SenseJoy, a pluggable solution for assessing user behavior during powered wheelchair driving tasks.
The complex task of Electric Powered Wheelchairs (EPW) prescription relies mainly on personal experience and subjective observations despite standardized processes and protocols. The most informative measurements come from joystick monitoring, but recording direct joystick outputs require to disassemble the joystick. We propose a new solution called "SenseJoy" that is easy to plug on a joystick and is suitable to characterize the driver behavior by estimating the joystick command. SenseJoy is a pluggable system embedded on EPW built with a 3D accelerometer and a 2D gyrometer placed within the joystick and another 3D accelerometer located at the basis of the joystick. Data is sampled at 39 Hz and processed offline. First, SenseJoy sensitivity is assessed on wheelchair driving tasks performed by a group of 8 drivers (31 ± 8 years old, including one driver with left hemiplegia, one with cerebral palsy) in a lab environment. Direct joystick measurements are compared with SenseJoy estimations in different driving exercises. A second group of 5 drivers is recorded in the ecological context of a rehabilitation center (41 ± 10 years old, with two tetraplegic drivers, one tetraplegic driver with cognitive disorder, one driver post-stroke, one driver with right hemiplegia). The measurements from all groups of drivers are evaluated with an unsupervised statistical analysis, to estimate driving profile clusters. The SenseJoy is able to measure the EPW joystick inclination angles with a resolution of 1.31% and 1.23% in backward/forward and left/right directions respectively. A statistical validation ensures that the classical joystick-based indicators are equivalent when acquired with the SenseJoy or with a direct joystick output connection. Using an unsupervised methodology, based on a similarity matrix between subjects, it is possible to characterize the driver profile from real data. SenseJoy is a pluggable system for assessing the joystick controls during EPW driving tasks. This system can be plugged on any EPW equipped with a joystick control interface. We demonstrate that it correctly estimates the performance indicators and it is able to characterize driving profile. The system is suitable and efficient to assist therapists in their recommendation, by providing objective measures with a fast installation process.


Peptides as targeting probes against tumor vasculature for diagnosis and drug delivery.
Tumor vasculature expresses a distinct set of molecule signatures on the endothelial cell surface different from the resting blood vessels of other organs and tissues in the body. This makes them an attractive target for cancer therapy and molecular imaging. The current technology using the in vivo phage display biopanning allows us to quickly isolate and identify peptides potentially homing to various tumor blood vessels. Tumor-homing peptides in conjugation with chemotherapeutic drugs or imaging contrast have been extensively tested in various preclinical and clinical studies. These tumor-homing peptides have valuable potential as targeting probes for tumor molecular imaging and drug delivery. In this review, we summarize the recent advances about the applications of tumor-homing peptides selected by in vivo phage display library screening against tumor vasculature. We also introduce the characteristics of the latest discovered tumor-penetrating peptides in their potential clinical applications.


Tumour necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6) and their soluble receptors (sTNF-alpha-Rp55 and slL-6R) serum levels in systemic lupus erythematodes.
We investigated a possible association between serum concentrations of tumour necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6) and their soluble receptors (sTNF-alpha-Rp55 and sIL-6R) using an enzyme-linked immunosorbent assay (ELISA) in 55 patients with systemic lupus erythematodes (SLE) and 16 healthy controls. We also examined a possible association between the serum levels of these peptides and SLE activity, as well as TNF-alpha and IL-6 concentrations and the levels of their soluble receptors. The median concentrations of TNF-alpha, sTNF-alpha-Rp55 and IL-6 were significantly higher in SLE patients than in normal individuals. In contrast, there was no difference between the serum level of sIL-6R in both groups. We found positive correlations between the serum concentrations of TNF-alpha and IL-6 as well as their soluble receptors and disease activity. There were also correlations between TNF-alpha and sTNF-alpha-Rp55 as well as IL-6 and sIL-6R serum levels in SLE patients but there were no such correlations in the normal control group. In conclusion, an increase in the serum levels of TNF-alpha, sTNF-alpha-Rp55 and IL-6 may become useful markers for SLE activity. Patients with SLE have sIL-6R serum concentration similar to that as in normal individuals. However, it correlates with disease activity and the level of IL-6.


Are risk factors for breast cancer similar in women with inflammatory breast cancer and in those with non-inflammatory breast cancer?
The aim of the study was to compare reproductive factors in patients with inflammatory breast cancer (IBC), and with non-inflammatory breast cancer (non-IBC). The study was performed in two centers: one French including 49 IBC patients and 140 non-IBC and another Tunisian including 97 IBC and 139 non-IBC. Unconditional logistic regression was used for the analyses. The French IBC patients had a lower educational level, a higher body mass index and a longer cumulative duration of breast-feeding, and they included a greater proportion of non-European women, than the non-IBC patients. In the multivariate analysis, only breast-feeding duration remained associated with the IBC status (P=10(-3)). These results could not be verified in the Tunisian series, because the duration of breast-feeding was unavailable in this center. This study suggests that the etiology of IBC might be different of that of non-IBC.


Efficacy of concurrent treatments in idiopathic pulmonary fibrosis patients with a rapid progression of respiratory failure: an analysis of a national administrative database in Japan.
Some IPF patients show a rapid progression of respiratory failure. Most patients are treated with high-dose corticosteroids. However, no large clinical studies have investigated the prognosis or efficacy of combined treatments including high-dose corticosteroids in IPF patients with a rapid progression of respiratory failure. We enrolled IPF patients who received mechanical ventilation and high-dose corticosteroids between April 2010 and March 2013. Records were extracted from a Japanese nationwide inpatient database. We conducted a retrospective epidemiologic and prognostic analysis. Two hundred nine patients receiving an average of 12.8 days of ventilatory support were enrolled. There were 138 (66 %) fatal cases; the median survival was 21 days. The short-term (within 30 days) and long-term (within 90 days) survival rates were 44.6 and 24.6 %, respectively. The average monthly admission rate among the IPF patients with the rapid progression of respiratory failure in the winter was significantly higher than that in spring (p = 0.018). Survival did not differ to a statistically significant extent in the different geographic areas of Japan. Survivors were significantly younger (p = 0.002) with higher rates of mild dyspnea on admission (p = 0.012), they more frequently underwent bronchoscopy (p < 0.001), and received anticoagulants (p = 0.027), co-trimoxazole (p < 0.001) and macrolide (p = 0.02) more frequently than non-survivors. A multivariate logistic analysis demonstrated that two factors were significantly associated with a poor prognosis: >80 years of age (OR = 2.94, 95 % Cl 1.044-8.303; p = 0.041) and the intravenous administration of high-dose cyclophosphamide (OR = 3.17, 95 % Cl 1.101-9.148; p = 0.033). Undergoing bronchoscopy during intubation (OR = 0.25, 95 % Cl 0.079-0.798; p = 0.019) and the administration of co-trimoxazole (OR = 0.28, 95 % Cl 0.132-0.607; p = 0.001) and macrolides (OR = 0.37, 95 % Cl 0.155-0.867; p = 0.033) were significantly associated with a good prognosis. The dosage of co-trimoxazole significantly correlated with survival. Co-trimoxazole and macrolides may be a good addition to high-dose corticosteroids in the treatment of IPF patients with a rapid progression of respiratory failure.


The effects of intravenous sildenafil on hemodynamics and cardiac sympathetic activity in chronic human heart failure.
Erectile dysfunction is common in patients with chronic heart failure and sildenafil is an effective treatment option in this population. Sildenafil has been reported to increase sympathetic outflow in normal volunteers. To date, experience with sildenafil in patients with congestive heart failure is limited and the impact of phosphodiesterase-5 inhibition on sympathetic activity in this population has not been evaluated. 10 patients with heart failure (ejection fraction 23+/-3%) were studied. Generalized and cardiac sympathetic activity responses to an intravenous infusion of sildenafil were measured by the norepinephrine spillover method. In response to sildenafil, there was a significant reduction in mean pulmonary artery (-26+/-5%, P<0.01) and mean arterial pressures (-8+/-1%, P<0.01). These hemodynamic responses were accompanied by a 22+/-5% reduction in cardiac norepinephrine spillover (P<0.02) but no change in total body norepinephrine spillover. The acute administration of sildenafil is associated with a modest reduction in systemic arterial blood pressure and a more substantial reduction in pulmonary arterial pressure. These hemodynamic changes are observed in the absence of systemic sympathetic activation and are associated with a reduction in cardiac norepinephrine spillover in patients with chronic heart failure. These observations are relevant given the high prevalence of erectile dysfunction in this patient population.


Translational development of a tumor junction opening technology.
Our goal is to overcome treatment resistance in ovarian cancer patients which occurs in most cases after an initial positive response to chemotherapy. A central resistance mechanism is the maintenance of desmoglein-2 (DSG2) positive tight junctions between malignant cells that prevents drug penetration into the tumor. We have generated JO4, a recombinant protein that binds to DSG2 resulting in the transient opening of junctions in epithelial tumors. Here we present studies toward the clinical translation of c-JO4 in combination with PEGylated liposomal doxorubicin/Doxil for ovarian cancer therapy. A manufacturing process for cGMP compliant production of JO4 was developed resulting in c-JO4. GLP toxicology studies using material from this process in DSG2 transgenic mice and cynomolgus macaques showed no treatment-related toxicities after intravenous injection at doses reaching 24 mg/kg. Multiple cycles of intravenous c-JO4 plus Doxil (four cycles, 4 weeks apart, simulating the treatment regimen in the clinical trial) elicited antibodies against c-JO4 that increased with each cycle and were accompanied by elevation of pro-inflammatory cytokines IL-6 and TNFα. Pretreatment with steroids and cyclophosphamide reduced anti-c-JO4 antibody response and blunted cytokine release. Our data indicate acceptable safety of our new treatment approach if immune reactions are monitored and counteracted with appropriate immune suppression.


A switch from low to high Shh activity regulates establishment of limb progenitors and signaling centers.
The patterning and growth of the embryonic vertebrate limb is dependent on Sonic hedgehog (Shh), a morphogen that regulates the activity of Gli transcription factors. However, Shh expression is not observed during the first 12 hr of limb development. During this phase, the limb bud is prepatterned into anterior and posterior regions through the antagonistic actions of transcription factors Gli3 and Hand2. We demonstrate that precocious activation of Shh signaling during this early phase interferes with the Gli3-dependent specification of anterior progenitors, disturbing establishment of signaling centers and normal outgrowth of the limb. Our findings illustrate that limb development requires a sweet spot in the level and timing of pathway activation that allows for the Shh-dependent expansion of posterior progenitors without interfering with early prepatterning functions of Gli3/Gli3R or specification of anterior progenitors.


Asthmatic cough and airway oxidative stress.
The mechanisms of cough in asthma are unclear. Asthma is associated with an oxidative stress. Many reactive oxygen species sensitize or activate sensory C-fibers which are capable to induce cough. It was hypothesized that oxidative stress in the airways might contribute to the cough severity in asthma. Exhaled breath condensate samples were collected in ten healthy and 26 asthmatic subjects. The concentration of 8-isoprostane was measured. In addition, the subjects filled in Leicester Cough Questionnaire and underwent cough provocation tests with dry air hyperpnoea and hypertonic saline, among other measurements. Among the asthmatic subjects, high 8-isoprostane was associated with severe cough response to hyperpnoea (p=0.001), low Leicester Cough Questionnaire values (indicating severe subjective cough, p=0.02), and usage of combination asthma drugs (p=0.03-0.04). However, the 8-isoprostane concentrations did not differ significantly between the healthy and the asthmatic subjects. Airway oxidative stress may be associated with experienced cough severity and measured cough sensitivity in asthma.


Nursing resource considerations for implementing an electronic documentation system.
Implementation of an or management information system (ORMIS) requires a significant commitment of human resources. The experiences of the personnel at The Johns Hopkins Hospital, Baltimore, MD, as they transitioned to using a single, unified, computerized ORMIS are detailed in this article. Included are discussions of the nursing resources involved in the process, the lessons learned, and the work that remains to be completed for the hospital to fully utilize the system.


Point mutations as an optimal search process in biological evolution.
Point mutations are pictured as jumps in a phase space representing the sequences of amino acids or nucleotides as discrete points. It is shown that this space can be given a natural metric by quantifying common physical and chemical properties of amino acid constituents in terms of a natural measure. Evolution through point mutations is simulated by the search for points in the phase space representing amino acid sequences of high survival fitness. Due to the local compactness of the distribution of these functionally allowed points in phase space any successful search procedure has characteristics qualitatively different from those in the case of a random distribution. This is demonstrated by model calculations. A specified distribution of allowed points is generated with subsequent evaluation of the success of the retrieval process as a function of the jump probabilities between lattice sites. The results of such simulations are compared with data obtained from the analysis of the DNA or mRNA sequences coding related proteins. By counting silent and expressed nucleotide replacement frequencies one can draw conclusions as to the efficacy of the natural evolutionary search processes in the phase space of amino acid sequences. There are cases, where the highest possible information gain of one bit per accepted point mutation is achieved. In general the information gain is found to be somewhat sub-maximal due to functional requirements.


Azathioprine with Allopurinol Is a Promising First-Line Therapy for Inflammatory Bowel Diseases.
Beneficial response to first-line immunosuppressive azathioprine in patients with inflammatory bowel disease (IBD) is low due to high rates of adverse events. Co-administrating allopurinol has been shown to improve tolerability. However, data on this co-therapy as first-line treatment are scarce. Retrospective comparison of long-term effectiveness and safety of first-line low-dose azathioprine-allopurinol co-therapy (LDAA) with first-line azathioprine monotherapy (AZAm) in patients with IBD without metabolite monitoring. Clinical benefit was defined as ongoing therapy without initiation of steroids, biologics or surgery. Secondary outcomes included CRP, HBI/SCCAI, steroid withdrawal and adverse events. In total, 166 LDAA and 118 AZAm patients (median follow-up 25 and 27 months) were evaluated. Clinical benefit was more frequently observed in LDAA patients at 6 months (74% vs. 53%, p = 0.0003), 12 months (54% vs. 37%, p = 0.01) and in the long-term (median 36 months; 37% vs. 24%, p = 0.04). Throughout follow-up, AZAm patients were 60% more likely to fail therapy, due to a higher intolerance rate (45% vs. 26%, p = 0.001). Only 73% of the effective AZA dose was tolerated in AZAm patients, while LDAA could be initiated and maintained at its target dose. Incidence of myelotoxicity and elevated liver enzymes was similar in both cohorts, and both conditions led to LDAA withdrawal in only 2%. Increasing allopurinol from 100 to 200-300 mg/day significantly lowered liver enzymes in 5/6 LDAA patients with hepatotoxicity. Our poor AZAm outcomes emphasize that optimization of azathioprine is needed. We demonstrated a long-term safe and more effective profile of first-line LDAA. This co-therapy may therefore be considered standard first-line immunosuppressive.


Lymphoproliferative conditions of the serosa.
A diverse and complex variety of lymphoproliferative diseases may involve the serosa, with widely differing clinical outcomes encompassing a spectrum of benign and malignant conditions. To review lymphoproliferative disease involving the serosa and to provide a practical approach to the evaluation of lymphoid and plasma cell infiltrates in the serosa, together with a review of various tumors and tumorlike conditions that may mimic lymphoproliferative disease. Analysis of published literature. All forms of hematologic malignancy may involve the various serosal sites, although this is usually observed as secondary involvement in persons with known lymph nodal, marrow-based, or extranodal disease. Primary pericardial, pleural, and peritoneal lymphomas are rare; many nonneoplastic conditions may mimic lymphoma and a variety of nonhematolymphoid tumors may simulate hematologic malignancies. An understanding of the role of ancillary tests, together with an appreciation of their limitations, will prevent misdiagnosis.


Follow-up of subjects labelled with putative pre-psychotic states: Viewed from a transdiagnostic clinical high-at-risk mental state (CHARMS) paradigm.
Follow-up of subjects with putative pre-psychotic states is essential to clarify the transition process to psychosis, while "non-converters" also deserve clinical attention as many may evolve into other psychiatric disorders with diverse outcomes. This study aimed to examine help-seeking individuals who have been labelled at clinical high-risk state but not converting to full-blown psychosis during first two years of follow-up. A retrospective observational cohort study of help-seeking subjects was conducted by reviewing medical records of participants in a previous early psychosis study at the study hospital between 2006 and 2020. We portrayed those who developed first episode psychosis after first 2-year follow-up in detail, and provided sketches of clinical macrophenotypes other than psychosis emerging from subjects among different risk groups. Among 132 eligible subjects, data of 98 (74.2%) were available for detailed evaluation. Of these, 15 transitioned to first-episode psychosis (11.4%) with time to psychosis from 2 to 11 years, 11 had anxiety spectrum (8.3%), 11 had depressive spectrum (8.3%), 10 had obsessive compulsive (7.6%), 5 had bipolar spectrum disorders (3.8%), 13 had predominantly schizotypal (9.8%) and 4 had other personality traits (3%), and 13 had problems attributable to adjustment or developmental issues (9.8%). Various diagnoses, either full- or sub-threshold, appropriately describe the diverse clinical phenomenology of a cohort presenting with non-specific and/or subthreshold psychotic symptoms. The clinical high-at-risk mental state (CHARMS) paradigm provides a reasonable transdiagnostic approach for orienting clinicians' attention toward young subjects seeking mental health help at an early stage of illness to potentially pluripotent trajectories.


Rehabilitation for Musculoskeletal Disorders: The Emergence of Serious Games and the Promise of Personalized Versions Using Artificial Intelligence.
According to the World Health Organization (WHO), musculoskeletal conditions are among the most common health problems, affecting approximately 1 [...].


Motif co-regulation and co-operativity are common mechanisms in transcriptional, post-transcriptional and post-translational regulation.
A substantial portion of the regulatory interactions in the higher eukaryotic cell are mediated by simple sequence motifs in the regulatory segments of genes and (pre-)mRNAs, and in the intrinsically disordered regions of proteins. Although these regulatory modules are physicochemically distinct, they share an evolutionary plasticity that has facilitated a rapid growth of their use and resulted in their ubiquity in complex organisms. The ease of motif acquisition simplifies access to basal housekeeping functions, facilitates the co-regulation of multiple biomolecules allowing them to respond in a coordinated manner to changes in the cell state, and supports the integration of multiple signals for combinatorial decision-making. Consequently, motifs are indispensable for temporal, spatial, conditional and basal regulation at the transcriptional, post-transcriptional and post-translational level. In this review, we highlight that many of the key regulatory pathways of the cell are recruited by motifs and that the ease of motif acquisition has resulted in large networks of co-regulated biomolecules. We discuss how co-operativity allows simple static motifs to perform the conditional regulation that underlies decision-making in higher eukaryotic biological systems. We observe that each gene and its products have a unique set of DNA, RNA or protein motifs that encode a regulatory program to define the logical circuitry that guides the life cycle of these biomolecules, from transcription to degradation. Finally, we contrast the regulatory properties of protein motifs and the regulatory elements of DNA and (pre-)mRNAs, advocating that co-regulation, co-operativity, and motif-driven regulatory programs are common mechanisms that emerge from the use of simple, evolutionarily plastic regulatory modules.


Immunophenotype of porcine oviduct epithelial cells during the oestrous cycle: a double-labelling immunohistochemical study.
The luminal epithelium of the porcine oviduct is composed of ciliated cells and secretory cells, but it is assumed for several species that under the control of steroid hormones secretory cells are able to be transformed into ciliated cells. In order to better understand such physiological changes during the different stages of the oestrous cycle, we evaluated epithelial cell proliferation together with oestrogen receptor alpha (ERalpha) expression of porcine ampullary oviducts. To identify the immunophenotype of proliferating cells, double immunohistochemistry was performed using anti-chromogranin A antibody (anti-CgA) as the second primary antibody. Anti-CgA, recently shown to be an immunocytochemical marker of ciliated cells of the cow, also labelled specifically the luminal surface of ciliated cells of the pig. Double labelling of sections with the monoclonal antibody MIB-1 against the proliferation-associated nuclear epitope Ki-67 and anti-CgA clearly demonstrates that MIB-1 was selectively localised in the nuclei of secretory cells. Proliferative activity was not observed in CgA-positive ciliated cells in all examined stages of the oestrous cycle. The percentage of Ki-67-positive epithelial cells was higher at pro-oestrus, compared with the other stages of the oestrous cycle. Furthermore, ERalpha immunoreactivity was exclusively detected in the nuclei of the epithelial cells, which were negative for CgA. We conclude, therefore, that oestrogen may induce the initial proliferation of secretory cells and promote the differentiation into ciliated cells.


Optimal parameters for in vitro growth of parvoviruses.
A procedure for optimal production or isolation of parvoviruses was found to be as follows: Indicator cells were infected in suspension using a cell concentration associated with full monolayer not before 3-4 days. The infected monolayer was passaged at similar cell concentrations, and the procedure repeated for up to 28 days culture of samples in this way. The optimal serum supplement used was free of or had low haemagglutination inhibitory activity to the virus studied and was used at minimal concentrations. Alternatively it was possible to remove serum supplement inhibitory activity by treatment with MnCl2/heparin dialysed and sterilized before use as serum supplement.


Prenatal diagnosis of abnormal course of umbilical vein and ductus venosus agenesis: report of three cases.
Ductus venosus connecting the portal and embryonic venous circulation into the inferior vena cava has a crucial role in fetal circulation. The absence of ductus venosus is a rare anomaly, in which the umbilical vein connection to the venous system may be extrahepatic, bypassing the liver or intrahepatic via the portal venous system. We report three cases of ductus venosus agenesis with associated anomalies. In two of them the connection was directly to the right atrium, whereas the umbilical vein drained to the left internal iliac artery in the third case.


Seroprevalence of enzootic bovine leukosis in Trakya district (Marmara region) in Turkey.
In this study, 481 cattle belonging to 77 farms from nine localities in Trakya district in the Marmara region of Turkey were blood sampled and serologically tested for enzootic bovine leukosis (EBL). Antibodies to bovine leukosis virus (BLV) were detected in 51 cattle sera (11%) belonging to nine farms in five localities. Cattle tested were mostly female Holstein or Brown Swiss of ages ranging between 18 months and 10 years. Analysis of the relationships between age, breed or sex and seropositivity to EBL in seropositive herds indicated no significant associations (p > 0.05). The relationship between seropositivity and haematological changes was also studied, and seropositive cattle had higher lymphocyte percentage and lower neutrophil percentage than seronegative cattle (p < 0.001).


Duration of oliguria and anuria as predictors of chronic renal-related sequelae in post-diarrheal hemolytic uremic syndrome.
Prior long-term retrospective studies have described renal sequelae in 25-50% of postdiarrheal hemolytic uremic syndrome (HUS) survivors, but the ability to predict the likelihood of chronic renal-related sequelae at the time of hospital discharge is limited. We surveyed 357 children in our HUS registry who survived an acute episode of post diarrheal HUS (D+HUS) and were without end-stage renal disease (ESRD) at the time of hospital discharge. Of the 357 patients surveyed, 159 had at least 1 year (mean 8.75 years) of follow-up. Of these, 90 individuals were identified as having had at least 1 day of oliguria, with 69 individuals having had at least 1 day of anuria. The incidences of renal-related sequelae [proteinuria, low glomerular filtration rate (GFR), and hypertension] were determined among experimental groups based on oliguria and anuria duration. One or more sequelae (e.g. proteinuria, low GFR, hypertension) was seen in 25 (36.2%) of those who had no recorded oliguria and 34 (37.8%) of those with no recorded anuria. The prevalence of chronic sequelae increased markedly in those with more than 5 days of anuria or 10 days of oliguria, with anuria being a better predictor than oliguria of most related sequelae. A particularly high incidence of hypertension was seen in patients with > 10 days of anuria (55.6%) in comparison with those with no anuria (8.9%) [odds ratio (OR) 12.8; 95% confidence interval (CI) 2.9-57.5]. Patients with > 10 days of anuria were also at substantially increased risk for low GFR and proteinuria (OR 35.2; 95% CI 5.1-240.5). These findings may help identify children who need periodic and extended follow-up after hospital discharge.


Sex differences in change of direction deficit and asymmetries in footballers with cerebral palsy.
The aims of this study were (1) to describe and examine differences in change of direction (COD) performance and the magnitude of asymmetries in para-footballers with cerebral palsy (CP) and controls and (2) to evaluate the association between COD outcomes and linear sprint performance. Twenty-eight international para-footballers with CP and thirty-nine non-impaired football players (control group) participated in this study. All participants completed a 10-m sprint and two attempts of the 505 COD test with the dominant and non-dominant leg. The COD deficit was calculated using the difference between the 505 test and the 10-m sprint time, while the asymmetry index was determined by comparing each leg's completion time and COD deficit. Players across groups showed interlimb asymmetries between the dominant and non-dominant legs in COD outcomes and deficit (p < 0.05, dg = -0.40 to -1.46), although these asymmetries imbalance were not significantly different between the sexes with and without impairment. Males with CP exhibited a faster directional COD speed and a shorter COD deficit than their female counterparts (p < 0.01, dg = -1.68 to -2.53). Similarly, the control group had faster scores than the CP groups of the same sex (p < 0.05, dg = 0.53 to 3.78). Lastly, the female CP group and male control groups showed a significant association between sprint and the COD deficit in the dominant leg (p < 0.05, r = -0.58 to 0.65). Therefore, the use of directional dominance, the COD deficit, and asymmetry outcomes could be helpful for classification purposes to assess the impact of the impairment on sport-specific activity testing according to sex.


A qualitative study on mindfulness-based stress reduction for breast cancer patients: how women experience participating with fellow patients.
Peer support groups for cancer patients show mixed findings regarding effectiveness on psychological wellbeing. When embedded in a psychosocial intervention, such as mindfulness-based stress reduction (MBSR), peer support might be of more benefit to participants. This study is a qualitative exploration of how women with breast cancer experience the possible benefits and impediments of participating with fellow patients in an MBSR training. Five focus groups (n = 37) and three individual interviews (n = 3) were conducted with breast cancer patients who participated in MBSR. The qualitative data were analysed with the constant comparative method in order to develop a grounded theory. We could identify a process where at the start of MBSR, patients experienced anticipatory fear for facing the suffering of fellow patients, especially for those who could not be cured anymore. In most women, this fear gradually subsided during the first two sessions. The atmosphere in the MBSR training was experienced as safe and supportive, providing a context where participants could connect with and trust one another. In turn, this facilitated participants to learn from one another. Our findings do not only show that the peer group facilitates the learning process in MBSR, but the MBSR also seemed to provide an atmosphere that promotes the experienced social support in participants. In addition, the results emphasize the importance for mindfulness teachers to acknowledge and explore the fear for facing fellow patients in the group. Future research should examine whether the results are generalizable to patients with other cancer types.


PEGylated insulin-like growth factor-I affords protection and facilitates recovery of lost functions post-focal ischemia.
Insulin-like growth factor-I (IGF-I) is involved in the maturation and maintenance of neurons, and impaired IGF-I signaling has been shown to play a role in various neurological diseases including stroke. The aim of the present study was to investigate the efficacy of an optimized IGF-I variant by adding a 40 kDa polyethylene glycol (PEG) chain to IGF-I to form PEG-IGF-I. We show that PEG-IGF-I has a slower clearance which allows for twice-weekly dosing to maintain steady-state serum levels in mice. Using a photothrombotic model of focal stroke, dosing from 3 hrs post-stroke dose-dependently (0.3-1 mg/kg) decreases the volume of infarction and improves motor behavioural function in both young 3-month and aged 22-24 month old mice. Further, PEG-IGF-I treatment increases GFAP expression when given early (3 hrs post-stroke), increases Synaptophysin expression and increases neurogenesis in young and aged. Finally, neurons (P5-6) cultured in vitro on reactive astrocytes in the presence of PEG-IGF-I showed an increase in neurite length, indicating that PEG-IGF-I can aid in sprouting of new connections. This data suggests a modulatory role of IGF-I in both protective and regenerative processes, and indicates that therapeutic approaches using PEG-IGF-I should be given early and where the endogenous regenerative potential is still high.


Vitamin D3 in ovarian antral follicles of mature gilts: Expression of its receptors and metabolic enzymes, concentration in follicular fluid and effect on steroid secretion in vitro.
Recent studies have reported that vitamin D3 (VD) regulates ovarian function under physiological and pathological conditions. Due to a lack of information concerning the expression of VD-related molecules (receptors: VDR, PDIA3, and metabolic enzymes: CYP27B1, CYP24A1) in the porcine ovary, this research aimed to determine the mRNA expression, protein abundance and localization of VDR, PDIA3, CYP27B1 and CYP24A1 in small (SFs), medium (MFs) and large (LFs) antral follicles of sexually mature gilts. We also examined the concentration of active VD in the follicular fluid of SFs, MFs and LFs, and the effect of 1,25(OH)2D3 on their steroidogenic activity in vitro. In the present study, we have demonstrated for the first time the patterns of VDR, PDIA3, CYP27B1 and CYP24A1 immunolocalization in porcine antral follicles of different sizes. Furthermore, the expression of VD-related molecules was influenced by follicle developmental stage. VDR and PDIA3 mRNA expression and protein abundance decreased with the follicle size: they were the greatest in SFs, and the lowest in LFs. CYP27B1 mRNA expression was the highest in MFs and differed from that in SFs, whereas protein abundance was greater in MFs and SFs than in LFs. The expression of mRNA for CYP24A1 was higher in MFs than in SFs and LFs, while protein abundance did not differ between follicle classes. We have also described changes in the concentration of 1,25(OH)2D3 in the follicular fluid of antral follicles with its highest level in MFs. These findings show that the porcine antral follicle is a target tissue for direct VD action and is a local site of VD metabolism. Furthermore, we found that 1,25(OH)2D3 increased the secretion of progesterone and estradiol-17β by SFs and MFs in vitro, implying a crucial role of VD in the regulation of ovarian steroidogenesis in mature gilts. Therefore, VD appears to be an important intraovarian factor that could regulate follicular development and function in pigs.


Fetuin-A is inversely associated with coronary artery calcification in community-living persons: the Multi-Ethnic Study of Atherosclerosis.
Fetuin-A is a hepatic secretory protein that inhibits arterial calcification in vitro. The association of fetuin-A with coronary arterial calcification (CAC) in the general population is uncertain. Among 2457 community-living individuals without cardiovascular disease (CVD), we measured serum fetuin-A concentrations by ELISA and evaluated the cross-sectional association of fetuin-A with CAC prevalence (any vs none) and severity; on follow-up 3.2 years (median) later, we evaluated the association of fetuin-A with CAC incidence and progression. The mean age was 62 (SD 10) years, and the mean fetuin-A concentration was 0.48 (0.10) g/L. At baseline, 1200 individuals (49%) had CAC, and 272 individuals developed CAC during follow-up. At baseline, there was a threshold effect at the lowest fetuin-A quartile with CAC prevalence. In models adjusted for demographics, traditional cardiovascular disease (CVD) risk factors and kidney function, the lowest fetuin-A quartile had 7% (95% CI 1%-13%; P = 0.04) greater CAC prevalence compared with quartiles 2-4. Similar associations were observed with CAC severity at baseline, but the association was more linear. Each SD (0.10 g/L) lower fetuin-A was associated with a 12% (95% CI 3%-21%; P = 0.01) greater CAC severity in adjusted models. There was no significant association of fetuin-A with CAC incidence or progression. Fetuin-A is inversely associated with CAC severity among community-living individuals without CVD. Whether fetuin-A concentrations are associated with incident CVD event in the general population requires future study.


Biochars as media for air pollution control systems: Contaminant removal, applications and future research directions.
Biochars are low-cost and renewable biomaterials with several applications, including soil amendment, mitigation of greenhouse gas emissions, and removal of both inorganic and organic contaminants in aqueous systems. An increasing body of recent evidence indicates that biochars can also remove gaseous chemical contaminants, such as those occurring in industrial flue gases. However, unlike other applications such as in agroecosystems, soil amendments, and aquatic systems, comprehensive reviews on biochar applications in the field of air pollution control are still lacking. The current paper examined existing evidence to understand the nature of contaminants, particularly the gaseous ones, potential applications, constraints, and future research needs pertaining to biochar applications in air pollution control. The preparation of biochars and their functionalized derivatives, and the properties influencing their capacity to remove gaseous contaminants are summarized. The removal capacity and mechanisms of various organic and inorganic gaseous contaminants by biochars are discussed. Evidence shows that biochars effectively remove metal vapours, particularly elemental mercury (Hg0), acidic gases (H2S, SO2, CO2), ozone, nitrogen oxides (NOx), and organic contaminants including aromatic compounds, volatile organic compounds, and odorous substances. The mechanisms for the removal of gaseous contaminants, including; adsorption, precipitation, and size exclusion were presented. Potential industrial application domains include remediation of gaseous emissions from incinerators, waste-to-energy systems, kilns, biomass and coal-fired boilers/cookers, cremation, smelters, wastewater treatment, and agricultural production systems including livestock husbandry. These industrial applications, coupled with the renewable, low-cost and sustainable nature of biochars, point to opportunities to further develop and scale up the biochar technology in the air pollution control industry. However, the biochar-based air filter technology still faces several challenges, largely stemming from constraints and several knowledge gaps, which were highlighted. Hence, further research is required to address these constraints and knowledge gaps before the benefits of the biochar-based air filters are realized.


Advances in Regenerative Dentistry Approaches: An Update.
Regenerative dentistry is a rapidly evolving field in dentistry, which has been driven by advancements in biomedical engineering research and the rising treatment expectations and demands that exceed the scope of conventional approaches. Tissue engineering, the foundation of regenerative dentistry, mainly focuses on 3 key components: stem cells, bioactive molecules, and scaffolds. Dental tissue-derived stem cells are especially significant in this regard due to their remarkable properties. Regenerative techniques have provided novel approaches to many conventional treatment strategies in various disciplines of dentistry. For instance, regenerative endodontic procedures such as pulp revascularisation have provided an alternative approach to conventional root canal treatment. In addition, conventional surgical and nonsurgical periodontal treatment is being taken over by modified approaches of guided tissue regeneration with the aid of 3-dimensional bioprinting and computer-aided design, which has revolutionised oral and maxillofacial tissue engineering. This review presents a concise overview of the latest treatment strategies that have emerged into clinical practice, potential future technologies, and the role of dental tissue-derived stem cells in regenerative dentistry.


Production and nitrogen responses of the African dwarf shrub Indigofera spinosa to defoliation and water limitation.
The dwarf shrub Indigofera spinosa Forsk. (Papilionacea), a native forage species of arid Northwest Kenya, was propogated from seed, grown in a controlled environment, and subjected to three treatments of defoliation and watering frequencies in a factorial experimental design. Biomass production and nitrogen accumulation in tissue components were measured to determine defoliation responses in a water-limited environment. We hypothesized that plants would maintain biomass and nitrogen flows despite removal of aboveground meristems and tissues by defoliation. Principal experimental results included a slight reduction (11%; P=0.08) of total biomass production by clipping ca. 1/3 or 2/3 of new leaves and stems and all apical meristems every month. Total aboveground production was not affected by clipping, while final root biomass was reduced 17% by the 2/3 clipping. The least water stressed plants were affected most negatively by defoliation, and the unclipped plants responded more negatively to greater water limitation. Plants achieved partial biomass compensation through alterations in shoot activity and continued allocation of photosynthate to roots. A smaller fraction of leaf production was directed to litter in clipped plants although clipping only removed the youngest tissues, suggesting that clipping increased leaf longevity. In turn, each leaf probably contributed a greater total quantity of photosynthate. Photosynthetic rates were also likely to have been increased by clipping water-stressed plants. In contrast to biomass, plants overcompensated for nitrogen lost to defoliation. Total nitrogen uptake by individual plants was stimulated by defoliation, as there was more total nitrogen in leaves and stems. Increased nitrogen uptake was achieved by clipping stimulation of total uptake per unit of root rather than of total root mass.


Expression and subcellular distribution of imp13 are regulated in brain development.
Imp13, a member of importin-β superfamily, is found to be one of two bidirectional transport receptors in many nuclear transport activities in mammals. Several cargoes of imp13 have been identified; most of these are essential factors involved in cell cycle and development. The expression and localization of imp13 may influence its cargoes in playing their roles in appropriate time and space. To gain insight into the role of imp13 in brain development, we generated an anti-imp13 polyclonal antibody and investigated the expressions of imp13 in mouse embryonic brains during development, including E13.5, E15.5, E17.5, P0, and adult, at both transcriptional and translational levels. In addition, we performed immunohistochemical analysis and revealed that imp13 tends to be localized in the cytoplasm at the early stages and relocates into the nucleus at the late stages in neuronal cells of mouse brains. These findings suggested that the expression and localization of imp13 in brain tissues are regulated developmentally, which extends our knowledge of the dynamic presence of imp13. These observations also imply that imp13 contributes to the neural cell-specific cargo trafficking and potentially to other functions during brain development.


A Simple Model for Diagnosis of Maladaptations to Exercise Training.
The concept of overreaching and super compensation is widely in use by athletes and coaches seeking to maximize performance and adaptations to exercise training. The physiological aspects of acute fatigue, overreaching and non-functional overreaching are, however, not well understood, and well-defined negative physiological outcomes are missing. Instead, the concept relies heavily on performance outcomes for differentiating between the states. Recent advancements in the field of integrated exercise physiology have associated maladaptations in muscular oxidative function to high loads of exercise training. Eleven female and male subjects that exercised regularly but did not engage in high-intensity interval training (HIIT) were recruited to a 4-week long training intervention where the responses to different training loads were studied. Highly monitored HIIT sessions were performed on a cycle ergometer in a progressive fashion with the intent to accomplish a training overload. Throughout the intervention, physiological and psychological responses to HIIT were assessed, and the results were used to construct a diagnostic model that could indicate maladaptations during excessive training loads. We here use mitochondrial function as an early marker of excessive training loads and show the dynamic responses of several physiological and psychological measurements during different training loads. During HIIT, a loss of mitochondrial function was associated with reduced glycolytic, glucoregulatory and heart rate responses and increased ratings of perceived exertion in relation to several physiological measurements. The profile of mood states was highly affected after excessive training loads, whereas performance staled rather than decreased. By implementing five of the most affected and relevant measured parameters in a diagnostic model, we could successfully, and in all the subjects, identify the training loads that lead to maladaptations. As mitochondrial parameters cannot be assessed without donating a muscle biopsy, this test can be used by coaches and exercise physiologists to monitor adaptation to exercise training for improving performance and optimizing the health benefits of exercise. Clinical trial registry number NCT04753021 . Retrospectively registered 2021-02-12.


Synthesis and structure-activity relationship of 2,6-disubstituted pyridine derivatives as inhibitors of β-amyloid-42 aggregation.
It is assumed that amyloid-β aggregation is a crucial event in the pathogenesis of Alzheimer's disease. Novel 2,6-disubstituted pyridine derivatives were designed to interact with the β-sheet conformation of Aβ via donor-acceptor-donor hydrogen bond formation. A series of pyridine derivatives were synthesized and tested regarding their potential to inhibit the aggregation of Aβ. The 2,6-diaminopyridine moiety was identified as a key component to inhibit Aβ aggregation. Overall, compounds having three 2,6-disubstituted pyridine units separated by at least one C2- or C3-linker displayed the most potent inhibition of Aβ aggregation.


Evolution of reconstructive techniques following endoscopic expanded endonasal approaches.
Harvey Cushing first popularized the transsphenoidal route to the sella turcica, and Jules Hardy subsequently refined it by adding the operating microscope. Over the ensuing decades, attempts at extending the application of this approach have been advanced by Edward Laws and others. With the evolution of endoscopic approaches, the natural expansion of their use to intradural lesions followed. For the expanded endonasal approach to become a viable option, the paramount concerns surrounding consistent reconstruction of the dura mater must be overcome. In this review the authors chronicle the evolution of the reconstruction technique they currently use after performing expanded endonasal approaches. They also report the use of a balloon stent to buttress the reconstruction and counter the effects of graft migration and cerebrospinal fluid fistula formation. The technique described in this report represents an important step forward in the reconstruction of defects resulting from expanded endonasal approaches.


Continuing care and long-term substance use outcomes in managed care: early evidence for a primary care-based model.
How best to provide ongoing services to patients with substance use disorders to sustain long-term recovery is a significant clinical and policy question that has not been adequately addressed. Analyzing nine years of prospective data for 991 adults who entered substance abuse treatment in a private, nonprofit managed care health plan, this study aimed to examine the components of a continuing care model (primary care, specialty substance abuse treatment, and psychiatric services) and their combined effect on outcomes over nine years after treatment entry. In a longitudinal observational study, follow-up measures included self-reported alcohol and drug use, Addiction Severity Index scores, and service utilization data extracted from the health plan databases. Remission, defined as abstinence or nonproblematic use, was the outcome measure. A mixed-effects logistic random intercept model controlling for time and other covariates found that yearly primary care, and specialty care based on need as measured at the prior time point, were positively associated with remission over time. Persons receiving continuing care (defined as having yearly primary care and specialty substance abuse treatment and psychiatric services when needed) had twice the odds of achieving remission at follow-ups (p<.001) as those without. Continuing care that included both primary care and specialty care management to support ongoing monitoring, self-care, and treatment as needed was important for long-term recovery of patients with substance use disorders.


[Physostigmine reversal of central anticholinergic syndrome induced by midazolam/fentanyl, benzoctamine/buprenorphine and etomidate/carticaine or by atropine/promethazine/pethidine for premedication? (author's transl)].
Five cases of post narcotic delirium, somnolence or coma are interpreted as central anticholinergic syndromes as they were reversed by physostigmine. There is to date no information whether the drug combinations midazolam/fentanyl, benzoctamine/buprenorphine and etomidate/carticaine may act as central anticholinergic agents.


Glucocorticoids regulate thrombopoiesis by remodeling the megakaryocyte transcriptome.
Glucocorticoids are widely known for their immunomodulatory action. Their synthetic analogs are used to treat several autoimmune diseases, including immune thrombocytopenia. However, their efficacy and mechanisms of action in immune thrombocytopenia are not fully understood. To investigate the mechanism of glucocorticoid actions on platelet production. The actions of glucocorticoids on platelet production were studied combining in vivo, ex vivo and in vitro approaches. Dexamethasone reduced bleeding in mice and rapidly increased circulating young platelet counts. In vitro glucocorticoid treatment stimulated proplatelet formation by megakaryocytes and platelet-like particle release. This effect was blocked by glucocorticoid receptor antagonist RU486, indicating a glucocorticoid receptor-dependent mechanism. Genome-wide analysis revealed that dexamethasone regulates the expression of >1000 genes related to numerous cellular functions, including predominant cytoplasm and cytoskeleton reorganization. Dexamethasone and other glucocorticoids induced the expression of Gda (the gene encoding guanine deaminase), which has been reported to have a role in dendrite development. Inhibition of guanine deaminase enzymatic activity blocked dexamethasone stimulation of proplatelet formation, implicating a critical role for this enzyme in glucocorticoid-mediated platelet production. Our findings identify glucocorticoids as new regulators of thrombopoiesis.


The effect of β-2 adrenoreceptor agonist inhalation on lungs donated after cardiac death in a canine lung transplantation model.
It is a matter of great importance in a donation after cardiac death to attenuate ischemia-reperfusion injury (IRI) related to the inevitable warm ischemic time. Donor dogs were rendered cardiac-dead and left at room temperature. The dogs were allocated into 2 groups: the β-2 group (n = 5) received an aerosolized β-2 adrenoreceptor agonist (procaterol, 350 μg) and ventilation with 100% oxygen for 60 minutes starting at 240 minutes after cardiac arrest, and the control group (n = 6) received an aerosolized control solvent with the ventilation. Lungs were recovered 300 minutes after cardiac arrest. Recipient dogs underwent left single-lung transplantation to evaluate the functions of the left transplanted lung for 240 minutes after the reperfusion. Oxygenation and dynamic compliance were significantly higher in the β-2 group than in the control group. The β-2 group revealed significantly higher levels of cyclic adenosine monophosphate and high-energy phosphates in the donor lung after the inhalation than before it. Histologic findings revealed that the β-2 group had less edema and fewer inflammatory cells. Our results suggest that β-2 adrenoreceptor agonist inhalation during the pre-procurement period may ameliorate IRI.


Fabrication and characterisation of novel chitosan-based polymer inclusion membranes and their application in environmental remediation.
Several water and wastewater technologies have been implored for the removal of dyes during wastewater treatments; however; different types have been reportedly found in surface and groundwater systems. Hence, there is a need to investigate other water treatment technologies for the complete remediation of dyes in aquatic environments. In this study, novel chitosan-based polymer inclusion membranes (PIMs) were synthesized for the removal of malachite green dye (MG) which is a recalcitrant of great concern in water. Two types of PIMs were synthesized in this study, the first PIM (PIMs-A) was composed of chitosan, bis-(2-ethylhexyl) phosphate (B2EHP), and dioctyl phthalate (DOP). While, the second PIMs (PIMs-B) were composed of chitosan, Aliquat 336, and DOP. The physico-thermal stability of the PIMs was investigated using Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and thermogravimetric analysis (TGA), both PIMs demonstrated good stability with a weak intermolecular force of attraction amongst the various components of the membranes. The effects of the initial concentration of MG, pH of the MG solution, stripping solution, and time were investigated. At optimum conditions, both membranes (PIM-A and B) recorded the highest efficiencies of 96 % and 98 % at pH 4 and initial contaminants concentration of 50 mg/L, respectively. Finally, both PIMs were used for the removal of MG in different environmental samples (river water, seawater, and tap water) with an average removal efficiency of 90 %. Thus, the investigated PIMs can be considered a potential suitable technique for the removal of dyes and other contaminants from aquatic matrices.


Different leafy vegetable cropping systems regulate growth, photosynthesis, and PSII functioning in mono-cropped eggplant by altering chemical properties and upregulating the antioxidant system.
Continuous cropping of eggplant threatened regional ecological sustainability by facilitating replanting problems under mono-cropping conditions. Therefore, alternative agronomic and management practices are required to improve crop productivity at low environmental cost for the development of sustainable agricultural systems in different regions. This study examined changes in soil chemical properties, eggplant photosynthesis, and antioxidant functioning in five different vegetable cropping systems over a 2-year period., 2017 and 2018. The results showed that welsh onion-eggplant (WOE), celery-eggplant (CE), non-heading Chinese cabbage-eggplant (NCCE), and leafy lettuce-eggplant (LLE) rotation systems significantly impacted growth, biomass accumulation, and yield than fallow-eggplant (FE). In addition, various leafy vegetable cropping systems, WOE, CE, NCCE, and LLT induced significant increases in soil organic matter (SOM), available nutrients (N, P, and K), and eggplant growth by affecting the photosynthesis and related gas exchange parameters with much evident effect due to CE and NCCE. Moreover, eggplant raised with different leafy vegetable rotation systems showed higher activity of antioxidant enzymes, resulting in lower accumulation of hydrogen peroxide and hence reduced oxidative damage to membranes. In addition, fresh and dry plant biomass was significantly increased due to crop rotation with leafy vegetables. Therefore, we concluded that leafy vegetable crop rotation is a beneficial management practice to improve the growth and yield of eggplant.


A simple and sensitive fluorimetric aptasensor for the ultrasensitive detection of arsenic(III) based on cysteamine stabilized CdTe/ZnS quantum dots aggregation.
A new approach for developing a fluorimetric aptasensor has been described and applied for determination of a highly toxic cation, As(III). In this method an aptamer was used to aggregate cationic cysteamine-stabilized CdTe/ZnS core/shell quantum dots, as a result fluorescence quenching was accrued. In the presence of As(III), the aptamer and As(III) make a complex, which prevents aggregation of the quantum dots. Thus, the fluorescence intensity of the quantum dots was enhanced upon the de-aggregation, which depends on the concentration of As(III). The fluorimetric assay has a very low detection limit of 1.3 pmolL(-1) As(III) with a dynamic range of 1.0 × 10(-11) to 1.0 × 10(-6) molL(-1). The interference effect of a wide variety of cations and anions was investigated, and the obtained results confirm high selectivity of the aptasensor for As(III) detection. The present assay was successfully applied for the determination of As(III) in several water samples.


High molecular weight Alzheimer's disease amyloid peptide immunoreactivity in human serum and CSF is an immunoglobulin G.
A radioimmunoassay (RIA) was developed to detect the 4200 Dalton amyloid (A4) peptide or it's precursor (A4P) in human serum or cerebrospinal fluid (CSF). A synthetic peptide containing the first 28 amino acids of the 43 amino acid A4 peptide was covalently coupled to bovine thyroglobulin and a polyclonal antiserum in rabbits was prepared. This antiserum was specific for vascular amyloid and neuritic plaques in Alzheimer's disease brain as detected by immunoperoxidase. The synthetic peptide, which has a tyrosine at residue 10, was iodinated with chloramine T and [125I]iodine and was purified to homogeneity by C4 reverse phase high performance liquid chromatography (HPLC). Extraction of human serum over a C18 Sep Pak cartridge indicated immunoreactive A4 peptide was not detectable in human serum. Conversely, high molecular weight A4 peptide immunoreactivity was detectable in human serum, at a concentration of 8.9 +/- 1.2 pmol-eq./ml, and in human CSF, at a concentration of 0.25 +/- 0.01 pmol-eq./ml, giving a CSF/serum ratio of 3.2%. The immunoreactivity in human serum was nearly completely removed by affinity deletion of serum immunoglobulin G (IgG), but not by affinity removal of IgA or IgM. Serum immunoreactivity was decreased 90% in hypogammaglobulinemia, and was increased 83% in human cord serum. There was no statistical difference in serum A4 immunoreactivity in Alzheimer's serum or CSF. Serum immunoreactivity in Down's syndrome was increased 50%. These studies indicate the high molecular weight A4P immunoreactivity in human serum or CSF is an IgG. Whether the A4 precursor in Alzheimer's disease is, in fact, an IgG, or whether there is an antibody in human serum and CSF that cross reacts with the A4 precursor cannot be determined until the serum immunoreactivity is purified and structurally characterized.


Intratesticular varicocele: evaluation using grey scale and color Doppler ultrasound.
Intratesticular varicocele is a rare condition with a variable clinical and ultrasound presentation. The purpose of this study was to evaluate the grey scale and color Doppler appearances of intratesticular varicocele (ITV). Herein we present seven new cases of intratesticular varicocele. From 2003 to 2005 we evaluated 342 patients referred to our department for routine andrological evaluation by scrotal color Doppler ultrasound. We detected seven entirely asymptomatic cases of ITV by use of grey scale ultrasound. In color Doppler sonography the patients showed retrograde blood flow, either spontaneously or during Valsalva manoeuvre. In all seven cases left side ITV with testicular volume disproportion between the right and left testis (2 ml) was found. Five patients had an extratesticular varicocele. In all patients the diameters of intratesticular vein were less than 2 mm. Intratesticular varicocele is a clinically occult lesion that may occur in association with extratesticular varicocele. Further investigations are needed to clarify its clinical significance, however, considering the temperature mediated damage on the affected testis, it is our opinion that all ITV must be considered for treatment even if an extratesticular varicocele is not present.


Magnesium ion is an effective inhibitor of the binding of Escherichia coli to heparin.
We investigated the effects of ions and temperature on the binding of E. coli to heparin using a chemiluminescence electrophoretic mobility shift assay. We found that magnesium ion is an effective inhibitor of the binding. The method can be readily applied to discover agents that can block the binding.


Porphyromonas gingivalis influences actin degradation within epithelial cells during invasion and apoptosis.
Porphyromonas gingivalis, a Gram-negative oral pathogen, has been shown to induce apoptosis in human gingival epithelial cells, yet the underlining cellular mechanisms controlling this process are poorly understood. We have previously shown that the P. gingivalis proteases arginine and lysine gingipains, are necessary and sufficient to induce host cell apoptosis. In the present study, we demonstrate that 'P. gingivalis-induced apoptosis' is mediated through degradation of actin leading to cytoskeleton collapse. Stimulation of human gingival epithelial cells with P. gingivalis strains 33277 and W50 at moi:100 induced β-actin cleavage as early as 1 h and human serum inhibited this effect. By using gingipain-deficient mutants of P. gingivalis and purified gingipains, we demonstrate that lysine gingipain is involved in actin hydrolysis in a dose and time-dependent manner. Use of Jasplakinolide and cytochalasin D revealed that P. gingivalis internalization is necessary for actin cleavage. Further, we also show that lysine gingipain from P. gingivalis can cleave active caspase 3. Taken together, we have identified actin as a substrate for lysine gingipain and demonstrated a novel mechanism involved in microbial host cell invasion and apoptosis.


Triiodothyronine thyrotoxicosis complicating primary hypothyroidism in a patient with autoimmune thyroiditis.
It is increasingly recognized that autoimmune thyroiditis can have a multifaceted presentation. Documented triiodothyronine thyrotoxicosis developed in a patient with a six-year history of primary hypothyroidism that was left untreated. Serologic and cytologic evidence confirmed the thyroid dysfunction as being on an autoimmune basis. Chronic lymphocytic thyroiditis may be seen with hyperthyroidism, hypothyroidism, or euthyroidism, and in an individual patients, spontaneous progression from one metabolic state to another may occur.


Prevalence and risk factors of diabetes mellitus and hypertension in North East Tunisia calling for efficient and effective actions.
Diabetes and hypertension are a serious public health problem worldwide. In the last decades, prevalence of these two metabolic diseases has dramatically increased in the Middle East and North Africa region, especially in Tunisia. This study aimed to determine the prevalence of type 2 diabetes (T2D) and High Blood Pressure (HBP) in Zaghouan, a North-East region of Tunisia. To this end, an exploratory study with stratified random sampling of 420 participants has been carried out. Various data were collected. Blood samples and urine were drawn for biochemical assay. Then, all data were analyzed using the statistical R software. Results showed an alarming situation with an inter-regional difference in prevalence of obesity (50.0%, CI 95.0%), HBP (39.0%, CI 95.0%) and T2D (32.0%, CI 95.0%). This study allowed the discovery of 24, 17 and 2 new cases of T2D, HBP and T2D&HBP respectively. The association of some socio-economic factors and biochemical parameters with these chronic diseases has been highlighted. To conclude, the health situation in the governorate of Zaghouan requires urgent interventions to better manage the growing epidemic of non-communicable diseases (NCD) in the region. This study demonstrated the importance of engaging health policy makers in road mapping and implementing national NCD prevention programs.


Comparison of third-year medical and physical therapy students' knowledge of anatomy using the carpal bone test.
The curricula of all health professionals have an important foundation of human anatomy. A comparison of the anatomy retention between students from different curricula has not been studied. Our aim was to examine the knowledge competency of third-year physical therapy and medical students in carpal bone anatomy. The testing was conducted on the third-year medical and physical therapy students at Universidad de Granada. Students were given 5 minutes to answer the carpal bone test, a test which requires the identification of the carpal bones in an illustration of the bony skeleton of carpal region. Differences in the distribution of the responses between groups were analyzed using the χ(2) test. One hundred thirty-four (n = 134) tests were analyzed (n = 54 [41%] physical therapy students, n = 80 [59%] medical students). Only 39 students correctly identified all of the carpal bones (42.6% physical therapy, 20% medical, P < .001). Physical therapy students correctly identified a greater number (P < .001) of carpal bones (mean ± SD, 5.8 ± 2.2) than medical students (mean ± SD, 3.1 ± 2.9). The capitate was the most frequently identified bone in both physical therapy (96%) and medical (46%) students (P < .001). The hamate bone was the least frequently identified bone by medical students (n = 29, or 36.3%), whereas the trapezoid bone was the least frequently identified bone by physical therapy students (n = 35, or 64.8%). There are few studies investigating anatomical knowledge levels between disciplines. This study found that physical therapy students exhibited better retention of anatomy of the carpal bones than medical students.


The role of pathologists in the quality control of diagnosis and treatment of rectal cancer-an overview.
Pathological examination of the rectal cancer resection specimen has an increasingly important role in influencing decisions about clinical management. Standardisation of the examination procedures and reporting are necessary. To evaluate the relevant pathological factors, data from randomised clinical trials with adequate follow-up are necessary. From a recently closed trial on the treatment of rectal cancer (preoperative radiotherapy or total mesorectal excision (TME) surgery alone?), the pathological data were used to evaluate the importance of pathological factors, like circumferential margin and tumour, lymph nodes, metastasis (TNM) stage. Furthermore, it was possible to evaluate the surgical procedures and correlate these findings to clinically relevant endpoints. In this review, we describe the standard evaluation of a rectal cancer specimen with special attention to preoperative irradiated specimens.


A comparison of methods for prediction of pharmacokinetics across factor concentrate switching in hemophilia patients.
This study proposes a method to predict individual pharmacokinetics of a future product by using the individual pharmacokinetic profile on the current product and the PopPK models of the current and future product. Individual dense data was collected from two PK crossover studies, one enrolling 29 patients switching from Advate to Eloctate and one enrolling 15 patients switching from Advate to Novoeight. Three methods were designed to predict the second product's individual PK parameters (CL, V1, Q, and V2). Method 1 used the second product's typical population value of PK parameters from its PopPK model. Method 2 used the second product's calculated PK parameters based on individual covariates and its PopPK model. Method 3 used method 2, along with the predicted η-values of CL and V1 from the first product and its PopPK model. Each method was used to assess PK prediction during switching from Advate to Novoeight, Novoeight to Advate, and Advate to Eloctate. The three methods produced different outcomes. The mean absolute relative errors for half-life were lowest for method 3 for each study (11.6%, 13.1%, 13.6%). The regression line between predicted and observed half-life for method 3 was closest to the line of identity for each study (0.84, 0.67, 0.66). Taking into account individual PK from a previous clotting factor product was shown to provide better means of estimating individual PK for a new product. This may improve regimen design across switches and reduce the time to tailor optimal dose of FVIII products.


Calcium/phosphate/vitamin D homeostasis and bone mass in patients after gastrectomy, vagotomy, and cholecystectomy.
Sixty-two outpatients were assessed and divided into the following groups: 20 patients who had had partial gastrectomy (PG group), 22 patients who had had truncal vagotomy and pyloroplasty (TV group) or high selective vagotomy (HSV group), and 20 patients who had had cholecystectomy (CH group). The patients' age ranged from 35 to 64 years (mean 45 years), and the average postoperative period was 9 years. None of the patients evidenced clinical or biochemical symptoms of malnutrition or malabsorption or of diseases affecting vitamin D metabolism. The function of the kidneys and the liver was normal. An age-matched group of volunteers served as a control group. The calcium dietary intake was determined using a standardized questionnaire; and the levels of serum calcium (Cas), phosphate (Ps), alkaline phosphatase (AP), and 25-hydroxyvitamin D [25(OH)D] and the excretion of Ca in a sample of fasting urine corrected for concurrent creatine excretion (FuCa/cr) were assessed by means of standard laboratory techniques. The bone mineral density (BMD) of the lumbar spine (L2-4) and femoral neck (neck-L) was determined by means of dual energy x-ray absorptiometry (DXA). The daily Ca dietary intake was lower than recommended (RDA) in 80% of the patients, with most of them ingesting less than 300 mg daily. The mean values of Cas, Ps, AP, and FuCa/cr did not differ from those in the controls. Significantly reduced 25(OH)D levels were observed in the PG group (7.0 ng/ml) (p < 0.001) and CH group (12.5 ng/ml) (p < 0.01) compared with the values in the control group (20.0 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)


Workplace foodservice meals are associated with higher nutritional quality among adult Korean workers: a nationwide cross-sectional study.
Adequate nutritional intake is essential for good health and well-being. We aimed to compare the nutrient intake from homemade meals, meals sourced externally ("eating out"), and meals from workplace foodservices, as well as the potential association between foodservices used and nutritional quality among adult Korean workers. We used data from the Korea National Health and Nutrition Examination Survey, a nationwide cross-sectional survey on the health and nutritional status of the Korean population. Data from 6,845 workers aged 20-64 years were included. A survey on dietary behavior and nutrition was conducted using the 24-h dietary recall method. Nutritional quality was examined using the index of nutritional quality (INQ) score. Higher INQ scores reflected poorer nutritional quality, with insufficient intake of a higher number of nutrients. Multivariate linear regression was used to identify the association between the foodservices used and INQ scores after adjusting for other covariates. We found that foodservice users exhibited a higher 1-day intake of total energy and macronutrients (all P < 0.05) and lower INQ scores (P < 0.01) than non-users. The INQ scores for total daily meals decreased with the frequency of foodservice use (P < 0.01). A significant association was observed between the non-use of foodservices and INQ scores (β = 0.29, P < 0.01) after adjusting for other covariates. The use of workplace foodservices contributed to higher dietary nutritional quality among workers. This study highlights the importance of expanding the scope of workplace foodservices to promote higher nutritional quality and healthy dietary habits among workers.


High serum levels of YKL-40 in patients with systemic sclerosis are associated with pulmonary involvement.
YKL-40, a growth factor of connective tissue cells, is elevated in sera from patients with diseases characterized by inflammation, tissue remodelling, or fibrosis. The aim of the study was to determine serum YKL-40 levels in patients with systemic sclerosis (SSc) and to explore any possible clinical and prognostic associations. YKL-40 was measured in sera from 88 patients with SSc (26 with diffuse and 62 with limited skin involvement) and in sera from 88 matched healthy controls. Immunohistochemical staining for YKL-40 antigen was performed in a biopsy from a patient with pulmonary SSc. Serum YKL-40 levels of the SSc patients were significantly higher than those of the controls (p<0.00001). Patients with pulmonary fibrosis by chest X-ray, obstructive ventilatory pattern, reduced diffusing capacity (DLco), and digital joint deformity due to skin retraction had significantly higher serum YKL-40 compared with patients without these findings. Patients with elevated serum YKL-40 had shorter survival times than patients with normal serum YKL-40 (p = 0.0005), although this was not independent of age and pulmonary function. YKL-40 protein expression was found in inflammatory cells in fibrosing pulmonary tissue from a patient with SSc. Serum YKL-40 is elevated in patients with SSc with pulmonary involvement.


Pancreatic retransplantation is associated with poor allograft survival: an update of the United Network for Organ Sharing database.
The aim of the study was to assess outcomes of pancreas retransplantation versus primary pancreas transplantation. Data from the United Network for Organ Sharing database on all adult (age, ≥18 years) subjects who received pancreas and kidney-pancreas transplants between 1996 and 2012 were analyzed (n = 20,854). The subjects were analyzed in the following 2 groups: retransplant (n = 1149) and primary transplant (n = 19,705). Kaplan-Meier analysis demonstrated significantly different patient survival (P < 0.0001) and death-censored graft survival (P < 0.0001) between the primary transplant versus retransplant subjects. Allograft survival was significantly poorer in the retransplantation group. Patient survival was greater in the retransplant group. The results of our study differ from previous studies, which showed similar allograft survival in primary and secondary pancreas transplants. Further studies may elucidate specific patients who will benefit from retransplantation. At the present time, it would appear that pancreas retransplantation is associated with poor graft survival and that retransplantation should not be considered for all patients with primary pancreatic allograft failure.


Effect of growth phase on harvesting characteristics, autoflocculation and lipid content of Ettlia texensis for microalgal biodiesel production.
The effect of growth phase on the recovery of the autoflocculating microalgae Ettlia texensis was studied. In the stationary phase, 90% recovery was achieved after 3h settling. Scanning electron microscopic pictures revealed that extracellular polymeric substances (EPS) on the cell surface were involved in autoflocculation. During the stationary phase an increase of the protein fraction in the EPS was observed while the total fatty acids content increased. The autoflocculating properties of E. texensis combined with favourite fatty acid content and composition make this microalgae an excellent candidate for biodiesel production if harvested at the end of the stationary phase.


AIDS in infancy: diagnostic, therapeutic, and ethical problems.
Congenital AIDS is on the rise and will pose multiple problems to society and to health care workers in particular, as more infants develop the disorder. Differentiation of AIDS from infantile grief reactions is of critical importance, as infants at risk for AIDS lose their mothers who have AIDS. Team approaches are optimal and should include psychiatric perspectives. Issues of diagnosis, maladaptive psychological reactions and ethical dilemmas are discussed and illustrated in a case history.


Upright versus supine MRI: effects of body position on craniocervical CSF flow.
Cerebrospinal fluid (CSF) circulation between the brain and spinal canal, as part of the glymphatic system, provides homeostatic support to brain functions and waste clearance. Recently, it has been observed that CSF flow is strongly driven by cardiovascular brain pulsation, and affected by body orientation. The advancement of MRI has allowed for non-invasive examination of the CSF hydrodynamic properties. However, very few studies have addressed their relationship with body position (e.g., upright versus supine). It is important to understand how CSF hydrodynamics are altered by body position change in a single cardiac phase and how cumulative long hours staying in either upright or supine position can affect craniocervical CSF flow. In this study, we investigate the changes in CSF flow at the craniocervical region with flow-sensitive MRI when subjects are moved from upright to supine position. 30 healthy volunteers were imaged in upright and supine positions using an upright MRI. The cranio-caudal and caudo-cranial CSF flow, velocity and stroke volume were measured at the C2 spinal level over one cardiac cycle using phase contrast MRI. Statistical analysis was performed to identify differences in CSF flow properties between the two positions. CSF stroke volume per cardiac cycle, representing CSF volume oscillating in and out of the cranium, was ~ 57.6% greater in supine (p < 0.0001), due to a ~ 83.8% increase in caudo-cranial CSF peak velocity during diastole (p < 0.0001) and extended systolic phase duration when moving from upright (0.25 ± 0.05 s) to supine (0.34 ± 0.08 s; p < 0.0001). Extrapolation to a 24 h timeframe showed significantly larger total CSF volume exchanged at C2 with 10 h spent supine versus only 5 h (p < 0.0001). In summary, body position has significant effects on CSF flow in and out of the cranium, with more CSF oscillating in supine compared to upright position. Such difference was driven by an increased caudo-cranial diastolic CSF velocity and an increased systolic phase duration when moving from upright to supine position. Extrapolation to a 24 h timeframe suggests that more time spent in supine position increases total amount of CSF exchange, which may play a beneficial role in waste clearance in the brain.


The so-called anterior meningeal artery of the cervical vertebral artery. Normal radioanatomy and anastomoses.
Following a review of the literature, the authors show that the posterior branch of the odontoid arch and the anterior meningeal artery are, in reality, the same vessel. Focusing attention on the metameric nature of the upper cervical spine and its blood supply makes a simplified approach to the pharyngovertebral anastomoses possible.


Operation of Thin-Film Electrolyte Metal-Supported Solid Oxide Fuel Cells in Lightweight and Stationary Stacks: Material and Microstructural Aspects.
In this study we report on the development and operational data of a metal-supported solid oxide fuel cell with a thin film electrolyte under varying conditions. The metal-ceramic structure was developed for a mobile auxiliary power unit and offers power densities of 1 W/cm² at 800 °C, as well as robustness under mechanical, thermal and chemical stresses. A dense and thin yttria-doped zirconia layer was applied to a nanoporous nickel/zirconia anode using a scalable adapted gas-flow sputter process, which allowed the homogeneous coating of areas up to 100 cm². The cell performance is presented for single cells and for stack operation, both in lightweight and stationary stack designs. The results from short-term operation indicate that this cell technology may be a very suitable alternative for mobile applications.


Fat Grafting for Facial Contouring (Nose and Chin).
The concept of microautologous fat transplantation (MAFT), proposed by Lin and colleagues in 2007, emphasized that the volume of each delivered parcel should be less than 0.01 mL to avoid potential fat grafting morbidities. The MAFT-GUN facilitates control of the parcel volume and therefore substantially avoids central necrosis and associated complications. In this article, the authors present a simple, reliable, and consistent procedure based on MAFT for profiloplasty. Favorable outcomes with sustainable long-term effectiveness were obtained, further confirming that the MAFT technique is an alternative for facial contouring in the nose and chin.


Relationships among tests for censored data.
In this paper we will give the relationships of several Score tests and Weighted tests for right censoring data with other classical tests. Special care will be taken with the case of ties and with the kind of estimation of the variance used. After the description of ten tests, a comparative study will be made among them. Finally, an application with a real example will be included.


Knowledge, Attitude and Practices Towards Cryptosporidium Among Public Swimming Pool Patrons and Staff in Western Australia.
There is a dearth of research conducted on the Knowledge, Attitude and Practices (KAP) of swimming pool patrons and staff to determine their understanding of the importance of Cryptosporidium and its transmission in swimming pools. We conducted a KAP survey of public swimming pool patrons (n = 380) and staff (n = 40) attending five public swimming pools in Western Australia (WA). Knowledge, attitudes and practices (KAP) of Cryptosporidium varied between patrons and staff but were generally limited. Only 26.1% and 25.0% of patrons and staff had heard of Cryptosporidium, while 17.4% and 10.0% knew that it causes diarrhoea, respectively. Thirty-one percent of patrons were aware of their pool policy concerning gastroenteritis and Cryptosporidium, compared to 62.5% of staff. Less than 50% of patrons demonstrated awareness of how features within the pool environment were relevant to the control of Cryptosporidium. Only about a third of patrons (35%) and staff (37.5%) were aware that showering before swimming reduced the risk of gastroenteritis. Raising awareness about hygiene-related practices through the delivery of targeted health education messages to the general public is essential to reduce the burden of Cryptosporidium infections in aquatic environments.


[The characteristics of shuttle avoidance learning in spontaneously hypertensive and normotensive rats].
In spontaneously hypertensive (strain SHR) and normotensive (strain WKY) rats was studied the elaboration of conditioned reflex of active avoidance in shuttle box. In case when the shuttle box was divided by a partition the SHR rats learned worse than WKY rats. In shuttle chamber without partition the SHR rats, on the contrary, learned better that WKY ones. Such character of interlinear differences can be connected with properties of formation of the instrumental habit of deliverance from electropainful stimulus, because the presence of partition significantly hampered its fulfillment. The obtained results, compared with literature data, testify to the fact that differences of SHR and WKY rats in elaboration of conditioned reflexes are explained basically by the properties of their unconditioned activity and not of the associative processes.


Flexible Out-of-Plane Wind Sensors with a Self-Powered Feature Inspired by Fine Hairs of the Spider.
The quest for out-of-plane and self-powered wind sensors has motivated the field of outdoor sports, exploration, space perception, and positioning. Fine hairs of spiders act as hundreds of individual wind sensors, allowing them to feel the nearby wind change caused by the predators or the prey. Inspired by this natural teacher, here, we demonstrate the fabrication of bioinspired self-powered out-of-plane wind sensors based on flexible magnetoelectric material systems. The shape of flexible sensors, by patterning silver nanoparticles on a thin polyethylene terephthalate film through a screen printing technique, mimics fine hairs of the spiders, allowing for out-of-plane tactile perceptual monitoring caused by the wind. Owing to the employment of flexible magnetoelectric materials, the sensors can distinguish forward/backward winds and are totally self-powered. The working mechanism for sensors has been explained by the Maxwell numerical simulation, allowing for further improvement of their performance by tuning diverse factors. Furthermore, the wind sensor can detect the wind with a velocity down to 1.2 m/s and distinguish multidegree wind by their arrays. It is expected that, in the near future, our design can provide new findings for out-of-plane wind sensors with superior self-powered properties toward new flexible electronics.


Pharmacological properties of Ciloprost, a stable prostacyclin analogue, on the gastrointestinal tract.
The effect of Ciloprost on the gastrointestinal tract was studied in rats and compared with prostacyclin (PGI2) and/or PGE2. In the anaesthetized rat continuous i.v. infusion of Ciloprost decreased pentagastrin stimulated gastric acid secretion with the same potency [ED 50 -35 micrograms/(kg x h)]as PGI2 [ED 50 -42 micrograms/(kg x h)]. In the pylorus-ligated rat Ciloprost reduced acid secretion with an ED50 of about 6.4 mg/kg p.o. whereas PGE2 and PGI2 were ineffective during submaximal stimulation of acid secretion by pentagastrin. In the same experimental design continuous i.v. infusion of Ciloprost and PGI2 caused 50% reduction in gastric acid output with doses of 80 and 24 micrograms/(kg x h), respectively. Ciloprost prevented indomethacin-induced gastric erosions at an ED50 of 60 micrograms/kg p.o., compared to 10 micrograms/kg p.o. of PGE2, whereas PGI2 showed only weak cytoprotective activity. The stable prostacyclin analogue inhibited castor oil induced enteropooling with a 4-5 fold higher potency than PGI2 and delayed castor oil induced diarrhoea more effectively than its natural counterpart. Intestinal motility was strongly reduced by both PGI2 and Ciloprost. Gastric emptying was also reduced after PGI2 and Ciloprost administration, with a 4-5 fold higher activity of the stable analogue. The present results demonstrate, that Ciloprost shows a biological profile similar to that of PGI2.


Barrett's esophagus: development of dysplasia and adenocarcinoma.
Barrett's esophagus is considered to be a premalignant condition, and long-term surveillance seems mandatory with a careful search for dysplasia and carcinoma by means of multiple and repeated sets of biopsies. Reliable nonhistologic markers indicative of dysplasia or developing carcinoma are not yet available. To investigate development of dysplasia and carcinoma a prospective follow-up study was performed on 50 patients with Barrett's esophagus, without carcinoma at entrance to the study, for a period of 1.5-14 yr (mean, 5.2 yr). Barrett's epithelium was classified as fundic type, junctional or cardia type, or specialized columnar type. When classification in one of these three types was not possible because of lack of the characteristic features of the epithelia, the epithelium was classified as intermediate type. At entrance to the study, low-grade dysplasia was found in 6 patients, high-grade in 1 patient. During follow-up, dysplasia increased in frequency as well as in severity and was found almost exclusively in the specialized columnar- and intermediate-type epithelium. At the end of the observation period dysplasia had been found in 13 patients, in 10 scored as low-grade and in 3 as high-grade, and adenocarcinoma had developed in another 5 patients. This prospective study shows an incidence of carcinoma in Barrett's esophagus of 1 in 52 patient-years, a 125-fold increase compared with the general Dutch population. A sequence of worsening of dysplasia with development of carcinoma was observed in specialized columnar and intermediate-type epithelium. The results of this study support the need for a long-term clinical, endoscopic, and histologic follow-up program in patients with Barrett's esophagus.


Comparative amino acid sequence analysis of Thermotoga maritima beta-glucosidase (BglA) deduced from the nucleotide sequence of the gene indicates distant relationship between beta-glucosidases of the BGA family and other families of beta-1,4-glycosyl hydrolases.
The primary structure of the bglA gene region encoding a beta-glucosidase of Thermotoga maritima strain MSB8 was determined. The bglA gene has the potential to code for a polypeptide of 446 amino acids with a predicted molecular mass of 51,545 Da. The T. maritima beta-glucosidase (BglA) was overexpressed in E. coli at a level comprising approximately 15-20% of soluble cellular protein. Based on its amino acid sequence, as deduced from the nucleotide sequence of the gene, BglA can be classified as a broad-specificity beta-glucosidase and as a member of the beta-glucosidase family BGA, in agreement with the results of enzymatic characterization of the recombinant protein. Comparative sequence analysis revealed distant amino acid sequence similarities between BGA family beta-glucosidases, a beta-xylosidase, beta-1,4-glycanases of the enzyme family F (mostly xylanases), and other families of beta-1,4-glycosyl hydrolases. This result indicates that BGA beta-glucosidases may comprise one enzyme family within a large 'enzyme order' of retaining beta-glycosyl hydrolases, and that the members of these enzyme groups may be inter-related at the level of active site architecture and perhaps even on the level of overall three-dimensional fold.


Targeting individual hemodynamics to maintain renal perfusion during pneumoperitoneum in a porcine model.
Although aggressive fluid hydration prevents a decrease in renal cortical perfusion (RCP) during laparoscopic donor nephrectomy, excess fluid is deleterious. We assessed whether goal-directed fluid administration, based on hemodynamic measures, would maintain RCP during pneumoperitoneum with less fluid loading. In a pilot study of 7 pigs, goal-directed fluid administration was guided by monitoring of stroke volume (SV) by esophageal Doppler measurement. During 15 mmHg CO(2) pneumoperitoneum, a bolus of 5 mL/kg 0.9% NaCl was given when SV decreased to 90% of baseline. Next, 18 pigs were randomized into 3 groups: low fluid (5 mL/kg per hour), high fluid (25 mL/kg per hour) and goal directed. Urine output, heart rate, mean arterial pressure, cardiac output, SV, and RCP were recorded every 15 minutes. Pilot data revealed mean RCP (mL/min per 100 g) was maintained (40 vs 39) during pneumoperitoneum using goal-directed therapy. In the randomized study, RCP was decreased in the low fluid group (43 vs 29; P= .02), but maintained in the high (46 vs 40) and goal-directed (42 vs 39) groups. Mean fluid administered in the goal-directed group during pneumoperitoneum was 10 mL/kg and only 3 of 6 of pigs required boluses. Urine output was decreased in all 3 groups. A goal-directed strategy during pneumoperitoneum allows for tailored fluid administration and maintains RCP with lower volumes of intravenous fluid.


Mechanical properties of mineralized collagen fibrils as influenced by demineralization.
Dentin and bone derive their mechanical properties from a complex arrangement of collagen type-I fibrils reinforced with nanocrystalline apatite mineral in extra- and intrafibrillar compartments. While mechanical properties have been determined for the bulk of the mineralized tissue, information on the mechanics of the individual fibril is limited. Here, atomic force microscopy was used on individual collagen fibrils to study structural and mechanical changes during acid etching. The characteristic 67 nm periodicity of gap zones was not observed on the mineralized fibril, but became apparent and increasingly pronounced with continuous demineralization. AFM-nanoindentation showed a decrease in modulus from 1.5 GPa to 50 MPa during acid etching of individual collagen fibrils and revealed that the modulus profile followed the axial periodicity. The nanomechanical data, Raman spectroscopy and SAXS support the hypothesis that intrafibrillar mineral etches at a substantially slower rate than the extrafibrillar mineral. These findings are relevant for understanding the biomechanics and design principles of calcified tissues derived from collagen matrices.


Reducing surgical site infection in arthroplasty of the lower limb: A multi-disciplinary approach.
To review the current best surgical practice and detail a multi-disciplinary approach that could further reduce joint replacement infection. Review of relevant literature indexed in PubMed. Surgical site infection is a major complication following arthroplasty. Despite its rarity in contemporary orthopaedic practice, it remains difficult to treat and is costly in terms of both patient morbidity and long-term health care resources. Emphasis on education of patients and all members of the health-care team and raising awareness in how to participate in preventative efforts is imperative.


A new parental cell line for human x human hybridoma production.
The potential of a new HAT-sensitive human lymphoblastoid cell line TK6 TG(r).P1. as a fusion partner was assessed, by comparison with the established human parental cell line UC729.6. Both of these cell lines were fused with the peripheral blood mononuclear cells of a patient with B-chronic lymphocytic leukaemia. The hybridomas generated in these fusion experiments were analysed by the fluorescence activated cell sorter and karyotyping. An anti-idiotype ELISA assay detected the presence of the patient's characteristic idiotype bearing immunoglobulin in the supernatant of a number of the hybridoma cell lines generated in both fusions.


Colonic adenocarcinoma: a delayed complication of ureterosigmoidostomy.
Two cases are reported of adenocarcinoma of the colon developing 26 and 33 years after the patients had undergone ureterosigmoidostomy. The literature is reviewed and the clinical implications are discussed.


Cardiovascular risk factors in patients discharged from departments of internal medicine---the Italian FADOI-2 study.
Background: The goal of this study was to describe mean levels, distribution, and treatment of cardiovascular risk factors among patients admitted to departments of internal medicine. Methods: Clinical records were obtained from patients discharged during the last week of October 1999 in 345 departments of internal medicine in Italy. A number of cardiovascular risk factors, diagnoses, and personal characteristics were analyzed in a total of 7476 patients aged 35 years or older. Not all of these personal characteristics were available for each patient. Results: In general, the levels of cardiovascular risk factors present in patients were high, with hypertension and diabetes the most frequently encountered. The risk of coronary heart disease (CHD) over 10 years was estimated using an Italian algorithm that provided high probability levels, mainly among cardiovascular patients (410 per 1000 in 10 years on average in both genders). Overall, 55% of the men and 50% of the women had levels above 200 per 1000 in 10 years, corresponding to the conventional threshold for intensive individual intervention on risk factors. At discharge, about 70% of hypertensive patients were being treated for their condition, while the same was true of only 25% of dyslipidemic patients. Conclusions: Although data are incomplete, the coronary risk profile of patients admitted to departments of internal medicine suggests a high probability of future events. Treatment of risk factors amenable to effective action is still far from optimal, especially in the area of elevated blood lipids.


[Content of basic lipid fractions in the myocardium of different regions of the heart in healthy people].
Content of lipids was studied in five parts of myocardium of healthy people by means of thin-layer chromatography on silica gel. The higher content of triglycerides and total lipids was found in dexter parts of heart as compared with sinister parts and septum interventriculare. The same distribution was not shown for free and esterified cholesterol.