Efficacy of cancer chemotherapy in relation to synchronization of cortisol rhythm, immune status and psychospiritual profile in metastatic non-small cell lung cancer.
The prognosis of cancer and the efficacy of the various anticancer therapies depend not only on tumor characteristics, but also on the endocrine and immune status of patients. Moreover, studies have shown that the clinical course of the neoplastic disease is also influenced by the psychospiritual status of patients. It is thus probable that the influence of psychospirituality on tumor growth may be mediated by the immunoneuroendocrine system, as demonstrated by the recent advances in psychoneuroendocrinological research. However, at present there are only few data on the possible link between the psychospiritual status and immunoendocrine functions of cancer patients. This study was carried out to investigate the relationships existing among the psychospiritual profile, cortisol rhythm and lymphocyte number before and after chemotherapy, and the efficacy of chemotherapy itself in advanced cancer patients. The study included 30 consecutive metastatic non-small cell lung cancer patients under chemotherapeutic treatment with cisplatin plus gemcitabine. The psychobiological investigations consisted of lymphocyte count, cortisol circadian rhythm, psychological profile using Rorschach test, and spiritual score, as assessed by a specific clinical test for spirituality. The control group consisted of 100 healthy volunteers. The patients who achieved a tumor regression, showed a significantly higher pre-treatment lymphocyte count and significantly lower alteration of the cortisol rhythm with respect to those who had no benefit from chemotherapy. Moreover, the lymphocyte mean number increased during chemotherapy in responder patients, whereas it progressively diminished in those who had disease progression. Lymphocytopenia and alterations of the cortisol rhythm prior to chemotherapy were associated with a loss of the psychosexual identity according the Rorschach test. Moreover, the mean spiritual score was lower in patients than in controls, although the difference was not significant. Finally, a low spiritual score prior to therapy was associated with a higher frequency of lymphocytopenia and cortisol rhythm alteration, as well as with a lower efficacy of chemotherapy itself. This preliminary study would suggest that the psychospiritual status of cancer patients may influence the efficacy of chemotherapy through the immunoneuroendocrine system.


Investigating #covidnurse Messages on TikTok: Descriptive Study.
During a time of high stress and decreased social interaction, nurses have turned to social media platforms like TikTok as an outlet for expression, entertainment, and communication. The purpose of this cross-sectional content analysis study is to describe the content of videos with the hashtag #covidnurse on TikTok, which included 100 videos in the English language. At the time of the study, this hashtag had 116.9 million views. Each video was coded for content-related to what nurses encountered and were feeling during the COVID-19 pandemic. Combined, the 100 videos sampled received 47,056,700 views; 76,856 comments; and 5,996,676 likes. There were 4 content categories that appeared in a majority (>50) of the videos: 83 showed the individual as a nurse, 72 showed the individual in professional attire, 58 mentioned/suggested stress, 55 used music, and 53 mentioned/suggested frustration. Those that mentioned stress and those that mentioned frustration received less than 50% of the total views (n=21,726,800, 46.17% and n=16,326,300, 34.69%, respectively). Although not a majority, 49 of the 100 videos mentioned the importance of nursing. These videos garnered 37.41% (n=17,606,000) of the total views, 34.82% (n=26,759) of the total comments, and 23.85% (n=1,430,213) of the total likes. So, despite nearly half of the total videos mentioning how important nurses are, these videos received less than half of the total views, comments, and likes. Social media and increasingly video-related online messaging such as TikTok are important platforms for social networking, social support, entertainment, and education on diverse topics, including health in general and COVID-19 specifically. This presents an opportunity for future research to assess the utility of the TikTok platform for meaningful engagement and health communication on important public health issues.


Gnathic Schwannomas: A Report of Two Cases and Systematic Review of the Literature.
The intraosseous schwannoma (IS) is a benign peripheral nerve sheath tumor postulated to arise de novo or from nerve fibers in preexisting nutrient canals. ISs are uncommon and comprise less than 1% of neoplasms originating in bone. We herein present two cases of mandibular schwannomas-the first case was a 66-year-old female with a four-month history of pain and pressure associated with an anterior mandibular radiolucency, and the second case was an asymptomatic 12-year-old female with separate radiolucencies of her mandibular symphysis and right posterior mandible. Incisional biopsies of all three lesions showed a benign spindle cell neoplasm with histologic features of a schwannoma; the tumor cells were strongly reactive for S-100. The patients underwent complete enucleation of their lesions and are without evidence of disease at ten months and five years, respectively. A systematic review was undertaken to evaluate the diagnostic features, treatment, and patient outcomes of gnathic schwannomas. A total of 93 cases were identified with the following demographic findings: predominance in females (57%); average age of occurrence of 37.3 years (8 to 77 years); mean size of 3.6 cm; and involvement of the mandibular body (37.6%), mandibular body and ramus (18.3%), and anterior mandible (18.3%). The predominant clinical sign was swelling (69.9%), and the most common radiographic presentation was a radiolucency (94.6%) with well-defined borders (72%). All cases were treated surgically, with an average follow-up interval of 22.9 months and a recurrence rate of 5.4.


Comparing set summary statistics and outlier pop out in vision.
Visual scenes are too complex to perceive immediately in all their details. Two strategies (among others) have been suggested as providing shortcuts for evaluating scene gist before its details: (a) Scene summary statistics provide average values that often suffice for judging sets of objects and acting in their environment. Set summary perception spans simple/complex dimensions (circle size, face emotion), various statistics (mean, variance, range), and separate statistics for discernible sets. (b) Related to set summary perception is detecting outliers from sets, called "pop out," which allows rapid perception of presence and properties of unusual, and thus, possibly salient items in the scene. To understand better visual system mechanisms underlying these two set-related perceptual phenomena, we now study their properties and the relationship between them. We present observers with two clouds of bars with distributed orientations and ask them to discriminate their mean orientations, reporting which cloud is oriented more clockwise, on average. In the second experiment, the two clouds had the same mean orientation, but one had a bar with an outlier orientation, which observers detected. We find that cloud mean orientation discrimination depends mainly on the difference in means, whereas outlier detection depends mainly on the distance of the outlier orientation from the edge of the cloud orientation range. Neither percept depends largely on the range of the set itself. A unified model of a population-code mechanism underlying these two phenomena is discussed.


A meta-analysis of the published research on the effects of child sexual abuse.
A meta-analysis of the published research on the effects of child sexual abuse (CSA) was undertaken for 6 outcomes: posttraumatic stress disorder (PTSD), depression, suicide, sexual promiscuity, victim-perpetrator cycle, and poor academic performance. Thirty-seven studies published between 1981 and 1995 involving 25,367 people were included. Many of the studies were published in 1994 (24; 65%), and most were done in the United States (22; 59%). All six dependent variables were coded, and effect sizes (d) were computed for each outcome. Average unweighted and weighted ds for each of the respective outcome variables were .50 and .40 for PTSD, .63 and .44 for depression, .64 and .44 for suicide, .59 and .29 for sexual promiscuity, .41 and .16 for victim-perpetrator cycle, and .24 and .19 for academic performance. A file drawer analysis indicated that 277 studies with null ds would be required to negate the present findings. The analyses provide clear evidence confirming the link between CSA and subsequent negative short- and long-term effects on development. There were no statistically significant differences on ds when various potentially mediating variables such as gender, socioeconomic status, type of abuse, age when abused, relationship to perpetrator, and number of abuse incidents were assessed. The results of the present meta-analysis support the multifaceted model of traumatization rather than a specific sexual abuse syndrome of CSA.


[Procalcitonin as sepsis predictor in cardiovascular surgery with cardiopulmonary bypass].
Cardiopulmonary bypass generates an exacerbated response that may lead to sepsis. To describe the association between procalcitonin levels and sepsis diagnosis in cardiovascular surgery subjects with cardiopulmonary bypass. A case-series study was conducted in 142 patients. Serum procalcitonin levels were measured at 24 hours and at 72 hours after surgery using a point of care testing based on quantitative immunochromatographic method. To assess association between procalcitonin levels and sepsis status, we calculated area under the curve (AUC) and sensitivity, specificity, and predictive values for the best cut-off point. From 142 patients studied, 7 developed sepsis after surgery (4.9%). For 24-hours procalcitonin levels AUC was 0.921 and best cut-off point was 3.8 ng/mL (sensitivity 0.857 and specificity 0.904). In the case of 72-hours procalcitonin levels, we observed a value of 0.868 for AUC and best cut-off point was 8.4 ng/mL (sensitivity 0.86 and specificity 0.97). Procalcitonin levels at 24 and 72 hours after cardiovascular surgery with cardiopulmonary bypass are associated with sepsis presence at cut-off points of 3.8 and 8.4 ng/mL respectively.


Canine distemper virus (CDV)-neutralizing activities of an anti-CDV canine-derived single-chain variable antibody fragment 4-15 (scFv 4-15) screened by phage display technology.
Canine distemper virus (CDV) is a highly contagious pathogen that causes severe diarrhea, fever and vomiting in domestic dogs, posing a serious threat to the dog breeding industry. Currently, there are no effective therapeutic agents for emergency treatment despite the availability of vaccines against CDV infection. Single-chain fragment variable (scFv) antibody has been demonstrated to effectively inhibit virus infections, suggesting a potential candidate as a therapeutic agent for canine distemper. In this study, a phage-displayed scFv library was constructed from the peripheral blood lymphocytes of dog immunized intramuscularly with live-attenuated CDV vaccine, and was subjected to four rounds of pannings against CDV. Subsequent indirect enzyme-linked immunosorbent assay screening revealed high-affinity scFv antibodies specific to CDV, and indirect immunofluorescence assay screening revealed CDV-neutralizing activity of scFv antibodies. Our results showed that a scFv antibody 4-15 (scFv 4-15) with high-affinity binding to CDV and neutralizing activity against CDV was obtained, which displayed effective therapeutic potential in vivo for dogs challenged with a lethal dose of CDV. Conclusively, the scFv 4-15 with high-affinity binding and neutralizing activity to CDV that was obtained by phage display technology provides a promising candidate for the therapeutic agents against CDV infection.


Static procedures for the management of the midface and lower face.
Facial reanimation for facial paralysis continues to be an evolving field in facial reconstruction. Static procedures in the management of mid and lower facial paralysis include the use of facial slings made from autologous tissue, freeze-dried acellular human dermis, and expanded polytetrafluoroethylene. A newly described suspension technique using a multivector suture suspension stands to expand the tools that can be used by the reconstructive surgeon. This article describes and contrasts each of these techniques.


Speaking out to improve the health of inmates. Interview by Vivienne Heines.
Prison public health is becoming increasingly important to our society as growing numbers of men and women are incarcerated and later released. Numerous studies indicate that the prison population has a higher risk of certain infectious diseases and a higher rate of mental illness than the general population. Two community leaders, Dr Melanie Spector in the area of public health and Judge Steven Leifman in the judicial system, have addressed the vital issues of women's health and mental illness, respectively. Their efforts have had a positive impact both on prisoners themselves and on the overall health of their communities.


Systematic review of lifestyle interventions to limit postpartum weight retention: implications for future opportunities to prevent maternal overweight and obesity following childbirth.
Postpartum weight retention can predict future weight gain and long-term obesity. Moreover, failure to lose weight gained during pregnancy can lead to increased body mass index for subsequent pregnancies, increasing the risk of adverse maternal and foetal pregnancy outcomes. This systematic review evaluates the effectiveness of lifestyle interventions aimed at reducing postpartum weight retention. Seven electronic databases were searched for intervention studies and trials enrolling women with singleton pregnancies and published in English from January 1990 to October 2012. Studies were included when postpartum weight was a main outcome and when diet and/or exercise and/or weight monitoring were intervention components. No limitations were placed on age, body mass index or parity. Eleven studies were identified as eligible for inclusion in this review, of which 10 were randomized controlled trials. Seven studies were successful in decreasing postpartum weight retention, six of which included both dietary and physical activity components, incorporated via a range of methods and delivered by a variety of health practitioners. Few studies utilized modern technologies as alternatives to traditional face-to-face support and cost-effectiveness was not assessed in any of the studies. These results suggest that postpartum weight loss is achievable, which may form an important component of obesity prevention in mothers; however, the optimal setting, delivery, intervention length and recruitment approach remains unclear.


Targeted next-generation sequencing identifies a novel mutation of LAMB3 in a Chinese neonatal patient presented with junctional epidermolysis bullosa.
Epidermolysis bullosa (EB) refers to a group of rare inherited mechanobullous disorders that present with great clinical and genetic heterogeneity. Its severity ranges from mild blistering to life-threatening. However, the clinical symptoms of different types of EB overlap significantly, especially at an early stage. Thus it is important to clarify the diagnosis for prognostic implications, patient management, and genetic counseling. Here, we report a 10-day-old male neonate from a nonconsanguineous Chinese family. He showed a bulla on the left lower limb lasting for 3 days, erosions around fingertips and toe tips at birth (predominantly on fingers), with the progressive spread of generalized blisters over the body as well as the development of the illness. The patient was diagnosed with suspected epidermolysis bullosa according to the blisters and erosions of the body as well as the pyogenic fingernails and toenails. The patient was performed targeted next-generation sequencing (NGS) with 9 candidate known genes, subsequently, his parents were screened for the mutations identified in the patient by Sanger sequencing. Then, prenatal diagnosis with amniotic fluid was performed in the subsequent pregnancy by Sanger sequencing. Targeted NGS revealed a previously unreported splice site variant c.822+1G>A (IVS 8) and a known recurrent nonsense variant c.124C>T (p.Arg42Ter, exon 3) in LAMB3 gene. The patient's father possessed a heterozygous c.822+1G>A mutation, his mother possessed a heterozygous c.124C>T mutation. For the subsequent pregnancy, the analyses of amniotic fluid sample indicated that the fetus carried neither of the mutations. Our finding will further enlarge LAMB3 genotype-phenotype correlations spectrum. Targeted capture sequencing is a valuable method to illustrate precise molecular pathology in patients with EB disorders, especially at an early stage of the clinical evaluation of complex disorders to avoid unnecessary and economically wasteful tests.


Inflammation, microenvironment, and the immune system in cancer progression.
Since Virchow first proposed in 1863 that tumors could originate from sites of chronic inflammation, it has been well established that chronic inflammation both contributes to cancer progression and predisposes tissue to various types of cancer. Experimental, clinical, and epidemiological studies have all demonstrated the strong association between chronic inflammation and cancer, and many studies have correlated the prolonged presence of the inflammatory milieu with an increased risk for developing cancer. Proinflammatory cytokines, chemokines and adhesion molecules, which regulate the sequential recruitment of leukocytes, are frequently observed in tumor microenvironment. These early desmoplastic changes could stimulate fibroblasts and endothelial cell division and produce components for tissue remodeling and neovascularization, ultimately promoting neoplastic processes. In this review article we overview the current understanding of the role of chronic inflammation in neoangiogenesis, tumor initiation, promotion, and progression.


Natural occurrence of aflatoxins in Korean meju.
Aflatoxin B1 (AFB1) was found in 35 of 60 (58.3%) meju samples with an average concentration of 7.3 ng/g by ELISA. Contamination of AFB1 was confirmed in 25 of 60 samples (41.6%) using HPLC, with an average concentration of 6.9 ng/g. Mean recoveries from meju ranged from 107% to 170% for AFB1 using ELISA at a spiking range of 1 to 50 ng/g. Over the same range, recoveries using HPLC were from 70% to 83%. The levels of AFB1 determined by ELISA and by HPLC demonstrated a close relationship between the two methods (r2 = 0.9324) employed in this study. In order to evaluate the potential health risks of AFB1 on Koreans consuming meju, we calculated the estimated probable daily intake (PDI) based on the average contamination levels and compared it with the estimated tolerable daily intake (TDI). The PDIs of AFB1 from kanjang and dwenjang were determined to be 0.04 and 0.21 ng/kg bw/day, respectively, and were higher than TDIs.


The curandero's apprentice: a therapeutic integration of folk and medical healing.
The author discusses alternative methods for dealing with folk illness in psychotherapy. Two case reports are presented that describe psychotic Mexican-American patients who were successfully treated with an approach that integrated curanderismo, the Hispanic concept of healing, and traditional therapy. The author discusses ethical aspects of this integrated approach and suggests that cultural considerations can be successfully incorporated into a treatment plan of optimum benefit for the individual patient.


Capsaicin-induced glutamate release is implicated in nociceptive processing through activation of ionotropic glutamate receptors and group I metabotropic glutamate receptor in primary afferent fibers.
Glutamate (Glu) is the major excitatory neurotransmitter in the central nervous system. The role of peripheral Glu and Glu receptors (GluRs) in nociceptive transmission is, however, still unclear. In the present study, we examined Glu levels released in the subcutaneous perfusate of the rat hind instep using a microdialysis catheter and the thermal withdrawal latency using the Plantar Test following injection of drugs associated with GluRs with/without capsaicin into the hindpaw. The injection of capsaicin into the rat hind instep caused an increase of Glu level in the s.c. perfusate. Capsaicin also significantly decreased withdrawal latency to irradiation. These effects of capsaicin were inhibited by pretreatment with capsazepine, a transient receptor potential vanilloid receptor 1 (TRPV1) competitive antagonist. Capsaicin-induced Glu release was also suppressed by combination with each antagonist of ionotropic GluRs (iGluRs: NMDA/AMPA receptors) and group I metabotropic GluR (mGluR), but not group II and group III mGluRs. Furthermore, these GluRs antagonists showed remarkable inhibition against capsaicin-induced thermal hyperalgesia. These results suggest that Glu is released from the peripheral endings of small-diameter afferent fibers by noxious stimulation and then activates peripheral iGluRs and group I mGluR in development and/or maintenance of nociception. Furthermore, the activation of peripheral NMDA/AMPA receptors and group I mGluR may be important in mechanisms whereby capsaicin evokes nociceptive responses.


Mania associated with antidepressant treatment: comprehensive meta-analytic review.
To review available data pertaining to risk of mania-hypomania among bipolar (BPD) and major depressive disorder (MDD) patients with vs. without exposure to antidepressant drugs (ADs) and consider effects of mood stabilizers. Computerized searching yielded 73 reports (109 trials, 114 521 adult patients); 35 were suitable for random effects meta-analysis, and multivariate-regression modeling included all available trials to test for effects of trial design, AD type, and mood-stabilizer use. The overall risk of mania with/without ADs averaged 12.5%/7.5%. The AD-associated mania was more frequent in BPD than MDD patients, but increased more in MDD cases. Tricyclic antidepressants were riskier than serotonin-reuptake inhibitors (SRIs); data for other types of ADs were inconclusive. Mood stabilizers had minor effects probably confounded by their preferential use in mania-prone patients. Use of ADs in adults with BPD or MDD was highly prevalent and moderately increased the risk of mania overall, with little protection by mood stabilizers.


Cellular mechanisms and control of KCl absorption in insect hindgut.
The hindgut of the desert locust possesses an unusual chloride transport system. The isolated locust rectum absorbs chloride from the mucosal (lumen) to the serosal (haemolymph) side at a rate which is equal to the short-circuit current (Isc). Net chloride transport (JClnet) persists in nominally Na-free or HCO3(CO2)-free saline, is insensitive to normal inhibitors of NaCl co-transport and anion exchange, and is independent of the net electrochemical gradient for sodium across the apical membrane. However, active chloride transport is strongly dependent on mucosal potassium (Ka = 5.3 mM-K). Chloride entry across the apical membrane is active, whereas the net electrochemical gradient across the apical membrane is active, whereas the net electrochemical gradient across the basal membrane favours passive Cl exit from the cell. Although mucosal potassium directly stimulates 'uphill' chloride entry, there is no evidence for coupled KCl co-transport, nor would co-entry with potassium be advantageous energetically. Net chloride absorption and Isc are stimulated by a peptide hormone from the central nervous system which acts via cyclic-AMP. Cyclic-AMP increases Isc and JClnet approximately 1000% and transepithelial conductance (Gt) approximately 100%. Approximately half of the delta Gt during stimulation results from increased Cl conductance at the basal cell border. This increase is also reflected in a shift of the basal membrane e.m.f. towards the Nernst potential for chloride. The remainder of the cAMP-induced delta Gt is due to an elevation of apical membrane K conductance, which causes a 400% increase in transepithelial potassium permeability as estimated by radiotracer diffusion. Because of this stimulation of K conductance, potassium serves as the principal counterion for active chloride transport under open-circuit conditions. Very high luminal levels of K oppose the stimulatory actions of cAMP on active Cl transport and K conductance. These and other results have been incorporated into a cellular model for KCl absorption across this insect epithelium.


Segmental omental infarction: an unusual cause of acute abdomen.
Omental infarction is a rare cause of acute abdominal pain, and the cause of omental infarction itself remains unknown. The diagnosis of omental infarction is occasionally made intra-operatively, because it is poorly known and presents no specific clinical features. Therefore omental infarction should always be considered in the differential diagnosis of abdominal inflammatory processes, mainly those affecting the right lower quadrant. The increasing use of computed tomography in cases of acute abdomen has facilitated the diagnosis of omental infarction in the pre-operative period. Here, we present the case of a 36-year-old, overweight female patient with clinical symptoms of acute abdomen. Computed tomography of the abdomen revealed indications of omental infarction. The patient was treated conservatively with analgesics and a nonsteroidal anti-inflammatory. The clinical evolution was favorable.


Temporal properties of the human taste system.
An attempt to apply linear systems methods to the temporal properties of the human taste system is described. The percentage modulation in concentration required to detect a fluctuation in intensity was measured as a function of frequency of modulation. Both a sine-wave and a square-wave input were used. The sensitivity of the taste system at its maximum, and also at the low frequencies, was greater than expected from previous work based on classical methodology. The sensitivity of the taste system at its maximum, and also at the low frequencies, was greater then expected from previous work base on classical methodology. The sensitivity of the taste system to the various qualities was, in decreasing order, salty, sweet, sour, and bitter. The taste system in insensitive to frequencies above about 5 Hz. Except for bitter, representatives of the various taste qualities yielded similar functions within qualities.


Association between gut microbiome-related metabolites and symptomatic hand osteoarthritis in two independent cohorts.
Since gut microbiome dysbiosis can cause inflammatory disorders by affecting host metabolism, we postulate that the gut microbiome and related metabolites could play a role in hand osteoarthritis. We characterised gut microbiome-related metabolites in people with symptomatic hand osteoarthritis (SHOA) in two independent cohorts. Using data collected from a large-sample community-based observational study (discovery cohort), we assessed the relations of the microbial function and plasma key metabolites related to altered microbial function with SHOA. Finally, we verified the relations of plasma metabolites to SHOA in an independent observational study (validation cohort). In the discovery cohort (n = 1359), compared to those without SHOA, participants with SHOA had significantly altered microbial functions related to tryptophan metabolism (Q = 0.025). Therefore we measured the plasma tryptophan metabolites and found that participants with SHOA had higher levels of 5-hydroxyindoleacetic acid (odds ratio [OR] = 1.25, 95% confidence interval [CI]: 1.09-1.42) and 5-hydroxytryptophol (OR = 1.13, 95% CI: 1.04-1.23), but lower levels of indole-3-lactic acid (ILA) (OR = 0.85, 95% CI: 0.72-1.00), skatole (OR = 0.93, 95% CI: 0.88-0.99) and 3-hydroxyanthranilic acid (OR = 0.90, 95% CI: 0.85-0.96). Findings from the validation cohort (n = 142) verified that lower levels of ILA were related to SHOA (OR = 0.70, 95% CI: 0.53-0.92). Alterations of the microbial function of tryptophan biosynthesis and tryptophan metabolites, especially lower levels of ILA, are associated with SHOA. These findings suggest the role of the microbiome and tryptophan metabolites in developing of SHOA and may contribute to future translational opportunities. National Key Research and Development Plan and National Natural Science Foundation of China.


Divergence in cell cycle progression is associated with shifted phenology in a multivoltine moth: the European corn borer, Ostrinia nubilalis.
Evolutionary change in diapause timing can be an adaptive response to changing seasonality, and even result in ecological speciation. However, the molecular and cellular mechanisms regulating shifts in diapause timing remain poorly understood. One of the hallmarks of diapause is a massive slowdown in the cell cycle of target organs such as the brain and primordial imaginal structures, and resumption of cell cycle proliferation is an indication of diapause termination and resumption of development. Characterizing cell cycle parameters between lineages differing in diapause life history timing may help identify molecular mechanisms associated with alterations of diapause timing. We tested the extent to which progression of the cell cycle differs across diapause between two genetically distinct European corn borer strains that differ in their seasonal diapause timing. We show the cell cycle slows down during larval diapause with a significant decrease in the proportion of cells in S phase. Brain-subesophageal complex cells slow primarily in G0/G1 phase whereas most wing disc cells are in G2 phase. Diapausing larvae of the earlier emerging, bivoltine E-strain (BE) suppressed cell cycle progression less than the later emerging, univoltine Z-strain (UZ) individuals, with a greater proportion of cells in S phase across both tissues during diapause. Additionally, resumption of cell cycle proliferation occurred earlier in the BE strain than in the UZ strain after exposure to diapause-terminating conditions. We propose that regulation of cell cycle progression rates ultimately drives differences in larval diapause termination, and adult emergence timing, between early- and late-emerging European corn borer strains.


Integrity of Cerebellar Fastigial Nucleus Intrinsic Neurons Is Critical for the Global Ischemic Preconditioning.
Excitation of intrinsic neurons of cerebellar fastigial nucleus (FN) renders brain tolerant to local and global ischemia. This effect reaches a maximum 72 h after the stimulation and lasts over 10 days. Comparable neuroprotection is observed following sublethal global brain ischemia, a phenomenon known as preconditioning. We hypothesized that FN may participate in the mechanisms of ischemic preconditioning as a part of the intrinsic neuroprotective mechanism. To explore potential significance of FN neurons in brain ischemic tolerance we lesioned intrinsic FN neurons with excitotoxin ibotenic acid five days before exposure to 20 min four-vessel occlusion (4-VO) global ischemia while analyzing neuronal damage in Cornu Ammoni area 1 (CA1) hippocampal area one week later. In FN-lesioned animals, loss of CA1 cells was higher by 22% compared to control (phosphate buffered saline (PBS)-injected) animals. Moreover, lesion of FN neurons increased morbidity following global ischemia by 50%. Ablation of FN neurons also reversed salvaging effects of five-minute ischemic preconditioning on CA1 neurons and morbidity, while ablation of cerebellar dentate nucleus neurons did not change effect of ischemic preconditioning. We conclude that FN is an important part of intrinsic neuroprotective system, which participates in ischemic preconditioning and may participate in naturally occurring neuroprotection, such as "diving response".


Shifts in plant respiration and carbon use efficiency at a large-scale drought experiment in the eastern Amazon.
*The effects of drought on the Amazon rainforest are potentially large but remain poorly understood. Here, carbon (C) cycling after 5 yr of a large-scale through-fall exclusion (TFE) experiment excluding about 50% of incident rainfall from an eastern Amazon rainforest was compared with a nearby control plot. *Principal C stocks and fluxes were intensively measured in 2005. Additional minor components were either quantified in later site measurements or derived from the available literature. *Total ecosystem respiration (R(eco)) and total plant C expenditure (PCE, the sum of net primary productivity (NPP) and autotrophic respiration (R(auto))), were elevated on the TFE plot relative to the control. The increase in PCE and R(eco) was mainly caused by a rise in R(auto) from foliage and roots. Heterotrophic respiration did not differ substantially between plots. NPP was 2.4 +/- 1.4 t C ha(-1) yr(-1) lower on the TFE than the control. Ecosystem carbon use efficiency, the proportion of PCE invested in NPP, was lower in the TFE plot (0.24 +/- 0.04) than in the control (0.32 +/- 0.04). *Drought caused by the TFE treatment appeared to drive fundamental shifts in ecosystem C cycling with potentially important consequences for long-term forest C storage.


Fertility and mortality estimation from the Panama Retrospective Demographic Survey, 1976.
Summary Data from the Retrospective Demographic Survey of Panama offer a unique opportunity to test a wide range of methods for estimating indirectly basic demographic parameters from inaccurate and incomplete data. Our primary emphasis is to evaluate methods for estimating adult mortality from information on widowhood and orphanhood, though estimates of childhood mortality obtained from information on sibling and child survivorship are assessed as well. The results for most of the estimating procedures are consistent; this finding is encouraging because it lends support to the hypothesis that the techniques can provide good estimates of mortality. Methods which produce results which are inconsistent provide valuable lessons. In particular, methods for providing unconditional estimates of values ofl (x) for adults by combining directly information on childhood mortality and adult mortality are shown to produce estimates which predominantly reflect the level of childhood mortality employed. Furthermore, within-method consistency of estimates appears to be a very poor indicator of reliable performance of the estimating technique or quality of data, since most methods yielded estimates which were internally consistent, though estimates made by different methods could differ considerably. In summary, the analysis indicates a birth rate of around 35 per thousand, a death rate of around 7.5 per thousand, a total fertility ratio of about 4.8, and expectations of life at birth of approximately 59 and 64 years for men and women respectively.


Clinical review 145: Pleiotropic effects of statins: lipid reduction and beyond.
There is accumulating evidence that statins have beneficial effects that are independent of their classical actions on lipoproteins. These effects include reductions in inflammation in the vasculature, kidney, and bone. Potential beneficial effects of these agents include enhancement of nitric oxide production in vasculature and the kidney. These agents appear to reduce bone fractures and may improve insulin sensitivity and reduce the likelihood of persons progressing from impaired glucose tolerance to type II diabetes. Potential beneficial pleiotropic effects of statins are covered in this review.


Vascularized options for reconstruction of the mandibular condyle.
The temporomandibular joint is elegant in its design, which may make it difficult if not impossible to comprehensively reconstruct. Although a broad range of nonvascularized options exists for reconstruction of degenerative conditions of the temporomandibular joint, vascularized reconstructions such as the fibula or the second metatarsal phalangeal joint are more appropriate for defects resulting from oncologic resection or in patients with compromised soft tissue. An anatomically based classification system for these defects is presented.


Mesocestoides corti intracranial infection as a murine model for neurocysticercosis.
Neurocysticercosis (NCC) is the most common parasitic disease of the central nervous system (CNS) caused by the larval form of the tapeworm Taenia solium. NCC has a long asymptomatic period with little or no inflammation, and the sequential progression to symptomatic NCC depends upon the intense inflammation associated with degeneration of larvae. The mechanisms involved in these progressive events are difficult to study in human patients. Thus it was necessary to develop an experimental model that replicated NCC. In this review, we describe studies of a murine model of NCC in terms of the release/secretion of parasite antigens, immune responses elicited within the CNS environment and subsequent pathogenesis. In particular, the kinetics of leukocyte subsets infiltrating into the brain are discussed in the context of disruption of the CNS barriers at distinct anatomical sites and the mechanisms contributing to these processes. In addition, production of various inflammatory mediators and the mechanisms involved in their induction by the Toll-like receptor signaling pathway are described. Overall, the knowledge gained from the mouse model of NCC has provided new insights for understanding the kinetics of events contributing to different stages of NCC and should aid in the formulation of more effective therapeutic approaches.


Large pleural effusion necessitates chest tube drainage in a patient with Kawasaki disease.
An 11-month-old Turkish boy was hospitalised with clinical and roentgen graphic evidence of large pleural effusion on the third day of fever and misdiagnosed as parapneumonic effusion. Due to worsening respiratory distress chest tube drainage was performed. Four days later the classic signs of Kawasaki disease appeared. His clinical condition improved gradually and fever subsided after intravenous gammaglobulin and aspirin treatment. A mild transient dilatation of the right coronary artery was seen and returned to the normal diameter within a few weeks. To our knowledge, large pleural effusion in a case of Kawasaki disease, in which chest tube drainage was needed, has not been reported. We describe here a patient with complete Kawasaki disease whose initial presentation mimicked a parapneumonic effusion.


Your place or mine? The neural dynamics of personally familiar scene recognition suggests category independent familiarity encoding.
Recognizing a stimulus as familiar is an important capacity in our everyday life. Recent investigation of visual processes has led to important insights into the nature of the neural representations of familiarity for human faces. Still, little is known about how familiarity affects the neural dynamics of non-face stimulus processing. Here we report the results of an EEG study, examining the representational dynamics of personally familiar scenes. Participants viewed highly variable images of their own apartments and unfamiliar ones, as well as personally familiar and unfamiliar faces. Multivariate pattern analyses were used to examine the time course of differential processing of familiar and unfamiliar stimuli. Time-resolved classification revealed that familiarity is decodable from the EEG data similarly for scenes and faces. The temporal dynamics showed delayed onsets and peaks for scenes as compared to faces. Familiarity information, starting at 200 ms, generalized across stimulus categories and led to a robust familiarity effect. In addition, familiarity enhanced category representations in early (250-300 ms) and later (>400 ms) processing stages. Our results extend previous face familiarity results to another stimulus category and suggest that familiarity as a construct can be understood as a general, stimulus-independent processing step during recognition.


A National Study of the Impact of Delayed Flap Timing for Treatment of Patients with Deep Sternal Wound Infection.
This study aimed to evaluate the impact of delayed flap closure on mortality and resource use for treatment of deep sternal wound infection. The authors analyzed the Truven MarketScan Databases from 2009 to 2013 to identify adult patients who developed deep sternal wound infection after open cardiac surgery and who underwent flap closure for treatment. A multivariable logistic regression model was created to evaluate the relationship between mortality and flap timing. Multivariable Poisson regressions were used to investigate the relationship between flap timing and number of procedures, number of hospitalizations, and length of stay outcomes. A multivariable log-linear regression model was created for cost analysis. All analyses were adjusted for patient risk factors and treatment characteristics. The authors identified 612 patients with deep sternal wound infection who underwent flap closure. The timing of flap closure was delayed more than 7 days after diagnosis in 39 percent of patients. Delayed time to flap closure greater than 3 days after diagnosis of infection was associated with higher mortality odds for delay 4 to 7 days (OR, 2.94) and delay greater than 7 days (OR, 2.75; p < 0.03), greater additional procedures for delay 4 to 7 days (incidence rate ratio, 1.72) and delay greater than 7 days (incidence rate ratio, 1.93; p < 0.001), and up to 43 percent longer hospital length of stay and 37 percent greater costs compared with patients undergoing flap closure 0 to 3 days after diagnosis. Delay in flap closure was associated with greater mortality and resource use. Prompt involvement of reconstructive surgeons may improve quality and efficiency of deep sternal wound infection care. Therapeutic, III.


Advanced pigmentary retinal degeneration: an ultrastructural study.
A case of advanced pigmentary retinal degeneration is described. Posterior subcapsular cataract and a remnant of the anterior hyaloid system on the posterior lens surface were found. Extensive dispersion of pigment and organization of the vitreous base were present. Gliosis was seen in the retina, and no photoreceptors were evident. The retinal blood vessel walls were extensively hyalinized, with cell debris and deposition of basement-membrane-like material, which may have originated from perivascular pigment-laden cells of pigment epithelial origin. The pigment epithelium showed extensive proliferation in clumps. Pigmented retinal pigment epithelium (RPE) cells without lipofuscin, migrating nonpigmented RPE cells, and macrophages with large lysosomal bodies could be identified in each clump. An abundance of extracellular basement-membrane-like material or mucopolysaccharide was seen in the retina and adjacent to the RPE. This material probably originated from the abnormal RPE. Abnormalities of the large and small choroidal vessels are present.


[Effect of negative intrathoracic pressure on venous return].
In acute experiments on cats and in observations made in human subjects, an increase of the negative intrathoracic pressure (NIP) leads to no significant changes of the venous return (VR) mean values. The peak values of the VR, however, increased and decreased more in inspiration and expiration following a deep breathing as compared with the normal breathing. The NIP seems to exert no direct effect upon the VR.


Effectiveness of ECG educational workshops among undergraduate medical students.
The electrocardiogram (ECG) remains one of the most important and commonly used diagnostic tools in medicine. At the faculty of Medicine of Tunis (FMT), teaching ECG interpretation to undergraduate medical students is an important part of the curriculum. To assess the effectiveness of pedagogical workshops in ECG learning among students of First-year of the primary cycle of medical studies (PCMS 1). In addition, we aimed to assess the students' perceptions of the tutorials. It was an exhaustive cross-sectional study that was carried out at the FMT during the academic year 2017-2018 and that included students from PCMS 1. All participants completed a pre-test, a workshop session and a post-test. Each of the tests consists of five Multiple Choice Questions (MCQs) covering the same topics. An evaluation of students' satisfaction with the tutorial was made at the end of the session. Ten workshops were held at the FMT, including 160 students. The overall score increased from 4 out of 10 points in the pre-test to 6.8 out of 10 points in the post-test (p <0.001). A statistically significant improvement was noted in all tests questions (p<0.001). Sixty-one learners (39.3%) were "Not satisfied" with the number of students per group. On the whole, 83.8% (n=130) of students found the session beneficial. Students indicated a positive attitude toward the workshop and its utility. More research among similar populations is needed to support these conclusions and to assess the effectiveness of medium- and long-term educational workshops on medical students.


Physiologically based pharmacokinetic modelling of drug penetration across the blood-brain barrier--towards a mechanistic IVIVE-based approach.
Predicting the penetration of drugs across the human blood-brain barrier (BBB) is a significant challenge during their development. A variety of in vitro systems representing the BBB have been described, but the optimal use of these data in terms of extrapolation to human unbound brain concentration profiles remains to be fully exploited. Physiologically based pharmacokinetic (PBPK) modelling of drug disposition in the central nervous system (CNS) currently consists of fitting preclinical in vivo data to compartmental models in order to estimate the permeability and efflux of drugs across the BBB. The increasingly popular approach of using in vitro-in vivo extrapolation (IVIVE) to generate PBPK model input parameters could provide a more mechanistic basis for the interspecies translation of preclinical models of the CNS. However, a major hurdle exists in verifying these predictions with observed data, since human brain concentrations can't be directly measured. Therefore a combination of IVIVE-based and empirical modelling approaches based on preclinical data are currently required. In this review, we summarise the existing PBPK models of the CNS in the literature, and we evaluate the current opportunities and limitations of potential IVIVE strategies for PBPK modelling of BBB penetration.


Autografts of uncrushed and crushed bone and cartilage. Experimental observations and clinical implications.
This study evaluated autografts of bone and cartilage, uncrushed and crushed, in the perichondrial space of the ear and subcutaneously in the paraspinal region in rabbits six weeks and six months after transplantation. The results support the belief that in a clinical setting it is important to preserve perichondrium because it facilitates growth of new cartilage. This study suggests that when autogenous tissue is to be used for subcutaneous augmentation, it is best to use crushed or uncrushed cartilage or uncrushed bone because they remain viable. In the perichondrial space, crushed and uncrushed cartilage grafts not only remain viable but also induce growth of new cartilage and bone. Autogenous crushed bone does not survive in the perichondrial space of the rabbit ear.


The quality of information provided by the most popular dementia videos on TikTok.
Dementia is among the leading causes of death and disability worldwide, having a major impact not only on the affected person but also on all of society. The Internet is a popular and growing source of health-related information for patients, family members, carriers, and physicians. TikTok, one of the most popular social media platforms, is an important source for knowledge access and adoption. However, the quality of health information on TikTok has not been sufficiently studied. To evaluate the quality of the information provided in the most popular videos on dementia shared on TikTok. A cross-sectional study. The top 100 most popular videos on TikTok obtained by searching the hashtag "dementia" were included in the study and grouped based on their source and content. The popularity of the videos was estimated based on the numbers of likes, comments, and shares. The quality of health-related information was evaluated using the DISCERN score and the Global Quality Score (GQS). Videos had a median duration of 33.29 s; the median number of likes was 635,100, with a total of 93,698,200 likes, 903,859 comments, and 5,310,912 shares. The source (uploader) of 65% of the videos was family members, while only 4% were uploaded by doctors. The content was lifestyle-related in 62% of the videos, while 12% of the videos were for fun. Videos had a median DISCERN score of 22.5 (IQR 20-27) and a median GQS of 2 (IQR 1-3). The videos uploaded by doctors had the highest quality scores and the lowest popularity. The most popular dementia videos on TikTok are mostly shared by family members and are of poor quality. Given the major public health issues associated with dementia, experts must provide appropriate and active assistance to patients in interpreting the information identified.


Pain Management Best Practices from Multispecialty Organizations During the COVID-19 Pandemic and Public Health Crises.
It is nearly impossible to overestimate the burden of chronic pain, which is associated with enormous personal and socioeconomic costs. Chronic pain is the leading cause of disability in the world, is associated with multiple psychiatric comorbidities, and has been causally linked to the opioid crisis. Access to pain treatment has been called a fundamental human right by numerous organizations. The current COVID-19 pandemic has strained medical resources, creating a dilemma for physicians charged with the responsibility to limit spread of the contagion and to treat the patients they are entrusted to care for. To address these issues, an expert panel was convened that included pain management experts from the military, Veterans Health Administration, and academia. Endorsement from stakeholder societies was sought upon completion of the document within a one-week period. In these guidelines, we provide a framework for pain practitioners and institutions to balance the often-conflicting goals of risk mitigation for health care providers, risk mitigation for patients, conservation of resources, and access to pain management services. Specific issues discussed include general and intervention-specific risk mitigation, patient flow issues and staffing plans, telemedicine options, triaging recommendations, strategies to reduce psychological sequelae in health care providers, and resource utilization. The COVID-19 public health crisis has strained health care systems, creating a conundrum for patients, pain medicine practitioners, hospital leaders, and regulatory officials. Although this document provides a framework for pain management services, systems-wide and individual decisions must take into account clinical considerations, regional health conditions, government and hospital directives, resource availability, and the welfare of health care providers.


Cognitive profiles of adult developmental dyslexics: theoretical implications.
The aim of this study was to establish cognitive profiles of dyslexic adults on tests developed within the three main theories of developmental dyslexia: phonological, visual magnocellular and cerebellar and to investigate which theory can account for these profiles. The sample consisted of 15 Polish university students or alumni with a formal diagnosis of dyslexia, without ADHD and 15 controls matched on education, age, gender, IQ and handedness. The results revealed a striking heterogeneity of profiles. Nine dyslexics exhibited only a phonological deficit; one a phonological and a visual magnocellular deficit; a further three a phonological and a cerebellar deficit; two either a cerebellar or a visual magnocellular deficit. None of the three main theories of dyslexia can account for all the cases studied here. It is suggested that the best account of these data is in terms of different sub-types of dyslexia with different underlying causes, such as phonological, visual magnocellular and cerebellar, or a combination of these. However, an account in terms of Ramus' (Trends, Neurosci. 2004; 27(12): 720-726) model, according to which the phonological deficit is a core deficit in dyslexia and other deficits (magnocellular and cerebellar), are just co-morbid markers without a causal relationship to dyslexics' literacy difficulties, cannot currently be ruled out.


[The Holt-Oram syndrome. Review of the literature and current orthopedic treatment concepts].
The clinical manifestation of the Holt-Oram-syndrome (HOS) shows congenital heart-disease and anomalies of the upper limb. The inheritance of this syndrome is autosomal dominant. The question arise, as to whether a contemporary orthopedic concept of treatment could developed based on own experiences and data from the literature. We revised data from five patients with HOS treated at the Clinic for Orthopaedics of the University of Heidelberg. The review of the literature revealed a comprehensive and detailed picture of the clinical syndrome and, furthermore, information in respect to a comparative analysis of methods of treatments. Our patients showed characteristic cardiac anomalies, i.e. atrio and ventricular septal defects, and persisting Botall's duct (three cases). The types of malformation of the upper limb corresponded with those found in the literature. Furthermore the indication for amputation of rudimentary or hypoplastic fingers in the Heidelberg clinic was in accordance with the clinical treatments described worldwide. The type of treatment of the clubhand in cases with HOS depends on (1) the age and (2) the pattern and degree of accompanying malformations of the upper limb. For patients with aplasia of the thumb or amputation of a rudimental one we recommend pollicisation of the index finger to improve its function.


[Clinical picture and development of transsexualism].
The results of a clinical study of 33 patients with transsexualism (TS) have shown that TS is a pathological state of the person whose essence lies in the polar discrepancy of the biological sex with the forming psychic sex. It can be described as a true inversion of sexual identification and orientation. The formation of TS has been found to have a regular pattern. Four types of TS development have been identified. It has been shown that TS predisposes toward a high risk of suicidal behavior. It is suggested that the development of TS may be evaluated as autochthonous.


Health effects of long-term use of the intrauterine levonorgestrel-releasing system. A follow-up study over 12 years of continuous use.
This report comprises women from one center, who all participated in a larger European multi-center study, which included 2758 healthy women, of whom 1821 were randomly allocated to the levonorgestrel-releasing intrauterine system (Lng-IUS) and 937 to a copper-IUD (Nova-T). At the end of the 5 year study period, 109 of the 300 women, who originally were allocated to the Lng-IUS at this center, were still using the Lng-IUS. The women were offered the opportunity to continue the Lng-IUS and 100 women chose to do so. After a total period of almost 7 years of continuous use, a second Lng-IUS was offered and 82 of the women chose to start a second segment of Lng-IUS use. After another 5 years, 69 of the women were fitted with their third Lng-IUS. These 82 women were examined yearly throughout the study period and bleeding pattern, hemoglobin, weight, blood-pressure, general well-being and intercurrent disease were analyzed to assess long-term effects. No pregnancy occurred during the follow-up. One case of partial expulsion occurred and one case of pelvic inflammatory disease. Seventy-seven percent of the women did not report any health problems at all during the entire follow-up period of 13 years. At the end of the second period with the Lng-IUS, 60% reported amenorrhea, 12% infrequent, scanty bleeds and 28% regular, scanty bleeds. As a consequence, the hemoglobin values increased, with a mean increase, after 12-13 years, being 1.35 g/dl. Blood pressure increased slightly and body weight increased with a mean increase of 0.49 kg/year. Seven women became postmenopausal during the follow-up and started estrogen replacement therapy with the Lng-IUS in situ. This follow-up study suggests that the Lng-IUS remains a safe and effective method of contraception, allowing women prolonged relief of menstrual problems, and for women in their late reproductive years, offering a convenient and bleeding-free transition into the menopause.


The amorphous state: first-principles derivation of the Gordon-Taylor equation for direct prediction of the glass transition temperature of mixtures; estimation of the crossover temperature of fragile glass formers; physical basis of the "Rule of 2/3".
Predicting the glass transition temperature (Tg) of mixtures has applications that span across industries and scientific disciplines. By plotting experimentally determined Tg values as a function of the glass composition, one can usually apply the Gordon-Taylor (G-T) equation to determine the slope, k, which subsequently can be used in Tg predictions. Traditionally viewed as a phenomenological/empirical model, this work proposes a physical basis for the G-T equation. The proposed equations allow for the calculation of k directly and, hence, they determine/predict the Tg values of mixtures algebraically. Two derivations for k are provided, one for strong glass-formers and the other for fragile mixtures, with the modeled trehalose-water and naproxen-indomethacin systems serving as examples of each. Separately, a new equation is described for the first time that allows for the direct determination of the crossover temperature, Tx, for fragile glass-formers. Lastly, the so-called "Rule of 2/3", which is commonly used to estimate the Tg of a pure amorphous phase based solely on the fusion/melting temperature, Tf, of the corresponding crystalline phase, is shown to be underpinned by the heat capacity ratio of the two phases referenced to a common temperature, as evidenced by the calculations put forth for indomethacin and felodipine.


Salmonella chronic carriage: epidemiology, diagnosis, and gallbladder persistence.
Typhoid (enteric fever) remains a major cause of morbidity and mortality worldwide, causing over 21 million new infections annually, with the majority of deaths occurring in young children. Because typhoid fever-causing Salmonella have no known environmental reservoir, the chronic, asymptomatic carrier state is thought to be a key feature of continued maintenance of the bacterium within human populations. Despite the importance of this disease to public health, our understanding of the molecular mechanisms that catalyze carriage, as well as our ability to reliably identify and treat the Salmonella carrier state, have only recently begun to advance.


[Large area, peripheral cryo-application in neovascularization glaucoma].
Nine eyes were treated by cryotherapy applied circularly over a large area: 4 rows in each quadrant, from 3 mm behind the limbus to the equator, with 4 burns in each row. Freezing time was 10 seconds. Clinical observations after an average of 19.4 months and histologic findings are communicated.


Comparative quality assessment of traditional vs. improved dried Bombay duck (Harpodon nehereus) under different storage conditions: Solar chimney dryer a low-cost improved approach for nutritional dried fish.
Dried fish and fishery products provide important and affordable dietary sources of animal protein. The present study compared the sensory, microbial, and biochemical quality of bombay duck (Harpadon nehereous) dried fish produced using improved versus traditional open-air drying method. The sensory, microbial, and biochemical quality was determined following quality index, total plate count (TPC), and Association of Official Analytical Chemists (AOAC) method, respectively. The sensory quality results indicate highly acceptable dried fish with the improved method compared to traditional method at both initial and storage condition. The microbial load (APC, TEC, TViC, and TSC) of improved dried fish was within internationally permissible microbiological standards for food whereas traditionally dried fish exceeded the permissible limit. The biochemical composition (protein, lipid, ash, and moisture) of improved dried fish had better nutritional value than the traditional dried fish. After 60 days storage time, samples packaged under HDPE conditions exhibited excellent organoleptic characteristics, lower microbial load, and lower biochemical decomposition than samples packaged in LDPE. The above results confirmed that the solar chimney dryer produced superior quality of dried fish compared to the traditional open-air drying method both initially and after storage, while packaging dried fish under HDPE conditions extended shelf life further.


[Oxygen-dissociation properties and the regulation of the oxygen affinity of a hemoglobin polymer in the bull].
Oxygen-dissociation properties and some aspects of allosteric regulation of bovine hemoglobin (Hb) and its polymerized form (HbP) have been examined. It has been shown that bovine HbP as well as bovine Hb does not require the presence of organic phosphates for normal functioning and has gas transport characteristics which are similar to those of the whole human blood. Pyridoxal-5'-phosphate (PP) works as an allosteric regulator of bovine HbP only in the absence of Cl- ions and vice versa. However, in covalent binding of PP to HbP both the effectors (PP and Cl- ions) can work simultaneously and independently. Thus, by varying the Hb/PP ratio it is possible to prepare HbP solutions with preset P50 values within the range 30-55 mm Hg. The results can be used in simulation of gas transport characteristics of artificial oxygen carriers.


A practical approach to the diagnosis, evaluation, and management of cutaneous small-vessel vasculitis.
Cutaneous small-vessel vasculitis (CSVV) is a disorder characterized by neutrophilic inflammation predominantly limited to the superficial cutaneous postcapillary venules. CSVV may be idiopathic or may have a defined cause such as infection, medication, connective tissue disease, or malignancy. CSVV may also be associated with extracutaneous disease or systemic vasculitis. The most common clinical presentation of CSVV consists of symmetrically distributed palpable purpura of the lower extremities. In general, lesional skin biopsy samples should be examined with light microscopy and direct immunofluorescence for adult patients with suspected CSVV. A complete history, review of systems, physical examination, and selected laboratory studies also should be performed to assess for inciting causes or extracutaneous involvement of CSVV. Treatment varies and depends on the chronicity of CSVV, the severity of cutaneous involvement, and the presence or absence of both an underlying cause and extracutaneous involvement of CSVV. An isolated episode of CSVV associated with a known inciting factor may be managed by removal or treatment of the trigger, along with symptomatic measures. First-line systemic treatments for chronic, idiopathic CSVV include colchicine or dapsone, used singly or in combination. Recurrent, chronic, or severely symptomatic CSVV that does not respond to the aforementioned therapies may require initiation of an immunosuppressive agent such as azathioprine, mycophenolate mofetil, methotrexate, cyclosporine, or rituximab.


4 S RNA in regenerating optic axons of goldfish.
Previous experiments have demonstrated that 4 S RNA is transported axonally during the reconnection period of optic nerve regeneration in goldfish. The present experiments were performed to determine whether 4 S RNA is transported axonally during later, maturational stages of nerve regeneration and to examine some of the characteristics of 4 S RNA in regenerating axons. [3H]Uridine was injected into both eyes of fish 18 days (near the time of reconnection) after bilateral optic nerve crush and the fish were sacrificed at various times up to 180 days after injection. [2H]RNA was isolated by phenol extraction and ethanol precipitation from 24 pooled tecta and fractionated by SDS-polyacrylamide tube gel electrophoresis. Data from these experiments showed that 70% of the [3H]RNA is present as 4 S RNA 12 days after injection, and 60 days after injection, this value is still approximately 50%. When nerves were cut 36 days after injection (54 days post-crush) and allowed to degenerate for 6 days before determining tectal [3H]RNA, the majority of the 4 S[3H]RNA was lost from the tectum. This indicates that up to 36 days after injection, 4 S [3H]RNA remains within regenerating axons and that it is unlikely that significant amounts of axonally transported 4 S RNA are transferred out of the axon to surrounding cells. In other experiments, the time of sacrifice after injection was held constant and the time of injection after nerve crush was varied. Analysis of tectal [3H]RNA showed that the major period of axonal transport of 4 S [3H]RNA was in early stages of regeneration at 24 and 36 days after nerve crush and that the amount of 4 S [3H]RNA which is transported axonally decreased at later time points. Calculations of the amount of axonal 4 S [3H]RNA versus what is synthesized in periaxonal cells gave results suggesting that 4 S RNA in regeneration axons turns over relatively slowly when compared with 4 S RNA in tectal cells.


Size-engineered biocompatible polymeric nanophotosensitizer for locoregional photodynamic therapy of cancer.
Current approaches in use of water-insoluble photosensitizers for photodynamic therapy (PDT) of cancer often demand a nano-delivery system. Here, we report a photosensitizer-loaded biocompatible nano-delivery formulation (PPaN-20) whose size was engineered to ca. 20nm to offer improved cell/tissue penetration and efficient generation of cytotoxic singlet oxygen. PPaN-20 was fabricated through the physical assembly of all biocompatible constituents: pyropheophorbide-a (PPa, water-insoluble photosensitizer), polycaprolactone (PCL, hydrophobic/biodegradable polymer), and Pluronic F-68 (clinically approved polymeric surfactant). Repeated microemulsification/evaporation method resulted in a fine colloidal dispersion of PPaN-20 in water, where the particulate PCL matrix containing well-dispersed PPa molecules inside was stabilized by the Pluronic corona. Compared to a control sample of large-sized nanoparticles (PPaN-200) prepared by a conventional solvent displacement method, PPaN-20 revealed optimal singlet oxygen generation and efficient cellular uptake by virtue of the suitably engineered size and constitution, leading to high in vitro phototoxicity against cancer cells. Upon administration to tumor-bearing mice by peritumoral route, PPaN-20 showed efficient tumor accumulation by the enhanced cell/tissue penetration evidenced by in vivo near-infrared fluorescence imaging. The in vivo PDT treatment with peritumorally administrated PPaN-20 showed significantly enhanced suppression of tumor growth compared to the control group, demonstrating great potential as a biocompatible photosensitizing agent for locoregional PDT treatment of cancer.


Characterization of ventral incisional hernia and repair using shear wave elastography.
To assess the integrity of hernia repair, imaging modalities such as computed tomography or ultrasound (US) are commonly used. Neither modality has currently the capacity to simultaneously image the mesh and quantify a prosthetic and surrounding tissue stiffness. In this pilot study, we hypothesize that US shear wave elastography (SWE) can be used to identify a polyester mesh and a biologic graft and to assess their stiffness noninvasively in a rat model of bridging hernia repair. Lewis rats underwent hernia creation and repair with Parietex or Strattice at 30 d. After 3 mo, the animals were euthanized, and the Young's Modulus was measured using SWE. Three-dimensional reconstructions of the hernia pre- and post-repair were performed using in-house image processing algorithms. SWE was capable of accurate and real-time assessment and diagnosis of the hernia defects in vivo. Young's Modulus of Parietex meshes and Strattice grafts as estimated from the shear wave elastograms were found to be statistically different from each other (P < 0.05). Accurate three-dimensional reconstructions of the hernia defects pre- and post-repair were generated. In this study, we demonstrate the feasibility of using US SWE to detect ventral hernias and evaluate mesh repair in vivo. Our results indicate that the presence of a hernia and repair can be reliably visualized by SWE and three dimensionally reconstructed. Thus, this technique may provide both structural and functional information regarding the hernia and the repair.


Climate change and commercial fishing practices codetermine survival of a long-lived seabird.
Understanding the environmental mechanisms that govern population change is a fundamental objective in ecology. Although the determination of how top-down and bottom-up drivers affect demography is important, it is often equally critical to understand the extent to which, environmental conditions that underpin these drivers fluctuate across time. For example, associations between climate and both food availability and predation risk may suggest the presence of trophic interactions that may influence inferences made from patterns in ecological data. Analytical tools have been developed to account for these correlations, while providing opportunities to ask novel questions regarding how populations change across space and time. Here, we combine two modeling disciplines-path analysis and mark-recapture-recovery models-to explore whether shifts in sea-surface temperatures (SSTs) influenced top-down (entanglement in fishing equipment) or bottom-up (forage fish production) population constraints over 60 years, and the extent to which these covarying processes shaped the survival of a long-lived seabird, the Royal tern. We found that hemispheric trends in SST were associated with variation in the amount of fish harvested along the Atlantic coast of North America and in the Caribbean, whereas reductions in forage fish production were mostly driven by shifts in the amount of fish harvested by commercial fisheries throughout the North Atlantic the year prior. Although the indirect (i.e., stock depletion) and direct (i.e., entanglement) impacts of commercial fishing on Royal tern mortality has declined over the last 60 years, increased SSTs during this time period has resulted in a comparable increase in mortality risk, which disproportionately impacted the survival of the youngest age-classes of Royal terns. Given climate projections for the North Atlantic, our results indicate that threats to Royal tern population persistence in the Mid-Atlantic will most likely be driven by failures to recruit juveniles into the breeding population.


The little shrimp that could: phylogeography of the circumtropical Stenopus hispidus (Crustacea: Decapoda), reveals divergent Atlantic and Pacific lineages.
The banded coral shrimp, Stenopus hispidus (Crustacea: Decapoda: Stenopodidea) is a popular marine ornamental species with a circumtropical distribution. The planktonic larval stage lasts ∼120-253 days, indicating considerable dispersal potential, but few studies have investigated genetic connectivity on a global scale in marine invertebrates. To resolve patterns of divergence and phylogeography of S. hispidus, we surveyed 525 bp of mitochondrial cytochrome c oxidase subunit I (COI) from 198 individuals sampled at 10 locations across ∼27,000 km of the species range. Phylogenetic analyses reveal that S. hispidus has a Western Atlantic lineage and a widely distributed Indo-Pacific lineage, separated by sequence divergence of 2.1%. Genetic diversity is much higher in the Western Atlantic (h = 0.929; π = 0.004) relative to the Indo-Pacific (h = 0.105; π < 0.001), and coalescent analyses indicate that the Indo-Pacific population expanded more recently (95% HPD (highest posterior density) = 60,000-400,000 yr) than the Western Atlantic population (95% HPD = 300,000-760,000 yr). Divergence of the Western Atlantic and Pacific lineages is estimated at 710,000-1.8 million years ago, which does not readily align with commonly implicated colonization events between the ocean basins. The estimated age of populations contradicts the prevailing dispersal route for tropical marine biodiversity (Indo-Pacific to Atlantic) with the oldest and most diverse population in the Atlantic, and a recent population expansion with a single common haplotype shared throughout the vast Indian and Pacific oceans. In contrast to the circumtropical fishes, this diminutive reef shrimp challenges our understanding of conventional dispersal capabilities of marine species.


Uptake of Bt endotoxins by nontarget herbivores and higher order arthropod predators: molecular evidence from a transgenic corn agroecosystem.
The planting of transgenic crops expressing Bacillus thuringiensis endotoxins is widespread throughout the world; the prolific increase in their application exposes nontarget organisms to toxins designed to control pests. To date, studies have focused upon the effects of Bt endotoxins on specific herbivores and detritivores, without consideration of their persistence within arthropod food webs. Here, we report the first quantitative field evaluation of levels of Bt endotoxin within nontarget herbivores and the uptake by higher order arthropods. Antibody-based assays indicated significant quantities of detectable Cry1Ab endotoxin within nontarget herbivores which feed on transgenic corn (including the corn flea beetle, Chaetocnema pulicaria, Japanese beetle, Popillia japonica and southern corn rootworm, Diabrotica undecimpunctata howardi). Furthermore, arthropod predators (Coccinellidae, Araneae, and Nabidae) collected from these agroecosystems also contained significant quantities of Cry1Ab endotoxin indicating its movement into higher trophic levels. This uptake by predators is likely to have occurred by direct feeding on plant material (in predators which are facultatively phytophagous) or the consumption of arthropod prey which contained these proteins. These data indicate that long-term exposure to insecticidal toxins occurs in the field. These levels of exposure should therefore be considered during future risk assessments of transgenic crops to nontarget herbivores and arthropod predators.


(E)-2-[(2,4,6-Tri-meth-oxy-benzyl-idene)amino]-phenol.
There are two independent mol-ecules in the asymmetric unit of the title compound, C16H17NO4, with similar conformations but some differences in their bond angles. Each mol-ecule adopts a trans configuration with respect to the methyl-idene C=N bond and is twisted with a dihedral angle between the two substituted benzene rings of 80.52 (7)° in one mol-ecule and 83.53 (7)° in the other. All meth-oxy groups are approximately coplanar with the attached benzene rings, with Cmeth-yl-O-C-C torsion angles ranging from -6.7 (2) to 5.07 (19)°. In the crystal, independent mol-ecules are linked together by O-H⋯N and O-H⋯O hydrogen bonds and a π-π inter-action [centroid-centroid distance of 3.6030 (9) Å], forming a dimer. The dimers are further linked by weak C-H⋯O inter-actions and another π-π inter-action [centroid-centroid distance of 3.9452 (9) Å] into layers lying parallel to the ab plane.


[In vitro activity of linezolid, moxifloxacin, levofloxacin, clindamycin and rifampin, alone and in combination, against Staphylococcus aureus and Staphylococcus epidermidis].
Information about the in vitro effect of combinations of anti-staphylococcal agents on staphylococci is scarce. The aim of the study was to evaluate the in vitro activity of linezolid, moxifloxacin, levofloxacin, clindamycin and rifampin, alone or in combination, against Staphylococcus spp. Two Staphylococcus aureus and two Staphylococcus epidermidis strains isolated from blood cultures were studied using the killing curve method. The combinations analyzed were linezolid+moxifloxacin, linezolid+levofloxacin, linezolid+clindamycin, linezolid+rifampin, moxifloxacin+rifampin, moxifloxacin+clindamycin, levofloxacin+rifampin and levofloxacin+clindamycin. The following concentrations (mg/l) were used: 8 and 16 for linezolid, 2 for moxifloxacin, 3 for levofloxacin, 2 for clindamycin and 2 and 5 for rifampin. The activity was considered synergistic when a reduction in growth of at least 2 log(10) was produced with the combination in comparison to the most active antibiotic alone; antagonistic when a growth of at least 2 log(10) was produced with the combination in comparison to the most active antibiotic alone; and indifferent if the variation was less than 1 log(10). Linezolid and clindamycin were bacteriostatic, while moxifloxacin and levofloxacin were bactericidal. Rifampin was bacteriostatic against S. aureus and bactericidal against S. epidermidis. Linezolid and clindamycin reduced the bactericidal activity of levofloxacin and moxifloxacin, however an antagonistic effect was only observed against S. aureus. Other combinations of linezolid, rifampin, clindamycin, levofloxacin or moxifloxacin were indifferent. Linezolid and clindamycin antagonize the bactericidal activity of fluorquinolones against staphylococci. There was no difference between any other combinations against either S. aureus or S. epidermidis.


Transfers to a public hospital. A prospective study of 467 patients.
In recent years there has been a dramatic increase in the number of patients transferred to public hospitals in the United States. We prospectively studied 467 medical and surgical patients who were transferred from the emergency departments of other hospitals in the Chicago area to Cook County Hospital and subsequently admitted. Eighty-nine percent of the transferred patients were black or Hispanic, and 81 percent were unemployed. Most (87 percent) were transferred because they lacked adequate medical insurance. Only 6 percent of the patients had given written informed consent for transfer. Twenty-two percent required admission to an intensive care unit, usually within 24 hours of arrival. Twenty-four percent were in an unstable clinical condition at the transferring hospital. The proportion of transferred medical-service patients who died was 9.4 percent, which was significantly higher than the proportion of medical-service patients who were not transferred (3.8 percent, P less than 0.01). There was no significant difference in the proportion of deaths on the surgical service between patients who were transferred and those who were not (1.5 vs. 2.4 percent). We conclude that patients are transferred to public hospitals predominantly for economic reasons, in spite of the fact that many of them are in an unstable condition at the time of transfer.


Effect of dietary fat intake and exercise on inflammatory mediators of the immune system in sedentary men and women.
Dietary fat intake and exercise affect the immune system. This study determined the changes in inflammatory components of the immune system in response to maximal exercise with three levels of dietary fat intake: 19%, 30%, and 50% of total calories. Five men and six women were randomly assigned to consume diets with 19% and 50% calories from fat for three weeks each, with a one-week washout. The habitual and washout diets were 30% calories from fat. At the beginning and the end of each diet, body composition and maximal exercise tests were performed. Blood samples were collected before and after exercise to determine the immunological parameters. The subject's energy intake was balanced to expenditure on the 30% and 50% diets, but was in negative balance on the 19% diet. Exercise led to significant increases in the concentrations of leukocytes, neutrophils, lymphocytes, monocytes, plasma tumour necrosis factor (TNF)-alpha, plasma interleukin (IL)-2, plasma soluble vascular cell adhesion molecule (sVCAM)-1, and the production of IL-1beta and IL-6 by peripheral blood mononuclear (PBMN) cells stimulated with lipopolysaccharide (LPS), irrespective of diets (p < 0.05). The 19% fat diet resulted in increased plasma soluble intercellular adhesion molecule (sICAM)-1 after exercise. Leukotriene (LT) B4 concentration released by neutrophils stimulated with LPS was higher in the 50% fat diet, compared to the lower fat diets, and the sICAM-1 production of neutrophils stimulated with LPS was significantly increased after exercise only with 30% fat diet. While a short, intense bout of exercise increased pro-inflammatory mediators of the immune system, decreasing fat intake to 19% on a caloric deficient diet caused a greater increase in plasma TNF-alpha, sVCAM-1 and sICAM-1 concentration than the 30% and 50% fat diets in male and female subjects. Increasing fat calories to 50% with caloric balance did not exacerbate pro-inflammatory mediators compared to a 30% fat diet.


Association of Air Pollution with a Urinary Biomarker of Biological Aging and Effect Modification by Vitamin K in the FLEMENGHO Prospective Population Study.
A recently developed urinary peptidomics biological aging clock can be used to study accelerated human aging. From 1990 to 2019, exposure to airborne particulate matter (PM) became the leading environmental risk factor worldwide. This study investigated whether air pollution exposure is associated with accelerated urinary peptidomic aging, independent of calendar age, and whether this association is modified by other risk factors. In a Flemish population, the urinary peptidomic profile (UPP) age (UPP-age) was derived from the urinary peptidomic profile measured by capillary electrophoresis coupled with mass spectrometry. UPP-age-R was calculated as the residual of the regression of UPP-age on chronological age, which reflects accelerated aging predicted by UPP-age, independent of chronological age. A high-resolution spatial-temporal interpolation method was used to assess each individual's exposure to PM10, PM2.5, black carbon (BC), and nitrogen dioxide (NO2). Associations of UPP-age-R with these pollutants were investigated by mixed models, accounting for clustering by residential address and confounders. Effect modifiers of the associations between UPP-age-R and air pollutants that included 18 factors reflecting vascular function, renal function, insulin resistance, lipid metabolism, or inflammation were evaluated. Direct and indirect (via UPP-age-R) effects of air pollution on mortality were evaluated by multivariable-adjusted Cox models. Among 660 participants (50.2% women; mean age: 50.7 y), higher exposure to PM10, PM2.5, BC, and NO2 was associated with a higher UPP-age-R. Studying effect modifiers showed that higher plasma levels of desphospho-uncarboxylated matrix Gla protein (dpucMGP), signifying poorer vitamin K status, steepened the slopes of UPP-age-R on the air pollutants. In further analyses among participants with dpucMGP ≥4.26μg/L (median), an interquartile range (IQR) higher level in PM10, PM2.5, BC, and NO2 was associated with a higher UPP-age-R of 2.03 [95% confidence interval (CI): 0.60, 3.46], 2.22 (95% CI: 0.71, 3.74), 2.00 (95% CI: 0.56, 3.43), and 2.09 (95% CI: 0.77, 3.41) y, respectively. UPP-age-R was an indirect mediator of the associations of mortality with the air pollutants [multivariable-adjusted hazard ratios from 1.094 (95% CI: 1.000, 1.196) to 1.110 (95% CI: 1.007, 1.224)] in participants with a high dpucMGP, whereas no direct associations were observed. Ambient air pollution was associated with accelerated urinary peptidomics aging, and high vitamin K status showed a potential protective effect in this population. Current guidelines are insufficient to decrease the adverse health effects of airborne pollutants, including healthy aging trajectories. https://doi.org/10.1289/EHP13414.


Predictors of functional improvement among patients with hip fracture at a rehabilitation ward.
To determine possible predictors of FIM scores in patients with hip fracture at discharge a prospective cohort study of 117 patients with either DHS or hip arthroplasty admitted to a rehabilitation service was done. They were classified into four subgroups of underweight (BMI < 18.5), normal (18.5 < BMI < 24.9), overweight (25 < BMI < 29.9) and obese (30 < BMI < 35). Functional evaluations using FIM score as well as sitting, standing, walking days and length of stay for each patient were assessed by a highly skilled therapist at rehabilitation admission; discharge and a post discharge follow up. Recovery was significant in terms of motor subscale. No significant correlation was evident between hospitalization and discharge time with respect to cognitive subscale. The study showed only the age and FIM score at hospitalization to be the independent predictors of total FIM score at discharge. Elevated BMI has not adverse effect on FIM gains in patients with hip fractures. Simple surgery methods such as DHS revealed earlier recovery time than complicated procedures.


Dyspareunia: an integrated approach to assessment and diagnosis.
Dyspareunia, or painful intercourse, is frequently referred to as the most common female sexual dysfunction. It can occur singly or be manifested in combination with other psychosexual disorders. Diagnosis of dyspareunia is appropriate in cases in which the experience of pain is persistent and severe. There has been little agreement concerning the origin of dyspareunia. Organic conditions and psychological variables have alternately been presented as major factors in causality. There is a presumed high incidence of physical disease associated with dyspareunia when compared with other female sexual dysfunctions. In the majority of cases, however, organic factors are thought to be rare in contrast with sexual issues and interpersonal or intrapsychic difficulties as a cause of continuing problems. The finding of an organic basis for dyspareunia does not rule out emotional or psychogenic causes. Thorough and extensive gynecologic and psychological evaluation is essential in cases of dyspareunia. The etiology of dyspareunia should be viewed on a continuum from primarily physical to primarily psychological with many women falling in the middle area.


Pentastomid nymph from the brain of a squirrel monkey (Saimiri sciureus). I. Morphology of the nymph.
A Pentastomid nymph of the genus Porocephalus was identified following its removal from the brain-meningeal interface of a squirrel monkey, Saimiri sciureus. It was characterized by two inner and two outer hooks adjacent to the mouth opening, the presence of accessory lobes (or spines) on the outer hooks, a vertical slit-like mouth opening surrounded by a U-shaped conformation of integument, and annulation of the body surface. Stigmata, representing the openings of integumental chloride cells, were present on the dorsum of the head and tail, on anterior aspects of annulae on the body, and on anterior and posterior edges of annulae located on the ventral surface of the tail. These openings were not present on integumental folds at the bases of the inner and outer hooks, on the dorsal aspect of the tail flap, or in the deep grooves separating annulae. Although it was not possible to determine the species, based on the number of annulae this specimen may represent P. stilesi.


Radiotherapy in the presence of contrast agents: a general figure of merit and its application to gold nanoparticles.
Delivering sufficient dose to tumours while sparing surrounding tissue is one of the primary challenges of radiotherapy, and in common practice this is typically achieved by using highly penetrating MV photon beams and spatially shaping dose. However, there has been a recent increase in interest in the possibility of using contrast agents with high atomic number to enhance the dose deposited in tumours when used in conjunction with kV x-rays, which see a significant increase in absorption due to the heavy element's high-photoelectric cross-section at such energies. Unfortunately, the introduction of such contrast agents significantly complicates the comparison of different source types for treatment efficacy, as the dose deposited now depends very strongly on the exact composition of the spectrum, making traditional metrics such as beam quality less valuable. To address this, a 'figure of merit' is proposed, which yields a value which enables the direct comparison of different source types for tumours at different depths inside a patient. This figure of merit is evaluated for a 15 MV LINAC source and two 150 kVp sources (both of which make use of a tungsten target, one with conventional aluminium filtration, while the other uses a more aggressive thorium filter) through analytical methods as well as numerical models, considering tissue treated with a realistic concentration and uptake ratio of gold nanoparticle contrast agents (10 mg ml (-1) concentration in 'tumour' volume, 10:1 uptake ratio). Finally, a test case of human neck phantom is considered with a similar contrast agent to compare the abstract figure to a more realistic treatment situation. Good agreement was found both between the different approaches to calculate the figure of merit, and between the figure of merit and the effectiveness in a more realistic patient scenario. Together, these observations suggest that there is the potential for contrast-enhanced kilovoltage radiation to be a useful therapeutic tool for a number of classes of tumour on dosimetric considerations alone, and they point to the need for further research in this area.


Family history and improving health.
This systematic review aimed to evaluate, within unselected populations: Question 1 (Q1) key elements of family history (FH) which usefully predict subsequent disease; Question 2 (Q2) the accuracy of reporting FH; Question 3 (Q3) the impact of FH-based risk information on the uptake of preventive interventions; Question 4 (Q4) the potential for harms associated with collecting cancer FH; Question 5 (Q5) factors that facilitate or hinder the collection of family history; and, Question 6 (Q6) future directions. MEDLINE, EMBASE, CINAHL, Cochrane Controlled Trial Register (CCTR), and PsycINFO were searched from 1995 to March 2, 2009 inclusive. Standard systematic review methodology was employed. Eligibility criteria varied by question, but overall, specified studies reported in English, excluded qualitative designs, and limited populations to those unselected for pre-existing risk (except for Q2). Study designs and outcomes varied by research question. One hundred and thirty-seven publications were eligible in total for this review. Q1: Key elements of FH: Eighty-nine studies were eligible for this question of which 59 reported FH and data on subsequent or current disease in subjects. The varied definitions of positive FH were consistently associated with elevated relative risks, but their value in predicting future risk or detecting current disease was difficult to assess without considering further information on other risk factors or the available preventive interventions. Q2: Accuracy of FH Reporting. Thirty-seven studies evaluated accuracy and showed relatively high specificity and low sensitivity across all disease categories. Q3: Uptake of preventive interventions. Two studies evaluated the impact of FH-based risk and the evidence was insufficient to establish any effect on change in clinical preventive behavior or uptake of interventions. Q4: Harms of FH taking. Three studies evaluated the impact of FH-based risk information on psychological outcomes and indicated no evidence of significant harm.Q5: Factors affecting FH collection: The evidence base for addressing Q5 is heterogeneous and limited to six studies exploring the association between various factors and family history reporting, documentation and discussion. Our review indicates: (Q1) Many FH definitions showed low discriminatory accuracy in predicting disease risk in individuals but further research is warranted; (Q2) accuracy of reporting is higher for relatives without, than those affected by, a given disease; (Q3) there is insufficient evidence to assess the effect of FH-based risk assessment on preventive behaviors; (Q4) there is limited evidence to assess whether the provision of FH-based personalized risk assessment results in adverse outcomes; (Q5) there is little evidence on factors affecting FH reporting and collection in primary care.


Effect of bisacodyl on gut lavage cleansing for colonoscopy.
The effect of 10 mg oral bisacodyl (n = 19) or placebo (n = 26) on colon cleansing with polyethylene glycol electrolyte lavage solution was studied during colonoscopy. Patient tolerance was evaluated by questionnaire. During colonoscopy endoscopists graded adequacy of cleansing and subjective amounts of residual fluid and recorded the actual amount of fluid suctioned. Patient tolerance and adequacy of cleansing were not different between bisacodyl and placebo. There was no difference in subjective and measured residual fluid between the two groups. Compared to placebo, 10 mg oral bisacodyl does not influence adequacy of cleansing, patient tolerance, or residual fluid following polyethylene glycol electrolyte lavage solution for colonoscopy. This suggests that the beneficial cleansing effects with bisacodyl for barium enema may occur by mechanisms other than simple fluid evacuation.


Characterization of a disulphide bridge-stabilized antigenic domain of tick-borne encephalitis virus structural glycoprotein.
Proteolytic digestion of purified whole tick-borne encephalitis virus or its isolated envelope glycoprotein (E) in the form of rosettes yields an Mr 9000 fragment that is resistant to further digestion and carries polyclonal and monoclonal antibody-defined antigenic determinants. In a denaturation/renaturation experiment it was demonstrated that the antigenic reactivity of this domain, which was lost upon reduction and carboxymethylation, could be regained if the reducing agent was dialysed out before carboxymethylation. By the use of [35S]cysteine-labelled E protein and amino acid analysis it was confirmed that the reacquisition of antigenic reactivity in the renaturation experiment was associated with the reformation of disulphide bridges, which apparently confer structural stability to this part of the molecule. By the experiments performed we have identified an independently folding antigenically active domain of the E protein that is stabilized by disulphide bridges and has a strong tendency for renaturation.


Seroprevalence of Hepatitis E Virus in Autoimmune Hepatitis Patients in the Netherlands.
In recent years chronic courses of hepatitis E virus (HEV) infection have been described in immunosuppressed individuals. This may implicate a potential role for HEV in the development of autoimmune diseases, including autoimmune hepatitis (AIH). Here we investigated the prevalence of HEV-antibodies in AIH patients in an endemic Central European country. HEV-specific immunoglobulin G (IgG) and HEV RNA were determined in 354 and 377 AIH patients, respectively. Clinical characteristics and disease outcome parameters were retrospectively collected. No HEV viraemic patients were identified in this cohort. A total of 106 AIH patients (29.9%) tested positive for anti-HEV IgG, and this figure was slightly higher compared to the prevalence in a reference cohort including 5,329 healthy Dutch blood donors (26.7%; P>0.05). This is the largest study on the association between HEV infection and AIH. Apparently silent HEV infection is present in a significant proportion of AIH patients, yet appears not to have significant clinical repercussions in this immune compromised group of patients. Nevertheless, since acute hepatitis E may present with histological and biochemical features of AIH, the possibility of a (concomitant) HEV infection should be considered in this category of patients.


Accuracy of Prader orchidometer in measuring testicular volume.
Seminiferous tubules comprise 80-90% of testicular mass. Thus, the testicular volume is believed to be an index of spermatogenesis. Therefore, accurate testicular volume is one way to assess testicular function. To determine the accuracy of Prader orchidometer for measuring the testicular volume by comparing the resultant measurement with the actual testicular volume in humans. The testicular volumes of 121 testes from 62 patients with prostate cancer (mean age 72.74 ± 9.38 years) were measured using Prader orchidometer before therapeutic bilateral orchidectomy. The actual testicular volumes were then determined by water displacement of the testis. The mean testicular volume of the 121 testes was 10.60 ± 3.5 ml and 13.26 ± 5.2 ml for water displacement and Prader orchidometer measurements, respectively. A strong correlation was found between the actual testicular volume and volumes obtained by Prader orchidometer ( r = 0.926, P = 0.0001). The Prader orchidometer however, over-estimated the mean actual testicular volume by 2.66 ± 2.37 ml (25.10%). The result of this study has shown that measuring the testicular volume by Prader orchidometer overestimates the actual testicular volume.