed to limit the use of WHO IS and minimize the need to replace it. Establish secondary standards for HEV NAAT assays and to calibrate these against the WHO IS. Stocks of genotype 3 HEV were prepared using both cell lysates and cell culture supernatants to produce non-enveloped and quasi-enveloped virus stocks, respectively. Both stocks were heat-inactivated, diluted in negative human plasma, and lyophilized to produce two candidate secondary standards: HEV-RR (non-enveloped virus) and HEV-RR.1 (quasi-enveloped virus). Both candidate standards were characterized and calibrated against the WHO IS for HEV RNA in an international collaborative study. The collaborative study returned a total of 15 data sets, with different RNA extraction and amplification methods. The estimated mean values relative to the WHO IS (250,000 IU/ml) are 229,000 IU/ml and 355,000 IU/ml for HEV-RR and HEV-RR.1, respectively. We have established two secondary standards for HEV RNA calibrated against the WHO IS. These standards are non-infectious and stable under different storage temperatures.


[The basic research on fabricating an ear model by means of rapid prototyping (FDM)].
The purpose of the study was to reconstruct a 3-D auricular model. Laser scanning was used to get the data of an auricular model, Fused Deposition Manufacturing (one of rapid prototyping technique) was chosen to fabricate an ear cast. The differences between the two models were compared. The result showed that the reconstructed model was precise. This study suggests that the technique of rapid prototyping is precise, convenient, effective and safe to auricular prosthesis.


Visual information from the lower visual field is important for walking across multi-surface terrain.
Visual information concerning characteristics of the environment is critical for safe navigation. The purpose of this study was to determine the importance of vision from the lower visual field for negotiating multi-surface terrain. Ten healthy young adults and ten healthy older adults walked across a walkway where the middle portion consisted of solid, rock, slippery, compliant, tilt, and irregular surfaces (i.e. multi-surface terrain). Participants performed the walking trials with and without special glasses that blocked the lower visual field. Head pitch angle along with step parameters were measured. Young and older adults demonstrated increased mean and maximum head pitch angle downward when the lower visual field was blocked suggesting the importance of vision from this area when stepping on multi-surface terrain. In addition, young and older adults altered their gait pattern by reducing gait speed and step length when the lower visual field was blocked. These results suggest that information from the lower visual field is normally used when walking across multi-surface terrain. The results have implications for those individuals who wear multi-focal glasses and who use them while walking in complex environments, which may challenge balance.


How effective is antenatal care in preparing mothers for newborn care? An exploratory survey of lactating women in a rural Nigerian district.
Neonatal death rates are high in sub-Saharan Africa and the majority of these deaths are preventable. Antenatal care (ANC) is a good channel for the reduction of neonatal deaths. This study aimed to assess newborn care practices among lactating women in Nigeria and determine their relationship with ANC attendance. This was a cross-sectional survey involving 241 lactating mothers selected using the cluster sampling method. A structured interviewer-administered questionnaire was employed to obtain data. The Chi-square test was used to assess the associations between categorical variables. Logistic regression was used to determine the predictors of umbilical cord care, thermal care, and neonatal vaccination status. Good cord care was defined as having minimum of three appropriate practices concerning the use of clean instruments to tie the cord, use of clean instruments to cut the cord, and application of chlorhexidine, 70% alcohol, saltwater, or nothing on the cord), Results were presented as odds ratios (ORs). P < 0.05 was taken as statistically significant. The mean age of participants was 29.0 ± 5.5 years. Most participants reported that sterile instruments were used to cut their baby's umbilical cords; that their babies were dried immediately after placenta delivery and that their babies were fully vaccinated (91.0%, 90.5%, and 85.1% respectively). ANC visits (aOR = 8.0, p = 0.02) and place of delivery (aOR = 10.6, p = 0.01) were significantly associated with good umbilical cord care practices. However, none of the participants' sociodemographic characteristics were significantly associated with newborn thermal care and vaccination status. The prevailing antenatal care services are ineffective in preparing mothers for newborn care. Place and frequency of ANC have positive associations with umbilical cord care. There is a need to implement quality ANC that will enhance maternal and neonatal outcomes and implement innovative interventions to enhance ANC attendance. The WHO positive pregnancy experience model should be implemented.


Abrasion arthroplasty increases mesenchymal stem cell content of postoperative joint effusions.
Abrasion arthroplasty (AAP) is a procedure by which intrinsic cartilage healing is believed to be stimulated. Although clinically accepted for degenerative and traumatic cartilage lesions scientific evidence at a molecular level that proves the effect of AAP is scarce. Mononuclear cells were extracted from postoperative joint effusions 21.5 h post AAP and simple debridement of cartilage lesions. Luminex, ELISA and FACS experiments were performed. Immunohistochemical stainings of cell cultures for cartilage markers were used to confirm the findings. Postoperative joint effusions after AAP showed increased contents of Mononuclear cells compared to Arthroscopic Chondroplasty (ACP). BMP-4 and IGF were increased in AAP as complared to ACP. Mononuclear cells isolated after AAP express the MSC markers CD 73, CD 105, CD 90, CD 44 and are CD34 negative. Chondrogenic differentiation was demonstrated by positive staining for Sox9, collagen II, proteoglycan, chondroitin-4-sulfate. Our results support the clinical application of AAP as a procedure that enhances cartilage repair as an alternative to far more complex procedures that have gained popularity. Furthermore the data presented supports clinical investigations that recommend not to use suction drainage as by this procedure a considerable amount of the regeneratory potential of postoperative joint effusions might be extracted.


Sonic hedgehog causes mural cells to jump 'n' run.
In this issue of Blood, Yao and colleagues report that the morphogen sonic hedgehog (Shh) is driven by platelet-derived growth factor B (PDGF-BB) in vascular smooth muscle cells, contributing to vessel maturation in an autocrine manner.


Entropy optimized MHD 3D nanomaterial of non-Newtonian fluid: A combined approach to good absorber of solar energy and intensification of heat transport.
The present work provides important insights regarding three dimensional unsteady magnetohydrodynamic flow and entropy generation of micropolar Casson Cross nanofluid subject to nonlinear thermal radiation and chemical reaction. The Buongiorno's nanofluid model featured with Brownian movement and thermophoresis is considered. Realistic aspects namely convective boundary condition, viscous dissipation and joule heating are introduced. The present problem is modeled by momentum, temperature, microrotation and nanoparticles concentration equations. The non-dimensional highly nonlinear differential equations are solved numerically via shooting iteration technique together with 4th order Runge-Kutta integration scheme. The current study imparts a reasonable, pragmatic and realistic approach to a good absorber of solar energy. In addition, strong and visionary profiles of velocity, microrotation, temperature, nanoparticles concentration, entropy generation rate and Bejan number for concern nanofluids are presented. Besides, intensive physical interpretation of the involved thermophycal parameters has been well-addressed. The present investigation shows that strengthening of Weissenberg number uplifts the axial as well transverse fluid velocities while that of Hartmann number turns out to be a reverse trend. Furthermore, heat and mass transfer rates exhibit ascending and descending trends for intensified Brownian motion and thermophoresis respectively. Improved thermal boundary layer due to the upgrading temperature ratio parameter is another outcome of the current analysis.


Discovery, characterization, and adipocyte differentiation regulation in perirenal adipose tissue of large yellow croaker (Larimichthys crocea).
Adipose tissue is an essential tissue for lipid deposition in fish and is associated with excess lipid accumulation in aquaculture. However, the knowledge of the distribution and characterization of adipose tissue in fish still needs further investigation. This study for the first time discovered perirenal adipose tissue (PAT) in large yellow croaker by MRI and CT technologies. Then, the morphological and cytological characteristics of PAT were observed, showing a typical characteristic of white adipose tissue. Meanwhile, the mRNA expression of marker genes of white adipose tissue was highly expressed in PAT compared with the liver and muscle in large yellow croaker. Moreover, based on the discovery of PAT, preadipocytes from PAT were isolated, and the differentiation system of preadipocytes was established. The lipid droplet and TG content of cell were gradually increased during adipocyte differentiation. In addition, mRNA expressions of lipoprotein lipase, adipose triglyceride lipase, and transcription factors related to adipogenesis (cebpα, srebp1, pparα, and pparγ) were quantified to explain the regulation mechanism during the differentiation process. In summary, the present study first discovered perirenal adipose tissue in fish, then explored the characterization of PAT, and revealed the regulation of adipocyte differentiation. These results could advance the understanding of adipose tissue in fish and provide a novel idea for the study of the mechanism of lipid accumulation.


A clinical comparison of AH8165 and pancuronium as muscle relaxants in patients undergoing cardiac surgery.
The non-depolarizing muscle relaxant AH8165 has been compared at two doses (0.5 and 1.0 mg/kg) with pancuronium (0.1 mg/kg) during induction of anaesthesia for patients having major cardiac surgery. After barbiturate-opiate premedication and thiopentone induction, administration of pancuronium was followed by no significant alteration in heart rate or arterial pressure. Both doses of AH8165 werr followed by significant tachycardia, and the higher dose by arterial hypotension. The lower dose of AH8165 was unsatisfactory for tracheal intubation, but the AH8165 1 mg/kg gave intubating conditions similar to those with pancuronium 0.1 mg/kg.


Direct anterior versus antero-lateral approach in hip joint hemiarthroplasty.
Femoral neck fractures are common injuries in the elderly and represent a major source of morbidity and mortality. Due to the benefits, bipolar hip hemiarthroplasty (BHH) is a popular method to treat. The purpose of this study is to evaluate the functional and radiographic outcomes for BHH comparing the direct anterior approach (DAA) to the anterolateral approach (ALA) to the hip joint. We used a prospective, randomized observational study design, where we enrolled 83 patients at a level-I-trauma center presenting with indication for BHH. We followed up the participants at defined intervals over a period of 1 year. The follow-up examinations were carried out at defined time intervals for a period of 1 year. Calculations were performed with Statistical Package for Social Sciences (SPSS) 21.0. Concerning postoperative pain sensation, the anterior group had statistically significantly decreased pain levels at one (p = 0.02), seven (p = 0.04) and 14 days (p = 0.02) following the intervention when compared to the ALA sample. The postoperative modified Barthel-Index showed a statistically significant difference on the first postoperative day at the anterior group. Although we compared two minimally invasive approaches, our results shows a statistically significant difference in pain intensity and mobility for the early postoperative period using the direct anterior approach.


Movement patterns in leiopelmatid frogs: Insights into the locomotor repertoire of basal anurans.
Movements and locomotor behaviour were studied in the most basal living frog family (Leiopelmatidae: Ascaphus+Leiopelmatidae), which includes two stream-dwelling species and several that have transitioned into terrestrial niches. These cryptic frogs remain immobile over 99.6% of the time above ground as they sit in wait of prey and only rarely use jumping to escape. Walking is their primary mode of locomotion. The two stream species, which are separated by deep time and extreme geographic distance, have nearly identical behavioural repertoires and locomotor performance, which included occasional jumping as a means to change foraging positions. The terrestrial species, one of which has become semi-arboreal, rarely jump in nature and rely on chemical and postural antipredator behaviours to avoid predation. If early frogs resembled leiopelmatids, they were not well versed in jumping. Locomotor behaviour and performance of leiopelmatid frogs do not support the hypothesis that frog jumping originally evolved primarily as a means to rapidly escape into water. Given the basal position of the leiopelmatids, the locomotor strategy of these cryptic, cold-adapted, belly-flopping anurans that usually walk may represent a successful initial step in the evolution of saltatorial locomotion in frogs.


A Qualitative Analysis on the Effectiveness of Peer Feedback in Team-Based Learning.
There is limited information on medical students' perceptions of peer feedback in team-based learning (TBL), both in terms of its value and how it has affected them as they move forward in their careers. The primary goals of this study were to examine students' perceptions about their peer feedback experiences throughout medical school and into residency and to identify areas for improvement to develop a more valuable experience. This study utilized exploratory qualitative research. A total of six focus group sessions were conducted, in which each group consisted of medical students or residents. All participants were asked for their thoughts about peer feedback using semi-structured interviews. The sessions were transcribed and thematic analysis of student responses was completed by independent reviewers. A total of 11 first-year, 12 second-year, 12 rising third-year, and 10 rising fourth-year medical students participated in the focus groups. In addition, three graduates participated in the study. Overall, four key themes were identified regarding the peer feedback experience. These included (1) preparation and training, (2) procedure and implementation, (3) evaluation of student feedback, and (4) student considerations. The participants indicated that the idea of providing and receiving effective peer feedback throughout the medical school curriculum was a valuable experience. This analysis raised awareness about several potential areas of difficulty for students in regard to the peer feedback process used in TBL. Quality improvement initiatives may include educating students about the use of constructive feedback, adding self-reflection, or using oral instead of written feedback.


Antisera to a synthetic peptide of the sis viral oncogene product recognize human platelet-derived growth factor.
It has recently been reported that the sequences of the sis oncogene of simian sarcoma virus (SSV) and of human platelet-derived growth factor (PDGF) are very similar, establishing the most solid link yet between the mitogenic actions of growth factors and the transforming proteins of retroviruses. To investigate molecular mechanisms of transformation I have produced antisera against synthetic peptides corresponding to segments of the protein sequences predicted by the nucleotide sequences of viral oncogenes. Applying this approach to the case of sis and PDGF, I report here the results of probing outdated human platelets with an antiserum directed against a synthetic peptide representing residues 139-155 of the predicted sequence of the SSV transforming protein, p28sis (ref. 3). I detected peptides of apparent molecular weights (MWs) 30,000 to 31,000 (30-31K) and 16-18K, which correspond to the apparent molecular weights of nonreduced and reduced PDGF. In addition, a peptide of MW 21,000 was detected in platelets and a protein of MW 56,000 was detected in SSV-infected marmoset cells.


Genotype-phenotype correlation in migraine without aura focusing on the rs1835740 variant on 8q22.1.
A large two-stage GWAS by Antilla et al. reported the minor allele of rs1835740 on 8q22.1 to be associated with common types of migraine. The objective of the present study was to determine the clinical correlate of the variant in migraine without aura (MO). Clinical data on 339 successfully genotyped MO patients (patients with attacks of migraine without aura and no attacks of migraine with aura) were obtained by an extensive validated semi-structured telephone interview performed by a physician or a trained senior medical student. Reliable, systematic and extensive data on symptoms, age of onset, attack frequencies and duration, relevant comorbidity, specific provoking factors including different hormonal factors in females, and effect and use of medication, both abortive and prophylactic, were thereby obtained. A comparison of carriers and non-carriers were performed. Comparison of homozygotes with heterozygotes was not performed as the number of homozygotes was too small for statistical purposes. Data from other MO populations in the GWAS by Antilla et al. were not included as phenotype and clinical data were obtained differently. While thousands of patients are needed to detect a genetic variant like rs1835740, 339 are sufficient to detect meaningful clinical differences. 136 of 339 patients were carriers of the variant, 15 were homozygous. Comparison of carriers with non-carriers showed no significant difference in any of the parameters studied. In conclusion, the rs1835740 variant has no significant influence on the clinical expression of MO.


Expansion of error thresholds for the Moran model.
We study a finite population of individuals evolving through mutation and selection. We generalize the Eigen quasispecies model to a finite population with the Moran model. This model also presents an asymptotic phase transition, and a proper definition of the critical parameter is discussed. We retrieve the same expression for the error threshold appearing in the Eigen model along with a correction term due to the finiteness of the population. To achieve this, we estimate the average lifetime of master sequences and find it grows like an exponential in the size of the population. Our technique consists in bounding from above and below the number of master sequences in the Moran model by two simpler birth and death chains. The expectation of this lifetime is then computed with the help of explicit formulas which are in turn expanded with Laplace method.


A comparison of speech intonation production and perception abilities of Farsi speaking cochlear implanted and normal hearing children.
Cochlear implant prosthesis facilitates spoken language development and speech comprehension in children with severe-profound hearing loss. However, this prosthesis is limited in encoding information about fundamental frequency and pitch that are essentially for recognition of speech prosody. The purpose of the present study is to investigate the perception and production of intonation in cochlear implant children and comparison with normal hearing children. This study carried out on 25 cochlear implanted children and 50 children with normal hearing. First, using 10 action pictures statements and questions sentences were extracted. Fundamental frequency and pitch changes were identified using Praat software. Then, these sentences were judged by 7 adult listeners. In second stage 20 sentences were played for child and he/she determined whether it was in a question form or statement one. Performance of cochlear implanted children in perception and production of intonation was significantly lower than children with normal hearing. The difference between fundamental frequency and pitch changes in cochlear implanted children and children with normal hearing was significant (P < 0/05). Cochlear implanted children performance in perception and production of intonation has significant correlation with child's age surgery and duration of prosthesis use (P < 0/05). The findings of the current study show that cochlear prostheses have limited application in facilitating the perception and production of intonation in cochlear implanted children. It should be noted that the child's age at the surgery and duration of prosthesis's use is important in reduction of this limitation. According to these findings, speech and language pathologists should consider intervention of intonation in treatment program of cochlear implanted children.


The α6β1 integrin is a laminin receptor for developing retinal neurons.
Cultured embryionic day 6 (E6) retinal neurons respond to laminin by making use of integrin receptors. We have recently shown that the laminin binding integrin receptor α6β1 is expressed in the chick retina on both retinal ganglion cells and other retinal neurons. Antibodies raised against a fusion protein containing a large fragment of the extracellular portion of the chick α6 integrin subunit dramatically inhibit the interactions between E6 retinal neurons and laminin. These data show that α6β1 functions as a laminin receptor in these cells. In previous work we have also shown that the levels of the mRNA for α6 decreases dramatically in retinal ganglion cells between E6 and E12. Data presented in this paper show that the decrease in α6 mRNA is not prevented by ablation of the optic tectum, indicating that contact with the target is not a major cause for this decrease.


Is repeated transurethral resection justified in patients with newly diagnosed superficial bladder cancer?
To assess the value of repeated transurethral resection (TUR) in patients with newly diagnosed superficial bladder cancer. A second TUR was performed in 110 consecutive patients (24 women and 86 men) with newly diagnosed superficial bladder cancer. The mean age was 66 years (range 30 to 85). A second TUR was performed within 4 to 6 weeks after the initial TUR. After the first TUR, the pathologic stage was pTa in 31 patients (28%), pT1 in 76 (70%), and carcinoma in situ in 3 (2%). The pathologic records of the second TUR were reviewed and compared with the findings of the first operation. Cystoscopy before the second TUR was negative in 79 patients. Of these cases, 14 (17.7%) had cancer histologically. The second TUR was negative in 70 patients (63.6%). Twenty-two (20%) had residual cancer of the same stage, 9 (8.2%) had a lower stage, and 9 (8.2%) had a higher stage. Of 31 patients with Stage pTa and 76 patients with Stage pT1 at the first TUR, 19 (61.3%) and 51 (67.1%) had a negative second TUR, respectively. We recommend a second TUR for patients with superficial bladder cancer for several reasons. A negative second TUR provides important prognostic information. In addition, removal of residual cancer is achieved early. Finally, patients with pT1 G3 tumors are at high risk of residual, or even invasive, cancer and should be offered definitive therapy as early as possible.


Real-world comparative effectiveness of three single-inhaler dual bronchodilators for the treatment of COPD.
Single-inhaler dual bronchodilators are now recommended as initial treatment of COPD for patients with multiple exacerbations or with moderate or severe dyspnoea. It is unclear whether there are differences in effectiveness among commonly used dual bronchodilators. We identified a cohort of COPD patients, aged ≥40 years, treated during 2017-2020, from the UK Clinical Practice Research Datalink, a real-world practice setting. Inhaled corticosteroid-naïve patients initiating vilanterol-umeclidinium (VIL-UME) were compared with those initiating olodaterol-tiotropium (OLO-TIO) or indacaterol-glycopyrronium (IND-GLY) dual bronchodilators primarily on the incidence of moderate and severe COPD exacerbation over 1 year, and corresponding hazard ratios (HRs), after adjustment by propensity score weighting. The cohort included 15 224 initiators of VIL-UME, 5536 initiators of OLO-TIO and 5059 initiators of IND-GLY. The HR of a moderate or severe exacerbation with VIL-UME was 0.91 (95% CI 0.85-0.97) compared with OLO-TIO and 0.96 (95% CI 0.89-1.03) compared with IND-GLY. The risk of severe exacerbation was not different for VIL-UME when compared with OLO-TIO (HR 1.04, 95% CI 0.86-1.26) and IND-GLY (HR 1.05, 95% CI 0.86-1.28). All-cause mortality was lower with VIL-UME compared with IND-GLY (HR 0.82, 95% CI 0.68-0.98), but not compared with OLO-TIO (HR 0.87, 95% CI 0.72-1.04). In a real-world setting of COPD treatment, the three dual bronchodilator combinations were similarly effective on the risk of a severe exacerbation of COPD. However, the VIL-UME and IND-GLY combinations may confer slightly superior effectiveness than OLO-TIO on the risk of moderate or severe exacerbation. The potential lower mortality with VIL-UME warrants further investigation.


High burden of skin sclerosis is associated with severe organ involvement in patients with systemic sclerosis and systemic sclerosis overlap syndrome.
The objective of this study is to investigate the impact of skin sclerosis burden on an internal organ involvement over a 1-year period, as measured by time-adjusted accrual-modified Rodnan skin score (TA-mRSS), and to evaluate association between TA-mRSS patterns and laboratory tests in patients with systemic sclerosis (SSc). This prospective study was conducted at Siriraj Hospital (Bangkok, Thailand) during the November 2013-November 2016. SSc patients by ACR/EULAR 2013 or ACR 1980 criteria were eligible. TA-mRSS was classified as low, intermediate, or high, and then compared between groups. Correlation between the arithmetic mean of laboratory tests and TA-mRSS was assessed by multiple linear regression analysis. A total of 118 patients, with 81.4% women, median (IQR) age 49.8 (43.8, 55.1) years, disease duration from onset of non-Raynaud symptoms to first visit of 3.3 (1, 6.8) years, 78% dcSSc, and 75.3% anti-Scl-70 positivity, were analyzed. TA-mRSS over 1 year ranged from 0 to 37.44. The high skin sclerosis burden group had a median TA-mRSS > 7.26 (> 67th percentile). Patients with high TA-mRSS were dcSSc, high initial and average mRSS, and had tendon friction rub, digital ischemic complications, usual interstitial pneumonia, diastolic dysfunction, gastrointestinal dysmotility, and low serum albumin. In multiple linear regression analysis, the arithmetic mean of hemoglobin (B = - 1.007, 95% CI - 1.779 to - 0.236), erythrocyte sedimentation rate (B = - 0.078, 95% CI - 0.126 to - 0.029), serum glutamic oxaloacetic transaminase (B = 0.073, 95% CI 0.026-0.12), creatine phosphokinase (B = 0.012, 95% CI 0.003-0.021), and albumin (B = - 4.117, 95% CI - 6.958 to - 1.276) were associated with TA-mRSS. This study found a higher cumulative course of mRSS over a 1-year period to be significantly associated with severe internal organ involvement.


In situ formation of fluorescence species for the detection of alkaline phosphatase and organophosphorus pesticide via the ascorbate oxidase mimetic activity of AgPd bimetallic nanoflowers.
Sensitive detection strategies for enzymes and their inhibitors not only have critical significance in clinical diagnosis but can be extended to food and environment analysis. Here, bimetallic AgPd alloy nanoflowers were synthesized using carbon dots as the reductant via a two-step reduction method. The AgPd bimetallic nanoflowers exhibit ascorbate oxidase mimetic activity, which can rapidly catalyze the oxidization of ascorbic acid to dehydroascorbic acid (DHA). The DHA can then react with o-phenylenediamine (OPD) to produce 3-(1, 2-dihydroxyethyl)furo[3,4-b] quinoxalin-1(3H)-one (DFQ), accompanying with the characteristic fluorescence peak at 440 nm for DFQ. Alkaline phosphatase catalyzes l-ascorbyl-2-phosphate to generate AA, while organic phosphorus pesticides (OPPs) such as chlorpyrifos can inhibit the activity of alkaline phosphatase. By utilizing the enzyme-nanozyme tandem catalytic reaction, the fluorescence of the system varies in the presence of different concentrations of ALP or OPPs, which can be used to detect ALP in serum and OPPs in vegetables and fruits.


Variations in (Na+ + K+)-ATPase and Mg2+-ATPase activity of the ground squirrel brain during hibernation.
1. The specific activity of brain (Na+ + K+)-ATPase and Mg2+ -ATPase of the ground squirrel (Spermophilus richardsonii) is significantly increased after long-term hibernation. 2. The markedly non-linear thermal dependence of (Na+ + K+)-ATPase is unchanged during hibernation whereas the near linear thermal dependence of Mg2+-ATPase undergoes minor alteration after prolonged hibernation. 3. The sensitivity of (Na+ + K+)-ATPase to inhibition by ouabain is significantly decreased after 100 days of hibernation as is both the rate and amount of [3H]-ouabain binding. 4. These changes may be related to alteration in the phospholipid matrix of the membrane rather than alteration in the protein structure of the enzyme.


The Evaluation of Air Quality in Albania by Moss Biomonitoring and Metals Atmospheric Deposition.
The air quality of Albania is evaluated by trace metals atmospheric deposition using moss biomonitoring method. Bryophyte moss (Hypnum cupressiforme Hedw.) samples were collected during August and September 2015 from 55 sampling points distributed over the entire territory of Albania. The concentrations of Cr, Cu, Fe, Ni, Pb, V, and Zn in moss samples was determined by ICP-AES, ETAAS (As and Cd), and CVAAS (Hg) analysis. Spatial distribution and temporal trend of the moss elements is discussed in this study. Different variability was found in moss metal concentrations that may reflect their spatial distribution patterns and may identify the location of the areas with high contamination of each element. Compared with the measurements of moss collected in 2010, significant differences were found in the concentrations of As, Cr, Cu, Hg, Ni, Pb, and Zn. The differences between two moss surveys may reflect changes in the bioavailability of the elements resulting from wet and dry deposition respectively during 2015 and 2010 moss biomonitoring survey. The pollution loading index that was applied to judge the content of metal contamination indicated moderate pollution throughout Albania. Examination of the potential ecological risk found that As, Cd, Cr, Hg, Ni, and Pb pose the highest potential ecological risks particularly in the areas with high metal contents. Factor analysis applied to investigate the probable sources of metals in the environment suggested that Al and Fe likely originated from natural sources. As, Cd, Hg, Pb, Cu, Zn, Ni, and Cr likely originated from anthropogenic sources associated with long-range transport, transboundary pollution and local emission sources.


Jejunal intussusception at the jejunojejunostomy after laparoscopic total gastrectomy: A case report.
Jejunal intussusception at the jejunojeunostomy after total gastrectomy with Roux-en-Y (RY) reconstruction is rare. We describe a case of jejunal intussusception at the jejunojeunostomy that developed in a 60-year-old woman who had undergone laparoscopic total gastrectomy with RY reconstruction for gastric cancer 4 years ago. The main presenting complaint was recurrent epigastric pain. Abdominal computed tomography showed a typical target sign suspected of antegrade intussusception into a blind loop at the jejunojeunostomy. We performed a laparoscopic operation, which revealed no intussusception or adhesions. We noted that the blind loop of the bilio-pancreatic limb was longer and expanded. We divided the blind loop at the distal side of the jejunojeunostomy and performed suture plication between the bilio-pancreatic limb and alimentary limb. Therefore, the appropriate length of the blind loop and the size of the jejunojeunostomy site should be carefully determined during RY reconstruction.


Synthesis, structure and biological activity of 6-r(3)si(ge, sn)-substituted 5-fluorouracils.
Direct lithiation of 1-(2-tetrahydrofuryl)-5-fluorouracil (Ftorafur) has been investigated. The treatment of ftorafur with lithium diisopropylamide (LDA)at -70 in ether-hexane, followed by the reaction with various electrophiles afforded the corresponding 6-substituted silicon, germanium and tin derivatives of ftorafur. The results of biological investigation indicate the ability of germanium-modified nucleoside analogues to interfere with transcription and replication processes.


One- and 2-day mifepristone-misoprostol intervals are both effective in medical termination of second-trimester pregnancy.
Termination of pregnancy because of fetal anomaly requires the utmost clinical sensitivity and individualized patient care. This study compared the efficacy of a 1-day mifepristone and misoprostol interval in medical termination of second-trimester pregnancy performed because of fetal anomaly with that of the standard 2-day interval among the first 100 women in each group. A 200 mg dose of mifepristone was used; 0.4 mg of misoprostol was administered vaginally at 3-h intervals until abortion occurred. When calculated from ingestion of mifepristone, the time to abortion was 28 h 25 min (28:25 h) [23:10-50:40 h; median (range)] and 52:43 h (45:55-83:15 h) (P < 0.0001) in the 1- and 2-day mifepristone-misoprostol groups respectively. However, following initiation of misoprostol administration, the time to abortion [7:25 h (1:00-23:15 h)] was longer (P < 0.05) in the 1-day interval group than in the 2-day interval group [6:20 h (0:45-36:30 h)]; by 12 h, 82 and 87% (n.s.) respectively of the subjects had aborted. The proportions of cases undergoing surgical evacuation of the uterus were 64 and 45% (P < 0.001), in the 1- and 2-day interval groups respectively. Thus both 1- and 2-day mifepristone-misoprostol intervals are valuable in termination of second-trimester pregnancy.


Cannabinoids may worsen gastric dysmotility induced by chronic cisplatin in the rat.
Although cannabinoids have traditionally been used for the treatment and/or prevention of nausea and/or emesis, anorexia and weight loss induced by clinical use of antineoplastic drugs, their efficacy and safety in long-term treatments are still controversial. Our aim was to analyze the effects of the non-selective cannabinoid agonist WIN 55 212-2 (WIN) on gastrointestinal (GI) dysmotility and other adverse effects induced by repeated cisplatin administration in the rat. Male Wistar rats received two intraperitoneal injections once a week for 4 weeks: the first one was WIN, at non-psychoactive doses (0.5 or 1 mg kg(-1)), its vehicle or saline; the second one was cisplatin (2 mg kg(-1)) or saline. Radiographic techniques were used to determine the acute (after first dose), chronic (after last dose), and residual (1 week after treatment finalization) effects of cisplatin and/or WIN on GI motility. Bodyweight gain, food ingestion, and mechanical sensitivity were also tested. Weekly cisplatin induced mechanical allodynia, which WIN prevented, as well as weight gain reduction and anorexia, which WIN did not. Gastric emptying was dose-dependently delayed by cisplatin and this effect was enhanced upon chronic treatment. WIN aggravated cisplatin-induced gastric dysmotility. One week after treatment finalization, only minor alterations of GI motor function were found in rats treated with cisplatin, WIN or both. WIN weekly administered at low doses prevents neuropathy, but does not prevent anorexia or weight loss and aggravates gastric dysmotility induced by cisplatin. Cannabinoids should be handled with caution if chronically administered during chemotherapy.


Postmortem genetic analysis of 17 sudden cardiac deaths identified nonsense and frameshift variants in two cases of arrhythmogenic cardiomyopathy.
Sudden death, or unexpected natural death of a healthy individual, is a serious problem in all nations. Sudden cardiac death (SCD) mainly due to ischemic heart diseases is the top cause of sudden death. However, there are pathophysiological conditions, referred to as sudden arrhythmic death syndrome, in which no apparent lesion can be identified even after complete conventional or ordinary autopsy. While postmortem genetic analyses have accumulated evidence about underlying genetic abnormality in such cases, the precise relationships between genetic background and the phenotype have been largely elusive. In this study, a retrospective investigation of 17 autopsy cases in which lethal arrhythmia was suspected to be the cause of death was carried out. Genetic analysis focusing on 72 genes reported to be associated with cardiac dysfunctions was performed, in combination with detailed histopathological and postmortem imaging examination, and a family study. As a result, in two cases of suspected arrhythmogenic cardiomyopathy (ACM), we found a nonsense variant in PKP2 and frameshift variant in TRPM4 gene. In contrast, the other 15 cases showed no morphological changes in the heart despite the presence of a frameshift variant and several missense variants, leaving the clinical significance of these variants obscure. The findings of the present study suggest that nonsense and frameshift variants could be involved in the morphological abnormality in cases of SCD due to ACM, while missense variants alone rarely contribute to massive structural changes in the heart.


Severe abacavir hypersensitivity reaction in a patient with human immunodeficiency virus infection: a case report.
Abacavir is a nucleoside reverse transcriptase inhibitor that is used as a component of the antiretroviral treatment regimen in the management of the human immunodeficiency virus for both adults and children. It is efficacious, but its use may be limited by a hypersensitivity reaction linked with the HLA-B*57:01 genotype. HLA-B*57:01 has been reported to be rare in African populations. Because of the nature of its presentation, abacavir hypersensitivity is prone to late diagnosis and treatment, especially in settings where HLA-B*57:01 genotyping is not routinely done. We report a case of a severe hypersensitivity reaction in a 44-year-old Kenyan female living with the human immunodeficiency virus and on abacavir-containing antiretroviral therapy. The patient presented to the hospital after recurrent treatment for a throat infection with complaints of fever, headache, throat ache, vomiting, and a generalized rash. Laboratory results evidenced raised aminotransferases, for which she was advised to stop the antiretrovirals that she had recently been started on. The regimen consisted of abacavir, lamivudine, and dolutegravir. She responded well to treatment but was readmitted a day after discharge with vomiting, severe abdominal pains, diarrhea, and hypotension. Her symptoms disappeared upon admission, but she was readmitted again a few hours after discharge in a hysterical state with burning chest pain and chills. Suspecting abacavir hypersensitivity, upon interrogation she reported that she had taken the abacavir-containing antiretrovirals shortly before she was taken ill. A sample for HLA-B*57:01 was taken and tested positive. Her antiretroviral regimen was substituted to tenofovir, lamivudine, and dolutegravir, and on subsequent follow-up she has been well. Clinicians should always be cognizant of this adverse reaction whenever they initiate an abacavir-containing therapy. We would recommend that studies be done in our setting to verify the prevalence of HLA-B*57:01.


HCV clearance from saliva of HIV-HCV-coinfected patients on treatment with interferon plus ribavirin.
To determine hepatitis C virus (HCV) RNA clearance from blood and saliva of HIV-HCV-coinfected patients undergoing combined therapy with pegylated interferon plus ribavirin (PEG-IFN-RIB). Study group was formed of 60 HIV-infected patients with chronic hepatitis C who were starting treatment with PEG-IFN-RIB. Blood and saliva samples were taken at baseline, at the end of treatment and 24 and 48 weeks later. A nested RT-PCR technique was used to detect HCV-RNA in saliva. HCV-RNA was detected in saliva at baseline in 64.7% of patients. Thirty-four patients completed follow-up. The response rate (undetectable HCV-RNA) in blood was 79.4% at the end of treatment; 55.8% at 24 weeks after the end of treatment and 50% at 48 weeks. HCV was detected in saliva of 13 (38.2%) patients at the end of treatment and in 18 (52.9%) patients at 24 and 48 weeks later. Concordance of HCV clearance from blood and saliva reached its maximum value at 48 weeks after the end of treatment (odds ratio, 112.51). In HIV-HCV-coinfected patients responders to PEG-IFN-RIB, the salivary glands do not appear to be a sanctuary site for HCV, although viral clearance from saliva may be slower than from blood.


Bone mineral assessments in the calcaneus after anterior cruciate ligament injury. An investigation of 92 male patients before and two years after reconstruction or revision surgery.
The aim of this study was to assess the Bone Mineral Areal mass (BMA) in the calcaneus of male patients with unilateral anterior cruciate ligament (ACL) injury before and after reconstruction and to assess whether the BMA ratio or the BMA of the injured and uninjured side correlated with the level of activity, functional performance or the time period between the injury and the reconstruction. Ninety-two male patients with unilateral ACL injury were included in the study. The BMA was analysed immediately prior to surgery: a median of 11 (2-192) months after the injury in 30 patients aged 26 (15-41) years scheduled for primary ACL reconstruction (Group A). Forty-nine patients aged 29 (18-49) years had their BMA analysed a median of 24 (23-29) months after the primary ACL reconstruction (Group B). Thirteen patients aged 27 (21-39) years had their BMA analysed a median of 24 (20-45) months after ACL revision surgery (Group C). The median BMA ratio (injured side/uninjured side) was 96 (88-105)% in Group A, 96 (86-118)% in Group B and 95 (83-111)% in Group C. In all three groups, the median BMA value in the calcaneus was significantly lower on the injured side compared with the uninjured side (P=0.001, P=0.0003, P=0.01 in Groups A, B and C, respectively). The time period between the injury and the reconstruction neither correlated with the BMA ratio nor the BMA of the injured or the uninjured side in Group A. The level of activity as measured by the Tegner activity level and the functional performance as measured by the one-leg-hop quotient did not correlate with the BMA ratio in any of the groups. In the 49 patients with a primary ACL reconstruction (Group B), the post-operative Tegner activity level correlated with the BMA, on both the injured and uninjured side (P=0.0003, P=0.0005, respectively), when the BMA was assessed two years after the index operation. Male patients with unilateral ACL injury had a significantly lower BMA in the calcaneus on the injured side compared with the uninjured side before primary reconstruction, two years after primary reconstruction and two years after revision surgery. The time period between the injury and the index operation did not correlate with the BMA. A high level of activity correlated with the BMA on both the injured and the uninjured side two years after primary reconstruction.


Wiskott-Aldrich syndrome/X-linked thrombocytopenia in China: Clinical characteristic and genotype-phenotype correlation.
Wiskott-Aldrich syndrome (WAS) and X-linked thrombocytopenia (XLT) are caused by mutations of the WAS gene. The genotype-phenotype association of WAS and XLT have not been fully elucidated. Here, we established the largest database of WAS in China to further determine the potential correlation between genotype and phenotype and long-term outcome. We collected clinical data of 81 WAS/XLT patients, analyzed mutations of WAS gene at the genomic DNA and transcriptional/translational levels, and quantified three different patterns of WAS protein (WASp) expression in PBMCs by flow cytometry. There were 60 unique mutations identified, including 20 novel mutations and eight hotspots, from 75 unrelated families with a total of 81 affected members. Nearly all the patients with XLT had missense mutations and were WASp-positive in the peripheral cells, while only half of the patients with missense mutations exhibited the XLT phenotype and detectable WASp. In contrast, patients with nonsense mutations, deletions, insertions, and complex mutations were WASp-negative and developed the classic WAS phenotype. An equal number of patients with splice anomalies were either WASp-positive or WASp-negative. Long-term survival rates were lower in WASp-negative patients compared to WASp-positive patients. The clinical phenotype of classic WAS or milder XLT and long-term outcome are potentially influenced by the effect of these defects on gene transcription and translation. Patients with missense mutations allowing expression of mutated WASp and those with splice anomalies, which result in generation of multiple products, including normal WASp, present the attenuated XLT phenotype and show better prognosis.


Patient-prosthesis mismatch after mitral valve replacement: myth or reality?
Determining the risk of patient-prosthesis mismatch after mitral valve replacement is still controversial. In this study, we aimed to clarify incidence and clinical implications of such a complication. The accuracy of preoperative prediction of patient-prosthesis mismatch using published in vitro hemodynamic parameters was also investigated. Ninety-two patients who underwent mitral valve replacement and received Carpentier-Edwards stented bioprosthesis (Edwards Lifesciences, LLC, Irvine Calif) were enrolled. Hemodynamic performances were evaluated at discharge, and the incidence of in vivo patient-prosthesis mismatch (indexed effective orifice area < or =1.2 cm2/m2) was evaluated. Correlation between in vivo patient-prosthesis mismatch and predicted patient-prosthesis mismatch, based on previously published in vitro hemodynamic parameters, was also investigated. Five patients died within 30 days of the operation (5.4% mortality). Mean prosthesis size was 29.8 +/- 2. Mean postoperative effective orifice area and indexed effective orifice area (2.5 +/- 0.8 cm2 and 1.5 +/- 0.4 cm2/m2, respectively) compared favorably with those predicted in vitro (2.2 +/- 0.7 cm2 and 1.3 +/- 0.5 cm2/m2, respectively). In the subgroup of patients receiving prosthesis size of 27 or smaller, the difference reached statistical significance (2.47 +/- 0.83 and 1.61 +/- 0.7 for postoperative and predicted effective orifice areas, respectively; P < .001). Postoperative patient-prosthesis mismatch was recorded in 8 patients (8.6%), comparing favorably with the predicted patient-prosthesis mismatch (39% for overall population and 80% for patients receiving prosthesis size < or = 27). No significant correlation between size of prosthesis and early hemodynamic and clinical outcomes was shown. In our study, stented mitral bioprostheses showed satisfactory postoperative hemodynamic performance, even in smaller prosthesis sizes (< or =27 mm). Risk of in vivo postoperative patient-prosthesis mismatch seems to be less relevant than preoperative risk prediction based on in vitro data. Further studies are needed to evaluate the potential clinical impact of mitral patient-prosthesis mismatch.


The exothermal behavior in the hydration process of calcium phosphate cement.
The exothermal behavior in the hydration process of calcium phosphate cement (CPC) and their effect factors were investigated systematically. One CPC formulation is composed of tetracalcium phosphate (TECP) and dicalcium phosphate anhydrous (DCPA), and its hydration reaction is an exothermic reaction. Hydration includes five processes, namely, the start, induction, acceleration, deceleration and the terminating process. The introduction of hydroxyapatite (HAP) as crystal seed shortens induction and advances on the reaction peak position, which resulted from the introduction of crystal seed that reduced the activation energy of heterogeneous nucleation. The increase in temperature not only makes the reaction advance but also enlarges it. The activation energy of the hydration reaction is 176kJ/mol by calculation. The particle size of the raw material and the ratio of calcium to phosphate in the specimen have large effects on the hydration process. Decrease in particle size of TECP and in the ratio of calcium to phosphate resulted in marked acceleration of reaction and made the reaction peak advance evidently, but the effect of particle size of DCPA is not so remarkable. Based on the heat liberation in the hydration of CPC specimens taking Ca/P as 1.5 and 1.67, the standard mole enthalpies of formation of TECP and calcium-deficient hydroxyapatite are -5908 and -11,119kJmol(-1), respectively.


Chaotic behavior of semigroups related to the process of gene amplification-deamplification with cell proliferation.
In the last few years there has been a renewed interest in infinite systems of differential equations, similar to the classical birth-and-death system of population dynamics, due to their rôle in modelling the evolution of drug resistance in cancer cells. In [J. Banasiak, M. Lachowicz, Topological chaos for birth-and-death models with proliferation, Math. Models Methods Appl. Sci. 12 (6) (2002) 755] such systems were shown to generate a chaotic dynamics under, however, very restrictive assumptions on the growth of coefficients. In this paper, using recently developed concept of subspace chaos [J. Banasiak, M. Moszyński, A generalization of Desch-Schappacher-Webb criteria for topological chaos with applications, Discrete Contin. Dyn. Syst. - A 12 (5) (2005) 959], we show that for a linear growth of the coefficients, which are more acceptable from biological point of view, the dynamics of these systems is chaotic in some subspaces of the original state space.


Cerebral palsy and bruxism: Effects of botulinum toxin injections-A randomized controlled trial.
Cerebral palsy (CP) includes disturbances in muscular control caused by perinatal brain injury. Masticatory muscle involvement hampers functions such as chewing and talking. Bruxism and temporomandibular disorders are overrepresented. Neuromuscular blocks with botulinum toxin type A (BTX-A) may alleviate problems due to muscular hyperactivity. The aim was to evaluate masticatory muscle BTX-A injections in subjects with CP and bruxism. A prospective, parallel, randomized, placebo-controlled, and double-blind trial in 12 patients with CP was performed. End points were alterations in objective and subjective oral capacities after two BTX-A or corresponding placebo injections. Matched, healthy references were also evaluated. The reference group demonstrated stronger and more efficient oral functions compared with the CP group. Subjective and objective oral capacities appeared to vary considerably between CP patients and also over time in this patient group and were poorly correlated. No significant effect of BTX-A compared with placebo on outcome variables was observed at group level, but continued treatment with BTX-A was requested by the majority of the patients. The evidence is unable to support the use of BTX-A for the treatment of affected masticatory muscles in CP, but the findings are inconclusive in certain respects. Larger, more homogeneous groups of CP patients need to be evaluated in future trials.


Mineralocorticoid receptor mediated liposomal delivery system for targeted induction of apoptosis in cancer cells.
Mineralocorticoid receptors (MRs) are nuclear hormone receptors that are ubiquitously present in all cell types and are known to mediate distinct physiological functions like regulating Na(+) and K(+) balance and water excretion. MRs are linked to cell proliferation and can be exploited for the targeted control of cell mass in cancer. The present study is aimed towards extending the concept of using MR ligand spironolactone for selective delivery of genes in cancer cells. The lipoplex (SP) has shown MR mediated targeted transfections as indicated by receptor down-regulation studies using MR antagonists and siRNA. SP-targeted delivery of genes resulted in apoptosis in cell-specific manner while free drug was found to be cytotoxic irrespective of the cancerous or non-cancerous nature. In conclusion, this study presents MR as a target for efficiently delivering anticancer genes and thereby treating cancer through MR-mediated pathway.


Role of Mitophagy in Myocardial Ischemia/Reperfusion Injury and Chinese Medicine Treatment.
Mitophagy is one of the important targets for the prevention and treatment of myocardial ischemia/reperfusion injury (MIRI). Moderate mitophagy can remove damaged mitochondria, inhibit excessive reactive oxygen species accumulation, and protect mitochondria from damage. However, excessive enhancement of mitophagy greatly reduces adenosine triphosphate production and energy supply for cell survival, and aggravates cell death. How dysfunctional mitochondria are selectively recognized and engulfed is related to the interaction of adaptors on the mitochondrial membrane, which mainly include phosphatase and tensin homolog deleted on chromosome ten (PTEN)-induced kinase 1/Parkin, hypoxia-inducible factor-1 α/Bcl-2 and adenovirus e1b19k Da interacting protein 3, FUN-14 domain containing protein 1 receptor-mediated mitophagy pathway and so on. In this review, the authors briefly summarize the main pathways currently studied on mitophagy and the relationship between mitophagy and MIRI, and incorporate and analyze research data on prevention and treatment of MIRI with Chinese medicine, thereby provide relevant theoretical basis and treatment ideas for clinical prevention of MIRI.


Effect of a Medicinal Agaricus blazei Murill-Based Mushroom Extract, AndoSan™, on Symptoms, Fatigue and Quality of Life in Patients with Ulcerative Colitis in a Randomized Single-Blinded Placebo Controlled Study.
Ingestion of AndoSan™, based on the mushroom Agaricus blazei Murill, has previously been shown to exhibit anti-inflammatory effects because of reduction of pro-inflammatory cytokines in healthy individuals and patients with ulcerative colitis. In this randomized single-blinded placebo controlled study we examined whether intake of AndoSan™ also resulted in clinical effects. 50 patients with symptomatic ulcerative colitis were block-randomized and blinded for oral daily intake of AndoSan™ or placebo for the 21 days' experimental period. The patients reported scores for symptoms, fatigue and health related quality of life (HRQoL) at days 0, 14 and 21. Fecal calprotectin and general blood parameters were also analyzed. In the AndoSan™ group (n = 24) symptoms improved from baseline (day 0) to days 14 and 21, with respective mean scores (95% CI) of 5.88 (4.92-6.83), 4.71 (3.90-5.52) (p = 0.002) and 4.50 (3.70-5.30) (p = 0.001). Corresponding improved mean scores (±SD) for total fatigue were 16.6 (5.59), 14.1 (4.50) (p = 0.001) and 15.1 (4.09) (p = 0.023). These scores in the placebo group (n = 26) were not improved. When comparing the two study groups using mixed model statistics, we found significant better scores for the AndoSan™-patients. HRQoL for dimensions bodily pain, vitality, social functioning and mental health improved in the AndoSan™ group. There were no alterations in general blood samples and fecal calprotectin. Beneficiary effects on symptoms, fatigue and HRQoL from AndoSan™ consumption were demonstrated in this per-protocol study, supporting its use as a supplement to conventional medication for patients with mild to moderate symptoms from ulcerative colitis. The patients did not report any harms or unintended effects of AndoSan™ in this study. ClinicalTrials.gov NCT01496053.


Modern Classification and Management of Pediatric B-cell Leukemia and Lymphoma.
Although pediatric hematopathology overlaps with that of adults, certain forms of leukemia and lymphoma, and many types of reactive conditions affecting the bone marrow and lymph nodes, are unique to children. As part of this series focused on lymphomas, this article (1) details the novel subtypes of lymphoblastic leukemia seen primarily in children and described since the 2017 World Health Organization classification and (2) discusses unique concepts in pediatric hematopathology, including nomenclature changes and evaluation of surgical margins in selected lymphomas.


Immunomodulation of autoimmune diabetes by dendritic cells.
The biology and properties of dendritic cells (DCs) have been intensely studied in the research areas of infectious diseases, tumor immunology, and vaccine development. This unique subset of immune cells has recently also moved to the center of interest for basic and clinical research in autoimmunity, owing not only to the extraordinary importance of DCs in the initiation and sustenance of adaptive immune responses, but also to more recent discoveries about their profound ability to control and downregulate ongoing T-cell responses. We review current progress of using DCs in mice for induction and propagation of autoimmune T-cell responses and their therapeutic potential to dampen or even stop beta-cell-specific autoimmunity. Finally, we offer our perspective on how basic research progress in DC technology, mostly from mouse models, may translate into emerging diagnostic and therapeutic applications for human type 1 diabetes.


The effect of tumor necrosis factor on normal human hematopoietic progenitors.
Tumor necrosis factor-alpha (TNF-alpha), a product of activated macrophages that is cytotoxic to tumor cells, could be used to purge tumor cells from bone marrow before autologous bone marrow transplantation for hematologic malignancies and/or solid tumors. To determine whether exposure to TNF-alpha would have an inhibitory effect on hematopoietic progenitors, we incubated normal human bone marrow with a wide range of concentrations of recombinant human TNF. In order to mimic the conditions that would be used in bone marrow purging, bone marrow cell suspensions were incubated with TNF in doses ranging from 500 to 100,000 U/ml for 24 hours, and were assayed for colony formation in agar. We noted a dose-dependent inhibition of total colony-forming units (CFU) at days 7 and 14, with 50% inhibition occurring at 60,000 U/ml of TNF. TNF exerted a differential effect on CFU so that colony formation by erythroid (CFU-E), multipotential (CFU-GEMM), and macrophage (CFU-M) progenitors was suppressed to a greater extent than that by granulocyte progenitors (CFU-G). However, even after preincubation with TNF at high doses such as 100,000 U/ml, the inhibitory effects of TNF could be abolished by washing cells before culturing. This study demonstrates that hematopoietic precursors survive treatment with TNF at doses that have been shown to be cytotoxic to tumor cells. Although TNF has a significant inhibitory effect on the growth of erythroid, multipotential, and macrophage progenitors in vitro, this effect depends on continuous exposure to TNF for more than 24 hours. Thus, TNF may be useful as a bone marrow purging agent against tumor cells, with relative sparing of normal marrow elements.


Reversed-phase argentation high-performance liquid chromatography in phytochemical analysis of ginkgolic acids in leaves from Ginkgo biloba L.
A reversed-phase argentation high-performance liquid chromatographic method has been achieved for the determination of ginkgolic acids. Liquid chromatography coupled with electrospray ionization (ESI) mass spectrometry in the negative ion mode is applied to identify ginkgolic acids from ginkgo leaves. The leaves are extracted with ethanol and then cleaned-up by extraction of analytes with hexane after addition of an acidified saturated solution of sodium sulfate and siliceous earth to the matrix solution. Ginkgolic acids are determined within 30 min on a C18 column with methanol-5% aqueous acetic acid (90:10) containing 0.03 mol l(-1) silver nitrate as eluent and with ultraviolet detection at 310 nm. Addition of silver ions as complexation agent into the mobile phase decreases retention time of ginkgolic acids with an unsaturated side chain. Four ginkgolic acids are successfully separated from each other and from other interfering components by the high selectivity of reversed-phase argentation HPLC, which is confirmed by the spectra identification. The average recovery of the method is around 97%. Good reproducibility is obtained with relative standard deviations varying from 2 to 5%.


The Na+ binding site of thrombin.
Thrombin is an allosteric serine protease existing in two forms, slow and fast, targeted toward anticoagulant and procoagulant activities. The slow --> fast transition is induced by Na+ binding to a site contained within a cylindrical cavity formed by three antiparallel beta-strands of the B-chain (Met180-Tyr184a, Lys224-Tyr228, and Val213-Gly219) diagonally crossed by the Glu188-Glu192 strand. The site is shaped further by the loop connecting the last two beta-strands and is located more than 15 A away from the catalytic triad. The cavity traverses through thrombin from the active site to the opposite surface and contains Asp189 of the primary specificity site near its midpoint. The bound Na+ is coordinated octahedrally by the carbonyl oxygen atoms of Tyr184a, Arg221a, and Lys224, and by three highly conserved water molecules in the D-Phe-Pro-Arg chloromethylketone thrombin. The sequence in the Na+ binding loop is highly conserved in thrombin from 11 different species and is homologous to that found in other serine proteases involved in blood coagulation. Mutation of two Asp residues flanking Arg221a (D221A/D222K) almost abolishes the allosteric properties of thrombin and shows that the Na+ binding loop is also involved in direct recognition of protein C and antithrombin.


Suicide Rates and Methods in Active Duty Military Personnel, 2005 to 2011: A Cohort Study.
Suicide prevention programs have become ubiquitous among military units; identifying temporal trends and nonclinical factors associated with the chosen suicide methods may help improve suicide prevention strategies. To calculate suicide rates of active duty military personnel and identify those who are at risk for firearm-specific suicide. Retrospective cohort study. Military units in the United States. All active duty enlisted U.S. military personnel from 2005 to 2011. Suicide rates per 100 000 were calculated for each branch. Adjusted odds ratios for firearm-specific suicide were calculated with 95% CIs. 1455 military personnel committed suicide from 2005 to 2011. From 2006 to 2011, the rates were highest among army personnel (19.13 to 29.44 cases per 100 000). Among suicides with a known cause of death, 62% were attributed to firearms. The results of this study also suggest that among army personnel or marines who committed suicide, those with infantry or special operations job classifications were more likely than those in noninfantry positions to use a firearm. Results are generalizable only to enlisted personnel and reflect only stateside suicides. Data regarding previous psychiatric illness, deployment history, and firearms ownership were lacking. These results may help inform policymakers and advisors about differences in risks of suicide and violent suicide among the armed services and may help guide efforts to prevent self-harm within the military. None.


Segmental fixation with U-shaped rod in the treatment of spondylolisthesis.
From 1987 to 1990 the authors treated 20 cases of spondylolisthesis by an improved operative procedure including excision of the medial part of the superior articular processes of the slipped vertebra, excision of the soft tissue between the ununited isthmi, and excision of the ligamentum flavum between the intervertebral space above the slipped segment. In some instances the lower portion of the lamina over the slipped vertebra should be resected. A U-shaped rod was used to hold sublaminar fixation of two segments above and below the slipped vertebra, with the slipped vertebra spared. Utilizing the U-shaped rod as support, bone strips were placed along the lateral and anterior sides of the rod to bridge the gap between the laminae of the displaced vertebra. Other bone grafts were focused on the facet joints. The patients were allowed ambulation early postoperatively. 19 cases could be evaluated at preliminary follow-up. All showed satisfactory results.


Determination of basic degradation products of chemical warfare agents in water using hollow fibre-protected liquid-phase microextraction with in-situ derivatisation followed by gas chromatography-mass spectrometry.
Hollow fibre-protected liquid-phase microextraction (HF-LPME) together with gas chromatography-mass spectrometry was, for the first time, investigated for the in-situ derivatisation and analysis of basic degradation products of chemical warfare agents in water samples. The degradation products studied were those of nerve and blister agents, and a psychotomimetic agent. Extractions with in-situ derivatisation were successfully performed using a mixture of solvent and derivatising agent. The protection of the moisture-sensitive derivatising agent was afforded by the hydrophobic hollow fibre. Parameters such as type of derivatising agent, extraction solvent, pH, salt concentration, stirring speed and extraction time were optimised using spiked deionised water samples. The linear range established was between 0.05 and 25 microg ml(-1) depending on analyte, with squared regression coefficients ranging from 0.9959 to 0.9996. Relative standard deviations (RSDs) ranged from 6% to 10%. As comparison, solid-phase microextraction (SPME) was also evaluated and extraction conditions such as pH, salt concentration, stirring speed and extraction time were optimised. This work also represented the first report of such an in-situ derivatisation approach for SPME of basic analytes. The linear range established was between 0.5 and 25 microg ml(-1) depending on analyte, with squared regression coefficients ranging from 0.9946 to 0.9998. RSDs ranged from 5% to 22%. The limits of detection of HF-LPME (0.04-0.36 microg l(-1)) showed improvement over those of SPME (0.06-0.77 microg l(-1)).


Role of Inflammation in Traumatic Brain Injury-Associated Risk for Neuropsychiatric Disorders: State of the Evidence and Where Do We Go From Here.
In the past decade, there has been an increasing awareness that traumatic brain injury (TBI) and concussion substantially increase the risk for developing psychiatric disorders. Even mild TBI increases the risk for depression and anxiety disorders such as posttraumatic stress disorder by two- to threefold, predisposing patients to further functional impairment. This strong epidemiological link supports examination of potential mechanisms driving neuropsychiatric symptom development after TBI. One potential mechanism for increased neuropsychiatric symptoms after TBI is via inflammatory processes, as central nervous system inflammation can last years after initial injury. There is emerging preliminary evidence that TBI patients with posttraumatic stress disorder or depression exhibit increased central and peripheral inflammatory markers compared with TBI patients without these comorbidities. Growing evidence has demonstrated that immune signaling in animals plays an integral role in depressive- and anxiety-like behaviors after severe stress or brain injury. In this review, we will 1) discuss current evidence for chronic inflammation after TBI in the development of neuropsychiatric symptoms, 2) highlight potential microglial activation and cytokine signaling contributions, and 3) discuss potential promise and pitfalls for immune-targeted interventions and biomarker strategies to identify and treat TBI patients with immune-related neuropsychiatric symptoms.


A high affinity, mu-opioid receptor-selective enkephalin analogue lacking an N-terminal tyrosine.
We report a high affinity, mu opioid receptor selective enkephalin analogue in which the N-terminal tyrosine residue thought to be required for such high affinity is replaced by phenylalanine. The high affinity can be traced to a shift of the ligand's N-terminal residue within the mu receptor binding pocket, which diminishes the importance of the usual hydrogen bond between the tyrosine phenolic moiety and the receptor.


Partial nephrectomy driven by cavitron ultrasonic surgical aspirator under zero ischemia: a pilot study.
To investigate the efficacy and technical applicability of cavitron ultrasonic surgical aspirator (CUSA)-driven zero-ischemia open partial nephrectomy in patients with renal tumors. We prospectively collected data of 13 consecutive patients, who underwent open partial nephrectomy under non-ischemic conditions. Tumor resection was done using an ultrasonic device (CUSA/SONOCA 300). Demographic and laboratory data, tumor characteristics, perioperative, and postoperative variables were evaluated. The median age was 60.0 years (range 40-76); body mass index 28.0 kg/m(2) (range 22.9-43.3); tumor size 37.0 mm (range 11-110 mm). Patient were stratified according to the PADUA score into low- (score 6-7; n - 4), intermediate- (score 8-9; n - 5), and high-risk (score of >10; n - 4) groups, and the median score was 9.0 (range 6-13; SD +2.3). The vast majority of kidney tumors were diagnosed incidentally (n - 11; 84.6 %). Median operative time was 175 min (55-270 min); median time of tumor extirpation was 12 min (6-25 min); and median blood loss was 250 ml. Serum creatinine, glomerular filtration rate, and hemoglobin were nearly unaltered before and after surgery in 11 cases (84.6 %). Three patients received a blood transfusion (Clavien-Dindo Grade II); one had Grade IIIa complication (insertion of double J stent without general anesthesia); and three had Grade IIIb complications (insertion of double J under general anesthesia). The ultrasonic device demonstrated acceptable hemostatic and resection properties during open partial nephrectomy without ischemia. Our series showed promising perioperative and postoperative outcomes that may help in maximizing preservation of renal function in partial nephrectomy candidates.


Role of preoperative 3D rendering for minimally invasive parenchyma sparing liver resections.
3D rendering (3DR) represents a promising approach to plan surgical strategies. The study aimed to compare the results of minimally invasive liver resections (MILS) in patients with 3DR versus conventional 2D CT-scan. We performed 118 3DR for various indications; the patients underwent a preoperative tri-phasic CT-scan and rendered with Synapse3D® Software. Fifty-six patients undergoing MILS with pre-operative 3DR were compared to a similar cohort of 127 patients undergoing conventional pre-operative 2D CT-scan using the propensity score matching (PSM) analysis. The 3DR mandated pre-operative surgical plan variations in 33.9% cases, contraindicated surgery in 12.7%, providing a new surgical indication in 5.9% previously excluded cases. PSM identified 39 patients in both groups with comparable results in terms of conversion rates, blood loss, blood transfusions, parenchymal R1-margins, grade ≥3 Clavien-Dindo complications, 90-days mortality, and hospital stay respectively in 3DR and conventional 2D. Operative time was significantly increased in the 3DR group (402 vs. 347 min, p = 0.020). Vascular R1 resections were 25.6% vs 7.7% (p = 0.068), while the conversion rate was 0% vs 10.2% (p = 0.058), respectively, for 3DR group vs conventional 2D. 3DR may help in surgical planning increasing resectability rate while reducing conversion rates, allowing the precise identification of anatomical landmarks in minimally invasive parenchyma-preserving liver resections.


The impact of transitions from employment to retirement on suicidal behaviour among older aged Australians.
Transition from employment to retirement may be detrimental to mental health, and associated with suicidal behaviour. This study investigated the association between employment and retirement status and suicidal behaviour among older aged Australians. This study was based on the '45 and Up Study', a large prospective cohort study of participants from New South Wales (Australia) aged 45 years and older (N = 267,153), followed up over the period 2006-2018. The risk of attempted suicide and suicide was compared between categories of employment and retirement status in a series of recurrent event survival analysis models adjusting for identified time variant and invariant confounders. Compared to those who were employed, the risk of attempted suicide was higher among those who were not in the labour force and not retired (predominantly those who were sick or disabled, or carers) (HR = 1.97-95% CI 1.49-2.62), those who retired involuntarily (HR = 1.35-95% CI 1.03-1.77), and to a lesser extent those unemployed (HR = 1.31-95% CI 0.89-1.92). Risk of attempted suicide among those who retired voluntarily was similar to those who remained employed (HR = 1.09-95% CI 0.82-1.45). A similar pattern was evident for suicide, with a higher risk of suicide among those who were not in the labour force or retired, and those who retired involuntarily, compared to those who remained employed; however, these differences were not statistically significant. Transition from employment to retirement may be an important precipitating factor for suicidal behaviour, affected by current and previous mental health status. Services and programs facilitating continued or re-employment in older age, and adjustment to the transition from employment to retirement may prevent suicidal behaviour.


Social and healthcare professionals' experiences of end-of-life care planning and documentation in palliative care.
To explore social and healthcare professionals' experiences of end-of-life (EOL) care planning and documentation in palliative care. A qualitative study with narrative methodology. A narrative method with interviews was used. Data were collected from purposively selected registered nurses (n = 18), practical nurses (n = 5), social workers (n = 5) and physicians (n = 5) working in palliative care unit in five hospitals in three hospital districts. Content analysis within narrative methodologies was undertaken. Two main categories - patient-oriented EOL care planning and multi-professional EOL care planning documentation- were formed. Patient-oriented EOL care planning included treatment goals planning, disease treatment planning and EOL care setting planning. Multi-professional EOL care planning documentation included healthcare professionals' and social professionals' perspectives. Healthcare professionals' perspectives on EOL care planning documentation included benefits of structured documentation and poor support of electronic health record (EHR) for documentation. Social professionals' perspective on EOL care planning documentation included usefulness of multi-professional documentation and externality of social professionals in multi-professional documentation. The results of this interdisciplinary study demonstrated a gap between what healthcare professionals consider important in Advance Care Planning (ACP), that is, proactive, patient-oriented and multi-professional EOL care planning and the ability to access and document this in a useful and accessible way in the EHR. Knowledge of the patient-centered EOL care planning and multi-professional documentation processes and their challenges are prerequisites for documentation to be supported by technology. The Consolidated Criteria for Reporting Qualitative Research checklist was followed. No patient or public contribution.


Studying ubiquitination of MHC class I molecules.
The covalent attachment of ubiquitin to a protein is one of the most common post-translational modifications and regulates diverse eukaryotic cellular processes. Ubiquitination of MHC class I was first described in the context of viral proteins which target MHC class I for degradation in the endoplasmic reticulum and at the cell surface. Study of viral-induced MHC class I degradation has been extremely instructive in elucidating cellular pathways for degradation of membrane and secretory proteins. More recently, ubiquitination of endogenous MHC class I heavy chains which fail to achieve their native conformation and undergo endoplasmic-reticulum associated degradation has been demonstrated.In this chapter we describe methods for identification of endogenous ubiquitinated MHC class I heavy chains by MHC class I-immunoprecipitation and ubiquitin-specific immunoblot or by metabolic labeling and immunoprecipitation.


The experimental study of hypoxia-inducible factor-1alpha and its target genes in spinal cord injury.
Animal model of compressive spinal cord injury (SCI), reverse transcription-polymerase chain reaction (RT-PCR), in situ hybridization (ISH), immunohistochemistry (IHC) and enzymehistochemistry (EHC) were used to test the hypothesis that hypoxia-inducible factor-1alpha (HIF-1alpha) and the target genes activated by HIF-1alpha are involved in cell hypoxia tolerance and tissue vascularity to help injured tissue to go through the stress disease. To determine whether HIF-1alpha and its target genes associated with hypoxia tolerance and neovascularization take part in the pathophysiological procedure of SCI in rats. Yunnan University, China. Random-bred adult male Sprague-Dawley (SD) rats weighing 250+/-50 g were prepared for compressive SCI models. After receiving compressive injury at T(10), rats were sacrificed at different times from 6 h to 1 week after injury. The injured cords were removed, and HIF-1alpha and its target genes were assayed by RT-PCR, ISH, IHC and EHC. The data were statistically analyzed. An increase in HIF-1alpha mRNA expression was observed 12 h postinjury, reached a maximum at 3 days, and reduced gradually thereafter. HIF-1alpha protein expressed earlier than HIF-1alpha mRNA. Additionally, two glycolytic enzymes and vascular endothelial growth factor (VEGF), which are regulated by HIF-1alpha, also increased after an interval postinjury, and their expression patterns shared a same trend with that of HIF-1alpha protein. The findings suggested that the most important hypoxic regulatory factor HIF-1alpha was upregulated in involved cells by activating the transcription and increasing protein stability, and subsequently activated the expression of HIF-1alpha target genes, including glycolytic enzymes and VEGF in SCI. Combined with the pathologic observation, it suggested that overexpression of HIF-1alpha and its target genes might take part in hypoxia tolerance and vascularity of the injured spinal cord.


Polymorphism of human cytomegalovirus glycoproteins characterized by monoclonal antibodies.
Monoclonal antibody panels selected in this and preceding studies were employed to begin to characterize the properties of human cytomegalovirus (CMV) glycoproteins. The results were as follows. (i) Four antigenically distinct CMV glycoproteins designated as gA, gB, gC, and gD have been identified. (ii) gA, gC, and gD each form several bands when immune precipitated from infected cell extracts by the corresponding monoclonal antibodies and electrophoretically separated in sodium dodecyl sulfate-polyacrylamide gels. In contrast, gB migrated at one broad band with an apparent molecular weight in the range of 116,000 to 123,000. Bands with different molecular weights were shown to share antigenic determinants by reactivity of monoclonal antibodies with electrophoretically separated polypeptides immobilized on nitrocellulose. (iii) A panel of 16 monoclonal antibodies to gA precipitated a family of glycoproteins 160,000-148,000, 142,000, 138,000, 123,000-107,000, 95,000, and 58,500 in apparent molecular weight designated as gA1 through gA6, respectively. (iv) To identify partially glycosylated precursors of gA, infected cells were treated with tunicamycin or deoxyglucose and reacted with different monoclonal antibodies. Tunicamycin-treated infected cells labeled for a short pulse or longer intervals contained only gA5. Whereas cells treated with deoxyglucose during a pulse contained gA4, those labeled for a longer interval contained gA6 and an additional band approximately 56,500 in apparent molecular weight designated gA7. (v) Precipitates of gA from infected cells labeled for a short pulse contained gA2 and gA3 which appear to be products of rapid glycosylation. After a chase, trace amounts of gA1 and gA6 were also precipitated suggesting that these are products of slow post-translational processing. (vi) Endo-beta-N-acetylglucosaminidase H was used to identify the forms of gA which contain high-mannose oligosaccharide chains. After treatment, the electrophoretic mobility of gA2, gA3, and gA6 increased significantly suggesting that these forms contain high-mannose chains cleaved by the enzyme. A hypothesis for processing gA is presented.


Ghrelin protects human umbilical vein endothelial cells against advanced glycation end products-induced apoptosis via NO/cGMP signaling.
The aim of this study was to investigate the intracellular mechanism involved in the anti-apoptotic effect of ghrelin on human umbilical vein endothelial cells (HUVECs). HUVECs were pretreated with ghrelin before exposure to 200 μg/ml advanced glycation end products (AGEs)-BSA for 48 h. Cell viability and apoptosis were determined by MTT assay and Annexin V/PI staining. Intracellular cGMP levels evaluation and cGMP analogs were employed to explore possible mechanisms. The inhibitory effect on AGEs induced HUVECs apoptosis could be exerted by ghrelin and co-incubation with growth hormone secretagogue receptor (GHSR)-1a antagonist [D-Lys(3)]-GHRP-6 abolished this inhibition. Decreased cGMP level in AGEs induced HUVECs apoptosis was restored by ghrelin pretreatment and abolished by [D-Lys(3)]-GHRP-6 co-incubation. cGMP analogs (8 Br-cGMP and DB-cGMP) pretreatment also exhibited inhibitory effect on AGEs induced HUVECs apoptosis. Our results demonstrated that ghrelin produces a protective effect on HUVECs through GHS-R1a and cGMP/NO signaling pathway mediates the effect of ghrelin. These observations suggest a novel intracellular mechanism in the process of AGEs induced HUVECs apoptosis.


A descriptive study of bottle-feeding opportunities in preterm infants.
The purposes of this study were to describe patterns of bottle feeding opportunities in preterm infants and to analyze the relationships between feeding opportunities and outcomes. The smaple was composed of 25 preterm infants who were bottle fed. Retrospective, correlational. Data were collected from medical records and analyzed descriptively. Correlation coefficients among variables were computed. Postconceptional age (PCA) at the time of full bottle feedings and transition time from the first to full bottle feedings. The number of bottle feedings received per day during the transition from first to full bottle feedings was inversely related to length of transition to full bottle feedings. There was no relationship between the number of bottle-feeding opportunities and PCA at full bottle feedings. The achievement of full bottle feedings may be facilitated by increased bottle-feeding opportunities. More research about the relationships among feeding readiness, outcomes, and opportunities is needed.


In vivo fracture of an extruded polymethylmethacrylate intraocular lens loop.
The inferior loop of a semiflexible, closed-loop anterior chamber intraocular lens in the eye of a 72-year-old female fractured at two sites. The loop was composed of extruded polymethylmethacrylate. The inferotemporal portion of the loop was first noted to be broken 25 months postoperatively, and the fractured nasal portion of the same loop was first observed 55 months after implantation. The patient denied any excessive rubbing of the eye or major trauma to the eye or head. Both fractures occurred near the loop-optic junction. The intermittent touch of the cornea by the broken loop caused endothelial damage and edema in the lower one third of the cornea. The two portions of the lens were removed and exchanged with another style of anterior chamber lens. The visual acuity at six weeks postexchange was 20/30.


Accumulation of p53 in response to adenovirus early region 1A sensitizes human cells to tumor necrosis factor alpha-induced apoptosis.
Many tumor cells are resistant to tumor necrosis factor alpha (TNFalpha)-induced apoptosis. Adenovirus early region 1A (AdE1A) sensitizes the otherwise resistant cells to TNFalpha. AdE1A also stabilizes the p53 protein. The present study demonstrates a correlation between AdE1A-induced sensitization and stabilization of p53 in TNFalpha-induced apoptosis since the N-terminal and CR2 regions, the binding sites for CBP/p300, Rb and 26S proteasome regulatory components, are required for both these actions of AdE1A. TNFalpha does not induce apoptosis and AdE1A fails to sensitize TNFalpha cytotoxicity in p53-negative cells. However, introduction of exogenous p53 overcomes the cellular resistance to TNFalpha toxicity and enhances AdE1A sensitization, demonstrating that AdE1A sensitizes TNFalpha-induced apoptosis by its stabilization of p53. A proteasome inhibitor, lactacystin, enhances TNFalpha cytotoxicity in p53-positive and -negative cells, suggesting that accumulation of cellular proteins other than p53 might also regulate the cellular response to TNFalpha signaling.


Thermosensitive polymer-modified liposomes that release contents around physiological temperature.
To obtain temperature-sensitive liposomes which release their contents around the physiological temperature, we designed dioleoylphosphatidylethanolamine liposomes modified with copolymers of N-isopropylacrylamide and acryloylpyrrolidine. Copolymers of acryloylpyrrolidine and N-isopropylacrylamide, which exhibit a lower critical solution temperature around the physiological temperature, were prepared by free radical copolymerization using azobis(isobutyronitrile) as the initiator. The copolymers with anchors to the liposome membrane were obtained by using N, N-didodecylacrylamide as an additional comonomer. The copolymer having the anchor group at the terminal of the polymer chain was also synthesized by copolymerization of these monomers in the presence of 2-aminoethanethiol and subsequent conjugation of N, N-didodecyl succinamic acid to the terminal amino group of the copolymer. Calcein-loaded dioleoylphosphatidylethanolamine liposomes modified with these copolymers were prepared and release of the contents from these liposomes was investigated. It was found that the release from these copolymer-modified liposomes was promoted around and above the lower critical temperature of the copolymer. Also, the liposomes modified with the terminal anchor-type copolymer released the contents more drastically responding to a small temperature change than the liposomes modified with random copolymers containing N,N-didodecylacrylamide units as the anchor.


Predictors of overall quality of care provided to vulnerable older people.
Prior research shows that the quality of care provided to vulnerable older persons is suboptimal, but little is known about the factors associated with care quality for this group. In this study, the influences of clinical conditions, types of care processes, and sociodemographic characteristics on the quality of care received by vulnerable older people were evaluated. Observational cohort study. Two senior managed care plans. Three hundred sixty-two community-dwelling patients aged 65 and older identified as vulnerable by the Vulnerable Elder Survey (VES-13). patients' observed-minus-expected overall quality score. types of care processes, types and number of clinical conditions, sex, age, VES-13 score (composite score of function and self-rated health), income, education, mental health status, and number of quality indicators triggered. Patients whose conditions required more history-taking, counseling, and medication-prescribing care processes and patients with diabetes mellitus received lower-than-expected quality of care. A greater number of comorbid conditions was associated with higher-than-expected quality of care. Age, sex, VES-13 score, and other sociodemographic variables were not associated with quality of care. Complexity, vulnerability, and age do not predispose older persons to receive poorer-quality care. In contrast, older patients whose care requires time-consuming processes such as history taking and counseling are at risk for worse quality of care and should be a target for intervention to improve care.


Effect of leucine or ketoleucine on nitrogen metabolism in postoperative patients receiving energy substrate.
It has been shown that ketoisocaproate (KIC) spares nitrogen (N) in fasting postoperative patients while leucine does not. The aim of the present study was to determine if KIC when compared with leucine, decreases nitrogen excretion in postoperative patients receiving energy substrate. Thirty patients undergoing gynecological surgery (hysterectomy with or without lymphadenectomy) were randomized to receive for the first 3 postoperative days one of the following I.V. solutions per kilo and per day: 3 g glucose (group A) 3 g glucose + 90 mg Leucine (group B), 3 g glucose + 100 mg ketoleucine (group C). The output of 3 methylhistidine (3 MEH), total nitrogen and creatinine were measured daily. Although muscle protein breakdown measured as 3 MEH/creatinine molar ratio was significantly reduced in group C as compared with A and B, total nitrogen and creatinine did not differ significantly in A, B and C. Thus, the metabolic effects of KIC in postoperative patients are appreciably influenced by glucose infusions and the usefulness of KIC infusions in such patients needs further study.