Beneficial effect of shikonin on experimental colitis induced by dextran sulfate sodium in BALB/c mice.
The naphthoquinone shikonin, a major component of the root of Lithospermum erythrorhizon, now is studied as an anti-inflammatory agent in the treatment of ulcerative colitis (UC). Acute UC was induced in Balb/C mice by oral administration of 5% dextran sodium sulfate (DSS). The disease activity index was evaluated, and a histologic study was carried out. Orally administered shikonin reduces induced UC in a dose-dependent manner, preventing the shortening of the colorectum and decreasing weight loss by 5% while improving the appearance of feces and preventing bloody stools. The disease activity index score was much lower in shikonin-treated mice than in the colitic group, as well as the myeloperoxidase activity. The expression of cyclooxygenase-2 was reduced by 75%, activation of NF-κB was reduced by 44%, and that of pSTAT-3 by 47%, as well as TNF-α, IL-1β, and IL-6 production. Similar results were obtained in primary macrophages culture. This is the first report of shikonin's ability to attenuate acute UC induced by DSS. Shikonin acts by blocking the activation of two major targets: NF-κB and STAT-3, and thus constitutes a promising potential therapeutic agent for the management of the inflammatory bowel disease.


Risk of bradykinin B2 receptor -58T/C gene polymorphism on hypertension: A meta-analysis.
The risk of bradykinin B2 receptor (BDKRB2)-58T/C gene polymorphism on hypertension remains controversial. The Cochrane Library, Chinese Biomedical Database, EBSCO, Embase, ISI, MEDLINE, and PubMed were retrieved, and relevant articles were selected. The significant association between BDKRB2 -58T/C gene polymorphism and risk of hypertension were found under C-allele comparison (odds ratio (OR): 1.22, 95% confidential intervals (CI): 1.05-1.42), recessive model (OR: 1.32, 95% CI: 1.07-1.64), dominant model (OR: 0.74, 95% CI: 0.58-0.94), homozygote model (OR: 1.66, 95% CI: 1.11-2.47) and heterozygote model (OR: 1.23, 95% CI: 1.06-1.43). The magnitude of the association between the BDKRB2-58T/C gene polymorphism and risk of hypertension was substantiated in Asians under C-allele comparison (OR: 1.24, 95% CI: 1.04-1.49), recessive model (OR: 1.39, 95% CI: 1.04-1.86), dominant model (OR: 0.72, 95% CI: 0.56-0.93), homozygote model (OR: 1.78, 95% CI: 1.09-2.90) and heterozygote model (OR: 1.26, 95% CI: 1.07-1.49). No publication bias was found in the meta-analysis. The meta-analysis suggested -58C allele and -58CC genotype increase the risk of hypertension in Asians and African-Americans. Inversely, -58TT genotype decreases the risk of hypertension in Asians and African-Americans.


Complex wavefront shaping for optimal depth-selective focusing in optical coherence tomography.
We report on an approach to exploit multiple light scattering by shaping the incident wavefront in optical coherence tomography (OCT). Most of the reflected signal from biological tissue consists of multiply scattered light, which is regarded as noise in OCT. A digital mirror device (DMD) is utilized to shape the incident wavefront such that the maximal energy is focused at a specific depth in a highly scattering sample using a coherence-gated reflectance signal as feedback. The proof-of-concept experiment demonstrates that this approach enhances depth-selective focusing in the presence of optical inhomogeneity, and thus extends the penetration depth in spectral domain-OCT (SD-OCT).


Exogenous sex hormone exposure and the risk for major malformations.
Several studies have suggested that maternal use of exogenous sex hormones during early pregnancy may be associated with various congenital malformations. We conducted a case-control study of first-trimester sex hormone exposure among mothers of 1,091 infants with Down syndrome or at least one of 11 major malformations. For each malformation category, the infants with other malformations served as the control group. Associations were found between esophageal atresia and any sex hormone exposure (odds ratio, 2.84); progestins (odds ratio, 2.87); nonspecified sex hormones (odds ratio, 2.99); and hormonal pregnancy tests (odds ratio, 2.81). We found no potentially confounding variables for these associations. We found no statistically significant association between any malformation category and oral contraceptive exposure. Even if the relationship between esophageal atresia and noncontraceptive sex hormone exposure is causal, the absolute risk would be low, on the order of six per 10,000 exposed live births.


Those in the shadow of the pandemic: impacts of the COVID-19 outbreak on the mental health of children with neurodevelopmental disorders and their parents.
This study aimed to investigate the emotional and behavioral responses of children with neurodevelopmental disorders and their parents during the recent novel coronavirus disease (COVID-19) pandemic and the associated factors. Our study included 299 children and adolescents with neurodevelopmental disorders and 299 mothers or fathers. Participant groups were as follows: autism spectrum disorder (n = 131, 43.8%); intellectual disability (n = 103, 34.4%); specific learning disorder (n = 46, 15.4%); and communication disorder (n = 19, 6.4%). A data form was created to investigate the emotional, behavioral, sleep problems, and appetite changes of the cases, and it was adapted for online application and conveyed to the parents in the form of emails. Our study indicated that children and adolescents' emotional problems were 44.5%, behavioral problems 33.4%, sleep problems 65.2%, and appetite problems 32.4%. Irritability (35.5%), hyperactivity (37.8%), stereotyped behavior (29.8%), delayed sleep phase (51.5%) were the most common problems reported by the parents. The frequencies of emotional and behavioral problems in the ASD group were higher than in the other groups (p < .05). In addition, the Hospital Anxiety Depression Scale (HADS) was used to determine the parents' anxiety and depression symptoms. Mean HADS anxiety and depression scores of parents were 8.5 ± 4.3 and 7.8 ± 4.2, respectively. Our study demonstrated that the COVID-19 pandemic and lockdown negatively affected children with neurodevelopmental disorders and their parents in many areas. It is necessary that these children and their families are evaluated and supported by local professionals, as the ongoing pandemic can exacerbate the current challenges. The findings of our study reflect the early period of the pandemic. For this reason, longitudinal studies about the long-term consequences of the pandemic are needed.


Computed tomographic pulmonary angiography for diagnosis of invasive mold diseases in patients with hematological malignancies.
Invasive mold diseases (IMDs) of the lung remain a challenge for immunocompromised patients. Although timely diagnosis and treatment are crucial for the outcome of the infection, the poor sensitivity of microbiological techniques and the limited specificity of chest high-resolution computed tomography (HRCT) often delay definitive diagnosis of these infections. To explore the diagnostic utility of computed tomographic pulmonary angiography (CTPA) for detecting angioinvasive patterns of pulmonary infection, we performed a single-center, prospective, nonrandomized trial involving 36 patients with hematological malignancies who had clinical suspicion of IMD, as defined by European Organization for Research and Treatment of Cancer/Mycosis Study Group diagnostic criteria. We found that 5 of 5 patients with proven IMD had CTPA-positive findings consistent with interruption of the arterial vessels (concordance, 100%). CTPA findings were positive in 5 of 7 patients with probable IMD (findings for 2 were considered false negative because lesions were too small or not evaluable). In 15 of 24 patients with a final diagnosis of possible IMD, CTPA findings were negative for 14 patients and were positive for 1 patient, who had septic emboli associated with Staphylococcus aureus bacteremia. CTPA findings were positive in the remaining 9 patients with a final diagnosis of possible IMD at the end of the study. We conclude that CTPA appears to be a promising tool to exclude the diagnosis of IMD in high-risk patients without specific findings on HRCT scans, and it is most useful in the presence of well-circumscribed lesions in which there is suspicion for IMD.


Open aortic valvotomy for congenital aortic stenosis. Late results.
Forty-nine consecutive patients, aged 2 to 28 years, were followed after open aortic valvotomy. Three late deaths occurred in relation to reoperation. Seventeen reoperations were performed 2 to 14 years after valvotomy for severe stenosis in 12 patients, aortic regurgitation in three patients, and aortic stenosis and regurgitation in two patients. Among the 12 patients who required reoperation for severe obstruction, five aged over 19 years had calcified valves with normal aortic roots and valve replacement was simple. Seven had tunnel obstruction with a hypoplastic aortic root, constituting a difficult surgical problem, and necessitating total aortic root replacement in four. The postoperative course after simple aortic valvotomy is determined by several factors; the basic pathological form of the obstruction is the most important. Those who present in the first decade with lumpy valves and small aortic roots tend to form a diffuse tunnel obstruction when residual stenosis remains after valvotomy; older patients with pliable domed valves slowly develop calcified cusps and present less problems as the aortic root is usually a good size. Although aortic valvotomy offers good early results with a low mortality, it should be regarded as palliative as all patients will ultimately require reoperation. Younger patients with lumpy valves and a small aortic root have more problems and may require different initial management.


[Development of glands of internal secretion in birds and immaturely-born mammals].
Certain general problems on foundation of the hormonal regulation mechanisms during the prenatal and early postnatal ontogenesis are discussed basing on the authors' own results and on the literature data. They concern development of the hypophysis and peripheral target-glands in immaturely-bone Mammalia and fowls. The data on foundation of the endocrine glands functional activity are compared in rats and hens. The notion on a relative autonomous hormonal function of the peripheral endocrine glands at early stages of ontogenesis is motivated.


Incidence of meningitis and of death from all causes among users of cochlear implants in the United Kingdom.
During 2002, there was an increase in reports of bacterial meningitis among people with cochlear implants in Europe and North America. One model of implant, which included a space-occupying 'positioner', was recalled. Implantation of a positioner was shown to be a risk factor for meningitis among children in the United States. The situation in the United Kingdom was not known. We ascertained the cohort of people who had received cochlear implants with intra-cochlear electrodes in UK hospitals prior to 1 October 2002 and were permanently resident in the United Kingdom. We compared the incidence of meningitis, and the causes and incidence of death from all causes, between the cohort and reference populations. Of 1851 children (66 with positioners), none had contracted meningitis. Neither the incidence rate of meningitis, nor the cumulative mortality from all causes, differed significantly between implanted children and values expected for the general population. Of 1779 adults (139 with positioners), five had contracted meningitis with three fatalities. No case of meningitis involved a positioner and four of the cases, including the fatalities, possessed risk factors unrelated to implantation. Although the incidence rate of meningitis was significantly higher in implanted adults than the general population, cumulative mortality from all causes was never higher, and was significantly lower at some time points after implantation. Specific evidence of the association between bacterial meningitis and implantation with a positioner that arose in the United States and mainland Europe during 2002 has not been found in the United Kingdom.


[Thrombosis of the portal vein].
Thrombosis of the portal vein is relatively rare disease which presents some difficulties to diagnose in patients with it. It is discussed in the article the case of thrombosis of the portal vein diagnosed after the patient's death.


The analysis and forecasting of male cycling time trial records established within England and Wales.
The format of cycling time trials in England, Wales and Northern Ireland, involves riders competing individually over several fixed race distances of 10-100 miles in length and using time constrained formats of 12 and 24 h in duration. Drawing on data provided by the national governing body that covers the regions of England and Wales, an analysis of six male competition record progressions was undertaken to illustrate its progression. Future forecasts are then projected through use of the Singular Spectrum Analysis technique. This method has not been applied to sport-based time series data before. All six records have seen a progressive improvement and are non-linear in nature. Five records saw their highest level of record change during the 1950-1969 period. Whilst new record frequency generally has reduced since this period, the magnitude of performance improvement has generally increased. The Singular Spectrum Analysis technique successfully provided forecasted projections in the short to medium term with a high level of fit to the time series data.


The exogenous administration of basic fibroblast growth factor to regenerating skeletal muscle in mice does not enhance the process of regeneration.
The effects, in vivo, of the exogenous administration of bFGF on myogenesis of regenerating skeletal muscle was assessed either morphometrically or autoradiographically in three separate models of muscle injury in mice: crush-injured, denervated, and dystrophic (mdx) muscles. The bFGF was administered at various doses and different time schedules, sometimes in combination with heparin, into injured tibialis anterior muscles of mice. Delivery of the bFGF was either by direct intramuscular injection or by the sustained release from 888polymers (Hydron or Elvax) implanted into the muscles. The bioactivity of bFGF was confirmed in vitro by measuring its ability to stimulate the proliferation of BALB/c-3T3 fibroblasts and muscle precursor cell lines. The ability of bFGF to stimulate angiogenesis in vivo was confirmed by the implantation of controlled-release polymers containing bFGF into the normally avascular cornea of rats. No measurable effect of bFGF was seen in any of the models of skeletal muscle injury under these experimental conditions, indicating that the availability of biologically active bFGF is not a limiting factor in the regeneration of skeletal muscle following injury.


Ankle and knee coupling in patients with spastic diplegia: effects of gastrocnemius-soleus lengthening.
Empirical observations of subjects with an equinus gait have suggested that there is coupled motion between the ankle and knee such that, during single-limb stance, the ankle moves into equinus as the knee extends. Since the gastrocnemius-soleus muscle-tendon unit spans both joints, we hypothesized that this muscle-tendon unit may be responsible for the coupling and that lengthening of the gastrocnemius-soleus muscle alone would result in greater ankle dorsiflexion as well as greater knee extension in single-limb stance, effectively uncoupling these joints. The concept that gastrocnemius-soleus lengthening may promote knee extension is counter to the popular notion that crouch gait may result if the hamstrings are not lengthened concomitantly. A retrospective review identified thirty-four subjects with specific kinematic characteristics of equinus gait, and their gait was compared with that of normal children. Of the thirty-four subjects, eleven (twenty-two limbs) subsequently underwent isolated midcalf lengthening of the gastrocnemius and soleus muscles with use of a recession technique. Gait analysis including joint kinematics and joint kinetics, electromyography, and physical examination were performed to test the hypothesis. We found that, unlike the normal subjects, the patients with an equinus gait pattern had a positive correlation (r = 0.7) between ankle and knee motion during single-limb stance. As hypothesized, ankle plantar flexion occurred while the knee moved into extension during single-limb stance. Calculations of the lengths of the gastrocnemius-soleus muscle-tendon units showed them to be short throughout the gait cycle (p < 0.0001). After gastrocnemius-soleus recession, peak ankle dorsiflexion (p < 0.001) and peak ankle power (p < 0.001) shifted to occur later in stance than they did in the preoperative gait cycle. Furthermore, the magnitude of peak power increased (p < 0.001) in late stance despite the added length of the gastrocnemius-soleus muscle-tendon unit. The electromyographic amplitude of the gastrocnemius-soleus was reduced during loading (p < 0.02), and this finding, together with the kinetic changes, suggested that muscle tension was reduced. Changes at the knee were less pronounced but included greater knee extension at foot contact (p < 0.01). No increase in the knee flexion angle or extension moment occurred in midstance after the surgery. Patients with an equinus gait pattern function with a shortened gastrocnemius-soleus muscle-tendon unit, and this results in coupled motion between the ankle and knee during single-limb stance. Lengthening, with use of a recession technique, shifted ankle power generation and dorsiflexion to a later time in stance with no tendency to increase midstance knee flexion. Knee extension did increase at foot contact, but excessive midstance knee flexion persisted and was likely due to concomitant contracture of the hamstrings.


D-dimer for risk stratification and antithrombotic treatment management in acute coronary syndrome patients: asystematic review and metanalysis.
Data on the prognostic role of D-dimer in patients with acute coronary syndrome (ACS) are controversial. Our aim was to summarize current evidence on the association between D-dimer levels and short/long-term poor prognosis of ACS patients. We also investigated the association between D-dimer and no-reflow phenomenon. Systematic review and metanalysis of observational studies including ACS patients and reporting data on D-dimer levels. PubMed and SCOPUS databases were searched. Data were combined with hazard ratio (HR) and metanalysed. The principal endpoint was a composite of cardiovascular events (CVEs) including myocardial infarction, all-cause and cardiovascular mortality. Overall, 32 studies included in the systematic review with 28,869 patients. Of them, 6 studies investigated in-hospital and 26 studies long-term outcomes. Overall, 23 studies showed positive association of high D-dimer levels with CVEs. D-dimer levels predicted poor prognosis in all studies reporting in-hospital outcomes. Five studies satisfied inclusion criteria and were included in the metanalysis, with a total of 8616 patients. Median follow-up was 13.2 months with 626 CVEs. The pooled HR for D-dimer levels and CVEs was 1.264 (95% CI 1.134-1.409). Five out of 7 studies (4195 STEMI patients) investigating the association between D-dimer levels and no-reflow showed a positive correlation of D-dimer levels with no-reflow. In patients with ACS, D-dimer was associated with higher in-hospital and short/long-term complications. D-dimer was also higher in patients with no-reflow phenomenon. The use of D-dimer may help to identify patients with residual thrombotic risk after ACS. The review protocol was registered in PROSPERO International Prospective Register of Systematic Reviews: CRD42021267233 .


AMP-activated protein kinase and muscle glucose uptake.
The AMP-activated protein kinase (AMPK) is an enzyme that is activated in situations where there are changes in the cellular energy status such as muscle contraction and hypoxia. AMPK can also be pharmacologically activated by the compound 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) and the antidiabetic agent metformin. Several studies support the hypothesis that AMPK plays an important role in the stimulation of muscle glucose uptake by these physiological and pharmacological stimuli. In isolated rat muscles, activation of AMPK is associated with increases in glucose uptake through an insulin-independent mechanism. Studies done in rodents have shown that the activation of AMPK by AICAR is accompanied by decreases in blood glucose concentrations, in part due to enhanced muscle glucose uptake. Similar to exercise, AICAR not only directly stimulates glucose uptake into the skeletal muscle, but also enhances insulin sensitivity. The activation of AMPK and associated increases in muscle glucose uptake are affected by factors such as glycogen content, exercise training and fibre type. The effects of AMPK on muscle glucose uptake makes this protein a promising pharmacological target for the treatment of type 2 diabetes.


Failure to report poor care as a breach of moral and professional expectation.
Cases of poor care have been documented across the world. Contrary to professional requirements, evidence indicates that these sometimes go unaddressed. For patients, the outcomes of this inaction are invariably negative. Previous work has either focused on why poor care occurs and what might be done to prevent it, or on the reasons why those who are witness to it find it difficult to raise their concerns. Here, we build on this work but specifically foreground the responsibilities of registrants and students who witness poor care. Acknowledging the challenges associated with raising concerns, we make the case that failure to address poor care is a breach of moral expectation, professional requirement and, sometimes, legal frameworks. We argue that reporting will be more likely to take place if those who wish to enter the profession have a realistic view of the challenges they may encounter. When nurses are provided with robust and applied education on ethics, when "real-world" cases and exemplars are used in practice and when steps are taken to develop and encourage individual moral courage, we may begin to see positive change. Ultimately however, significant change is only likely to take place where practice cultures invite and welcome feedback, promote critical reflection, and where strong, clear leadership support is shown by those in positions of influence across organisations.


Does Living near Trees and Other Vegetation Affect the Contemporaneous Odds of Asthma Exacerbation among Pediatric Asthma Patients?
Vegetation may influence asthma exacerbation through effects on aeroallergens, localized climates, air pollution, or children's behaviors and stress levels. We investigated the association between residential vegetation and asthma exacerbation by conducting a matched case-control study based on electronic health records of asthma patients, from the Children's Hospital of Philadelphia (CHOP). Our study included 17,639 exacerbation case events and 34,681 controls selected from non-exacerbation clinical visits for asthma, matched to cases by age, sex, race/ethnicity, public payment source, and residential proximity to the CHOP main campus ED and hospital. Overall greenness, tree canopy, grass/shrub cover, and impervious surface were assessed near children's homes (250 m) using satellite imagery and high-resolution landcover data. We used generalized estimating equations to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between each vegetation/landcover measure and asthma exacerbation, with adjustment for seasonal and sociodemographic factors-for all cases, and for cases defined by diagnosis setting and exacerbation frequency. Lower odds of asthma exacerbation were observed in association with greater levels of tree canopy near the home, but only for children who experienced multiple exacerbations in a year (OR = 0.94 per 10.2% greater tree canopy coverage, 95% CI = 0.90-0.99). Our findings suggest possible protection for asthma patients from tree canopy, but differing results by case frequency suggest that potential benefits may be specific to certain subpopulations of asthmatic children.


Warfarin-related bleeding following open heart surgery in Nairobi.
To review anticoagulant-related bleeding in heart valve patients on warfarin at the Kenyatta National Hospital and to determine the variables associated with anticoagulant-related bleeding. A combined retrospective and prospective review of patients operated at the Kenyatta National Hospital. Retrospective period from June 1973 to 31st July 1997, while prospective period from August 1st 1997 to June 1st 2000. Surgical Outpatient Department, Kenyatta National Hospital, Nairobi. Linearised occurrence rate of anticoagulant-related bleeding and the one- five- and ten- year bleed free rates. Independent risk factors associated with anticoagulant-related bleeding determined using Cox's proportional hazards. Thirty one bleeding episodes were recorded in 150 patients followed up for a total of 745 patient-years. The risk of occurrence of the first bleed was 16.0%; while the risk of a subsequent bleed increased thereafter with a 16.7%, 50% and 50% risk after the first, second and third bleeds respectively. The linearised rate for minor anticoagulant-related bleed was 4.16% per patient per year however, half the bleeds occurred within the first year of valve implantation or previous bleeding episode. The one-, five- and ten-year bleed free rates for all valves combined were 93%, 85% and 78% respectively. There was no statistically signicant difference between the curves comparing the bleed free rates for the first and second bleeding episodes (p=0.098). The number of valves implanted, the site of implant and the time to the occurrence of bleeding were independent risk factors associated with the occurrence of bleeding (p<.05). The occurrence of anticoagulant-related bleeding is relatively common being slightly above the internationally reported range. Most episodes of bleeding will occur within one year of hospital discharge or the previous bleeding episode. The risk of another bleeding episode occurring increases with each episode with up to a 50% risk of re-bleed after the second bleeding episode. In this study, the number of valves implanted, their position and the time of occurrence of the bleed were risk factors to the occurrence of bleeding.


[Mechanics as a basic physical discipline in orthopedics and traumatology].
Among the various relationships between fields of the clinical medicine and fields of physics, the relationship between orthopaedics and traumatology and mechanics is of a particularly close and manifold nature. We try to present in this contribution a description of the physical principles of mechanics and to give a survey of its various fields of application in orthopaedic and traumatologic basic research.


Transient expression of doublecortin during adult neurogenesis.
During development of the central nervous system, expression of the microtubule binding protein doublecortin (DCX) is associated with migration of neuroblasts. In addition to this developmental role, expression of DCX remains high within certain areas of the adult mammalian brain. These areas, mainly the dentate gyrus and the lateral ventricle wall in conjunction with the rostral migratory stream and olfactory bulb, retain the capacity to generate new neurons into adulthood. Adult neurogenesis is typically detected by incorporation of bromodeoxyuridine (BrdU) into dividing cells and colabeling of BrdU-positive cells with markers for mature neurons. To elucidate whether DCX could act as an alternative indicator for adult neurogenesis, we investigated the temporal expression pattern of DCX in neurogenic regions of the adult brain. Analysis of newly generated cells showed that DCX is transiently expressed in proliferating progenitor cells and newly generated neuroblasts. As the newly generated cells began expressing mature neuronal markers, DCX immunoreactivity decreased sharply below the level of detection and remained undetectable thereafter. The transient expression pattern of DCX in neuronal committed progenitor cells/neuroblasts indicates that DCX could be developed into a suitable marker for adult neurogenesis and may provide an alternative to BrdU labeling. This assumption is further supported by our observation that the number of DCX-expressing cells in the dentate gyrus was decreased with age according to the reduction of neurogenesis in the aging dentate gyrus previously reported.


Coupled differentiation and division of embryonic stem cells inferred from clonal snapshots.
The deluge of single-cell data obtained by sequencing, imaging and epigenetic markers has led to an increasingly detailed description of cell state. However, it remains challenging to identify how cells transition between different states, in part because data are typically limited to snapshots in time. A prerequisite for inferring cell state transitions from such snapshots is to distinguish whether transitions are coupled to cell divisions. To address this, we present two minimal branching process models of cell division and differentiation in a well-mixed population. These models describe dynamics where differentiation and division are coupled or uncoupled. For each model, we derive analytic expressions for each subpopulation's mean and variance and for the likelihood, allowing exact Bayesian parameter inference and model selection in the idealised case of fully observed trajectories of differentiation and division events. In the case of snapshots, we present a sample path algorithm and use this to predict optimal temporal spacing of measurements for experimental design. We then apply this methodology to an in vitro dataset assaying the clonal growth of epiblast stem cells in culture conditions promoting self-renewal or differentiation. Here, the larger number of cell states necessitates approximate Bayesian computation. For both culture conditions, our inference supports the model where cell state transitions are coupled to division. For culture conditions promoting differentiation, our analysis indicates a possible shift in dynamics, with these processes becoming more coupled over time.


Nuclear architecture dictates HIV-1 integration site selection.
Long-standing evidence indicates that human immunodeficiency virus type 1 (HIV-1) preferentially integrates into a subset of transcriptionally active genes of the host cell genome. However, the reason why the virus selects only certain genes among all transcriptionally active regions in a target cell remains largely unknown. Here we show that HIV-1 integration occurs in the outer shell of the nucleus in close correspondence with the nuclear pore. This region contains a series of cellular genes, which are preferentially targeted by the virus, and characterized by the presence of active transcription chromatin marks before viral infection. In contrast, the virus strongly disfavours the heterochromatic regions in the nuclear lamin-associated domains and other transcriptionally active regions located centrally in the nucleus. Functional viral integrase and the presence of the cellular Nup153 and LEDGF/p75 integration cofactors are indispensable for the peripheral integration of the virus. Once integrated at the nuclear pore, the HIV-1 DNA makes contact with various nucleoporins; this association takes part in the transcriptional regulation of the viral genome. These results indicate that nuclear topography is an essential determinant of the HIV-1 life cycle.


Pharmacotherapy for posttraumatic stress disorder.
Posttraumatic stress disorder (PTSD) is a prevalent and disabling disorder. By definition prior psychological trauma plays a causal role in the disorder, and psychotherapy is a widely accepted intervention. Nevertheless there is growing evidence that PTSD is characterized by specific psychobiological dysfunctions, and this has contributed to a growing interest in the use of medication in its treatment. The authors aimed to undertake a systematic review of randomized controlled trials (RCTs) of the pharmacotherapy of posttraumatic stress disorder (PTSD) following the guidelines and using the software of the Cochrane Collaboration, and to provide an estimate of the effects of medication in this disorder. Secondary objectives were to explore questions about whether particular classes of medication are more effective and/or acceptable than others in the treatment of PTSD, and about which factors (clinical and methodological) predict response to pharmacotherapy. Studies of the pharmacotherapy of PTSD were identified using literature searches of MEDLINE (1966 to 1999, using the textwords posttraumatic, post-traumatic, medication, pharmacotherapy) and other electronic databases (PSYCLIT; National PTSD Center Pilots database; Dissertation Abstracts; Cochrane Collaboration Depression, Anxiety & Neurosis Controlled Trials Register). In addition, published and unpublished RCTs were requested from PTSD researchers and pharmaceutical companies. An initial broad strategy was undertaken to find not only RCTs, but also open-label trials and reviews of the pharmacotherapy of PTSD; additional studies were sought in reference lists of retrieved articles and included studies in any language. All RCTs of PTSD (including both placebo controlled and comparative trials), whether published or unpublished, but completed prior to the end of 1999 were considered for the review. Selected RCTs were independently assessed and collated by 2 raters, and Review Manager (RevMan) software was used to capture data on treatment response and PTSD symptom ratings. Ratings of subtypes of PTSD symptoms (intrusive/re-experiencing, avoidant/numbing, hyperarousal), of comorbid symptoms (depression, anxiety), and of quality of life were included where possible. A range of additional information, which may explain possible clinical and methodological heterogeneity amongst the trials, was also captured. Summary statistics for dichotomous and continous measures were calculated, heterogeneity was assessed, and subgroup/sensitivity analyses undertaken. 15 short-term (12 weeks or less) RCTs were found, of which 9 had sufficient data for inclusion in the analysis. Methodological limitations were particularly apparent in early work; these included short (5 weeks or less) duration of trials and a reliance on self-report scales (rather than use of standardized clinician-rated scales). Despite these and other potentially important differences between the trials, many trials demonstrated efficacy for medication over placebo. Summary statistics were calculated for the Clinical Global Impressions scale change item (CGI-C) or close equivalent from 10 sets of data including various antidepressants and other agents - the proportion of non-responders was lower in the pharmacotherapy group than in the control group (relative risk (95% CI) = 0.72 (0.64, 0.83)). Similarly, summary statistics for the intrusion, avoidance and total scales of the Impact of Events Scale (IES) from 4sets of data again including various agents showed a statistically (and clinically) significant difference between medication and placebo (Weighted Mean Difference (95% CI) = -3.81 (-6.72,-0.91), -3.31(-5.24,-1.37), -7.18 (-11.86,-2.50) respectively). Medication treatments can be effective in PTSD, acting to reduce its core symptoms, and should be considered as part of the treatment of this disorder. The existing evidence base does not provide sufficient data to suggest particular predictors of response to treatment, or to demonstrate that any particular class of medication is more effective or better tolerated than any other. However, the largest trials showing efficacy to date have been with the SSRIs, and in contrast, there have been negative studies of some agents. Given the high prevalence and enormous personal and societal costs of PTSD, there is a need for additional controlled trials in this area. Additional questions for future research include the effects of medication on quality of life in PTSD, appropriate dose and duration of medication, the use of medication in different trauma groups, in pediatric and geriatric subjects, and the value of early (prophylactic), combined (with psychotherapy), and long-term (maintenance) medication treatment.


Homocysteine and cognitive function in the Sacramento Area Latino Study on Aging.
Elevated plasma homocysteine (hyperhomocysteinemia), an independent risk factor for vascular disease, has been reported to be inversely correlated with objective measures of cognitive function in patients with Alzheimer disease and in community-dwelling older adults. We evaluated the cross-sectional relation between total plasma homocysteine concentration and cognitive function in elderly Latinos (aged > or = 60 y; n = 1789) participating in the Sacramento Area Latino Study on Aging. Global cognitive function was assessed by using the Modified Mini-Mental State Examination, and specific cognitive functions were assessed by using 6 instruments developed for cross-cultural and multilingual neuropsychological evaluation of older persons. Associations between the cognitive function scores and total plasma homocysteine concentrations were then measured by multiple regression analysis with control for potential confounding by nutrient status (red blood cell folate, plasma vitamin B-12), kidney function (serum creatinine), demographic variables (age, sex, education, acculturation), and depressive symptoms. Modest inverse associations were found between homocysteine concentrations and several indexes of cognitive function, including the global Modified Mini-Mental State Examination assessment and the picture-association, verbal attention-span, and pattern-recognition tests (P < or = 0.05). Demographic variables, particularly age and education, were more strongly associated with cognitive function scores than was homocysteine. Homocysteine is a modest independent predictor of cognitive function in community-dwelling elderly Latinos. Reducing plasma homocysteine concentrations by administering B-vitamin supplements may provide some protection against cognitive decline in this and other elderly populations, but the effect may be limited.


Utilizing alkoxyphenyl substituents for side-chain engineering of efficient benzo[1,2-b:4,5-b']dithiophene-based small molecule organic solar cells.
A new two-dimensional (2D) conjugated small molecule, namely DCA3TBDTP, with an alkoxyphenyl substituted benzo[1,2-b:4,5-b']dithiophene (BDT) unit as the central core, octyl cyanoacetate as the end-capped groups and terthiophene as the π-linked bridge, was designed and synthesized for solution-processed organic solar cells (OSCs) as an electron donor material, in which an alkoxyphenyl group was introduced as a weak electron-donating side chain of the BDT moiety. The DCA3TBDTP molecule exhibited good solubility, a deep highest occupied molecular orbital (HOMO) level (-5.25 eV), an appropriate optical band-gap (1.82 eV) and a high decomposition temperature (362 °C). By applying the simple solution spin-coating fabrication process, the bulk heterojunction (BHJ) OSCs based on DCA3TBDTP and [6,6]-phenyl-C61-butyric acid methyl ester (PC61BM) exhibited a good power conversion efficiency (PCE) of 4.51% with a high open-circuit voltage (Voc) of 0.90 V when thermal annealing at only 70 °C.


Ancient Venom Systems: A Review on Cnidaria Toxins.
Cnidarians are the oldest extant lineage of venomous animals. Despite their simple anatomy, they are capable of subduing or repelling prey and predator species that are far more complex and recently evolved. Utilizing specialized penetrating nematocysts, cnidarians inject the nematocyst content or "venom" that initiates toxic and immunological reactions in the envenomated organism. These venoms contain enzymes, potent pore forming toxins, and neurotoxins. Enzymes include lipolytic and proteolytic proteins that catabolize prey tissues. Cnidarian pore forming toxins self-assemble to form robust membrane pores that can cause cell death via osmotic lysis. Neurotoxins exhibit rapid ion channel specific activities. In addition, certain cnidarian venoms contain or induce the release of host vasodilatory biogenic amines such as serotonin, histamine, bunodosine and caissarone accelerating the pathogenic effects of other venom enzymes and porins. The cnidarian attacking/defending mechanism is fast and efficient, and massive envenomation of humans may result in death, in some cases within a few minutes to an hour after sting. The complexity of venom components represents a unique therapeutic challenge and probably reflects the ancient evolutionary history of the cnidarian venom system. Thus, they are invaluable as a therapeutic target for sting treatment or as lead compounds for drug design.


Earliest expansion of animal husbandry beyond the Mediterranean zone in the sixth millennium BC.
Since their domestication in the Mediterranean zone of Southwest Asia in the eighth millennium BC, sheep, goats, pigs and cattle have been remarkably successful in colonizing a broad variety of environments. The initial steps in this process can be traced back to the dispersal of farming groups into the interior of the Balkans in the early sixth millennium BC, who were the first to introduce Mediterranean livestock beyond its natural climatic range. Here, we combine analysis of biomolecular and isotopic compositions of lipids preserved in prehistoric pottery with faunal analyses of taxonomic composition from the earliest farming sites in southeast Europe to reconstruct this pivotal event in the early history of animal husbandry. We observe a marked divergence between the (sub)Mediterranean and temperate regions of Southeast Europe, and in particular a significant increase of dairying in the biochemical record coupled with a shift to cattle and wild fauna at most sites north of the Balkan mountain range. The findings strongly suggest that dairying was crucial for the expansion of the earliest farming system beyond its native bioclimatic zone.


ARDB--Antibiotic Resistance Genes Database.
The treatment of infections is increasingly compromised by the ability of bacteria to develop resistance to antibiotics through mutations or through the acquisition of resistance genes. Antibiotic resistance genes also have the potential to be used for bio-terror purposes through genetically modified organisms. In order to facilitate the identification and characterization of these genes, we have created a manually curated database--the Antibiotic Resistance Genes Database (ARDB)--unifying most of the publicly available information on antibiotic resistance. Each gene and resistance type is annotated with rich information, including resistance profile, mechanism of action, ontology, COG and CDD annotations, as well as external links to sequence and protein databases. Our database also supports sequence similarity searches and implements an initial version of a tool for characterizing common mutations that confer antibiotic resistance. The information we provide can be used as compendium of antibiotic resistance factors as well as to identify the resistance genes of newly sequenced genes, genomes, or metagenomes. Currently, ARDB contains resistance information for 13,293 genes, 377 types, 257 antibiotics, 632 genomes, 933 species and 124 genera. ARDB is available at http://ardb.cbcb.umd.edu/.


Age-Related Changes in the Clinical Phenotype of Compressive Optic Neuropathy in Thyroid Eye Disease.
This study compares the age-related clinical features of thyroid eye disease-compressive optic neuropathy (TED-CON) to those with noncompressive disease (TED-NC). A retrospective case series review of 165 orbits from 121 patients with TED-CON were compared with an age- and gender-matched cohort of 88 orbits from 44 patients with TED-NC with institutional review board approval. Clinical features including exophthalmos, dyschromatopsia, restricted ocular motility, visual acuity, and mean deviation on 24-2 Humphrey Visual Field were compared in 5 age groups. A previously validated formula, the Columbia TED-CON Diagnostic formula, used to mathematically predict the presence or absence of compressive optic neuropathy was applied, and the sensitivity and specificity of the formula was measured in each age group. Exophthalmos, dyschromatopsia, restricted ocular motility, and mean deviation on 24-2 Humphrey Visual Field vary significantly across age groups in patients with TED-CON. Conversely, only visual acuity and dyschromatopsia vary significantly across age groups in patients with TED-NC. There was a significant difference between the TED-CON and the TED-NC groups when comparing the 2 groups by decade. The Columbia TED-CON Diagnostic formula had high sensitivity and specificity (74-90%) in all age groups. This is the first study to date demonstrating the age-related variability of clinical characteristics in a large series of patients with either TED-CON or TED-NC. The clinical phenotype of TED-CON varies significantly by decade when examining exophthalmos, dyschromatopsia, ocular motility restriction, and mean deviation on 24-2 Humphrey Visual Field. These clinical characteristics are also significantly different when compared with a population of patients with TED-NC.


Ultracompact resonator with high quality-factor based on a hybrid grating structure.
We numerically investigate the properties of a hybrid grating structure acting as a resonator with ultrahigh quality factor. This reveals that the physical mechanism responsible for the resonance is quite different from the conventional guided mode resonance (GMR). The hybrid grating consists of a subwavelength grating layer and an un-patterned high-refractive-index cap layer, being surrounded by low index materials. Since the cap layer may include a gain region, an ultracompact laser can be realized based on the hybrid grating resonator, featuring many advantages over high-contrast-grating resonator lasers. The effect of fabrication errors and finite size of the structure is investigated to understand the feasibility of fabricating the proposed resonator.


Health care disparities and cervical cancer.
We compared cervical cancer incidence, stage at diagnosis, and survival in Medicaid-insured and non-Medicaid-insured populations. We stratified the sample by age and used ordered logistic regression to predict stage at diagnosis and used Cox proportional hazards regression to predict survival. Medicaid insured nearly one quarter of women diagnosed with cervical cancer. The likelihood of late-stage disease was greatest for women who enrolled in Medicaid after diagnosis. Women younger than 65 years who enrolled in Medicaid after diagnosis were more likely to die from cervical cancer than were women who were not insured by Medicaid (hazard ratio=2.40, 95% confidence interval=1.49, 3.86). Our study underscores the importance of cervical cancer screening programs targeted at low-income women.


COVID-19 instructional approaches (in-person, online, hybrid), school start times, and sleep in over 5,000 U.S. adolescents.
To examine associations among instructional approaches, school start times, and sleep during the COVID-19 pandemic in a large, nationwide sample of U.S. adolescents. Cross-sectional, anonymous self-report survey study of a community-dwelling sample of adolescents (grades 6-12), recruited through social media outlets in October/November 2020. Participants reported on instructional approach (in-person, online/synchronous, online/asynchronous) for each weekday (past week), school start times (in-person or online/synchronous days), and bedtimes (BT) and wake times (WT) for each identified school type and weekends/no school days. Sleep opportunity was calculated as BT-to-WT interval. Night-to-night sleep variability was calculated with mean square successive differences. Respondents included 5,245 racially and geographically diverse students (~50% female). BT and WT were earliest for in-person instruction; followed by online/synchronous days. Sleep opportunity was longer on individual nights students did not have scheduled instruction (>1.5 h longer for online/asynchronous than in-person). More students obtained sufficient sleep with later school start times. However, even with the same start times, more students with online/synchronous instruction obtained sufficient sleep than in-person instruction. Significantly greater night-to-night variability in sleep-wake patterns was observed for students with in-person hybrid schedules versus students with online/synchronous + asynchronous schedules. These findings provide important insights regarding the association between instructional approach and school start times on the timing, amount, and variability of sleep in U.S. adolescents. Given the public health consequences of short and variable sleep in adolescents, results may be useful for education and health policy decision-making for post-pandemic secondary schools.


Challenges to uptake of cancer education resources by rural Aboriginal Health Workers: the Cancer Healing Messages flipchart experience.
The Australian Aboriginal and Torres Strait Islander (Aboriginal) population has a higher age-standardised cancer mortality rate and a significantly lower 5-year survival rate for all cancers than the non-Aboriginal population. Aboriginal people from regional and remote South Australia and the Northern Territory, are often required to travel to Adelaide to access specialist cancer care services. The burden and expenses associated with transport and accommodation and cultural and linguistic factors have been identified as barriers to accessing medical treatment and health services. In collaboration with community and stakeholders, Cancer Council South Australia led the development of the Cancer Healing Messages flipchart and patient flyer to assist health professionals in explaining cancer and the cancer journey to Aboriginal cancer patients and their families. This study examined the usage, acceptability and perceived usefulness of the resources, barriers to uptake, and strategies to improve their utilisation and sustainability. An evaluation survey was conducted among Aboriginal Health Workers (AHWs) and other health professionals working with Aboriginal clients in South Australia (n=18). Participants indicated whether they agreed that the resources are valuable, culturally appropriate, helpful for explaining aspects of cancer to Aboriginal cancer patients, and useful with regard patient outcomes, how frequently they used or would use the resources for information, and how they use the flipchart in practice. Participants were also asked to report any usage barriers. The resources were considered useful, valuable and culturally appropriate by almost all participants; however, there was a discrepancy between intentions to use the resources and actual uptake, which was low. The most commonly reported barriers related to appropriateness for certain patients and lack of availability of resources in some contexts. The Cancer Healing Messages flipchart and patient flyer are perceived as appropriate, valuable, and useful tools for AHWs. A long-term strategy and clear implementation plan involving education, training and promotion of the materials, is required to achieve broad reach and sustainable utilisation of the Cancer Healing Messages flipchart and patient flyer.


[The conditions for the possible formation of foci of diphyllobothriasis on the lower Don].
There are conditions for forming a diphyllobothriasis focus in the basin of the lower Don. In terms of the population affliction, low risk for its infection and the size of copepods, the focus is differentiated as an Oligocopepoda one of low epidemiological intensity. Its formation is favoured by the activation of the population's migration, favourable ecological and biological conditions for the existence of intermediate and supplementary hosts, the population's habit of having ill-disinfected fish, the pathways of infected material delivery into the reservoirs, the survival periods for broad tape-worm eggs, which are sufficient for diphyllobothriasis pathogens to develop their biological cycle under the conditions of Rostov Province.


Molecular analysis of common wheat genes encoding three types of cytosolic heat shock protein 90 (Hsp90): functional involvement of cytosolic Hsp90s in the control of wheat seedling growth and disease resistance.
Heat shock protein 90 (Hsp90) molecular chaperones play important roles in plant growth and responses to environmental stimuli. However, little is known about the genes encoding Hsp90s in common wheat. Here, we report genetic and functional analysis of the genes specifying cytosolic Hsp90s in this species. Three groups of homoeologous genes (TaHsp90.1, TaHsp90.2 and TaHsp90.3), encoding three types of cytosolic Hsp90, were isolated. The loci containing TaHsp90.1, TaHsp90.2 and TaHsp90.3 genes were assigned to groups 2, 7 and 5 chromosomes, respectively. TaHsp90.1 genes exhibited higher transcript levels in the stamen than in the leaf, root and culm. TaHsp90.2 and TaHsp90.3 genes were more ubiquitously transcribed in the vegetative and reproductive organs examined. Decreasing the expression of TaHsp90.1 genes through virus-induced gene silencing (VIGS) caused pronounced inhibition of wheat seedling growth, whereas the suppression of TaHsp90.2 or TaHsp90.3 genes via VIGS compromised the hypersensitive resistance response of the wheat variety Suwon 11 to stripe rust fungus. Our work represents the first systematic determination of wheat genes encoding cytosolic Hsp90s, and provides useful evidence for the functional involvement of cytosolic Hsp90s in the control of seedling growth and disease resistance in common wheat.


Clean air actions in China, PM2.5 exposure, and household medical expenditures: A quasi-experimental study.
Exposure to air pollution, a leading contributor to the global burden of disease, can cause economic losses. Driven by clean air policies, the air quality in China, one of the most polluted countries, has improved rapidly since 2013. This has enabled a unique, quasi-experiment to assess the economic impact of air pollution empirically. Using a series of nation-scale longitudinal surveys in 2011, 2013, and 2015, we first examined the questionnaire-based medical expenditure changes before and after the policy intervention for air pollution. Using a state-of-the-art estimator of the historical concentration of particulate matters with diameter less than 2.5 μm (particulate matter (PM)2.5), we further quantified the association between household medical expenditure and PM2.5 using mixed-effect models of the repeated measurements from 26,511 households in 126 cities. Regression models suggest a robust linear association between reduced PM2.5 and saved medical expenditures, since the association did not vary significantly across models with different covariate adjustments, subregions, or subpopulations. Each 10 μg/m3 reduction in PM2.5 was associated with a saving of 251.6 (95% CI: 30.8, 472.3; p-value = 0.026) Yuan in per capita annual medical expenditure. However, due to limitations in data quality (e.g., self-reported expenditures), and imperfect control for unmeasured confounders or impact from concurrent healthcare reform in China, the causality underlying our findings should be further confirmed or refuted. In this study, we observed that compared with the PM2.5 reduction in 2013, the PM2.5 reduction in 2017 was associated with a saving of 552 (95% CI: 68, 1036) Yuan / (person × year), or approximately 736 billion Yuan (equivalent to 111 billion US dollar) per year nationally, which is equivalent to approximately 1% of the national gross domestic product of China.


The UTX gene escapes X inactivation in mice and humans.
We recently have identified a ubiquitously transcribed mouse Y chromosome gene, Uty , which encodes a tetratricopeptide repeat (TPR) protein. A peptide derived from the UTY protein confers H-Y antigenicity on male cells. Here we report the characterization of a widely transcribed X-linked homologue of Uty , called Utx , which maps to the proximal region of the mouse X chromosome and which detects a human X-linked homologue at Xp11.2. Given that Uty is ubiquitously transcribed, we assayed for Utx expression from the inactive X chromosome (Xi) in mice and found that Utx escapes X chromosome inactivation. Only Smcx and the pseudoautosomal Sts gene on the mouse X chromosome have been reported previously to escape inactivation. The human UTX gene was also found to be expressed from Xi. We discuss the significance of these data for our understanding of dosage compensation of X-Y homologous genes in humans and mice.


Aetiology of bilateral sensori-neural deafness in children.
The study was carried out in the Department in children born during the four year period 1981-1984 in a well defined geographical areas known as the Greater Manchester County. The children were investigated for possible congenital infections. Perinatal assessment was carried out in conjunction with the Paediatricians for aetiological adverse factors. Family histories were obtained and parents and siblings were examined for any hearing impairment. A total of 155 cases were investigated. Cases with a positive family history with deafness in siblings or parents constituted 18.7% of cases. An even larger group (35.5%) was found to have no known positive cause and negative family history. Adverse perinatal factors accounted for 15.5% of cases while congenital infections were found to be the cause of deafness in 10.3%. Meningitis led to deafness in 6.5% and chromosomal abnormality was the aetiological factor in 3.8% of cases.


Reversible binding of the starch-related R1 protein to the surface of transitory starch granules.
Intact starch granules were isolated from leaves of Solanum tuberosum L. (and from Pisum sativum L.), and the patterns of starch-associated proteins were determined by SDS-PAGE. Depending on the pretreatment of the leaves the protein patterns varied: a 160 kDa compound was present in the starch-associated protein fraction when the leaves were darkened and performed net starch degradation. However, following illumination (i.e. during net starch biosynthesis) the 160 kDa protein was recovered almost exclusively in a soluble state. The 160 kDa protein was identified to be the recently described starch-related R1 protein. In in vitro assays recombinant R1 did bind to starch granules isolated from either illuminated or darkened leaves. However, binding to the latter was more effective. It is concluded that, depending upon the metabolic state of the cells, the starch granule surface changes and thereby affects binding of the R1 protein.


[To the question of reasonability of lung biopsy in primary spontaneous pneumothorax].
A biopsy of lung tissues was a conventional diagnostic method for detection of disseminated processes in the lung, which weren't diagnosed on preoperative stage. It was used during surgical anti-relapse treatment of spontaneous pneumothorax (SP). A retrospective analysis of the results of lung parenchyma biopsy was made in 143 patients, who have been operated for SP. Basic entry criteria of the research were: the age younger than 40 years old, a presence of one episode of spontaneous pneumothorax, an absence of complaints for respiratory organs before the development of the first episode of spontaneous pneumothorax. The biopsy with following pathomorphological investigation allowed a formulation of exact variant of disseminated processes, which gave the reason for the development of spontaneous pneumothorax in 9 (6%) patients out of 143. The presence of disseminated processes in the lung was detected with multispiral CT in all these patients on preoperative stage. The study of biopsy material found out the presence of emphysema of different degree of manifestation or fibrosis sites in the rest of the patients. An analysis of presented materials allowed the conclusion, that a performance of biopsy was indicated in the case of suspicion for lung disseminated processes in patients with SP. The biopsy with the following histological study didn't explain the reason of the development of emphysematous and fibrous changes in lung parenchyma in all other cases. At the same time, it didn't give the option for pathogenetic treatment and it wasn't possible to predict the following pathogenesis.


Psychometric Properties of the General Movement Optimality Score using Rasch Measurement.
To explore the psychometric properties of the general movements optimality score (GMOS) by examining its dimensionality, rating scale functioning, and item hierarchies using Rasch measurement. Secondary data analysis of the GMOS data for video-recording of 383 infants with uni-, multidimensional, and mixed Rasch partial credit models. Videos were scored based on the global General Movement Assessment categories, and on the amplitude, speed, spatial range, proximal and distal rotations, onset and offset, tremulous and cramped components of the upper and lower extremities (21 items), resulting in the GMOS. The GMOS data fits best to a unidimensional mixed Rasch model with three different classes of infants, with all but two items contributing to the infants' separation. Rating scales functioned well for 19 items. Item difficulty hierarchies varied depending on infants' class. No floor effect and no substantive gaps between item difficulty estimates were found. The GMOS has strong psychometric properties to distinguish infants with different functional motor performance and provides a quantitative measure of quality of movement. The GMOS can be confidently used to assist with early diagnosis, grade motor performance, and provide a solid base to study individual general movement developmental trajectories.


Drivers of air pollution variability during second wave of COVID-19 in Delhi, India.
To curb the 2nd wave of COVID-19 disease in April-May 2021, a night curfew followed by full lockdown was imposed over the National Capital Territory, Delhi. We have analyzed the observed variation in pollutants and meteorology, and role of local and transboundary emission sources during night-curfew and lockdown, as compared to pre-lockdown period and identical periods of 2020 lockdown as well as of 2018 and 2019. In 2021, concentration of pollutants (except O₃, SO₂, and toluene) declined by 4-16% during night-curfew as compared to the pre-lockdown period but these changes are not statistically significant. During lockdown in 2021, various pollutants decreased by 1-28% as compared to the night-curfew (except O₃ and PM₂.₅), but increased by 31-129% compared to the identical period of 2020 lockdown except O₃. Advection of pollutants from the region of moderate lockdown restrictions and an abrupt increase in crop-residue burning activity (120-587%) over Haryana and Punjab increased the air pollution levels over NCT during the lockdown period of 2021 as compared to 2020 in addition to a significant contribution of long-range transport. The increase in PM₂.₅ during the lockdown period of 2021 compared to 2020 might led to 5-29 additional premature mortalities.


Characterizing ontogenetic habitat shifts in marine fishes: advancing nascent methods for marine spatial management.
Niche requirements and habitat resource partitioning by conspecific fishes of different sizes are significant knowledge gaps in the species distribution modelling domain. Management actions and operations are typically concentrated on static habitats, or specific areas of interest, without considering movement patterns of species associated with ontogenetic shifts in habitat usage. Generalized additive models were used to model the body-length-habitat relationships of six fish species. These models were used to identify subsets of environmental parameters that drive and explain the continuous length-habitat relationships for each of the study species, which vary in their degree of ecological and/or commercial importance. Continuous predictive maps of the length distributions for each of the six study species across approximately 200 km2 of the study area were created from these models. The spatial patterns in habitat partitioning by individuals of different body lengths for all six study species provide strong evidence for ontogenetic shifts. This highlights the importance of considering ontogenetic processes for marine spatial management. Importantly, predictive hotspot maps were created that identify potential areas that accumulate individuals of similar life stages of multiple species (e.g., multispecies nursery areas). In circumstances where limited resources are available for monitoring and management of fish resources, predictive modelling is a valuable tool for studying previously overlooked processes such as ontogenetic habitat shifts. Predictive modelling provides crucial information that elucidates spatial patterns in community composition across mosaics of benthic habitats. This novel technique can contribute to the spatial management of coastal fish and fisheries by identifying areas that are important for different life history stages of multiple fish species.


Hemoperitoneum after a Bothrops snakebite: Case report.
Snakebites are frequent in tropical countries. Brazil has an average of 27,000 cases per year, with a fatality rate of 0.5%, and the Bothrops genus is the most common causative agent, accounting for about 70-90% of the accidents. This report describes a case of human envenomation by a juvenile Bothrops jararaca snake in São Paulo, Brazil, in a 71 years-old man, previously healthy. He presented a life-threatening envenomation, which developed to severe hypotension, acute kidney injury and extensive peritoneal hemorrhage. The hemoperitoneum was diagnosed due to persistent hypotension associated with anemia, pain and gastrointestinal complaints. Abdominal Computed Tomography scans showed a moderate to large amount of presumable hematic material inside the abdominal cavity, predominantly in the perihepatic and perisplenic spaces. The intra-abdominal hemorrhage was not surgically addressed, and the patient was discharged 5 days after hospitalization, with the progressive absorption of the hemoperitoneum. Systemic bleeding is one of the complications and main causes of death in Bothrops envenomations. Acute peritoneal hemorrhage is one of these serious complications that must be carefully addressed since its management must take into account the risk of bleeding caused by toxins that affect hemostasis. The case described highlights the importance of early diagnosis and adequate management of this potentially fatal complication in snakebites.


HIV prevalence in patients with herpes zoster.
To monitor HIV seroprevalence and to determine the sexual risk behaviour of men with herpes zoster (HZ), a study was conducted from Jan 98 to Dec 99 among 115 men of 21 to 55 years of age suffering from HZ. The diagnosis of HZ was clinical and relevant investigations when indicated were carried out to exclude immunodeficiency state. None of the cases were on immunosuppressive drugs. All cases were tested for HIV by immunocomb method and if found positive were confirmed by Western blot assay. Out of 115 cases of HZ 11 (9.5%) were found to be HIV positive. 11 (10.8%) of HIV positive cases were 21-40 years of age. More than one dermatome was involved in 7 (63.6%) HIV positive and in 2 (1.9%) HIV negative cases. 2 HIV positive cases had multiple cranial nerve involvement and one had generalized HZ. None of the cases showed evidence of progression to symptomatic HIV disease. Out of 11 HIV positive cases 9 (81.8%) gave history of multiple unprotected sexual exposures with female commercial sex workers and 2 (18.1%) with amateurs. None of our cases had used condom during sexual intercourse. None gave history of blood transfusion in the past or intravenous drug use.


Treatment of chronic fatigue syndrome with 5-HT3 receptor antagonists--preliminary results.
The serotonin system presumably is involved in the pathogenesis of chronic fatigue syndrome (CFS). Results from a few studies led to the hypothesis of a "postsynaptic hyperresponsiveness" in CFS. Therefore we intended to evaluate the efficacy of 5-HT3 receptor antagonists in the treatment of CFS. 2 patient groups (10 patients each; CFS according to the CDC classification criteria) received either oral tropisetron (5 mg once daily) or oral ondansetron (2 x 8 mg daily), open-labelled. Treatment duration was 15 days. Treatment response was evaluated by visual analog scales (VAS) for fatigue and capability. 19 patients finished their respective study. In the tropisetron group 6/9 (VAS fatigue) and 7/9 (VAS capability) patients documented benefit, 8/10 rsp. 8/10 patients in the ondansetron group. The score changes (VAS before and after treatment) in case of response were more pronounced in the tropisetron group. The frequency of concomitant symptoms did not differ significantly in the treatment groups. The overall analysis of both studies showed a remarkable improvement (> or = 35%) of approximately one third of the patients in both VAS. Treatment was well tolerated. Our preliminary results encourage to perform placebo-controlled, double-blind studies to further evaluate the efficacy of 5-HT3 receptor antagonists in the treatment of CFS.


Familial liability to psychosis is associated with attenuated dopamine stress signaling in ventromedial prefrontal cortex.
Patients diagnosed with a psychotic disorder and their first-degree relatives display increased reactivity to stress. Theory predicts that experience of psychosocial stress is associated both with ventromedial prefrontal and mesolimbic dopamine neurotransmission. However, while there is evidence of aberrant striatal dopamine processing in psychotic disorder, the role of the prefrontal cortex remains under-researched. This study aimed at investigating stress-induced in vivo dopamine release in ventromedial prefrontal cortex (vmPFC) of individuals at familial risk for psychosis. Fourteen healthy first-degree relatives of patients with a diagnosis of psychotic disorder and 10 control subjects underwent a single dynamic positron emission tomography (PET) scanning session after intravenous administration of 183.2 (SD = 7.6) MBq [(18)F]fallypride. Psychosocial stress was initiated at 100 min postinjection using a computerized mental arithmetic task with social evaluative threat components. PET data were analyzed using the linearized simplified reference region model. Regression analyses were performed to compare the spatial extent of task-related ligand displacement between control subjects and relatives and to find how it related to self-rated experiences of psychosocial stress and psychosis. First-degree relatives displayed hyporeactive dopamine signaling in the vmPFC in response to stress. Increased levels of subjectively rated stress were associated with increased intensity of psychotic experiences. This effect was particularly pronounced in first-degree relatives. Although previous studies have hypothesized a role for prefrontal dopamine dysfunction in psychosis, this study, to our knowledge, is the first in vivo human imaging study showing attenuated (ie, hyporeactive) dopamine stress neuromodulation in vmPFC of individuals at familial risk for psychosis.


Description of the larva of Popanomyia kerteszi James & Woodley (Diptera: Stratiomyidae) and identification key to immature stages of Pachygastrinae.
The larva of Popanomyia kerteszi James & Woodley is described based on individuals collected under tree barks in initial stages of decomposition in Marambaia island (23 degrees 4'15''S, 43 degrees 53'59''W, at sea level), Rio de Janeiro state, Brazil. The immatures of P. kerteszi were compared with other species of the subfamily Pachygastrinae and an identification key to the described immature stages of this subfamily is presented. This is also the first record of P. kerteszi to Rio de Janeiro.


Computation of the equation of state of the quantum hard-sphere fluid utilizing several path-integral strategies.
The compressibility factor of the quantum hard-sphere fluid within the region (rho(N) (*)</=0.8,lambda(B) (*)</=0.9) is computed by following four distinct routes involving the three pair radial correlation functions that are significant in the path-integral context, namely, instantaneous, pair linear response, and centroids. These functions are calculated with path-integral Monte Carlo simulations involving the Cao-Berne propagator. The first route to the equation of state is the instantaneous standard one, i.e., the usual volume derivative of the partition function expressed in terms of the instantaneous pair radial correlations. The other three routes stem from the extended compressibility theorem, which associates the isothermal compressibility with the three pair radial structures mentioned above and involves the solving of appropriate Ornstein-Zernike equations. An analysis of the error bars in the quantities computed is reported, and it is proven the usefulness of the centroid pair correlations to fix quantum equations of state. Also, the regions where the fluid-solid changes of phase should take place are identified with the use of indicators sensitive to order in the sample. The consistency of the current results is assessed and comparison with data available in the literature is made wherever possible.


Prognostic factors in low-stage nonseminomatous testicular cancer.
Whether patients with clinical stage I nonseminomatous testicular germ-cell cancer (NSGCT) should be treated with orchiectomy and retroperitoneal lymph node dissection (RPLND) or orchiectomy and surveillance remains controversial. Proponents of the former approach cite the uncertainty and risks of monitoring young men who may harbor occult metastases, while proponents of the latter strategy contend that surgical staging overtreats 60% to 70% of men. Over the last few years, prognostic factors in the primary testicular tumor have helped clinicians make more rational decisions about whether RPLND or surveillance should follow initial orchiectomy. As of 1996, the most clinically useful prognostic factors are the percentage of embryonal carcinoma and the presence or absence of vascular invasion by tumor cells in the primary tumor. Ongoing work with flow cytometry, image analysis, proliferation markers, and oncogene and tumor-suppressor gene markers may allow us to further stratify patients as to their likelihood of occult metastases and permit rational "risk-adaptive" treatment.


The role of boldness in psychopathy: A study of academic and clinical perceptions.
The relevance of boldness to psychopathy has recently become a major flashpoint of scientific controversy. Although some authors have contended that boldness is a necessary (although insufficient) component of psychopathy, others have asserted that it is largely or entirely irrelevant to psychopathy. We addressed this issue by examining clinical perceptions of the relevance of the 3 triarchic dimensions (boldness, disinhibition, and meanness) to psychopathy among a sample of mental health professionals and graduate students (N = 228) using a vignette-based, person-centered methodology. A vignette comprising boldness descriptors afforded statistically significant and moderate to large (Cohen's ds ranged from .47 to .99) increases in perceived resemblance to overall psychopathy above and beyond the other triarchic dimensions, both singly and jointly; these findings extended largely to clinical perceptions of Factor 1 (i.e., interpersonal and affective aspects of psychopathy) but not Factor 2 (i.e., impulsive and antisocial aspects of psychopathy) resemblance. Contrary to the claims of some recent authors, boldness alone was perceived as being as relevant to psychopathy as was disinhibition, although both dimensions were perceived as less relevant to psychopathy than was meanness. These findings offer strong support for the contention that boldness is regarded as a key feature of classical psychopathy and are broadly consistent with interpersonal models of psychopathy. (PsycINFO Database Record


Oral anticoagulation cost in primary antiphospholipid syndrome: comparison between warfarin and hypothetical rivaroxaban.
: The objective of the study is to perform a cost comparison of 1 year of oral anticoagulation management with warfarin vs. hypothetical rivaroxaban (RRX) in thrombotic primary antiphospholipid syndrome. Longitudinal study on 20 primary antiphospholipid syndrome patients followed-up for 1 year after anticoagulation stabilisation with warfarin: a dedicated software calculated number of clinic visits, time in therapeutic range and warfarin consumption for each patient; for RRX, we considered a visit every 3 months (baseline done in hospital before attending anticoagulant clinic); knowing the cost of both anticoagulants, the laboratory cost and the human cost we calculated and compared the yearly expenditure. Average time in therapeutic international normalized ratio range was 69 ± 11%: warfarin management required a total of 375 of visits compared with the 60 for RRX; the yearly cost of RRX was superior to that of warfarin (12 012 vs. 446.4 euros, P < 0.0001), and in spite of lower laboratory (738 vs. 1853 euros, P < 0.0001) and human costs (774.6 vs. 4841 euros), RRX thromboprophylaxis still yielded a hefty bill (13 525 vs. 7140 euros, P < 0.0001). Switching from warfarin to RRX will be 48% more expensive to our Healthcare Authority; unless ongoing clinical trials demonstrate improved long-term outcomes for RRX over warfarin, we feel that a 69% time in therapeutic range does not warrant a change to RRX at a 48% increased cost.


Radiographic scale grid for supervoltage radiographs.
This paper deals with the construction and practical application of a radiographic scale grid incorporated into high energy radiation therapy machines in making port radiographs. The gadet is designed especially for the numerous small radiation therapy departments in community hospitals and private practices that do not have the sophistication provided by a simulator.


Rapid N transport to pods and seeds in N-deficient soybean plants.
Non-nodulated soybean (Glycine max (L.) Merr.) plants were cultivated hydroponically under N-sufficient (5 mM NaNO(3)) or N-deficient (0.5 mM NaNO(3)) conditions. (13)N- or (15)N- labelled nitrate was fed to the cut end of the stems, and the accumulation of nitrate-derived N in the pods, nodes and stems was compared. Real-time images of (13)N distribution in stems, petioles and pods were obtained using a Positron Emitting Tracer Imaging System for a period of 40 min. The results indicated that the radioactivity in the pods of N-deficient plants was about 10 times higher than that of N-sufficient plants, although radioactivity in the stems and nodes of N-deficient versus N-sufficient plants was not different. A similar result was obtained by supplying (15)NO(3) to cut soybean shoots for 1 h. The fact that the N translocation into the pods from NO(3) fed to the stem base was much faster in N-deficient plants may be due to the strong sink activity of the pods in N-deficient plants. Alternatively, the redistribution of N from the leaves to the pods via the phloem may be accelerated in N-deficient plants. The temporal accumulation of (13)NO(3) in nodes was suggested in both N-sufficient and N-deficient plants. In one (13)NO(3) pulse-chase experiment, radioactivity in the stem declined rapidly after transferring the shoot from the (13)NO(3) solution to non-labelled NO(3); in contrast, the radioactivity in the node declined minimally during the same time period.


Hybridization of a flexible cyclooctatetraene core and rigid aceneimide wings for multiluminescent flapping π systems.
The hybridization of flexible and rigid π-conjugated frameworks is a potent concept for producing new functional materials. In this article, a series of multifluorescent flapping π systems that combine a flexible cyclooctatetraene (COT) core and rigid aceneimide wings with various π-conjugation lengths has been designed and synthesized, and their structure/properties relationships have been investigated. Whereas these molecules have a V-shaped bent conformation in the ground state, the bent structure changes to a planar conformation in the lowest excited singlet (S1 ) state irrespective of the lengths of the aceneimide wings. However, the fluorescence behavior in solution is distinct between the naphthaleneimide system and the anthraceneimide system. The former has a nonemissive S1 state owing to the significant contribution of the antiaromatic character of the planar COT frontier molecular orbitals, thereby resulting in complete fluorescence quenching in solution. In contrast, the latter anthraceneimide system shows an intense emission, which is ascribed to the planar but distorted S1 state that shows the allowed transition between the π-molecular orbitals delocalized over the COT core and the acene wings. The other characteristic of these π systems is the significantly redshifted fluorescence in the crystalline state relative to their monomer fluorescence. The relationship between the packing structures and the fluorescence properties was investigated by preparing a series of hybrid π systems with different sizes of substituents on the imide moieties, which revealed the effect of the twofold π-stacked structure of the V-shaped molecules on the large bathochromic shift in emission.


Binary Multidimensional Scaling for Hashing.
Hashing is a useful technique for fast nearest neighbor search due to its low storage cost and fast query speed. Unsupervised hashing aims at learning binary hash codes for the original features so that the pairwise distances can be best preserved. While several works have targeted on this task, the results are not satisfactory mainly due to the over-simplified model. In this paper, we propose a unified and concise unsupervised hashing framework, called binary multidimensional scaling, which is able to learn the hash code for distance preservation in both batch and online mode. In the batch mode, unlike most existing hashing methods, we do not need to simplify the model by predefining the form of hash map. Instead, we learn the binary codes directly based on the pairwise distances among the normalized original features by alternating minimization. This enables a stronger expressive power of the hash map. In the online mode, we consider the holistic distance relationship between current query example and those we have already learned, rather than only focusing on current data chunk. It is useful when the data come in a streaming fashion. Empirical results show that while being efficient for training, our algorithm outperforms state-of-the-art methods by a large margin in terms of distance preservation, which is practical for real-world applications.


Lameness and foot lesions in adult British dairy goats.
In the first population-based study of lameness and foot lesions in adult goats in the UK, a random sample of 307 adult goats from four large commercial dairy farms was examined. The overall proportion of lame goats was 9.1 per cent (2.6 to 24.4 per cent). The abnormalities detected were horn separation (29.6 per cent), white line lesions (13.0 per cent) slippering (10.1 per cent), abscess of the sole (4.2 per cent), foreign body, and granulomatous lesions (1.0 per cent). Between 83.1 and 95.5 per cent of the goats had overgrown horn on at least one foot. The number of feet of individual goats with horn separation followed a Poisson distribution suggesting that it was associated with environmental rather than genetic or nutritional factors. Horn separation, abscess of the sole and footrot were significantly associated with lameness, but white line lesions, slippering and granulomatous lesions were not. There were differences between the farms in the prevalence of lameness and foot lesions. Routine foot trimming was associated with a lower prevalence of lameness.


The effects of isotretinoin on follicular and sebaceous gland differentiation.
Follicular and sebaceous gland cell differentiation was investigated during treatment of acne patients with isotretinoin. Sebaceous glands were significantly reduced in volume and showed decreased metabolic activity as measured by glucose-6-phosphate dehydrogenase and succinic dehydrogenase enzyme activities. There was no measurable change in the volume of follicular duct epithelium or in its metabolic activity during treatment. Metabolic activity was also unchanged in the interfollicular epidermis, contrasting with the effects of another retinoid, etretinate. These findings provide no support for the proposition that alteration in the process of follicular keratinization forms a substantial part of the mode of action of isotretinoin.


Primary biliary cirrhosis.
Primary biliary cirrhosis is a chronic liver disease characterised by intrahepatic bile-duct destruction, cholestasis, and, in some cases, cirrhosis. Evidence supporting the autoimmune nature of this disorder includes the appearance of highly specific antimitochondrial antibodies (AMAs) and autoreactive T cells. Concordance rates in monozygotic twins, familial prevalence, and genetic associations underscore the importance of genetic factors, whereas findings of epidemiological studies and murine models suggest a possible role for exogenous chemicals and infectious agents through molecular mimicry. The incidence of primary biliary cirrhosis has increased over recent decades, possibly attributable to augmented testing of liver biochemistry rather than a rise in disease incidence. AMAs remain the hallmark of diagnosis in most cases and allow detection of asymptomatic patients. Symptomatic individuals usually present with either pruritus or fatigue and, more rarely, with either jaundice or complications of cirrhosis. The prognosis of primary biliary cirrhosis has improved because of early diagnosis and use of ursodeoxycholic acid, the only established medical treatment for this disorder. Although not a cure, treatment can slow disease progression and delay the need for liver transplantation. However, some patients do not respond adequately to ursodeoxycholic acid and might need alternative therapeutic approaches.


Circumstances and causes of out-of-hospital cardiac arrest in sudden death survivors.
To study the circumstances and medical profile of out-of-hospital sudden cardiac arrest (SCA) patients in whom resuscitation was attempted by the ambulance service, and to identify causes of SCA in survivors and factors that influence resuscitation success rate. During a five year period (1991-95) all cases of out-of-hospital SCA between the ages of 20 and 75 years and living in the Maastricht area in the Netherlands were studied. Information was gathered about the circumstances of SCA, as well as medical history for all patients in whom resuscitation was attempted by the ambulance personnel. Causes of SCA in survivors were studied and logistic regression analysis was performed to identify factors associated with survival. Of 288 SCA patients in whom cardiopulmonary resuscitation (CPR) and advanced life support were applied, 47 (16%) were discharged alive from the hospital. Their mean (SD) age was 58 (11) years, 37 (79%) were men, and 24 (51%) had a history of cardiac disease. Acute myocardial infarction was diagnosed in 24 (51%) of the survivors; seven with and 17 without a history of cardiac disease. Ventricular fibrillation (VF) or ventricular tachycardia (VT) as the first documented rhythm was significantly positively associated with survival (odds ratio (OR) 5.7, 95% confidence interval (CI) 2.1 to 15.9). A time interval of less than four minutes between the moment of collapse and the start of resuscitation, and an ambulance delay time of less than eight minutes were significantly positively associated with survival (OR 3.3, 95% CI 1.3 to 8.6, and OR, 3.6, 95% CI 1.3 to 10.5, respectively). A history of cardiac disease was negatively associated with survival (OR 0.46, 95% CI 0.21 to 0.98). Acute myocardial infarction was the underlying mechanism of SCA in most of the survivors, especially in those without a history of cardiac disease. CPR within four minutes, an ambulance delay time less than eight minutes, and VT or VF diagnosed by the paramedics were positively associated with success.


Predicting breast cancer risk using personal health data and machine learning models.
Among women, breast cancer is a leading cause of death. Breast cancer risk predictions can inform screening and preventative actions. Previous works found that adding inputs to the widely-used Gail model improved its ability to predict breast cancer risk. However, these models used simple statistical architectures and the additional inputs were derived from costly and / or invasive procedures. By contrast, we developed machine learning models that used highly accessible personal health data to predict five-year breast cancer risk. We created machine learning models using only the Gail model inputs and models using both Gail model inputs and additional personal health data relevant to breast cancer risk. For both sets of inputs, six machine learning models were trained and evaluated on the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial data set. The area under the receiver operating characteristic curve metric quantified each model's performance. Since this data set has a small percentage of positive breast cancer cases, we also reported sensitivity, specificity, and precision. We used Delong tests (p < 0.05) to compare the testing data set performance of each machine learning model to that of the Breast Cancer Risk Prediction Tool (BCRAT), an implementation of the Gail model. None of the machine learning models with only BCRAT inputs were significantly stronger than the BCRAT. However, the logistic regression, linear discriminant analysis, and neural network models with the broader set of inputs were all significantly stronger than the BCRAT. These results suggest that relative to the BCRAT, additional easy-to-obtain personal health inputs can improve five-year breast cancer risk prediction. Our models could be used as non-invasive and cost-effective risk stratification tools to increase early breast cancer detection and prevention, motivating both immediate actions like screening and long-term preventative measures such as hormone replacement therapy and chemoprevention.


Pure culture studies of Erwinia carotovora with 3,5-diiodo-4-hydroxybenzonitrile.
Interactions of ioxynil (3,5-diiodo-4-hydroxybenzonitrile) with a pure culture of Erwinia carotovora grown in a glucose-simple salts medium were studied. Growth of E. carotovora was inhibited by ioxynil and, to a lesser extent, by its acid form at 25 and 50 mug/ml. Growth was not inhibited by the amide or ester forms of ioxynil or p-hydroxybenzonitrile at the same concentrations. E. carotovora could be trained to grow in 50 mug or higher concentrations of ioxynil per ml by serial transfers of the organism through increasing ioxynil concentrations. No degradation or detoxification of ioxynil was detected. Toxicity tests indicated that, in the adapted culture, cell-free supernatant fluid remained toxic to a nonadapted culture. Adaptation of E. carotovora resulted in a lengthened lag phase, a decreased growth rate, and very few adverse effects on the total population. The adapted resistant culture retained this characteristic only when ioxynil was present. Adaptation was demonstrated to be a physiological variation, not a selection of a mutant or of preexisting resistant cells. Ioxynil slightly stimulated the respiration rate of E. carotovora and moderately inhibited that of an adapted culture. Because the respiration rate of an adapted culture in the absence of ioxynil surpassed that of a parent culture still in the presence of ioxynil, a competition of two alternate routes of electron transport is implied. These data support the conclusion that an alternate growth mechanism is involved in the adaptation mechanism.


[Epithelioid amelanotic melanoma of the nose and paranasal sinuses].
Mucous melanomas are rare, representing 1-3% of melanomata and 3% of malignant nasosinusal tumors. The more usual location is the nasal cavity and paranasal sinuses. In early stages occur with a poor and unespecific features, which delays the diagnosis and worsen the prognosis. An amelanotic melanoma case is reported and bibliographic review of these tumors are made.


Effect of cholesterol on the motility and plasma membrane integrity of frozen equine spermatozoa after thawing.
The aim of the present study was to investigate the cryoprotectant properties of cholesterol after incorporation into the plasma membranes of equine spermatozoa. A cholesterol-methyl-beta-cyclodextrin complex was used to alter sperm plasma membrane cholesterol content. Ejaculates from six stallions were centrifuged in a non-fat skimmed milk glucose-sucrose extender (MK) or a modified Tyrode's medium (TALP). The sperm pellets were resuspended in the appropriate extender with or without added cholesterol (0.125 mmol cholesterol-methyl-beta-cyclodextrin complex l(-1)) and incubated at 24 degrees C for 15 min. After incubation, the aliquots were centrifuged and the sperm pellets were resuspended in lactose-EDTA-egg yolk freezing extender, frozen in static nitrogen vapour and stored at -196 degrees C. The straws were thawed and the motility and plasma membrane integrity of the spermatozoa were analysed. Addition of cholesterol to the incubation extenders improved the mean percentages of motile, progressively motile and rapidly motile spermatozoa in both the MK and TALP extenders containing cholesterol compared with extenders without cholesterol (P < 0.05). The percentage of spermatozoa with intact plasma membranes was higher in samples incubated in extenders containing cholesterol than in those without cholesterol (P < 0.05). The results of this study indicate that cyclodextrins can be used to incorporate cholesterol into equine sperm plasma membranes and that cholesterol incorporation imparts protection to the spermatozoa during cryopreservation.


Intraoperative distensibility measurement in POEM for achalasia: impact on patient outcome and associations with other outcome variables at 1-year follow-up.
The functional luminal imaging probe (FLIP) can provide measurements of lower esophageal sphincter (LES) distensibility. Studies report that use of intraoperative FLIP examination during peroral endoscopic myotomy (POEM) for achalasia is associated with treatment success, but evidence is limited and inconsistent. The main aim of the present study was to assess associations between intraoperative FLIP values and 1-year outcomes. Additionally, associations between 1-year FLIP measurements and other 1-year outcome variables were studied. We performed a single-center prospective study of consecutive achalasia patients treated with POEM with a standardized 1-year follow-up. The inclusion period was from June 2017 to January 2020. We compared 1-year outcomes (FLIP measurement values, Eckardt score (ES), reflux esophagitis, timed barium esophagogram (TBE), and lower esophageal sphincter resting pressure (LES-rp)) in patients with and without intraoperative FLIP examination. We also assessed associations between intraoperative FLIP values, 1-year FLIP values, and other 1-year outcomes. Results are given as median (IQR), and non-parametrical statistical analyses were applied. Sixty-two patients (27 females) with median age 45 years (35-54) were included. Baseline characteristics were similar in patients with (n = 32) and without (n = 30) intraoperative FLIP examination. In patients with intraoperative FLIP, ES was 2 (1-3) and LES distensibility index (DI) 3.7 (2.6-5.4) after 1 year, compared with ES 2 (1-3) and DI 4.0 (3.1-6.8)) in patients without intraoperative FLIP (ns). Intraoperative DI was not correlated with 1-year ES or DI. One-year DI correlated significantly with 1-year ES (rs - 0.42), TBE (rs - 0.34), and LES-rp (rs - 0.29). Use of intraoperative FLIP measurements in POEM for achalasia is not associated with improved 1-year outcome, and the clinical value of intraoperative FLIP in POEM for achalasia is questioned. Follow-up FLIP measurements are moderately associated with symptomatic outcome, and may serve as an additional diagnostic modality in post-treatment evaluation.


Neuropathic component of low back pain in patients with ankylosing spondylitis.
The aim of this cross sectional study was to evaluate frequency of neuropathic back pain in ankylosing spondylitis (AS) patients and to determine the relation with disease variables and occurrence of neuropathic pain. Fifty-eight AS patients who were not having any comorbid disease and/or using drugs that would cause neuropathy, were recruited to the study. Demographic properties and clinical characteristics (functional status and disease activity assessed by BASFI and BASDAI respectively, ESR, CRP) and quality of life determined by AS quality of life-QoL questionnaire, were recorded. The neuropathic property of back pain was assessed by both Leeds Assessment of Neuropathic symptoms and signs (LANSS) and Douleur Neuropathique 4 (DN4) scales. 58 AS patients (17 female, 41 male) with a mean age of 45 ± 18 years were included. 33 patients (56.9%) and 31 patients (53.4%) were defined as having neuropathic pain depending on the LANSS (scores > 12) and DN4 (scores > 4) questionnaire scores respectively. The mean score of LANSS scale was correlated with ASQoL, BASFI, BASDAI, and DN4; and the mean score of DN4 scale was correlated with ASQoL, BASFI and LANSS. The mean levels of BASFI and ASQoL scores were significantly higher in patients having neuropathic pain than in patients not having (p < .05). Neuropathic pain is common and determined in more than half of the patients with AS and related with functional status and quality of life. Diagnosis and treatment of neuropathic pain are warranted in order to increase functional ability and quality of life in patients suffering from AS.