Miracle-dz/UniFAR-FTUs huggingface dataset:
Ocular novel drug delivery: impacts of membranes and barriers

Background: Ocular drug delivery is an extremely challenging area due to its restrictive barrier functionalities. Objective: Drug transport via corneal/non-corneal routes involves several intricate biological processes such as drug penetration across the ocular barriers and transfer to the anterior or posterior chambers, thus the influence of these processes on the pharmacotherapy of the eye should be fully addressed. Methods: To pursue the impacts of such impediments in novel drug therapy, recent publications were reviewed regarding advanced strategies such as nanomedicines. Conclusion: The ocular barriers are highly specialized and selectively control the inward/outward traverse of compounds, hence a better understanding of these biological obstacles would provide a platform to advance ophthalmic drug therapy towards specified delivery/targeting with minimal adverse consequences.
Photosynthate partitioning to starch in Arabidopsis thaliana is insensitive to light intensity but sensitive to photoperiod due to a restriction on growth in the light in short photoperiods.

Photoperiod duration can be predicted from previous days, but irradiance fluctuates in an unpredictable manner. To investigate how allocation to starch responds to changes in these two environmental variables, Arabidopsis Col-0 was grown in a 6 h and a 12 h photoperiod at three different irradiances. The absolute rate of starch accumulation increased when photoperiod duration was shortened and when irradiance was increased. The proportion of photosynthate allocated to starch increased strongly when photoperiod duration was decreased but only slightly when irradiance was decreased. There was a small increase in the daytime level of sucrose and twofold increases in glucose, fructose and glucose 6-phosphate at a given irradiance in short photoperiods compared to long photoperiods. The rate of starch accumulation correlated strongly with sucrose and glucose levels in the light, irrespective of whether these sugars were responding to a change in photoperiod or irradiance. Whole plant carbon budget modelling revealed a selective restriction of growth in the light period in short photoperiods. It is proposed that photoperiod sensing, possibly related to the duration of the night, restricts growth in the light period in short photoperiods, increasing allocation to starch and providing more carbon reserves to support metabolism and growth in the long night.
On the detection of newer Epo forms in serum and urine using isoelectric focusing

To the Editor: In a recent article in your journal, Delanghe et al. [1]. reviewed both the indirect and direct methods for the detection of recombinant human erythropoietin (rhEPO) in doping analysis. However, some of the statements made are incorrect and some others deserve clarification. The direct detection of the misuse of rhEPO and analogues in sports is currently done in World Antidoping Agency (WADA) accredited laboratories following the method developed by Lasne [2], which is based on the differences in the isoelectric focusing (IEF) behavior between endogenously produced urinary EPO (uEPO) and the recombinant products (epoetin alpha, beta, etc.) and analogues (i.e., darbepoetin alpha). Those differences are claimed to reside in the glycans of those glycoproteins, resulting from the enzymatic endowment of the particular cell in which the protein is expressed as well as from the selective purification applied to obtain each pharmaceutical product. The article, however, is wrong in stating that epoetin omega is produced in human cells. Epoetin omega is produced in Baby Hamster Kidney (BHK) cells [3]. Its glycosylation profile is monitored using the same IEF method and it is perfectly distinguishable from endogenous EPO (Fig. 1). Epoetin delta (Dynepo, Shire Pharmaceuticals) is expressed in human cells, although it
Breastfeeding is negatively affected by prenatal depression and reduces postpartum depression

Background This prospective cohort study explored the effects of prenatal and postpartum depression on breastfeeding and the effect of breastfeeding on postpartum depression. Method The Edinburgh Postpartum Depression Scale (EPDS) was administered to 145 women at the first, second and third trimester, and at the neonatal period and 3 months postpartum. Self-report exclusive breastfeeding since birth was collected at birth and at 3, 6 and 12 months postpartum. Data analyses were performed using repeated-measures ANOVAs and logistic and multiple linear regressions. Results Depression scores at the third trimester, but not at 3 months postpartum, were the best predictors of exclusive breastfeeding duration (β = −0.30, t = −2.08, p < 0.05). A significant decrease in depression scores was seen from childbirth to 3 months postpartum in women who maintained exclusive breastfeeding for ⩾3 months (F 1,65 = 3.73, p < 0.10, η p 2 = 0.05). Conclusions These findings suggest that screening for depression symptoms during pregnancy can help to identify women at risk for early cessation of exclusive breastfeeding, and that exclusive breastfeeding may help to reduce symptoms of depression from childbirth to 3 months postpartum.
Análise das velocidades: referencial de 4mM, de equilíbrio de 30 min e velocidade crítica em nadadoras adolescentes

OBJECTIVE: To compare the results of the calculation of the anaerobic threshold velocity (AT), corresponding to 4 mM lactate, obtained in 2 x 400 m (V4-2), 4 x 400 m (V4-4) tests and critical velocity (CV) relating to the mean velocity determined in the 30 min test (VMT30) in female adolescent swimmers. METHODS: Twenty female swimmers (14.36 ± 1.22 years old; 52.75 ± 5.32 kg ; 159.97 ± 11.26 cm; % body fat 22.5 ± 4.73),with city and state level with at least two years of sistematic training participated in this study. Performed tests: 30 min test (MVT30), two-distance test (V4-2), four-distance test (V4-4) and critical velocity (CV). Statistical analysis: the procedure adopted to compare all methodologies, two by two, was the single regression analysis technique. RESULTS: The mean velocities were: T30: 1.12 ± 0.06 m/s; V4-2: 1.14 ± 0.12 m/s; V4-4: 1.12 ± 0.06 m/s and CV mean = 1.14 ± 0.07 m/s. Single regression analysis between metodologies, two by two: V4-4 and V4-2 (r = 0.324); CVand V4-2 (r = 0,058); MVT30 and V4-2 (r = 0.595); CV and V4-4 (r = 0.807); MVT30 and V4-4 (r = 0,796) and MVT30 and CV (r = 0,77). The adjusted regression lines presented in relation to the bisectrix the values of p = 0.3060; 0.1716 and 0.0058. CONCLUSIONS: The VMT30 determination is a good instrument for training prescription for the female adolescent swimmers studied, unlike the V4-2 model. The 4mM [La] with four points and lactate threshold calculation using random effects technique was useful for the AT determination in female adolescent swimmers, when compared to the MVT30; the CV and V4-4 presented a good correlation as well as the CV and MVT30.
Immediate Weightbearing of First Metatarsophalangeal Joint Fusion Comparing Buried Crossed Kirschner Wires Versus Crossing Screws: Does Incorporating the Sesamoids Into the Fusion Contribute to Higher Incidence of Bony Union?

First metatarsophalangeal joint (MTPJ) arthrodesis remains a commonly used and reliable procedure for a variety of pathologies of the first MTPJ. Many costly fixation constructions have been described to achieve union with first MTPJ arthrodesis. We hypothesized that the incidence of union would be the same for both buried Kirchner (K)-wire and solid crossed screw fixation with immediate weightbearing. To test this hypothesis, we retrospectively reviewed first MTPJ fusions performed by the senior author (C.A.C.) during a 6-year period and compared the incidence of union. Only patients who were immediately weightbearing in a surgical shoe and had undergone first MTPJ arthrodesis using K-wires or crossed screws were included. All patients had undergone incorporation of their sesamoids into the fusion. A total of 97 feet in 89 patients met the inclusion criteria. Of the 97 first MTPJ fusions, 48 (49.5%) had buried K-wire fixation and 49 (50.5%) crossed screw fixation. The mean age was 62 (range 41 to 75) years in the K-wire group and 60 (range 22 to 73) years in the crossed screw group. The mean follow-up period was 12.4 months in the K-wire group and 12.9 months in the crossed screw group. The rate of union in the K-wire group was 98% (1 nonunion) and the rate of union in the crossed screw group was 96% (2 nonunions). The 2 groups demonstrated similar high rates of fusion with immediate weightbearing, suggesting that less costly fixation is acceptable and effective for uncomplicated first MTPJ fusion.
Fingertip replantation at or beyond the nail base in children

Although success of digital replantations in children has been reported by many authors, the very distal fingertip replantation remains technically demanding. The aim of this article is to review our experience with fingertip replantations at or distal to the nail base in pediatric patients and evaluate the clinical outcomes. From October 2000 to May 2007, 12 pediatric fingertips amputated at or distal to the nail base were replanted. Only one artery was anastomosed for revascularization with or without nerve repair; vein drainage was provided by the controlled bleeding technique. Eleven of the 12 replants (91%) survived; one replant of crushed digit failed. An average of 26 month (range, 6 to 36 months) follow‐up revealed excellent restoration of finger motion and appearance. The regained static 2‐point discrimination (S2PD) sensation was from 3.2 to 5.0 mm (mean, 4.2 mm). Both the parents and the children were satisfied with the final results. In conclusion, fingertip replantation in children allows good functional and esthetical recovery and should be attempted if technically feasible. © 2010 Wiley‐Liss, Inc. Microsurgery 30:380–385, 2010.
Reinforcement Learning based Voice Interaction to Clear Path for Robots in Elevator Environment

Efficient use of the space in an elevator is very necessary for a service robot, due to the need for reducing the amount of time caused by waiting for the next elevator. To provide a solution for this, we propose a hybrid approach that combines reinforcement learning (RL) with voice interaction for robot navigation in the scene of entering the elevator. RL provides robots with a high exploration ability to find a new clear path to enter the elevator compared to traditional navigation methods such as Optimal Reciprocal Collision Avoidance (ORCA). The proposed method allows the robot to take an active clear path action towards the elevator whilst a crowd of people stands at the entrance of the elevator wherein there are still lots of space. This is done by embedding a clear path action (voice prompt) into the RL framework, and the proposed navigation policy helps the robot to finish tasks efficiently and safely. Our model approach provides a great improvement in the success rate and reward of entering the elevator compared to state-of-the-art navigation policies without active clear path operation.
Treatment of Relapsing Clostridium difficile Diarrhea with Lactobacillus GG

Thirty-two patients with relapsing C. difficile diarrhea were treated with a lyophilized preparation of Lactobacillus GG; 23 were outpatients treated in Boston, Massachusetts, and nine were nursing-home patients in Baltimore, Maryland. After receiving Lactobacillus GG, all subjects improved symptomatically. Twenty-seven (84%) patients were cured by the single treatment, based on a minimum follow-up of 2 months. Five others relapsed within 10 days after initial Lactobacillus GG treatment; three were retreated and cured, and two were lost to follow-up and are considered failures. The use of Lactobacillus GG offers a safe and. relatively effective alternative to antibiotic therapy for relapsing C. difficile diarrhea.
The quality of the interparental relationship does not moderate the etiology of child conduct problems

Background Although there is a clear phenotypic relationship between the quality of the interparental or marital relationship and child conduct problems (CP), the etiology of this association is as yet unclear. One possibility is that this association takes the form of a genotype–environment interaction (G × E), whereby the quality of the interparental relationship acts to moderate the etiology of child CP. The current study sought to evaluate this possibility. Method We examined multiple measures and informant reports of the quality of the interparental relationship in a sample of more than 700 child twin families from the Michigan State University Twin Registry (MSUTR). Analyses consisted of a series of latent G × E models. Results The ‘no moderation’ model provided the best fit to the data in nearly all cases, findings that collectively provide strong evidence against the possibility that the etiology of CP is moderated by the quality of the interparental relationship. Conclusions Our findings suggest that, contrary to implicit (and sometimes explicit) assumptions in the field, it is not the case that every environmental risk (or protective) factor exacerbates (or suppresses) genetic influences on CP. Future research should seek to delineate the specific environmental experiences that do serve as etiologic moderators of CP, and to clarify how this G × E interplay might change over the course of development.
Critical analysis of empiric antibiotic utilization: establishing benchmarks.

AIM We critically evaluated empiric antibiotic practice in the surgical and trauma intensive care unit (STICU) with three specific objectives: (1) To characterize empiric antibiotics practice prospectively; (2) to determine how frequently STICU patients started on empiric antibiotics subsequently have a confirmed infection; and (3) to elucidate the complications associated with unnecessary empiric antibiotic therapy. METHODS We collected data prospectively using the Surgical Intensive Care-Infection Registry (SIC-IR) including all 1,185 patients admitted to the STICU for >2 days from March 2007 through May 2008. Empiric antibiotics were defined as those initiated because of suspected infections. RESULTS The mean patient age was 56 years and 62% were male. The mean STICU length of stay was eight days, and the mortality rate was 4.6%. Empiric antibiotics were started for 26.3% of the patients. The average length of antibiotic use was three days. Of the 312 patients started on empiric antibiotics, only 25.6% were found to have an infection. Factors associated with correctly starting empiric antibiotics were a longer STICU stay (5 vs. 3 days), prior antibiotics (29% vs. 17%), and mechanical ventilation (93% vs. 79%). Patients who were started on antibiotics without a subsequent confirmed infection were compared with patients not given empiric antibiotics. Incorrect use of empiric antibiotics was associated with younger age (p < 0.001), more STICU days (10.6 vs. 5.9 days; p < 0.001), more ventilator days (p < 0.001), more development of acute renal failure (24.1% vs. 12.1%; p < 0.001), and a significant difference in mortality rate (8.6% vs. 3.2%; p < 0.001). CONCLUSIONS After admission to the STICU, 26% of patients received at least one course of empiric antibiotics. Only 25.6% of these patients were confirmed to have an infection. These results provide key benchmark data for the critical care community to improve antibiotic stewardship.
Anti‐inflammatory effects of anthocyanins from black soybean seed coat on the keratinocytes and ischemia‐reperfusion injury in rat skin flaps

Ischemia‐reperfusion injury is a phenomenon that occurs when tissues are subjected to ischemia for a variable period of time, and then reperfused. Inflammatory reaction has been implicated as one of the most important mechanism of ischemia‐reperfusion injury. The purpose of this study was to evaluate the anti‐inflammatory effects of anthocyanins from black soybean seed coat on keratinocytes in vitro and ischemia‐reperfusion injury in vivo. We investigated the inhibition, by anthocyanins, of the expression of various inflammatory genes associated with ischemia‐reperfusion injury in the tumor necrosis factor‐alpha‐treated (TNF‐α) immortalized epidermal keratinocyte cell line (HaCaT). We also investigated the effects of anthocyanins on the survival of skin flaps after ischemia‐reperfusion injury in the rats. According to Western blot analysis and a luciferase activity assay, anthocyanins inhibited TNF‐α‐induced intercellular adhesion molecule‐1 and cyclooxygenase‐2 (COX‐2) levels through the NF‐κB‐dependent pathway. Administration of anthocyanins (50 and 100 mg/kg) significantly improved the flap area survival in the 10‐hour ischemic model from 62% to 74.5% and 83%, respectively (P = 0.001). The related cytokines in skin flap also changed as the same pattern as in vitro. Our results indicate that anthocyanins from black soybean seed coat had anti‐inflammatory effects on the HaCaT cell line and increase the survival of skin flaps through anti‐inflammatory properties against ischemia‐reperfusion injury. © 2012 Wiley Periodicals, Inc. Microsurgery, 2012.
Age-specific suicide mortality following non-fatal self-harm: national cohort study in Sweden

Background. Possible age-related differences in risk of completed suicide following non-fatal self-harm remain unexplored. We examined associations between self-harm and completed suicide across age groups of self-harming patients, and whether these associations varied by violent index method, presence of mental disorder, and repeated self-harm. Method. The design was a cohort study with linked national registers in Sweden. The study population comprised individuals aged ⩾10 years hospitalized during 1990–1999 due to non-fatal self-harm (n = 53 843; 58% females) who were followed for 9–19 years. We computed hazard ratios (HRs) across age groups (age at index self-harm episode), with time to completed suicide as outcome. Results. The 1-year HR for suicide among younger males (10–19 years) was 14.6 [95% confidence interval (CI) 4.1–51.9] for violent method and 8.4 (95% CI 1.8–40.0) for mental disorder. By contrast, none of the three potential risk factors increased the 1-year risks in the youngest females. Among patients aged ⩾20 years, the 1-year HR for violent method was 4.6 (95% CI 3.8–5.4) for males and 10.4 (95% CI 8.3–13.0) for females. HRs for repeated self-harm during years 2–9 of follow-up were higher in 10- to 19-year-olds (males: HR 4.0, 95% CI 2.0–7.8; females: HR 3.7, 95% CI 2.1–6.5). The ⩾20 years age groups had higher HRs than the youngest, particularly for females and especially within 1 year. Conclusions. Violent method and mental disorder increase the 1-year suicide risk in young male self-harm patients. Further, violent method increases suicide risk within 1 year in all age and gender groups except the youngest females. Repeated self-harm may increase the long-term risk more in young patients. These aspects should be accounted for in clinical suicide risk assessment.
Minor physical anomalies and craniofacial measures in patients with treatment-resistant schizophrenia

Background Schizophrenia patients have higher rates of minor physical anomalies (MPAs) than controls, particularly in the craniofacial region; this difference lends support to the neurodevelopmental model of schizophrenia. Whether MPAs are associated with treatment response in schizophrenia remains unknown. The aim of this case–control study was to investigate whether more MPAs and specific quantitative craniofacial features in patients with schizophrenia are associated with operationally defined treatment resistance. Method A comprehensive scale, consisting of both qualitatively measured MPAs and quantitative measurements of the head and face, was applied in 108 patients with treatment-resistant schizophrenia (TRS) and in 104 non-TRS patients. Treatment resistance was determined according to the criteria proposed by Conley & Kelly (2001; Biological Psychiatry 50, 898–911). Results Our results revealed that patients with TRS had higher MPA scores in the mouth region than non-TRS patients, and the two groups also differed in four quantitative measurements (facial width, lower facial height, facial height, and length of the philtrum), after controlling for multiple comparisons using the false discovery rate. Among these dysmorphological measurements, three MPA item types (mouth MPA score, facial width, and lower facial height) and earlier disease onset were further demonstrated to have good discriminant validity in distinguishing TRS from non-TRS patients in a multivariable logistic regression analysis, with an area under the curve of 0.84 and a generalized R 2 of 0.32. Conclusions These findings suggest that certain MPAs and craniofacial features may serve as useful markers for identifying TRS at early stages of the illness.
Associations between serotonin transporter gene (SLC6A4) methylation and clinical characteristics and cortical thickness in children with ADHD

Background. Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable psychiatric disorder. Additionally, environmental factors such as perinatal stress and early adversities contribute to the occurrence and severity of ADHD. Recently, DNA methylation has emerged as a mechanism that potentially mediates gene–environmental interaction effects in the aetiology and phenomenology of psychiatric disorders. Here, we investigated whether serotonin transporter gene (SLC6A4) methylation patterns were associated with clinical characteristics and regional cortical thickness in children with ADHD. Method. In 102 children with ADHD (age 6–15 years), the methylation status of the SLC6A4 promoter was measured. Brain magnetic resonance imaging was obtained and ADHD symptoms were evaluated. Results. A higher methylation status of the SLC6A4 promoter was significantly associated with worse clinical presentations (more hyperactive-impulsive symptoms and more commission errors). Additionally, a negative correlation was observed between SLC6A4 methylation levels and cortical thickness values in the right occipito-temproral regions. Conclusions. Our results suggest that the SLC6A4 methylation status may be associated with certain symptoms of ADHD, such as behavioural disinhibition, and related brain changes. Future studies that use a larger sample size and a control group are required to corroborate these results.
The extent of whole‐genome copy number alterations predicts aggressive features in primary melanomas

Recent evidence indicates that melanoma comprises distinct types of tumors and suggests that specific morphological features may help predict its clinical behavior. Using a SNP‐array approach, we quantified chromosomal copy number alterations (CNA) across the whole genome in 41 primary melanomas and found a high degree of heterogeneity in their genomic asset. Association analysis correlating the number and relative length of CNA with clinical, morphological, and dermoscopic attributes of melanoma revealed that features of aggressiveness were strongly linked to the overall amount of genomic damage. Furthermore, we observed that melanoma progression and survival were mainly affected by a low number of large chromosome losses and a high number of small gains. We identified the alterations most frequently associated with aggressive melanoma, and by integrating our data with publicly available gene expression profiles, we identified five genes which expression was found to be necessary for melanoma cells proliferation. In conclusion, this work provides new evidence that the phenotypic heterogeneity of melanoma reflects a parallel genetic diversity and lays the basis to define novel strategies for a more precise prognostic stratification of patients.