Period of remission after treatment with UVA-1 in sclerodermic skin diseases.
Sclerodermic skin diseases can cause severe morbidity and disability. UVA-1 has shown to be an effective therapy for sclerodermic skin diseases. However, the period of remission in these patients is not clear. In this study, the effect and remission period of UVA-1 phototherapy in various sclerotic skin diseases is described using a semiquantitative clinical score combined with the durometer score as an objective apparatus to measure the hardness of the skin. Our purpose was to determine the effectiveness of UVA-1 phototherapy and the duration of remission in sclerodermic skin diseases. In this prospective study, 10 patients with various sclerodermic skin diseases were treated with UVA-1 phototherapy. The durometer was used to observe the hardness of the skin. Hardness of the skin was measured by one investigator at 10 locations, distributed evenly on the representative sclerotic skin. Each spot was measured three times, and the average of each of these measurements was summed to give the total durometer score. Durometer scores were recorded weekly until the final treatment date and 4 weeks after treatment. Clinical scores were carried out at the end date of the treatment using a 6-point scale semiquantitative score. Long-term effects were evaluated up to 29-46 months. The patients were treated with UVA-1 in a cumulative dose of 1286 +/- 58.8 (SEM) J/cm(2) (range, 846-1470 J/cm(2)) divided over five times a week for 4 weeks. In all patients studied, the sclerotic skin lesions were markedly softer after UVA-1 treatment. All durometer scores improved highly significant during the first 3 weeks of treatment and borderline significant during the last week of treatment. There was no significant improvement between the end of UVA-1 phototherapy and 1 month after ending the therapy (P > 0.05). All patients noted improvement of the semiquantitative clinical score during treatment. Clinical improvement was associated with improvement of the durometer score (95% confidence interval). With a follow-up until 46 months, the remission period was stable up to 26 months in six patients. The duration of sclerodermic skin diseases before start of treatment did not influence improvement in the clinical or durometer score. One patient had an acute side effect of minimal erythema. No other side effects, except tanning and fatigue, were noted. This is an open-label uncontrolled study. UVA-1 is an effective treatment for sclerodermic skin diseases with a long period of remission and clinical improvement even in patients with a long history of a sclerotic skin disease. UVA-1 should be considered among the first approaches in the management of sclerotic skin diseases.


The CHRNA5/A3/B4 gene cluster and tobacco, alcohol, cannabis, inhalants and other substance use initiation: replication and new findings using mixture analyses.
Multiple studies have provided evidence for genetic associations between single nucleotide polymorphisms (SNPs) located on the CHRNA5/A3/B4 gene cluster and various phenotypes related to Nicotine Dependence (Greenbaum et al. 2009). Only a few studies have investigated other substances of abuse. The current study has two aims, (1) to extend previous findings by focusing on associations between the CHRNA5/A3/B4 gene cluster and age of initiation of several different substances, and (2) to investigate heterogeneity in age of initiation across the different substances. All analyses were conducted with a subset of the Add Health study with available genetic data. The first aim was met by modeling onset of tobacco, alcohol, cannabis, inhalants, and other substance use using survival mixture analysis (SMA). Ten SNPs in CHRNA5/A3/B4 were used to predict phenotypic differences in the risk of onset, and differences between users and non-users. The survival models aim at investigating differences in the risk of initiation across the 5-18 age range for each phenotype separately. Significant or marginally significant genetic effects were found for all phenotypes. The genetic effects were mainly related to the risk of initiation and to a lesser extent to discriminating between users and non-users. To address the second goal, the survival analyses were complemented by a latent class analysis that modeled all phenotypes jointly. One of the ten SNPs was found to predict differences between the early and late onset classes. Taken together, our study provides evidence for a general role of the CHRNA5/A3/B4 gene cluster in substance use initiation that is not limited to nicotine and alcohol.


[Patient participation in its own safety].
Patient-centered approach to care and regulatory advances developed in recent years have promoted patient involvement in decision-making about diagnostic tests and treatments. In other aspects, such as participating in their own safety, there is still a lot to do. Until recently, the patient has been considered as a simple health services receiver, not as an active part of the system, much less as a safety barrier against failures and errors that occur in health care. Some patients have been activated thanks to their experiences. However, many others do not. That is why it is necessary to proactively sensitize, inform and train patients to participate in their own safety. It is not about holding them responsible, but about facilitating and promoting their participation by reinforcing their safety during the care process. The health system must be committed, and the patient informed and trained. We provide tools and online resources to apply in primary care.


Acid-mediated coupling of γ-hydroxybutenolides and aldehydes: Synthesis of a new class of spirocyclic ketal-lactones.
In the presence of trimethylsilyl trifluoromethanesulfonate (TMSOTf), γ-methyl-γ-hydroxybutenolide reacts with aromatic aldehydes to generate a new class of stereochemically rich spirocyclic ketal-lactones in good yields and with excellent stereoselectivities. We believe that this process takes place through the in situ generation of protoanemonin followed by a Prins reaction. Herein, we describe this discovery, along with substrate scope and preliminary mechanistic studies.


Comparison of higher-order aberrations after LASIK using disposable microkeratome 130 and 90 micron heads.
To analyze and compare higher-order aberrations (HOAs) in cases of laser in situ keratomileusis (LASIK) flaps made using the Moria M2 disposable 130-micronm head with those made using the 90-micronm head. Consecutive prospective comparative clinical trial. Ninety-four consecutive eyes of 48 patients were enrolled in this study. They were divided into two equal groups of 47 eyes that underwent wavefront-guided LASIK using VISX CustomVue (VISX, Santa Clara, CA) system. Corneal flap was created using the disposable Moria M2 130 micronm in the first group and the 90 micronm head in the second one. All patients were followed up for 6 months. Wavefront aberrations were measured at baseline, 1 month, and 6 months after surgery using the WaveScan (VISX Inc.) aberrometer. Root mean square (RMS) of HOAs, coma, and spherical aberration (SA) values were analyzed and compared in the two groups. At 6 months, values of RMS of HOAs, coma, and SA obtained from the 130-micronm head group were 0.32+/-0.10 micronm, 0.20+/-0.11 micronm, and 0.18+/-0.08 micronm, respectively. Values of RMS of HOAs, coma, and SA obtained from 90-micronm head group were 0.33+/-0.12 micronm, 0.19+/-0.10 micronm, and 0.15+/-0.08 micronm, respectively. Analyzing the data obtained revealed no statistically significant differences between the two groups. In each group, there was a significant decay of higher-order RMS and coma values from 1 month to 6 months. HOAs following use of Moria M2 disposable 90 micronm head are similar to those arising following use of the 130 micronm.


Subject-independent EEG emotion recognition with hybrid spatio-temporal GRU-Conv architecture.
Recently, various deep learning frameworks have shown excellent performance in decoding electroencephalogram (EEG) signals, especially in human emotion recognition. However, most of them just focus on temporal features and ignore the features based on spatial dimensions. Traditional gated recurrent unit (GRU) model performs well in processing time series data, and convolutional neural network (CNN) can obtain spatial characteristics from input data. Therefore, this paper introduces a hybrid GRU and CNN deep learning framework named GRU-Conv to fully leverage the advantages of both. Nevertheless, contrary to most previous GRU architectures, we retain the output information of all GRU units. So, the GRU-Conv model could extract crucial spatio-temporal features from EEG data. And more especially, the proposed model acquires the multi-dimensional features of multi-units after temporal processing in GRU and then uses CNN to extract spatial information from the temporal features. In this way, the EEG signals with different characteristics could be classified more accurately. Finally, the subject-independent experiment shows that our model has good performance on SEED and DEAP databases. The average accuracy of the former is 87.04%. The mean accuracy of the latter is 70.07% for arousal and 67.36% for valence.


Management of locoregional recurrent oropharyngeal carcinoma.
Sixty-seven patients with recurrent locoregional squamous cell epithelioma of the oropharynx were reviewed to determine the curative potential of secondary therapy for recurrent carcinoma. Of the 37 patients in whom recurrent carcinoma developed after radical surgery, only 11 percent (4 of 37) had a 2 year disease-free survival following secondary treatment. Recurrence developed in 30 patients after radiation therapy. Surgical resection of the recurrent carcinoma was possible in 13 of the patients, 38 percent (5 of 13) of whom were free of disease for a minimum of 2 years. Though treatment results in patients with recurrent oropharyngeal carcinoma are discouraging, secondary therapy in selected patients can yield 2 year disease survival in over a third of cases. Favorable prognostic factors included the development of recurrent carcinoma following radiation therapy and a tumor initially classified as stage I or II, irrespective of the initial mode of therapy.


Urinary flow velocity as an index of male voiding function.
Urinary velocity and urinary peak flow rate developed by 463 male patients were measured before and after treatment for prostatic obstruction, stricture or prostatitis and compared to 121 documented normal males. It was shown that peak flow rate does discriminate partially between the normal and non-normal populations, but that many subjects who presented with ostensibly normal flow rates were actually obstructed when measured by peak urinary velocity. Velocity is shown to be a valuable secondary measurement in the clinic, and the flow velocity vs. flow rate diagram is demonstrated to be a good tool for classifying patients urodynamically.


Binding of the erlin1/2 complex to the third intralumenal loop of IP3R1 triggers its ubiquitin-proteasomal degradation.
Long-term activation of inositol 1,4,5-trisphosphate receptors (IP3Rs) leads to their degradation by the ubiquitin-proteasome pathway. The first and rate-limiting step in this process is thought to be the association of conformationally active IP3Rs with the erlin1/2 complex, an endoplasmic reticulum-located oligomer of erlin1 and erlin2 that recruits the E3 ubiquitin ligase RNF170, but the molecular determinants of this interaction remain unknown. Here, through mutation of IP3R1, we show that the erlin1/2 complex interacts with the IP3R1 intralumenal loop 3 (IL3), the loop between transmembrane (TM) helices 5 and 6, and in particular, with a region close to TM5, since mutation of amino acids D-2471 and R-2472 can specifically block erlin1/2 complex association. Surprisingly, we found that additional mutations in IL3 immediately adjacent to TM5 (e.g., D2465N) almost completely abolish IP3R1 Ca2+ channel activity, indicating that the integrity of this region is critical to IP3R1 function. Finally, we demonstrate that inhibition of the ubiquitin-activating enzyme UBE1 by the small-molecule inhibitor TAK-243 completely blocked IP3R1 ubiquitination and degradation without altering erlin1/2 complex association, confirming that association of the erlin1/2 complex is the primary event that initiates IP3R1 processing and that IP3R1 ubiquitination mediates IP3R1 degradation. Overall, these data localize the erlin1/2 complex-binding site on IP3R1 to IL3 and show that the region immediately adjacent to TM5 is key to the events that facilitate channel opening.


Robust Photothermal Icephobic Surface with Mechanical Durability of Multi-Bioinspired Structures.
Photothermal superhydrophobic surfaces are potential to become ideal anti-/deicing surfaces due to their rapid water removal, icing delay, and photothermal deicing performance. Here, a robust photothermal icephobic surface with mechanical durability is shown that is integrated with a microspine array inspired by honeycomb and cactus thorn (i.e., MAHC), which is developed by a laser-layered microfabrication strategy. The maximum stress on the microspine of the MAHC is reduced by ≈2/3, due to the protection of the bionic honeycomb structure. Even after 200 linear abrasions by a steel blade, the MAHC remains superior water repellency with a water contact angle of 150.7° and roll-off angles of 10.3°, stable icing delay time (578.2 s), and rapidly photothermal deicing capabilities (401 s). As the MAHC is fabricated on a curvature surface such as a copper alloy transmission line for an overhead high-speed rail, a stable photothermal anti-/deicing in a low-temperature environment still can be achieved effectively. The freezing rain covering the functional transmission line completely slides off within 758 s under one sun illumination. This studying offers insight into the design of novel materials with stable anti-icing/icephobic structures, which would be extended into some applied realms, for example, transportation fields or power systems in cold or low-temperature climates.


Enhanced dopamine detection sensitivity by PEDOT/graphene oxide coating on in vivo carbon fiber electrodes.
Dopamine (DA) is a monoamine neurotransmitter responsible for regulating a variety of vital life functions. In vivo detection of DA poses a challenge due to the low concentration and high speed of physiological signaling. Fast scan cyclic voltammetry at carbon fiber microelectrodes (CFEs) is an effective method to monitor real-time in vivo DA signaling, however the sensitivity is somewhat limited. Electrodeposition of poly(3,4-ethylene dioxythiophene) (PEDOT)/graphene oxide (GO) onto the CFE surface is shown to increase the sensitivity and lower the limit of detection for DA compared to bare CFEs. Thicker PEDOT/GO coatings demonstrate higher sensitivities for DA, but display the negative drawback of slow adsorption and electron transfer kinetics. The moderate thickness resulting from 25 s electrodeposition of PEDOT/GO produces the optimal electrode, exhibiting an 880% increase in sensitivity, a 50% decrease in limit of detection and minimally altered electrode kinetics. PEDOT/GO coated electrodes rapidly and robustly detect DA, both in solution and in the rat dorsal striatum. This increase in DA sensitivity is likely due to increasing the electrode surface area with a PEDOT/GO coating and improved adsorption of DA's oxidation product (DA-o-quinone). Increasing DA sensitivity without compromising electrode kinetics is expected to significantly improve our understanding of the DA function in vivo.


Exploring the utility of high-resolution MS with post-acquisition data mining for simultaneous exogenous and endogenous metabolite profiling.
The utility of high-resolution MS (HRMS) with post-acquisition data mining in DMPK goes much further than the now established approach to simultaneously acquire quantitative and qualitative information for lead compounds at the discovery stage. Indeed, HRMS has promise for addressing multiple complex drug-development applications in a single experiment. In the present study, one HRMS dataset acquired for in vitro incubations of the model compound dasatinib was mined post-acquisition to address four different issues: stability, metabolite profiling, glutathione conjugate analysis, and endogenous lipid profiling. The derived results demonstrated that HRMS has potential for generating high information content datasets that can be stored and mined as needed to answer numerous complex development-stage questions without the need for additional sample generation or analysis.


Aspects related to the outcomes of the treatment, in international borders, of cases of tuberculosis as associated to comorbidities.
analyzing the aspects associated with case outcomes and the international border situation when it comes to patients with tuberculosis (TB) associated with comorbidities. exploratory descriptive epidemiological study, analyzing all new cases of TB with comorbidities reported in 2013 on SISNAN in the cities at the border of the state of Paraná and Paraguay. The variables used were: sociodemographic, clinical and operational. To analyze the data, descriptive analysis and the chi-square test were applied. 227 cases of tuberculosis associated with comorbidities were reported and 70.9% were from cities bordering Paraguay. Alcoholism (22.0%) and AIDS (13.7%) were the most common comorbidities. The chi-square test presented a statistical association of border cities with negative outcomes and not performing directly observed treatments. Through the study, it was possible to find that the location of border cities can be determinant for a negative outcome.


Measurement of invasive potential provides an accurate prognostic marker for giant cell tumour of tendon sheath.
Giant cell tumours of tendon sheath vary from solitary nodules to a multinodular variety that exhibits local infiltration. Recent advances in molecular oncology have defined a gene, nm23, expressed in normal cells which is responsible for inhibiting infiltration. The aim of this study was to investigate the expression of nm23 in a series of 52 giant cell tumours using immunohistochemistry and to assess its prognostic potential. nm23 expression was absent in 21%, of tumours and this was associated with a highly significant risk of local recurrence (P<0.0001). Multivariate analysis of outcome showed nm23 expression to be more reliable than other clinicopathological parameters for predicting outcome. This immunohistochemical test for nm23 is easily performed on standard paraffin sections and is recommended as an accurate prognostic marker for giant cell tumours of tendon sheath.


Lifespan healthcare transitions among individuals with intersex traits in Canada: a mixed-methods and qualitative study.
To: (1) complete an integrative literature review of transition studies that focus on individuals with intersex traits; (2) conduct an environmental scan of the current resources (practice guidelines, policies and procedures) used by healthcare providers working with Canadians with intersex traits; (3) investigate the experiences of Canadians with intersex traits in their healthcare transitions across the lifespan and (4) assess the understanding of healthcare providers about these transitions. A qualitative prospective community participation study was conducted. It used mixed methods including an environmental scan and semistructured engagement sessions. The environmental scan examined resources available throughout Canada. The engagement sessions took place in British Columbia and Ontario, Canada. Sixteen participants were recruited. These included 13 individuals with intersex traits (a heterogeneous group of congenital conditions affecting the development of sex characteristics) and three caregivers. Mixed methods included an integrated literature review, environmental scan and qualitative approaches developed in collaboration with community partners. The literature review identified gaps in transition care for individuals with intersex traits. The environmental scan uncovered no specific resources used by healthcare providers working with patients with intersex traits, though several general guidelines were used. Engaging providers in the study was problematic. Thematic analysis generated three main themes that emerged from the engagement sessions: (1) transition is a lifespan activity; (2) building personal agency is valuable and (3) well-being promotion is an application of health literacy. Transition resources for individuals living in Canada with intersex are scarce. Transitions happen across the lifespan with ownership of thought and actions seen as acts of personal agency. Health literacy skills and knowledge change with increased age, yet the primary source of knowledge often remained important in the individual's autobiographical self.


Hemispheric specialization for mental rotation.
A sample of 133 normal subjects, and one commissurotomized subject, were given a "mental-rotation" task, in which they were timed as they decided whether rotated letters, flashed in the left or right visual hemifield, were normal or backward. The normal subjects showed a significant right-hemifield advantage in reaction time, while the commissurotomized subject showed a pronounced left-hemifield advantage in both accuracy and reaction time. We argue that mental-rotation is primarily a right-hemispheric specialization, but that this was offset in the normal subjects by a stronger left-hemispheric specialization for letter identification.


The anterior translation of the humeral head leads to a decrease in the coracohumeral distance in subscapularis tear.
A total of 297 patients who classified as subscapularis (SC) tears through arthroscopic evaluation were retrospectively enrolled, and Fifty-seven patients with impingement syndrome were also enrolled as the control group for normal-population comparison. The coracohumeral distance (CHD) and humeral head anterior translation (HHAT) were measured on magnetic resonance imaging. Our study demonstrated that the anterior translation of the humeral head is related with a decrease in the coracohumeral distance in subscapularis tear. Although, correlation between radiologic parameters (coracohumeral distance and anterior translation of the humeral head) and severity of subscapularis tear was note detected. Level IV, retrospective study.


Residency Program Diversity Recruitment and Education: Survey of Efforts and Barriers to Implementation.
Examine underrepresented minority (URM) recruitment and diversity education initiatives provided by residency programs in ophthalmology and other specialties, and identify means to support programs as they work to enhance diversity efforts. Cross-sectional study. Multi-center survey of residency program leadership of the Association of University Professors of Ophthalmology, Johns Hopkins Medicine, University of Utah, and the University of California, Los Angeles. Residency program leadership (i.e., residency program directors and associate residency program directors) RESULTS: Our survey response rate was 34% (63/188); 56% percent of responses were from ophthalmology and 44% were from other specialties. Across all specialties, programs with a large number of clinical faculty and trainees were associated with having ≥1 URM resident in their program (p = 0.026 and p = 0.028, respectively). There was no significant difference between ophthalmology and other specialties with regard to the number of URM residents. Ninety-two percent of programs utilized strategies to recruit URM applicants. While certain strategies were more common for ophthalmology than other specialties, information sessions for URM students (62%) and a unique review of all URM residency applicants by a separate committee/person (46%) were most commonly used overall. Although 92% of residency program leadership believed it was highly important for health professionals to receive formal diversity training, only 54% of programs had a diversity education curriculum for both trainees and faculty, 11% had a curriculum for faculty only, and 3% had a curriculum for trainees only. Barriers to implementation of curricula included lack of faculty expertise (30%) and curricular time (30%). An overwhelming majority of programs in our study utilized strategies to recruit URM applicants, but 22% had 0 URM residents in their program. To address the reported barriers to diversity education implementation, shared central resources/diversity education toolkits should be created to provide programs with needed support.


Prevalence of metabolic syndrome among patients with schizophrenia in Japan.
In an Asian population, the criteria for metabolic syndrome (MetS) are different from those for Western populations. The aim of this study was to assess the MetS prevalence among patients with schizophrenia or schizoaffective disorder in Japan. We recruited patients (n=1186), aged 54.8±14.8 (mean±SD) years old with the DSM-IV diagnosis of schizophrenia or schizoaffective disorder who were admitted to seven psychiatric hospitals using a cross-sectional design. MetS prevalence was assessed by three different definitions, including the adapted National Cholesterol Education Program Adult Treatment Panel (ATP III-A). Comparative analysis was performed with schizophrenic subjects and 886 participants from the Iwaki Health Promotion Project 2008 as representative of general population. The overall MetS prevalence based on the ATP III-A definition was 27.5%, with 29.8% in male and 25.3% in female patients. In a logistic regression model with age and body mass index as covariates, being schizophrenic was a significant independent factor (odds ratio=2.00 for males, 2.13 for females) in the development of MetS under the ATP III-A definition. The difference of MetS prevalence between patients and the general population was observed for those under 60 years of age. Patients with schizophrenia or schizoaffective disorder in Japan had high prevalence of MetS compared to the general population, and was most apparent for those under 60 years of age. The MetS in schizophrenic patients should be carefully monitored to minimize the risks.


Discordant risk: overweight and cardiometabolic risk in Chinese adults.
Recent US work identified "metabolically healthy overweight" and "metabolically at risk normal weight" individuals. Less is known for modernizing countries with recent increased obesity. Fasting blood samples, anthropometry and blood pressure from 8,233 adults aged 18-98 in the 2009 nationwide China Health and Nutrition Survey, were used to determine prevalence of overweight (Asian cut point, BMI ≥ 23 kg/m(2) ) and five risk factors (prediabetes/diabetes (hemoglobin A1c ≥ 5.7%) inflammation (high-sensitivity C-reactive protein (hsCRP) ≥ 3 mg/l), prehypertension/hypertension (Systolic blood pressure/diastolic blood pressure ≥ 130/85 mm Hg), high triglycerides (≥ 150 mg/dl), low high-density lipoprotein cholesterol (<40 (men)/ <50 mg/dl (women)). Sex-stratified, logistic, and multinomial logistic regression models estimated concurrent obesity and cardiometabolic risk, with and without abdominal obesity, adjusting for age, smoking, alcohol consumption, physical activity, urbanicity, and income. Irrespective of urbanicity, 78.3% of the sample had ≥ 1 elevated cardiometabolic risk factor (normal weight: 33.2% had ≥ 1 elevated risk factor; overweight: 5.7% had none). At the age of 18-30 years, 47.4% had no elevated risk factors, which dropped to 6% by the age 70, largely due to age-related increase in hypertension risk (18-30 years: 11%; >70 years: 73%). Abdominal obesity was highly predictive of metabolic risk, irrespective of overweight (e.g., "metabolically at risk overweight" relative to "metabolically healthy normal weight" (men: relative risk ratio (RRR) = 39.06; 95% confidence interval (CI): 23.47, 65.00; women: RRR = 22.26; 95% CI: 17.49, 28.33)). A large proportion of Chinese adults have metabolic abnormalities. High hypertension risk with age, underlies the low prevalence of metabolically healthy overweight. Screening for cardiometabolic-related outcomes dependent upon overweight will likely miss a large portion of the Chinese at risk population.


An optimized approach for estimating benzene in ambient air within an air quality monitoring network.
Benzene is a carcinogenic air pollutant for which European legislation has set an annual limit and criteria for the number of fixed monitoring sites within air quality networks (AQMN). However, due to the limited number of fixed sites for benzene measurement, exposure data are lacking. Considering the relationship between benzene levels and other variables monitored within an AQMN, such as NO2, O3, temperature, solar radiation, and accumulated precipitation, this study proposes an approach for estimating benzene air concentrations from the related variables. Using the data of the aforementioned variables from 23 fixed stations during 2016-2017, the proposed approach was able to forecast benzene concentration for 2018 with high confidence, providing enriched data on benzene exposure and its trends. Moreover, the spatial distribution of the estimated versus the most representative benzene levels was quite similar. Finally, an artificial neural network identified the most representative fixed benzene monitoring sites within the AQMN.


[The use of intraosseous appliances considering the anatomical features of the hard palate].
The aim of the study. To improve the effectiveness of patients' treatment with narrow upper jaw by improving the stability of intraosseous devices. 40 patients with the narrow upper jaw, from 12 to 40 years old, were treated. 50 self-drilling orthodontic miniscrews of each manufacturer, i.e. «BioRay», Taiwan, «Turbo», Russia, a total of 100 items, were inserted into a palate. The greatest thickness of the cortical bone relative to the sagittal plane was observed at a distance of 6 mm from the incisor canal, which averages 6.32 mm. Relative to the transversal plane, the greatest bone thickness was observed 3 mm laterally from the median palatine suture and averages 7.62 mm. The smallest thickness of the mucous membrane of the hard palate is noted 6 mm distal from the incisor canal and 3 mm laterally from the palatine suture is on average 4.56 mm. The protocol for determining the individual position of the miniscrew for each patient, taking into account all his anatomical features, is a necessary tool for clinical success.


Upper extremity musculoskeletal disorders in hospital workers.
Seventy-six women who worked in a hospital were surveyed for symptoms and signs of upper limb musculoskeletal disorders. The investigation was originally intended to study the effects of repetitive manual work that was performed by a group of garment assembly workers. Hospital workers were selected as the referent group on the assumption that they were unexposed to ergonomic stressors. However, the study showed that the prevalence of shoulder, wrist, and hand pain in these workers was sufficiently high (32%) to require that this assumption be reexamined. The hospital workers that were affected the most were employed in the nursing field and in manual work, i.e., food preparation, serving, and laundry. The women with upper limb pain were older and had been employed somewhat longer in hospital work than those without pain. Several jobs were observed to identify possible occupational risk factors for cumulative trauma disorders (CTDs). In addition to repetitive motion, these factors included forceful manual exertions and awkward postures required by work station design and layout.


Neural correlates of inefficient filtering of emotionally neutral distractors from working memory in trait anxiety.
Research has indicated that highly trait-anxious (HTA) individuals exhibit a specific deficit in filtering threat-related distractors from visual-spatial working memory (WM). Prior demonstrations of impaired inhibition control in HTA individuals have mainly focused on tasks that required the inhibition of prepotent response tendencies. Studies on the suppression of emotionally neutral distractors from WM in trait anxiety have also been minimal. In this article, we present a study on the manifestation of general inefficient filtering of neutral distractors during visual-spatial WM maintenance stages in HTA individuals. Female participants performed a visual-spatial WM task while event-related potentials were recorded. They were made to remember the orientations of red rectangles within half of the screen and to ignore all salient green rectangles. As predicted, no significant main effect of group and no interaction between group and condition were found in the N2pc component, suggesting that group differences did not manifest in the initial process of object individuation. During the subsequent WM maintenance phase, HTA individuals were highly inefficient at filtering the irrelevant items from WM, as reflected not only by parallel late contralateral delay activity (CDA; 450 to 900 ms) amplitudes for the distractor condition and the four red items, but also by a smaller filtering efficiency score in the HTA group than in the low-trait-anxiety group. Extending previous studies, our findings verify a general filtering impairment in HTA individuals for task-irrelevant salient distractors during a WM maintenance phase.


Pulmonary blastoma as a unique cause of fatal respiratory distress in a newborn.
Pulmonary blastoma is a very rare malignant primary lung neoplasm, especially in the pediatric population. No more than 50 cases have been described in children, with none if these children diagnosed before the age of 1 month. Speculation regarding its congenital nature has been made. Although is has a uniformly poor prognosis, the case presented is that of congenital pulmonary blastoma as a unique cause of fatal respiratory distress in a neonate.


Severe occlusive vasculitis as a complication of cat scratch disease.
The purpose of this communication is to report a severe occlusive vasculitis as a complication of cat scratch. A 34-year-old Hispanic woman presented with a sudden visual loss of the right eye associated with shivers, high fever and arthritis which developed 2 months after a cat's bite. Fundus examination showed papillitis and a palor of the paramacular zone of the retina. Fluorescein angiography revealed multiple arterial and venous vasculitic occlusions. Auto-immune disease and endocarditis were ruled out by an extensive medical work-up. The diagnosis of Bartonella henselae was confirmed by a positive serology. A systemic antibiotherapy with azithromycin, doxycyclin, rifampicin and steroid therapy resulted in a good clinical response, including a rapid visual recovery with a visual acuity of 20/20 and no relapse of the disease at 6 months follow-up. Ocular complications associated with cat scratch disease may include vasculitis with both arterial and venous occlusions causing severe visual loss.


Activation of paraspinal and abdominal muscles during manually assisted and nonassisted therapeutic exercise.
To assess the activities of the paraspinal and abdominal muscles during manually assisted therapeutic exercises (MATEs) and nonassisted therapeutic exercises (NATEs) that are used in the initial phases of the progressive exercise programs designed for the treatment of low back pain. Thirteen healthy subjects volunteered in the study. Surface electromyography (EMG) was recorded. The recorded EMG signal was averaged and normalized to the maximal EMG amplitude obtained during the maximal voluntary contraction (%EMGmax). In general, the %EMGmax values were higher during NATEs than during MATEs. Sitting seemed to activate lumbar L5 level paraspinal muscles to the same extent as MATEs. MATEs require only minimal trunk muscle activities, and thus, they may not be sufficiently intense to improve the trunk muscle performance. NATEs require high trunk muscle activities that are adequate for improving the trunk muscle performance, but they may cause high compressive loading of the lumbar spine, and if unchecked, this can aggravate low back pain.


Determination of nitrophenols using ultrahigh pressure liquid chromatography and a new manual shaking-enhanced, ultrasound-assisted emulsification microextraction method based on solidification of a floating organic droplet.
Nitrophenols are toxic compounds in the wastewater. In the proposed method, a new technique using a manual shaking-enhanced, ultrasound-assisted emulsification microextraction (MS-USAEME) method based on solidification of a floating organic droplet combined with ultrahigh pressure liquid chromatography (UHPLC) has been developed for the extraction and determination of nitrophenols in aqueous samples. In this method, the low toxicity extraction solvent 1-undecanol was used to extract the nitrophenols. After centrifugation, ice bath was used to solidify the floating extraction solvent, using microtubes to collect the floated extraction solvent and diluting with 30 μL of dimethyl sulfoxide, then injecting into the UHPLC for further analysis. The relative standard deviations (RSD) were 6-12%, enrichment factors (EFs) were 62-500, the relative recoveries (RR) of this method were 80-110% for spiked lake water samples. The detection limits of this method were 0.5-3.0 μg L⁻¹ for spiked lake water and 0.6-3.2 μg L⁻¹ for spiked agriculture water. The further performance of the proposed method was gauged by analyzing field samples.


Macrophages in skin cancer: quantitative and functional studies.
The number of tumor-infiltrating macrophages was estimated in 43 patients with skin cancer, including 18 cases of squamous cell and 25 cases of basal cell carcinoma. Macrophages were identified in cell cultures by 2 assays, namely phagocytosis and resistance to detachment by trypsin. The average percentage of adherent cells for the 2 groups of skin tumors was 4.5 +/- 2.6 and 10.2 +/- 5.2, respectively, and the difference was statistically significant. Follow-up studies after surgical excision of the primary neoplasm showed a relatively low macrophage content in 2 of the 4 cases in which local recurrences occurred. Preliminary functional studies suggested that soluble factors may be released by neoplastic cells, accounting for the inhibitory effect of tumor cell supernatants on macrophage chemotaxis in vitro.


Review of urinary continence care products using sensor technology to improve effectiveness.
There have been many treatment and management modalities for urinary incontinence including absorbent products and urine collecting devices, but these modalities are manual in nature, requiring significant time and effort from caregivers. Recently, the application of sensor technology for urine detection in absorbent products and urine collection devices has helped to create new modalities for urinary incontinence and to automate some of the incontinence care processes. In this article, we review the new products and devices for incontinence care which make use of urine detection sensors.


Cognitive Enhancement: Treating or Cheating?
In this article I provide an overview of the moral and medical questions surrounding the use of cognitive enhancers. This discussion will be framed in light of 4 key considerations: (1) is there a difference between therapy and enhancement? (2) How safe are these interventions? (3) Is the use of nootropics cheating? (4) Would enhancers create a further divide of social inequality where only the very wealthy have access to them?


How I Do It: Suicidal Ideation During Surgical Training: Is an Innovative Surgical Trainee Check Ins Program a Part of the Solution?
Mental health distress and suicidal ideation are leading contributors to the silent epidemic of physician suicide leading to approximately 300 to 400 physician deaths per year. The Second Trial has illuminated the alarming fact that several of our residents have experienced suicidal thoughts within the last year. Unfortunately, our institution is not an outlier. Suicidal ideation and under- or untreated mental health disorders are increasingly prevalent in the surgical trainee population. Given the major concern for our residents' well-being, our department consulted a licensed mental health professional familiar with resident training and the GME to develop a program to provide access to a mental health professional that is free of cost for trainees, safe and confidential. Implementation of a 30 minute opt-out resident check-in program with a licensed mental health professional and a post-session survey that provided retrospective survey data for analysis. This program was implemented at the University of Virginia Health System in Charlottesville, VA. General surgery categorical and preliminary residents participated in this program. Thirty residents participated in the program and an overwhelming majority would like to continue this program at regular intervals. Sessions were 25 minutes on average and 27.7% of participants requested additional sessions. Implementation of this program for our surgical trainees was favorably perceived with request for continuation of the program and provided access to a safe space with a familiar provider.


Polymorphism of doxazosin mesylate.
Nine polymorphic modifications of doxazosin mesylate have been obtained by recrystallization in organic solvents under variable conditions. Different polymorphs of doxazosin mesylate were characterized by powder X-ray crystallography diffractometry (PXRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TG). Transformation of Form 1 and Form 2 was not occurred in three relative humidities (0%, 51%, and 99%) at 20 +/- 0.5 for 30 days.


Partial lung shield for TBI.
In this study, AP/PA setup was used with a 4 MV linear accelerator. The prescribed dose is 1000 cGy, with a dose per fraction of 200 cGy. One of the simplest lung dose determinations is the nomograph relating dose correction factor and patient thickness. To save time in taking port film in every treatment, lung block is used in alternating fashion: anterior blocks are used in the second and fourth fraction and posterior block is used in the third and fifth fraction. If we set the average correction factor for the lower density lung to 1.18, the six open fields will deliver an average of 708 cGy to the lung. To limit the lung dose to 10 Gy, each blocked field should deliver 73 cGy. Measurements showed that a thickness of slightly less than 1 cm of cerrobend provides approximately 65% transmission, which approximates the desired 73% broad beam transmission. The proper transmission of the partial lung shield is verified by measurements made for the patients with diodes placed at the entrance and the exit side of the lung. While we describe a particular setup, the procedure can be modified to accommodate different dose fraction. There are many ways to deliver the TBI dose, and the method of constructing the partial lung shield described here is one of the many methods that may be used to limit the dose to the lung.


Renal scarring in spinal cord injury: a progressive process?
A retrospective analysis. To examine the natural history of renal scarring in the spinal cord injured population. United Kingdom. All spinal cord injured patients with renal scars at our establishment were considered eligible. A total of 27 patients with renal scars were identified. No patient had renal scarring at presentation on radiological imaging. All patients had annual renal imaging with a mean follow up period of 19.1 years. The presence of new scars was considered as evidence of progression. In all, 59% of kidneys developed renal scars with a mean time interval between spinal injury and renal scar development of 13 years. Of these kidneys with scars, only 15.6% demonstrated progression of the scarring process. There were no deaths due to renal causes. The aetiology of renal scarring is multifactorial. The findings of this study suggest that renal scarring in the spinal cord injured population is predominantly a nonprogressive process once a scar has developed. This is in concordance with the belief that renal scarring in the paediatric population with vesicoureteric reflux is also a stable, nonprogressive process.


Fibrocyte and T cell interactions promote disease pathogenesis in rheumatoid arthritis.
Rheumatoid arthritis (RA) is a systemic autoimmune disease. We previously identified a circulating cell population, fibrocytes, which is activated early in disease. As RA is characterized by the formation of autoantibodies and autoreactive T cells, which often precede symptom onset, the objective of these studies was to characterize fibrocyte activation in the context of T cell activation. Multidimensional flow cytometry was used to characterize the activation status of peripheral blood (PB) fibrocytes and T cells derived from RA patients with different levels of disease activity. Compared to healthy controls, fibrocytes from RA patients exhibited increased activation, denoted as elevated levels of phosphorylation of STAT3 and NF-κB. RA patients had higher numbers of circulating activated Th17 cells and Tregs compared with healthy controls, Th17 cell numbers being higher in patients with moderate to high disease activity. Additionally, increased numbers of FOXP3+ RORγt+ double positive CD4+ T cells were observed in RA patients with more severe disease. Our data confirm that circulating fibrocytes are expanded in RA and that there is a direct correlation between the increase in number of activated fibrocytes and increased number of CD4+ T cells. Moreover, our data suggest that interactions between circulating fibrocytes and activated T cells may promote disease activity. Specifically, we provide in vitro evidence that mouse-derived CD4+ T cells produce GM-CSF which induces fibrocyte proliferation. In turn, activated fibrocytes produce IL-6, promoting Th17 polarization.


Nonradioactive telomerase activity assay by microchip electrophoresis: privileges to the classical gel electrophoresis assay.
The present study accents on the privileges of microchip-based electrophoresis to the conventional gel electrophoresis in separation of telomerase repeat amplification protocol/polymerase chain reaction (PCR) ladder products obtained in telomerase-catalyzed reaction in cancer cells. We try to clarify the interpretation of the results obtained by both electrophoretic procedures and to avoid misinterpretation as a result of PCR-dependent artefacts.


Safety belt promotion: theory and practice.
The purpose of this paper is to provide practitioners a rationale and description of selected theoretically based approaches to safety belt promotion. Theory failure is a threat to the integrity and effectiveness of safety belt promotion. The absence of theory driven programs designed to promote safety belt use is a concern of this paper. Six theoretical models from the social and behavioral sciences are reviewed with suggestions for application to promoting safety belt use and include Theory of Reasoned Action, the Health Belief Model, Fear Arousal, Operant Learning, Social Learning Theory, and Diffusion of Innovations. Guidelines for the selection and utilization of theory are discussed.


Expression of Shh, Gli1, and Cyr61 in Gastric Cancer Predicts Overall Survival of Patients: A Retrospective Study.
This study aimed to evaluate the expression levels of Shh, Gli1, and Cyr61 proteins in gastric cancer tissues and analyze the relationship between these three proteins and the clinicopathological factors and prognosis of patients. This was a retrospective study. Four hundred gastric cancer tissue specimens from patients who underwent radical gastrectomy in Zhangye People's Hospital affiliated to Hexi University between February 2013 and February 2021 underwent immunohistochemical analysis. The positive expression rates of Shh, Gli1, and Cyr61 in gastric cancer tissues were 55.5%, 56.5%, and 64.5%, respectively. The expressions of Shh, Gli1, and Cyr61 in gastric cancer tissues were significantly correlated with tumor size, depth of invasion, and degree of differentiation (P < .05). The expression of Shh protein was positively correlated with the expression of Gli1 protein (P < .01), and the expression of Gli1 protein was positively correlated with the expression of Cyr61 protein (P < .01). Univariate and multivariate analyses showed that the expression of Shh, Gli1, and Cyr61 could predict the prognosis of patients (P < .05). Receiver operating characteristic curve analysis combined with TNM staging could better predict the three-year overall survival of patients (P < .05). Shh, Gli1, and Cyr61 proteins are significantly expressed in gastric cancer tissues and are risk factors for the prognosis of patients with gastric cancer.


Capsaicin and nociception in the rat and mouse. Possible role of substance P.
Newborn or adult rats and mice were treated with capsaicin. The effect of systemic or intrathecal treatment on thermonociception, chemonociception, content and release of immunoreactive substance P (I-SP) was investigated. Treatment of two day old rats caused a small, but life-long elevation of the hot plate or tail withdrawal latency. Treatment of adult rats led to a large increase in the reaction time on the hot plate for 4--10 days but the tail withdrawal latency was only slightly elevated for not more than 1--2 days. Mice treated on the 2nd day of life had normal reaction times on the hot plate and a small and inconsistent prolongation of the tail withdrawal latency. In contrast, mice treated on day 7, 10 or as adults had greatly prolonged latencies in both tests for at least 3 months. The changes in latencies were not affected by naloxone or methysergide. Responses to noxious chemical stimuli were moderately inhibited in mice treated on the 2nd day of life, but almost abolished in mice treated on day 7, 10 or as adults. Neonatal capsaicin treatment of rats resulted in a depletion of I-SP in spinal cord and sciatic nerve for 20 months. Capsaicin-evoked release of I-SP from rat spinal cord was reduced by 93% after neonatal treatment, but only by 69% 2 weeks after adult treatment. Treatment of mice on day 2 caused a similar decrease of the I-SP content in spinal cord and of the capsaicin-evoked I-SP release (88%) as treatment on day 4 or 7 although behavioral changes were different. After treatment of adult mice release of I-SP was reduced by 93%. Capsaicin administered intrathecally to rats or mice depleted I-SP in the spinal cord but not in the sciatic nerve. The animals were almost insensitive to noxious heat (tail withdrawal test) and to local application of mustard oil or capsaicin to the hindpaw. Chemosensitivity of the eye, however, remained unchanged. The experiments indicate that systemic or intrathecal capsaicin treatment of rats or mice affects thermo- and chemonociception but species differences were found. It appears, furthermore, that changes in substance P alone cannot explain all the observed behavioral effects after capsaicin treatment.


Cytomegalovirus (CMV) infections and CMV-specific cellular immune reconstitution following reduced intensity conditioning allogeneic stem cell transplantation with Alemtuzumab.
We studied the incidence and recurrence of Cytomegalovirus (CMV) infection and reactivation in 38 recipients of Alemtuzumab reduced intensity conditioning-stem cell transplantation, and used CMV-HLA tetramer studies to discover if these events correlated with recovery of circulating CMV-specific CD8+ T cells (cytotoxic T lymphocyte (CTLs)). The cumulative incidence of CMV infection was 60% at 1 year (95% CI, 45-78%) with a median reactivation time of 24 days (range 5-95 days). All patients with CMV reactivation received Ganciclovir or Foscarnet, and only one developed CMV disease. More strikingly, only 8/21 patients had relapse of CMV antigenemia. Tetramer analysis in 13 patients showed that 11 reconstituted CMV CTLs (7/11 by day 30 and 10/11 by day 90). The development of CMV infection was accompanied by a >5-fold rise of CMV CTLs. Recurrence of CMV infection occurred only in the patients who failed to generate a CTL response to the virus. Hence, recipients of SCT using Alemtuzumab-RIC are initially profoundly immunosuppressed and have a high incidence of early CMV reactivation. However, in the majority of patients, infection is transient, and antiviral T cell reconstitution is rapid. Monitoring with CMV-specific CTLs may help identify the subset of patients at risk from recurrent infection or disease.


Expression and regulation of WISP2 in rheumatoid arthritic synovium.
Numbers of growth factors expressed in the synovium deeply impact on the pathology of rheumatoid arthritis (RA). The WISP family was identified as growth factors, which are upregulated by WNT signaling. In the present study, we investigated expression pattern and regulatory mechanisms of WISPs in the synovium in patients with RA and osteoarthritis (OA). Among three members of WISP family, WISP2 mRNA was only preferentially detected in RA synovium by RT-PCR. WISP2 expression was immunohistochemically identified in RA fibroblasts in an extensive fibrotic area. WNT signaling-activated (s/abeta-catenin-expressing) synovial fibroblasts upregulated WISP2 at 2.9-fold, but -inactivated (Deltabeta-catenin-expressing) cells downregulated the expression. Quantitative RT-PCR demonstrated that WISP2 expression was increased upon 17-beta-estradiol stimulation and synergistically enhanced by WNT signaling. These data demonstrate that the expression of WISP2 is synergistically upregulated in RA synovial fibroblasts by estrogen and WNT pathways, and suggest an involvement in the pathology of the disease.


Amoxicillin-sulbactam versus amoxicillin-clavulanic acid for the treatment of non-recurrent-acute otitis media in Argentinean children.
Streptococcus pneumoniae (Sp) and Haemophilus influenzae (Hi) are the leading bacterial cause of acute otitis media (AOM), having the nasopharynx (NP) as their reservoir. In October 2001 we began a prospective, multicenter, randomized, evaluator blind study, comparing the efficacy of amoxicillin-sulbactam (Ax/S) and amoxicillin-clavulanic acid (Ax/C) for the treatment of non-recurrent AOM (nr-AOM). Both antimicrobial susceptibility (AS) to Ax/S and Ax/C from Sp and Hi carried by study children (aged 6-48 months with nr-AOM) and, clinical outcome after treatment with high dose of either Ax/C (7:1) or Ax/S (4:1) (amoxicillin dose: 80 mg/(kg day), b.i.d. for 10 days) were assessed. Nasal cultures (NCs) were taken at Day 0. Follow-up NCs, were done only for Sp carriers. On final analysis 247/289 pts (85.5%) were fully evaluable (120 Ax/S and 127 Ax/C). NP carriage rate of Hi and Sp at Day 0 was 32.2% (93/289 pts) and 28.7% (83/289 pts), respectively. Persistent Sp carriage was detected only in 2 pts. Hi betalactamase positive rate was 13% (12/93). MICs for Ax/S and Ax/C were identical when tested against Sp and Hi isolates (range < or = 0.016-1.0 and < or = 0.016-0.25 mg/L, respectively). Clinical efficacy at Days 12-14 and 28-42 were 98.3% (115/117) and 94.2% (97/103) for Ax/S; and 98.3% (115/117) and 95.1% (98/103) for Ax/C, respectively (pNS). We conclude, that Sp and Hi isolated from NCs of nr-AOM pts were highly sensitive to both drugs and correlated with high clinical efficacy rate.


Influence of Val16Ala SOD2 polymorphism on the in-vitro effect of clomiphene citrate in oxidative metabolism.
This study investigated the in-vitro antioxidant properties of the ovulation induction drug, clomiphene citrate, and assessed whether its effects are influenced by the Val16Ala polymorphism in the SOD2 gene, which encodes manganese superoxide dismutase enzyme. The investigation involved an in-vitro experimental protocol testing the effect of different concentrations of clomiphene citrate on antioxidant capacity, reactive oxygen species (ROS) production and peripheral blood mononuclear cell (PBMC) culture viability. A total of 58 healthy adult women were genotyped for the Val16Ala SOD2 polymorphism, and blood samples were collected to perform in-vitro experiments. ROS production and cytotoxicity assays were performed on blood and PBMC from carriers of different Val16Ala SOD2 genotypes. Clomiphene citrate exhibited antioxidant capacity and effects and decreased ROS production. The AA genotype displayed a more responsive antioxidant effect with clomiphene citrate treatment than other genotypes. AA and AV PBMC showed an increase in viability following treatment with 10 μmol/l clomiphene citrate when compared with control groups. The results suggest that clomiphene citrate exhibits antioxidant activity similar to that observed with other selective oestrogen receptor modulators, and the intensity of the effect appears to be SOD2 polymorphism dependent. This study was performed to investigate whether clomiphene citrate, a drug broadly used to evaluate reproductive function in women, presents antioxidant effects and if these effects could be influenced by genetic variation in the women. We found evidence that clomiphene citrate has some antioxidant properties similar to those observed with other selective oestrogen receptor modulators such as tamoxifen. As the antioxidant enzyme manganese superoxide dismutase (SOD2) is considered a key molecule involved in female reproductive metabolism, we also tested if a functional SOD2 gene polymorphism (Val16Ala) could influence the in-vitro antioxidant clomiphene citrate response. Significant differences of the clomiphene citrate antioxidant effect on PBMC with different Val16Ala SOD genotypes were observed in this study. Based on these results, we could speculate that alterations in SOD2 activity caused by the Val16Ala polymorphism can result in differential responses to drugs such as clomiphene citrate. In assisted reproduction clinics, clomiphene citrate is commonly used to induce ovulation, especially in patients with polycystic ovary syndrome. However, some women have clomiphene citrate resistance and either ovulation is not triggered by the drug or ovulation is induced but the pregnancy still fails. The causes of no effect of clomiphene citrate remain unclear and we cannot discard the influence of genetic effects including the Val16Ala SOD2 polymorphism. Therefore, it is important to perform complementary investigations considering the potential pharmacogenetic influence of Val16Ala SOD2 polymorphism on the treatment of polycystic ovary syndrome or in ovulation to elucidate this question.


Regional lymph nodes in infants with embryonal carcinoma of testis.
Clinical and pathologic material from 16 infants with embryonal carcinoma of the testis was reviewed specifically as to the route of metastatic spread and the findings obtained from retroperitoneal lymphadenectomy. Hematogenous metastases were noted in 3 patients (19 per cent) and lymphatic metastases were observed in 2 patients (13 per cent). In 12 patients in whom disease was clinically limited to the testis retroperitoneal lymphadenectomy was negative, although a review of the literature suggests that unsuspected metastases might be expected in 6 per cent of such patients. The 2 patients who had lymph node metastases had large, clinically evident but unresectable retroperitoneal lymph node masses. The low yield of retroperitoneal metastases in early disease makes lymphadenectomy suspect as a primary staging or treatment procedure, but the occasional patient presenting with retroperitoneal disease requires that the procedure not be abandoned at this time.


Impact of noncovalent interactions between apple condensed tannins and cell walls on their transfer from fruit to juice: studies in model suspensions and application.
The adsorption of procyanidins (condensed tannins) on cell-wall material was quantified by bringing into contact solutions of procyanidins and suspensions of cell-wall material. A model was developed on the basis of the Langmuir isotherm formulation and a factorial experimental design. The parameters that influenced the adsorption were the concentration and molecular weight of the procyanidins, the ionic strength of the solution, the temperature, and the apple cell-wall concentration. The model was applied to partitioning of procyanidins from apple between juice and mash. The parameters to be taken into account are the composition of the apples and, specifically, (i) the concentration and molecular weight of the procyanidins, (ii) their acidity and pH as a determinant of the ionic strength, and (iii) their cell-wall content and the temperature at pressing. To estimate the ability of the model to relate procyanidin concentrations in the juice to their concentration in the apple, apples of three varieties of widely different procyanidin compositions were pressed in conditions that prevent oxidation. In these conditions, yields in the juice were >80% for phenolic acids or catechin monomers but <50% for procyanidins, with the lowest rates obtained for the higher polymers in accordance with the model.


A diet rich in (n-3) fatty acids increases peroxisomal beta-oxidation activity and lowers plasma triacylglycerols without inhibiting glutathione-dependent detoxication activities in the rat liver.
By using comparisons with a safflower oil diet (15% w/w) and a control, low-fat diet, the ability of a fish oil diet (15% MaxEPA) rich in the (n-3) fatty acids, eicosapentaenoic acid and docosahexaenoic acid, to alter hepatic activities has been determined in adult, male rats. Compared with the safflower diet, treatment for 2 weeks with the fish oil diet caused significant increases in the ratio of liver weight/body weight and the specific activities in liver homogenates of peroxisomal enzymes fatty acyl-CoA oxidase (263%) and catalase (149%) and caused a significant lowering of plasma triacylglycerol levels. Fish oil diets rich in (n-3) fatty acids should thus be placed in the category of hypotriglyceridemic agents which stimulate peroxisomal beta-oxidation activity. In contrast to the effects seen with the other hypotriglyceridemic, peroxisomal proliferating agents such as clofibrate, hepatic glutathione peroxidase and glutathione S-transferase activities are unchanged or are increased rather than inhibited with the fish oil diet.


Four-Factor Prothrombin Complex Concentrate in Left Ventricular Assist Device Implantation: Inverse Propensity Score-Weighted Analysis.
We compare the effect of intraoperative administration of four-factor prothrombin complex concentrates (PCCs) versus fresh frozen plasma (FFP) on major bleeding, transfusions, and complications. Out of 138 patients undergoing left ventricle assist device (LVAD) implantation, 32 received PCCs as first-line hemostatic agents and 102 FFP (standard group). The crude treatment estimates indicated that, compared with the standard group, the PCC group required more FFP units (odds ratio [OR]: 4.17, 95% confidence interval [CI]: 1.58-11; p = 0.004) intraoperatively, whereas a greater number of patients received FFP at 24 hours (OR: 3.01, 95% CI: 1.19-7.59; p = 0.021) and less packed red blood cells (RBC) at 48 hours (OR: 0.61, 95% CI: 0.01-1.21; p = 0.046). After the inverse probability of treatment weighting (IPTW) adjusted analyses, in the PCC group there was still a higher number of patients who required FFP (OR: 2.9, 95% CI: 1.02-8.25; p = 0.048) or RBC (OR: 6.23, 95% CI: 1.67-23.14; p = 0.007] at 24 hours and RBC at 48 hours (OR: 3.09, 95% CI: 0.89-10.76; p = 0.007). Adverse events and survival were similar before and after the ITPW adjustment. In conclusion, the PCCs, although relatively safe with respect to thrombotic events, were not associated with a reduction of major bleeding and blood product transfusions.


Penile strangulation and amputation in schizophrenic patients: A reports of two cases.
Strangulation or amputation of the penis is the preserve of psychotic patients in the majority of cases. This situation can be the cause of major complications both urinary and sexual. The management is multidisciplinary between urologist and psychiatrist. We report two observations of strangulation and amputation in schizophrenic patients.


Cardiac troponin T and cardiac dysfunction in extremely low-birth-weight infants.
Extremely low-birth-weight (ELBW) infants frequently manifest signs of cardiac dysfunction requiring inotropic support. It is not clear if this is due to cardiac injury, which can be monitored by measuring cardiac troponin T (cTnT). We performed a nested prospective cohort study at a university level III neonatal intensive care unit. The study included 27 infants weighing between 500 and 999 g. Exclusion criteria included evidence of sepsis, use of postnatal steroids, and cardiac anomalies. Measurements included serum cTnT and echocardiogram in the first 48 hours of life. The mean serum cTnT level of the study population was 0.52 +/- 0.38 ng/ml. It was higher in those with lower Apgar scores (0.89 +/- 0.37 if 5-minute Apgar < 4 vs 0.36 +/- 0.26 ng/ml, p < 0.001) and correlated to initial base deficit (r = -0.37, p < 0.05). Infants who required inotropic support had higher cTnT levels than those who did not (0.73 +/- 0.43 vs 0.39 +/- 0.29 ng/ml, p < 0.03). cTnT concentrations did not relate to simultaneous echocardiographic measures of cardiac function. In ELBW infants, serum cTnT levels are higher than normally seen in term infants and adults, and they are higher in infants with greater perinatal stress as well as those who show evidence of cardiac dysfunction requiring pressor support.


Frequent isolation of capnophilic bacteria in aspirate from Bartholin's gland abscesses and cysts.
Aspirate samples were obtained from 73 patients undergoing surgery for a Bartholin's gland abscess or cyst. Capnophilic bacteria were isolated from 22% of cases, in contrast to previous reports of sporadic isolation. The three Streptococcus pneumoniae isolates were serotype 3 or 4. The eight Haemophilus influenzae isolates could not be serotyped; six of them were biotype II but the electrophoretic band patterns of their outer membrane proteins were heterogeneous, indicating that non-serotypable strains from the same anatomical site may not be related. Four Neisseria gonorrhoeae isolates and one strain of Neisseria subflava were recovered. The role of capnophilic bacteria in the pathogenesis of infections of the Bartholin's gland remains to be clarified.


Characterization of two deletions of the CTRC locus.
Novel variants associated with chronic pancreatitis are being increasingly reported. However, most studies have so far only analyzed point mutations and small insertions or deletions. Here we report the characterization of two distinct deletions of the CTRC locus. Variants in four chronic pancreatitis genes, PRSS1, SPINK1, CTRC and CFTR, were systematically analyzed in the studied cases. Copy number change of the CTRC gene was analyzed by quantitative fluorescent multiplex PCR (QFM-PCR). Walking QFM-PCR followed by long-range PCR and direct sequencing were employed to identify the deletion breakpoints at the nucleotide level. A heterozygous CTRC-deleting complex rearrangement, which was co-inherited with different trans variants in SPINK1, CFTR or PRSS1, is associated with variable phenotypes (chronic pancreatitis; pancreatic cancer and chronic pancreatitis; and type 1 diabetes). Moreover, a different homozygous deletion of the CTRC locus was found in an unrelated patient with asymptomatic chronic pancreatitis. Our findings revealed a hitherto unrecognized level of complexity of genotype-phenotype correlation in chronic pancreatitis. The CTRC-deleting complex rearrangement probably resulted from LINE-1-mediated Alu insertion, which represents a novel mutational mechanism causing chronic pancreatitis.


Effects of postpartum anxiety disorders and depression on maternal self-confidence.
Low maternal self-confidence may damage the early mother-infant relationship and negatively influence infant development. The goal of this study was to test whether a current and previous history of DSM-IV anxiety and depressive disorders is associated with maternal self-confidence two weeks after delivery. Postpartum anxiety disorder and depression was diagnosed according to DSM-IV criteria in a community sample of 798 women. The data showed a significant link between current postpartum anxiety and depressive disorders and maternal self-confidence. Furthermore, women with a depression or anxiety disorder in their previous psychiatric history scored lower in maternal self-confidence. There is a need for appropriate preventive programmes to promote maternal self-confidence. With such programmes it is possible to prevent infant developmental disorders which might result from reduced feelings of maternal self-confidence and associated maternal interaction behaviour.


Tobacco product use and the risks of SARS-CoV-2 infection and COVID-19: current understanding and recommendations for future research.
Heterogeneity in the clinical presentation of SARS-CoV-2 infection and COVID-19 progression underscores the urgent need to identify individual-level susceptibility factors that affect infection vulnerability and disease severity. Tobacco product use is a potential susceptibility factor. In this Personal View, we provide an overview of the findings of peer-reviewed, published studies relating tobacco product use to SARS-CoV-2 infection and COVID-19 outcomes, with most studies focusing on cigarette smoking in adults. Findings pertaining to the effects of tobacco product use on the incidence of SARS-CoV-2 infection are inconsistent. However, evidence supports a role for cigarette smoking in increasing the risk of poor COVID-19 outcomes, including hospital admission, progression in disease severity, and COVID-19-related mortality. We discuss the potential effects of tobacco use behaviour on SARS-CoV-2 transmission and infection, and highlight the pathophysiological changes associated with cigarette smoking that could promote SARS-CoV-2 infection and increased disease severity. We consider the biological mechanisms by which nicotine and other tobacco product constituents might affect immune and inflammatory responses to SARS-CoV-2 infection. Finally, we identify current knowledge gaps and suggest priorities for research to address acute and post-acute health outcomes of COVID-19 during and after the pandemic.


uPAR-expressing melanoma exosomes promote angiogenesis by VE-Cadherin, EGFR and uPAR overexpression and rise of ERK1,2 signaling in endothelial cells.
Exosomes (Exos) have been reported to promote pre-metastatic niche formation, proliferation, angiogenesis and metastasis. We have investigated the role of uPAR in melanoma cell lines-derived Exos and their pro-angiogenic effects on human microvascular endothelial cells (HMVECs) and endothelial colony-forming cells (ECFCs). Melanoma Exos were isolated from conditioned media of A375 and M6 cells by differential centrifugation and filtration. Tunable Resistive Pulse Sensing (TRPS) and Nanoparticle tracking analysis were performed to analyze dimension and concentration of Exos. The CRISPR-Cas 9 technology was exploited to obtain a robust uPAR knockout. uPAR is expressed in melanoma Exos that are internalized by HMVECs and ECFCs, enhancing VE-Cadherin, EGFR and uPAR expression in endothelial cells that undergo a complete angiogenic program, including proliferation, migration and tube formation. uPAR loss reduced the pro-angiogenic effects of melanoma Exos in vitro and in vivo by inhibition of VE-Cadherin, EGFR and uPAR expression and of ERK1,2 signaling in endothelial cells. A similar effect was obtained with a peptide that inhibits uPAR-EGFR interaction and with the EGFR inhibitor Gefitinib, which also inhibited melanoma Exos-dependent EGFR phosphorylation. This study suggests that uPAR is required for the pro-angiogenic activity of melanoma Exos. We propose the identification of uPAR-expressing Exos as a potentially useful biomarker for assessing pro-angiogenic propensity and eventually monitoring the response to treatment in metastatic melanoma patients.


Relaxin for preventing preterm birth.
Preterm birth is a leading cause of perinatal morbidity and mortality. Early animal and clinical studies have provided some evidence to support an inhibitory effect of relaxin on preterm birth for women in preterm labour. To assess the effects of relaxin for women in preterm labour on preterm birth and associated maternal and neonatal/infant health outcomes. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2013), and the reference lists of relevant papers. Randomised and quasi-randomised controlled trials assessing the effects of relaxin compared with no treatment, a placebo, or an alternative tocolytic, for preventing preterm birth for women in preterm labour. Primary review outcomes included birth within 28 hours of treatment, birth within seven days of treatment, perinatal mortality, and a serious neonatal adverse outcome composite. Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of included studies. We included three quasi-randomised controlled trials, with a total of 149 women and their babies. All three trials were at a high risk of bias. When comparing women receiving relaxin with those who did not receive relaxin, there was a significant reduction in birth within seven days of treatment in one trial of 30 women (risk ratio (RR) 0.50, 95% confidence interval (CI) 0.29 to 0.87), yet no significant difference was seen for perinatal mortality in this trial (RR 0.83, 95% CI 0.32 to 2.15). The second and third included trials did not report on any of the primary outcomes pre-specified in the review, including birth within 48 hours of treatment, birth within seven days of treatment, perinatal mortality, and serious neonatal adverse outcomes.One trial found a significant increase in pregnancy prolongation for women receiving relaxin (RR 8.00, 95% CI 1.14 to 56.33; 30 women). None of the three included trials found significant differences in the outcomes of fetal death, neonatal death, birthweight or preterm birth, and no trial reported on longer-term outcomes for the babies. There is limited randomised controlled trial evidence available on the effect of relaxin during pregnancy for preventing preterm birth for women in preterm labour. Evidence from one quasi-randomised trial suggested a reduction in birth within seven days of treatment for women receiving relaxin, compared with women in a control group, however this trial was at a high risk of bias and included only 30 women. There is thus insufficient evidence to support or refute the use of relaxin in women in preterm labour for preventing preterm birth.


Timing of treatment with ICRF-187 and its effect on chronic doxorubicin cardiotoxicity.
Studies were conducted to evaluate whether the timing of administration of ICRF-187 [(+)-1,2-bis(3,5 dioxopiperazinyl-1-yl)propane] would influence the degree of cardioprotection provided by this agent against the development of doxorubicin-induced chronic cardiomyopathy. Beagle dogs (8.5-14 kg) received either doxorubicin alone (1.75 mg/kg, i.v., n = 8), doxorubicin (1.75 mg/kg) simultaneously with ICRF-187 (35 mg/kg, i.v., n = 8), or doxorubicin (1.75 mg/kg) followed 2 h later by ICRF-187 (35 mg/kg, n = 8). Control animals received ICRF-187 (35 mg/kg, n = 4) or saline (n = 4). All animals received a course of seven treatments, each given 3 weeks apart, and were killed 3 weeks after the last treatment. Semiquantitative grading of histologic sections of myocardium showed that as compared with animals treated with doxorubicin alone, the incidence and the severity of the doxorubicin-induced myocardial lesions were reduced in the two groups of animals given doxorubicin plus ICRF-187. However, protection was significantly better in dogs receiving ICRF-187 and doxorubicin simultaneously than in those given ICRF-187 2 h after doxorubicin. These observations were interpreted as indicating that the timing of administration of ICRF-187 with respect to that of doxorubicin is an important factor in determining the degree of cardioprotection and that there is a "time window" in which ICRF-187 exerts optimal effects.


Lung cancer‑associated transcript 1 facilitates tumorigenesis in laryngeal squamous cell carcinoma through the targeted inhibition of miR‑493.
Long non‑coding RNAs (lncRNAs) serve important roles in the tumorigenesis of a diverse range of cancer types. The lung cancer‑associated transcript 1 (LUCAT1), has been reported to promote the proliferation, migration and invasion of oral squamous cell carcinoma cells. However, the exact role of LUCAT1 in laryngeal squamous cell carcinoma (LSCC) remains to fully understood. The present study aimed to interrogate the role and modulatory mechanism of LUCAT1 in LSCC. Reverse transcription‑quantitative PCR and western blotting were used to investigate the expression of LUCAT1 and miR‑493, as well as the protein expression of cyclin‑dependent kinase 2, cyclin E1, p21, matrix metalloproteinase (MMP)2, MMP9, vascular endothelial growth factor‑C, Bcl‑2, Bax, cleaved caspase‑3 and procaspase‑3. Cell Counting Kit‑8, flow cytometry, wound healing and Transwell assays were performed to analyze the proliferation, cell cycle, apoptosis levels, and the migratory and invasive abilities, respectively, of the LSCC AMC‑HN‑8 cell line. In addition, dual‑luciferase reporter and ribonucleoprotein immunoprecipitation assays were used to investigate the binding between LUCAT1 and microRNA (miR)‑493. The results of the present study revealed that the expression levels of LUCAT1 were upregulated in AMC‑HN‑8 cells. The genetic knockdown of LUCAT1 expression levels significantly suppressed the cell proliferation, alongside downregulating the expression levels of CDK2 and cyclin E1 and upregulating p21 expression levels. In addition, the knockdown of LUCAT1 inhibited cell migration and invasion, as demonstrated using the wound healing and Transwell assays, respectively. Moreover, LUCAT1 knockdown promoted cell apoptosis and upregulated the expression levels of Bax and cleaved caspase‑3, whilst downregulating the expression levels of Bcl‑2. Furthermore, LUCAT1 was discovered to directly bind to and inhibit the well‑known tumor suppressor, miR‑493. Notably, the specific inhibition of miR‑493 partly blocked the anticancer effects of LUCAT1 knockdown in AMC‑HN‑8 cells. In conclusion, these results suggested that LUCAT1 may facilitate tumorigenesis in LSCC through the targeted inhibition of miR‑493, which provides evidence for a novel target for the treatment of LSCC.


PSTPIP2 alleviates obesity associated adipose tissue inflammation and insulin resistance in diabetes mice through promoting M2 macrophage polarization via activation of PPARγ.
Proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2) plays a role in inflammatory disease. In diabetes, very little is known about PSTPIP2 until now. Hence, this study aimed to determine PSTPIP2 functional role in diabetes. Diabetes mouse model was constructed by feeding high fat diet (HFD). Intraperitoneal glucose tolerance test and intraperitoneal insulin tolerance test were examined the glucose and insulin tolerance. The expression of genes and proteins was detected by quantitative real time PCR, immunohistochemistry and western blotting. The pathological changes of epididymal adipose tissues were examined by hematoxylin-eosin staining. RAW264.7 macrophages were treated with GW9662 (PPARγ antagonist). Flow cytometry examined the proportion of M1/M2 macrophages. HFD enhanced the body weight, glucose and insulin tolerance, and inhibited PSTPIP2 expression in mice. PSTPIP2 overexpression alleviated glucose and insulin tolerance, reduced inflammation and macrophage accumulation in the epididymal adipose tissues of diabetic mice. The expression of iNOS and TNF-α was increased, the expression of IL-10 and Arg-1 was decreased in diabetic mice, which was abrogated by PSTPIP2 overexpression. In vitro, PSTPIP2 overexpression reduced the proportions of iNOS-positive cells and enhanced the proportions of CD206-positive cells in RAW264.7 cells. PPARγ and p-STAT6 were up-regulated, STAT6 was down-regulated in RAW264.7 cells. GW9662 impaired PSTPIP2 overexpression-mediated up-regulation of Arg-1, YM-1 and FIZZ1 in RAW264.7 cells. PSTPIP2 alleviates obesity associated adipose tissue inflammation and insulin resistance in diabetic mice through promoting M2 macrophage polarization via activation of PPARγ, suggesting that PSTPIP2 is a prospective target for diabetes treatment.


Electrocardiographic measurements in children with pre-dialysis chronic kidney disease and undergoing kidney replacement therapy.
Cardiovascular diseases are the main causes of morbidity in children with chronic kidney disease (CKD). Electrocardiography (ECG) can provide important information about cardiac functions and parameters associated with sudden cardiac death. This study aims to evaluate the potentially dangerous changes in CKD and kidney replacement therapies by ECG and to determine the value of ECG in predicting cardiovascular outcome compared with echocardiography. 101 patients with CKD were divided into subgroups according to treatment modalities as pre-dialysis CKD, hemodialysis (HD), peritoneal dialysis (PD) and kidney transplantation (KTx). Differences in anthropometric measurements, laboratory results, blood pressures, ECG monitoring were compared within groups as well as with 40 healthy controls. Available echocardiographic findings were noted. In the patients, HD group had highest frequency of hypertension. ECG revealed prolonged QTc as more frequent (16.8% vs 0%, p = 0.006) and higher QTcD (56.7 ± 6.5 vs 39.9 ± 5.1 ms, p = 0.001) in the patients compared to controls, especially in dialysis patients, whereas lowest values were in KTx subgroup. Left ventricular (LV) hypertrophy (LVH) was more frequent (47.1%) in HD compared to other CKD subgroups in ECG (p = 0.052). Echocardiography also showed LV mass index as highest in HD and lowest in KTx (121.4 ± 55.7 vs 63.7 ± 18.3 g/m2, p = 0.000), with numerically highest LVH in HD (58.3%, p = 0.063). Conclusion: ECG can be used to detect cardiovascular problems in patients with CKD, especially in HD. As ECG results were in line with echocardiography, patients with ECG abnormalities suggestive of LVH should be referred for echocardiographic assessment. What is Known: • Cardiovascular diseases such as coronary artery disease, congestive heart failure, arrhythmias and sudden cardiac death are major causes of morbidity and mortality in chronic kidney disease. • Electrocardiography has significant advantages in demonstrating cardiac functions in children because it is readily available, non-invasive and often non-experts can interpret the results. What is New: • The heart rate is higher, QTc is longer and QTcD is higher in dialysis patients and the prolonged QTc is more frequent in patients with underlying glomerular diseases. • Left ventricular hypertrophy is more common in HD patients and those with hypertension, hypercalcemia, anemia or glomerular etiology. The cardiovascular risky conditions are less frequent in the patients with kidney transplantation.


The Rapid Prediction of Focal Wavefront Origins: Integration With a 3-Dimensional Mapping System.
This study assessed the accuracy of an algorithm that predicts the origin of focal arrhythmias using a limited number of data points. Despite advances in technology, ablations can be time-consuming, and activation mapping continues to have inherent limitations. The authors developed an algorithm that can predict the origin of a focal wavefront using the location and activation timing information in 2 pairs of sampled points. This algorithm was incorporated into an electroanatomic mapping (EAM) system to assess its accuracy in a 3-dimensional clinical environment. EAM data from patients who underwent successful ablation of a focal wavefront using the CARTO3 system were loaded onto an offline version of the software modified to contain the algorithm. Prediction curves were retrospectively generated. Predictive accuracy, defined as the distance between true and predicted origin wavefront origins, was measured. Seventeen wavefronts in as many patients (2 with atrial tachycardia, 3 with orthodromic re-entrant tachycardia, 8 with premature ventricular complex and/or ventricular tachycardia, 4 with focal pulmonary vein isolation breakthroughs) were studied. Thirty-three origin predictions were attempted (1.9 ± 0.4 per patient) using 132 points. Predictions were successfully calculated in 31 of 33 (93.9%) attempts and were accurate to within 5.7 ± 6.9 mm. Individual prediction curves were accurate to within 3.0 ± 4.7 mm. Focal wavefront origins may be accurately predicted in 3 dimensions using a novel algorithm incorporated into an EAM system.


Incidence of Anal Cancer and Related Risk Factors in HIV-Infected Patients Enrolled in the National Prospective Spanish Cohort CoRIS.
People living with HIV have an increased risk of anal cancer. To estimate anal cancer incidence and related risk factors in a national cohort of HIV-infected patients. Prospective multicenter cohort study. Multicenter study including patients from the Spanish HIV Research Network. We collected data from 16,274 HIV-infected treatment-naive adults recruited from January 2004 to November 2020. The primary outcome measures of this study were the incidence and prevalence of anal carcinoma. The secondary outcome measures included the associations between baseline and time-dependent covariables and the primary end point. Twenty-six cases of anal cancer were diagnosed, 22 of which were incident cases resulting in a cumulative incidence of 22.29 of 100,000 person-years, which was stable during the study period. At the end of the study, 20 of the 43 centers had screening programs for high-grade anal dysplasia. Patients with anal cancer were males (26/26; 100% vs 13,833/16,248; 85.1%), were mostly men who have sex with men (23/26; 88.5% vs 10,017/16,248; 61.6%), had a median age of 43 years (interquartile range, 35-51), were more frequently previously diagnosed with an AIDS-defining illness (9/26; 34.6% vs 2429/16,248; 15%), and had lower nadir CD4 cell counts (115 vs 303 µL). About a third (34.6%, 9/26) were younger than 35 years. In multivariable analysis, men who have sex with men and patients with previous AIDS-defining illness had an 8.3-fold (95% CI, 1.9-36.3) and 2.7-fold (95% CI, 1.1-6.6) increased HR for developing anal cancer, respectively. Patients with higher CD4 cell counts during the follow-up showed a 28% lower risk per each additional 100 CD4 cell/µL (95% CI, 41%-22%). Lack of information on some potential risk factors, screening, and treatment of high-grade anal dysplasia were not uniformly initiated across centers during the study period. Although the overall incidence in our study was low, there was a significant number of patients younger than 35 years with anal cancer. In addition to age, other factors, such as men who have sex with men and patients with severe immunosuppression (current or past), should be prioritized for anal cancer screening. ANTECEDENTES:Las personas portadoras del virus de la inmunodeficiencia humana tienen un mayor riesgo de cáncer anal.OBJETIVO:Nosotros queremos estimar la incidencia de cáncer anal y los factores de riesgo relacionados en una cohorte nacional española de pacientes infectados por VIH.DISEÑO:Estudio de cohortes de tipo multicéntrico y prospectivo.ÁMBITO:Se incluyeron pacientes de la Red Española de Investigación en VIH.PACIENTES:Recolectamos los datos de 16,274 adultos infectados por el VIH que nunca habían recibido tratamiento, reclutados desde enero de 2004 hasta noviembre de 2020.MEDIDAS DE RESULTADO PRINCIPALES:Las medidas de resultado primarias de este estudio fueron la incidencia y la prevalencia del carcinoma anal. Las medidas de resultado secundarias incluyeron las asociaciones entre las covariables basales y dependientes del tiempo y el criterio principal de valoración.RESULTADOS:Se diagnosticaron 26 casos de cáncer anal, de los cuales 22 fueron casos incidentales resultando con una incidencia acumulada de 22,29/100.000 personas-año que se mantuvo estable durante el período de estudio.Al final de nuestro estudio, 20 de los 43 centros referentes tenían programas de detección de displasia anal de alto grado. Los pacientes con cáncer anal eran hombres (26/26; 100% vs 13 833/16 248; 85,1%), en su mayoría hombres que mantenían sexo con otros hombres (23/26; 88,5% vs 10 017/16 248; 61,6%), la mediana de edad fue de 43 años (IQR: 3 -51), 34,6% (9/26) < 35 años, previa y frecuentemente diagnosticados con una enfermedad definitoria de SIDA (9/26; 34,6% vs 2429/16248; 15%) y que tenían un punto opuesto mucho más bajo en el recuentos de células CD4 (115 µL frente a 303 µL).En el análisis multivariable, los hombres que tenían relaciones sexuales con otros hombres y los pacientes con enfermedades definitorias de sida anteriores, tenían un aumento de 8,3 veces (IC del 95%: 1,9 a 36,3) y de 2,7 veces (IC del 95%: 1,1 a 6,6) en el cociente de riesgos instantáneos para desarrollar cáncer anal, respectivamente. Los pacientes con recuentos de células CD4 más altos durante el seguimiento mostraron un riesgo 28 % menor por cada 100 células CD4/µl adicionales (95% IC: 41%- 22%).LIMITACIONES:La falta de información sobre algunos factores potenciales de riesgo, la detección y el tratamiento de la displasia anal de alto grado no se iniciaron uniformemente en todos los centros durante el período de estudio.CONCLUSIONES:Si bien la incidencia general en nuestro estudio fue baja, hubo un número significativo de pacientes de <35 años con cáncer anal. Además de la edad, otros factores como los hombres que tienen sexo con hombres y los pacientes con inmunosupresión severa (actual o pasada) deben priorizarse para la detección del cáncer anal. ( Traducción-Dr. Xavier Delgadillo ).


[Early cancer detection--advanced vulvar cancer: a contradiction?].
Gynecologic cancer screening examination is not accepted on a large scale. The reasons for this have been discussed by means of an example of a progressive vulvar cancer. Women should be urgently referred to self examination.


Hand-assisted versus straight laparoscopy for colorectal surgery - a systematic review and meta-analysis.
Hand-assisted laparoscopic surgery (HALS) is an alternative to straight laparoscopy (LAP) in colorectal surgery. Many studies have compared the two in terms of efficacy, complications, and outcomes. This meta-analysis aims to uncover if there are any significant differences in conversion rates, operative times, body mass index (BMI), incision lengths, intraoperative and postoperative complications, and length of stay. Comprehensive searches were performed on databases from their respective inceptions to 16 December 2021, with a manual search performed through Scopus. Randomized controlled trials (RCTs), cohort studies, and case series involving more than 10 patients were included. A total of 47 studies were found fitting the inclusion criteria, with 5 RCTs, 41 cohort studies, and 1 case series. Hand-assisted laparoscopic surgery was associated with lower conversion rates (odds ratio [OR] 0.41, 95%CI 0.28-0.60, p < 0.00001), shorter operative times (Mean Difference [MD] - 8.32 min, 95%CI - 14.05- - 2.59, p = 0.004), and higher BMI (MD 0.79, 95%CI 0.46-1.13, p < 0.00001), but it was also associated with longer incision lengths (MD 2.19 cm, 95%CI 1.66-2.73 cm, p < 0.00001), and higher postoperative complication rates (OR 1.15, 95%CI 1.06-1.24, p = 0.0004). Length of stay was not different in HALS as compared to Lap (MD 0.16 days, 95%CI - 0.06-0.38 days, p = 0.16, and intraoperative complications were the same between both techniques. Hand-assisted laparoscopy is a suitable alternative to straight laparoscopy with benefits and risks. While there are many cohort studies comparing HALS and LAP, more RCTs would be needed for a better quality of evidence.


The Relationship Between Mother-Child Bonding Impairment and Suicidal Ideation in São Paulo, Brazil.
To evaluate the association between mother-child bonding at 6-9 months after birth and suicidal ideation METHODS: A cross-sectional study embedded in a clinical trial with 358 low-income postpartum women who had antenatal depression in São Paulo, Brazil. The Postpartum Bonding Questionnaire and the Patient Health Questionnaire-9 were used RESULTS: The percentage of the main outcome, suicidal ideation (SI) was 10.3%. Using logistic regression models, bonding impairment (BI) was associated with SI even after controlling for postpartum depression and other covariates. SI affects 10% of vulnerable postpartum women. BI is independently associated with SI. Treating BI may prevent SI.


[Polypropylene synthetic mesh modifies growth of human cells in vitro. An experimental study].
The aim of our study was to investigate the influence of polypropylene meshes on the proliferation and apoptosis of human cell cultures in vitro. Human fibroblasts and HeLa cells were incubated in different densities (10(4), 3.10(4), 10(5) cells/well) together with polypropylene meshes (Prolene, 2 x 2 cm) in six-well culture dishes over a 48-h period. Cells without meshes served as controls. Cells were spun on slides and stained with the monoclonal antibody MIB-1. To calculate the proliferation indices, stained nuclei were counted. Apoptotic indices were determined by flow cytometric analysis, using FITC-conjugated Annexin-V and propidiumjodide for staining. Fibroblasts showed only a slight reduction of the proliferation index (PI) from 64% (controls) to 60% (meshes). Increasing cell density leads to a decrease in the PI of both groups. The PI of HeLa cells was similar in mesh groups and controls and independent of cell density. The apoptotic index (AI) of fibroblasts was significantly higher in the mesh group (3.7%) in comparison with the controls (1.9%). The same was observed for HeLa cells (AI mesh group: 4.5%, AI controls: 1.2%). Furthermore, an increase of AI was found with increasing cell density in both cell lines. Whereas meshes did not influence the proliferation of the cell lines examined, they seem to have a marked influence on apoptosis, as a significant increase of AI was observed in the mesh group in contrast to controls.


[Sclerochoroidal calcifications with vision-threatening choroidal neovascularisation].
Sclerochoroidal calcification is an uncommon ocular condition in elderly patients. The lesions are frequently bilateral and located at the superotemporal quadrant. The diagnosis is made by fundoscopic appearance, angiography and echography. A 75-year-old man was referred with bilateral choroidal lesions and visual deterioration in the right eye. Examination revealed apart from old signs of a multifocal choroiditis also bilateral, elevated, yellow lesions located at the upper temporal arcades. In the right eye one lesion was accompanied by hemorrhages, edema and lipid exudates. A subsequent fluorescein angiography disclosed choroidal neovascularisation. Ultrasonography showed the characteristic findings of highly reflective lesions with acoustic shadowing. Serum calcium and phosphate levels were normal. Because of rapid visual deterioration on the right eye Ranibizumab (Lucentis) was injected intravitreal. Despite their good prognosis, sclerochoroidal calcifications associated with neovascular membranes can become a vision-threatening disorder.


Unaffected blood boron levels in newborn infants treated with a boric acid ointment.
No rise in the boron content of the plasma of 22 newborn infants was demonstrated following repeated daily application of a water-emulsifying ointment containing the equivalent of 3% boric acid to the napkin region. The mean plasma-boron concentration fell over 5 days from a pretreatment value of 0.49 to 0.29 mg/litre, the corresponding values in ten untreated neonates being 0.62 and 0.21 mg/litre, respectively. No statistically significant differences were found. The results confirm the safety of such ointments for application to the skin, a conclusion predicted by theoretical estimates of the maximum possible boric acid absorption following application of the ointment.


Development and validation of the Uniform Data Set (v3.0) executive function composite score (UDS3-EF).
Cognitive composite scores offer a means of precisely measuring executive functioning (EF). We developed the Uniform Data Set v3.0 EF composite score (UDS3-EF) in 3507 controls from the National Alzheimer's Coordinating Center dataset using item-response theory and applied nonlinear and linear demographic adjustments. The UDS3-EF was validated with other neuropsychological tests and brain magnetic resonance imaging from independent research cohorts using linear models. Final model fit was good-to-excellent: comparative fit index = 0.99; root mean squared error of approximation = 0.057. UDS3-EF scores differed across validation cohorts (controls > mild cognitive impairment > Alzheimer's disease-dementia ≈ behavioral variant frontotemporal dementia; P < 0.001). The UDS3-EF correlated most strongly with other EF tests (βs = 0.50 to 0.85, Ps < 0.001) and more with frontal, parietal, and temporal lobe gray matter volumes (βs = 0.18 to 0.33, Ps ≤ 0.004) than occipital gray matter (β = 0.12, P = 0.04). The total sample needed to detect a 40% reduction in UDS3-EF change (n = 286) was ≈40% of the next best measure (F-words; n = 714). The UDS3-EF is well suited to quantify EF in research and clinical trials and offers psychometric and practical advantages over its component tests.


A bonanza-blank pollinator reward schedule in Delphinium nelsonii (Ranunculaceae).
Data indicate a non-random distribution of nectar among plants in a population of Delphinium nelsonii Greene. More plants than expected had no nectar (blanks) or large amounts of nectar (bonanzas), while fewer plants than expected had intermediate amounts of nectar. This bonanza-blank pollinator reward schedule suggests that a high proportion of the nectar obtained by pollinators comes from occasional bonanza plants encountered in the population.