Difference in clinical features and HLA antigens between familial and non-familial vitiligo of non-segmental type.
Of 131 patients with non-segmental vitiligo studied, 29 (22%) had a family history of this disorder. The clinical features and HLA antigens were assessed, and a comparison made between patients with familial and those with non-familial, non-segmental vitiligo. Familial patients developed skin lesions significantly earlier than non-familial patients. There was a significant association between HLA-B46 and familial non-segmental vitiligo, whereas HLA-A31 and CW4 were found in non-familial patients. The differences in clinical features and HLA phenotypes suggest heterogeneity in the pathogenic process between familial and non-familial vitiligo patients.


[Rowell's syndrome or systemic lupus erythematosus and erythema multiforme. Association or coincidence?].
Rowell's syndrome is characterized by the association of systemic lupus erythematosus (SLE) and erythema multiforme-like lesions with the presence of immunological markers such as antinuclear antibodies with speckled pattern, anti-La antibodies and rheumatoid factor. We present the case of a 22-year-old woman with a diagnosis of SLE and erythema multiforme and discuss the possibility of distinguishing these entities from Rowell's syndrome.


High resolution ultrasonography of the parotid gland in children.
High resolution ultrasonography has revolutionized imaging of the superficial parotid gland. The fine morphology of the parotid gland can be exquisitely visulized. Anatomical landmarks such as the mastoid tip, the sternocleidomastoid muscle, the styloid process, the posterior facial vein, the internal jugular vein, and the external carotid artery can easily be identified in relationship to the parotid. The course of the facial nerve can be inferred by visualization of these landmarks. Common masses within the parotid in children such as hemangiomas, mixed parotid tumors, and lymphadenopathy can be demonstrated. Parotid masses are uncommon in children but can be easily evaluated by high resolution ultrasonography.


Percutaneous endoscopic sigmoidopexy using T-fasteners for management of sigmoid volvulus.
Sigmoid volvulus (SV) is the third leading cause of large bowel obstruction after colonic neoplasms and diverticular disease. SV has traditionally been managed via endoscopic detorsion and decompression followed by non-emergent surgical resection owing to the high risk of recurrence. Most cases of SV occur in elderly debilitated patients with multiple comorbidities and may not be candidates for surgical resection. Endoscopic sigmoidopexy has been described as an alternative to surgical resection. Here, we describe our experience with endoscopic sigmoidopexy using T-fasteners. Three patients with recurrent SV that were identified as poor surgical candidates by our colorectal surgery team underwent endoscopic sigmoidopexy. The patients received preoperative bowel preparation. A colonoscope was inserted and the site of the volvulus was visualized and assessed for adequate decompression. Subsequently, four points of fixation were identified and T-fasteners were deployed. Two patients underwent successful sigmoidopexy without any complications or recurrence on follow-up. One patient developed post procedure pneumoperitoneum that was successfully treated conservatively; however, he passed away from their underlying comorbidities. Overall, preliminary results for sigmoidopexy using T-fasteners have been promising, offering a potential option to prevent recurrence in high risk patients unsuitable for surgical intervention.


Machine learning prediction of emesis and gastrointestinal state in ferrets.
Although electrogastrography (EGG) could be a critical tool in the diagnosis of patients with gastrointestinal (GI) disease, it remains under-utilized. The lack of spatial and temporal resolution using current EGG methods presents a significant roadblock to more widespread usage. Human and preclinical studies have shown that GI myoelectric electrodes can record signals containing significantly more information than can be derived from abdominal surface electrodes. The current study sought to assess the efficacy of multi-electrode arrays, surgically implanted on the serosal surface of the GI tract, from gastric fundus-to-duodenum, in recording myoelectric signals. It also examines the potential for machine learning algorithms to predict functional states, such as retching and emesis, from GI signal features. Studies were performed using ferrets, a gold standard model for emesis testing. Our results include simultaneous recordings from up to six GI recording sites in both anesthetized and chronically implanted free-moving ferrets. Testing conditions to produce different gastric states included gastric distension, intragastric infusion of emetine (a prototypical emetic agent), and feeding. Despite the observed variability in GI signals, machine learning algorithms, including k-nearest neighbors and support vector machines, were able to detect the state of the stomach with high overall accuracy (>75%). The present study is the first demonstration of machine learning algorithms to detect the physiological state of the stomach and onset of retching, which could provide a methodology to diagnose GI diseases and symptoms such as nausea and vomiting.


Progress and Future Goals for Neuroscience.
Scientists reflect on how neuroscience has quickly progressed and continues to open new avenues for great discovery with improvements in imaging, interrogating, and interfacing with the nervous system of experimental model systems and humans.


Effect of the antiandrogen, WIN 49,596, on the descent of the testis in the male rat.
Testicular descent in the male rat is believed to be an androgen dependent event with dihydrotestosterone the most likely active androgen. To provide further insight into the endocrinology of this important physiological event, we treated male rats with the antiandrogen, WIN 49596 (50 mg./kg./day), from day 1 to day 27 of age and evaluated its effect on the post-natal androgen-dependent events in this animal model. It was determined that while treatment with WIN inhibited the weights of the ventral prostate, seminal vesicles and penis when compared to those seen in castrate animals, the drug only caused a 19% (3/16) inhibition in the descent of the testes when compared to the control group (0/16; p = 0.112). These data together with those previously obtained in animals exposed to selective inhibitors of the 5-alpha reductase enzyme suggest that other factors possibly working in tandem with androgens play a predominant role in testicular descent in the rat.


Repair of fresh open tear of Achilles tendon Tension regulation at the suture line.
Lack of the timely mechanical loading of the repaired tendon is detrimental for healing progress. The current knowledge knows the appropriate time for the mechanical loading, but need to find out a suitable tool for this purpose. Therefore we present a technique based on using of an absorbable reinforcement device for tension regulation at the suture line. 24 patients with open tear of Achilles tendon were repaired surgically, the repair was reinforced using an absorbable suture and the outcomes were prospectively assessed at 24 months. No tendon lengthening or reruptures were reported; patients returned to pre-injury daily activates by fourth month. One patient reported 1cm atrophy of the calf, scar adhesion Grade 1 and ankle dorsiflexion decreased 5°. Restoration of the continuity and actual length of repaired tendons support use of the absorbable reinforcement device for regulation of the mechanical environment at the suture line.


Electroencephalogram and heart rate variability features as predictors of responsiveness to vagus nerve stimulation in patients with epilepsy: a systematic review.
Vagus nerve stimulation (VNS) is a mainstay treatment in people with medically refractive epilepsy with a growing interest to identify biomarkers that are predictive of VNS efficacy. In this review, we looked at electroencephalography (EEG) and heart rate variability (HRV) parameters as potential biomarkers. A comprehensive search of several databases limited to the English language and excluding animal studies was conducted. Data was collected from studies that specifically reviewed preoperative EEG and HRV characteristics as predictive factors of VNS outcomes. Ten out of 1078 collected studies were included in this review, of which EEG characteristics were reported in seven studies; HRV parameters were reported in two studies, and one study reported both. For EEG, studies reported a lower global rate of synchronization in alpha, delta, and gamma waves as predictors of the VNS response. The P300 wave, an evoked response on EEG, had conflicting results. Two studies reported high P300 wave amplitudes in nonresponders and low amplitudes in responders, whereas another study reported high P300 wave amplitudes in responders. For HRV, one study reported high-frequency power as the only parameter to be significantly lower in responders. In contrast, two studies from the same authors showed that HRV parameters were not different between responders and nonresponders. HRV parameters and EEG characteristics including focal seizures and P300 wave have been reported as potential biomarkers for VNS outcomes in people with medically refractive epilepsy. However, the contradictory findings imply a need for validation through clinical trials.


ELECTROMYOGRAPHIC ANALYSIS OF GLUTEAL RECRUITMENT: AN EXPLORATION OF ACTIVATION DURING JUMPING TASKS.
Inability to maintain proper alignment of the pelvis and femur due to gluteal muscle weakness has been associated with numerous lower extremity pathologies. Therefore, many lower extremity rehabilitation and injury prevention programs employ exercises that target gluteal muscle strength and activation. While information regarding muscle activation during exercises that are typically done in the beginning stages of rehabilitation is available, evidence regarding the gluteal muscle activity during more functional and advanced exercises used during later stages of rehabilitation is sparse. To explore the recruitment of the gluteal muscles during jumping tasks in healthy participants to determine which jumping exercise best elicits gluteal muscle activation. Prospective cohort design. Eighteen healthy recreational athletes (23.5 ± 3.8 years, 8M/10F, 67.56 ± 3.2 inches, 66.73 ± 9.5 kg) completed three trials of four jumping tasks: hurdle jump, split jump, V2 lateral jump, and cross-over jump in random order. Surface EMG electrodes were placed on each participant's bilateral gluteus medius (GMed) and maximus (GMax) to measure muscle activity during the jumping tasks. Maximal voluntary isometric muscle contraction (MVIC) was established for each muscle group in order to express each jumping task as a percentage of MVIC and allow standardized comparison across participants. EMG data were analyzed for all jumps using a root-mean-square algorithm and smoothed with a 62.5 millisecond time reference. Rank ordering of muscle activation during jumping tasks was performed utilizing the peak percent MVIC recorded during each jumping task. Three of the jumping tasks produced greater than 70% MVIC of the GMed muscle. In rank order from highest EMG value to lowest, these jumping tasks were: crossover jump (103% MVIC), hurdle jump (93.2% MVIC), and V2 lateral jump (84.7% MVIC). Two of the exercises recruited GMax with values greater than 70% MVIC. In rank order from highest EMG value to lowest, these jumping tasks were: hurdle jump (76.8% MVIC) and split jump (73.1% MVIC). Only the hurdle jump produced greater than 70% MVIC for both GMed and GMax muscles. The jumping task that resulted in greatest activation of the GMed was the crossover jump, while hurdle jump led to the greatest activation of the GMax. The high %MVIC for the GMed during the crossover jump may be attributed to lack of maximal effort or lack of motivation during performance of maximal contractions during the manual muscle testing. Alternatively, substantial co-contraction of core muscles during the crossover jumping task may have led to higher values. 2b Individual Cohort Study.


Laparoscopy versus laparotomy gastric pull-up following thoracoscopic esophagectomy: A propensity score-matched analysis.
Because of its capacity to reduce surgical trauma to the chest wall, thoracoscopic esophagectomy is considered paramount for decreasing the risk of pulmonary complications in the context of minimally invasive esophagectomy. Whether laparoscopy (LS) following thoracoscopic esophagectomy can further improve outcomes compared with open laparotomy (OL) is unknown. We retrospectively reviewed the clinical and imaging records of 428 patients who received McKeown esophagectomy with a thoracoscopic approach for cancer. Using propensity score matching based on eight parameters (age, sex, body mass index, Charlson comorbidity index, tumor location, type of preoperative therapy, reconstruction route, and occurrence/severity of postoperative vocal cord palsy), 60 pairs were identified and compared with regard to perioperative complications and overall survival (OS). Compared with OL, LS resulted in lower blood loss (mean: 171.21 versus 107.58 mL, respectively, p = 0.023) and a reduced incidence of pneumonia (13.3% versus 3.3%, respectively, p = 0.048), albeit at the expense of a longer operating time (mean: 399.37 versus 443.93 min, respectively, p = 0.003). Notably, lymph node yields and OS of patients who were treated with LS were similar to those observed in those who underwent OL. Patients who receive LS after thoracoscopic esophagectomy experience lower blood loss and have a reduced risk of pneumonia than those treated with OL.


Muscle fibre type composition in infant and adult populations and relationships with obesity.
To investigate the fibre type composition of skeletal muscle in infants and young children and to compare the findings to an adult population. To relate the fibre type profile of skeletal muscle in adults to measures of adiposity. Cross-sectional studies of skeletal muscle fibre composition in infants and adults with measures of adiposity in the adults. 21 healthy infants and young children (age: 3-21 months) and 40 healthy adult Australian Caucasians (age: 26-62 y; BMI: 18-48 kg/m2). Skeletal muscle fibre type composition (by myosin ATPase method) and relative body fatness (BMI, waist circumference and waist/hip ratio (WHR)). Infants and young children had significantly lesser proportions of glycolytic Type 2b fibres (6.2 +/- 1.1%; range 0.3-18.9%) compared with adults (20.5 +/- 1.6%; range 4.9-36.0%) (p < 0.0001). The percentage of Type 2b fibres was directly related to BMI (r = 0.44, p = 0.02), waist circumference (r = 0.49, p = 0.009) and WHR (r = 0.44, p = 0.02) in adults. A significant, direct relationship was also found between the proportion of glycolytic Type 2b fibres and age in the adults (r = 0.45, p = 0.01). Skeletal muscle fibre type composition is different in infants and adults and there is an age-dependent increase in Type 2b fibres over the lifespan. An increased proportion of glycolytic Type 2b fibres is associated with obesity in adults. Results support a gene-environment interaction on fibre type composition in human skeletal muscle.


Drug targets in Leishmania.
Leishmaniasis is a major public health problem and till date there are no effective vaccines available. The control strategy relies solely on chemotherapy of the infected people. However, the present repertoire of drugs is limited and increasing resistance towards them has posed a major concern. The first step in drug discovery is to identify a suitable drug target. The genome sequences of Leishmania major and Leishmania infantum has revealed immense amount of information and has given the opportunity to identify novel drug targets that are unique to these parasites. Utilization of this information in order to come up with a candidate drug molecule requires combining all the technology and using a multi-disciplinary approach, right from characterizing the target protein to high throughput screening of compounds. Leishmania belonging to the order kinetoplastidae emerges from the ancient eukaryotic lineages. They are quite diverse from their mammalian hosts and there are several cellular processes that we are getting to know of, which exist distinctly in these parasites. In this review, we discuss some of the metabolic pathways that are essential and could be used as potential drug targets in Leishmania.


Parental presence after significant procedures and medical events in the neonatal intensive care unit.
Very low birth weight (VLBW) and extremely preterm (EPT) infants typically experience multiple significant medical events, while in the neonatal intensive care unit (NICU), we aimed to identify how major medical and procedural events were associated with parental presence in this patient population. We retrospectively identified VLBW/EPT neonates at a single center and determined parental presence in the first 60 days of hospitalization based on routine documentation in the electronic medical record. The presence on each day was regressed on medical events and procedures occurring within the previous day using mixed-effects logistic regression. The analysis included 174 infants contributing 8750 days (observations), including 6061 days (69%) with parental presence, and 607 days (7%) with major medical events or procedures. The occurrence of a medical event or procedure within the past day increased the odds of parental presence by 28% (odds ratio: 1.28; 95% confidence interval: 1.04, 1.57; p = .018). Further analysis found this association was limited to severe (versus moderate) events and procedures, and was absent when considering events over the past week (versus the past day). Major medical events or procedures are associated with increased parental presence in the NICU. Future studies are needed to determine how interventions around the time of major medical events can support parental presence in the NICU and involvement in the child's care.


Differential induction of glucose-regulated and heat shock proteins: effects of pH and sulfhydryl-reducing agents on chicken embryo cells.
Glucose-regulated and heat shock proteins are two subsets of eukaryotic stress proteins that can be induced differentially, simultaneously, and reciprocally. Two new inducers, low extracellular pH and 2-mercaptoethanol, that stimulate chicken embryo cells to synthesize glucose-regulated proteins rapidly were found. Two classes of cellular targets for mercaptoethanol were defined operationally, one dependent on and the other independent of protein synthesis. A new inducer of heat shock proteins, high extracellular pH, was found as well. Inductions by low and high extracellular pH were inhibited by actinomycin D but were insensitive to cycloheximide. Inductions of glucose-regulated and heat shock proteins are discussed in terms of changes in intracellular pH and sulfhydryl oxidation states.


Non-immune hydrops fetalis associated with two umbilical cord hemangiomas and vascular malformation of the transverse mesocolon. Case report.
Umbilical cord hemangioma is a rare tumor that can be associated with significant fetal and perinatal complications. Although usually described as a single anomaly, sometimes these tumors are reported in association with other vascular lesions. We report an unusual case of simultaneous occurrence of two umbilical cord hemangiomas and vascular malformation of the transverse mesocolon in a stillborn fetus with hydrops. To our knowledge, this is the first report of two simultaneously occurring umbilical cord hemangiomas. Moreover, presence of associated vascular malformation of transverse mesocolon could support the hypothesis of underlying predisposition to the development of vascular tumors.


Effects of prenatal cocaine exposure on pubertal development.
The purpose of the current study was to examine the relationship between prenatal cocaine exposure (PCE) and pubertal development. Children (n=192; 41% with PCE) completed the Pubertal Development Scale (Petersen et al. 1988) and provided salivary dehydroepiandrosterone (DHEA) samples at 6month intervals from 11 to 13years. PCE was examined as a predictor of pubertal status, pubertal tempo, and DHEA levels in mixed models analyses controlling for age, sex, environmental risk, neonatal medical problems, other prenatal exposures, and BMI. PCE interacted with age such that PCE predicted slower pubertal tempo during early adolescence. PCE also interacted with age to predict slower increases in DHEA levels during early adolescence. These findings suggest that PCE may affect pubertal development and, if slower pubertal tempo continues, could lead to delayed pubertal status in mid-adolescence.


Aneurysmal bone cysts of the spine.
The article reviews aneurysmal bone cysts of the spine and current diagnostic tests approaches and therapeutic interventions are discussed.


Early life stress and development: potential mechanisms for adverse outcomes.
Chronic and/or extreme stress in early life, often referred to as early adversity, childhood trauma, or early life stress, has been associated with a wide range of adverse effects on development. However, while early life stress has been linked to negative effects on a number of neural systems, the specific mechanisms through which early life stress influences development and individual differences in children's outcomes are still not well understood. The current paper reviews the existing literature on the neurobiological effects of early life stress and their ties to children's psychological and behavioral development. Early life stress has persistent and pervasive effects on prefrontal-hypothalamic-amygdala and dopaminergic circuits that are at least partially mediated by alterations in hypothalamic-pituitary-adrenal axis function. However, to date, this research has primarily utilized methods of assessment that focus solely on children's event exposures. Incorporating assessment of factors that influence children's interpretation of stressors, along with stressful events, has the potential to provide further insight into the mechanisms contributing to individual differences in neurodevelopmental effects of early life stress. This can aid in further elucidating specific mechanisms through which these neurobiological changes influence development and contribute to risk for psychopathology and health disorders.


Gated magnetic resonance imaging for assessment of cardiac function and myocardial infarction.
Gated magnetic resonance imaging (MRI) is a promising noninvasive imaging modality capable of evaluating cardiac function and blood flow in the great vessels. MRI detects acute and chronic myocardial infarctions in experimental animals and in man.


A novel differential diagnosis algorithm for chronic lymphocytic leukemia using immunophenotyping with flow cytometry.
The availability of a clinical decision algorithm for diagnosis of chronic lymphocytic leukemia (CLL) may greatly contribute to the diagnosis of CLL, particularly in cases with ambiguous immunophenotypes. Herein we propose a novel differential diagnosis algorithm for the CLL diagnosis using immunophenotyping with flow cytometry. The hierarchical logistic regression model (Backward LR) was used to build a predictive algorithm for the diagnosis of CLL, differentiated from other lymphoproliferative disorders (LPDs). A total of 302 patients, of whom 220 (72.8%) had CLL and 82 (27.2%), B-cell lymphoproliferative disorders other than CLL, were included in the study. The Backward LR model comprised the variables CD5, CD43, CD81, ROR1, CD23, CD79b, FMC7, sIg and CD200 in the model development process. The weak expression of CD81 and increased intensity of expression in markers CD5, CD23 and CD200 increased the probability of CLL diagnosis, (p < 0.05). The odd ratio for CD5, C23, CD200 and CD81 was 1.088 (1.050 - 1.126), 1.044 (1.012 - 1.077), 1.039 (1.007 - 1.072) and 0.946 (0.921 - 0.970) [95% C.I.], respectively. Our model provided a novel diagnostic algorithm with 95.27% of sensitivity and 91.46% of specificity. The model prediction for 97.3% (214) of 220 patients diagnosed with CLL, was CLL and for 91.5% (75) of 82 patients diagnosed with an LPD other than CLL, was others. The cases were correctly classified as CLL and others with a 95.7% correctness rate. Our model highlighting 4 markers (CD81, CD5, CD23 and CD200) provided high sensitivity and specificity in the CLL diagnosis and in distinguishing of CLL among other LPDs.


Treatment of cutaneous leishmaniasis by photodynamic therapy.
Cutaneous leishmaniasis represents a common health problem and standard treatments are often ineffective or yield poor cosmetic results. We compared the efficacy of photodynamic therapy (PDT) with paromomycin sulfate in 10 lesions of cutaneous leishmaniasis. Five lesions were treated by PDT with Metvix (Photocure, Oslo, Norway) and 75 J/cm(2) red light. PDT was performed twice weekly and, after 12 weeks, once weekly. The other 5 lesions were treated with paromomycin sulfate once daily. All nonresponding lesions of the paromomycin-treated plaques finally also underwent PDT. All 5 lesions treated by PDT and 2 of the paromomycin sulfate-treated plaques were clinically and histologically Leishmania free. Three lesions with poor response to paromomycin sulfate finally responded to subsequent PDT. Ten months after therapy there was no recurrence, and cosmetic outcome after PDT was excellent. PDT may be an effective therapeutic alternative in cutaneous leishmaniasis.


In vitro demonstration of in utero larval development in an oviparous parasitic nematode: Haemonchus contortus.
The life-cycle of Haemonchus contortus, a pathogenic stomach nematode of sheep, is typical of those of the other members of the superfamily Trichostrongyloides, all of which require a period of development outside the definitive host. Classically, gravid H. contortus, known as strictly oviparous, releases her eggs into the abomasal lumen. The eggs are passed out in the faeces in which they hatch into the 1st-stage larvae and then develop into the infective 3rd-stage larvae. We have developed a method to study the fate of eggs within gravid worms. Using this procedure, we have shown that H. contortus may also exhibit viviparity with apparently normal development from the egg to the 4th larval stage taking place within the gravid female maintained in vitro. On the basis of these observations we speculate that viviparity might occur in vivo with consequent autoinfections; if so, this might explain some puzzling clinical and epidemiological features of haemonchosis, as well as the incomplete efficacy of current control measures.


Intravenous methylprednisolone is a potential add on therapy for Ring chromosome 20 syndrome.
Ring 20 syndrome is a rare cause of refractory epilepsy and non-convulsive status epilepticus in children. We report a patient with Ring 20 syndrome with refractory focal seizures and non-convulsive status epilepticus who showed good treatment response with intravenous steroids. We wish to highlight that intravenous pulse methylprednisolone is a useful treatment strategy in this setting.


Poor implementation of the EU clinical trial regulation is a major threat for pragmatic trials in European countries.
The principle of pragmatism in clinical trials has been broadly recognised as a way to close the gap between research and practice. In this contribution, we argue that the conduct of pragmatic clinical trials in Europe may be hampered by poor implementation of current European Union's Clinical Trial Regulation No. 536/2014.


Posttreatment prostate-specific antigen nadir highly predictive of distant failure and death from prostate cancer.
To link posttreatment biochemical profiles to distant failure and cause-specific survival by assessing the relationship between posttreatment prostate-specific antigen (PSA) nadir and PSA doubling time (PSADT) with these outcome measures. A total of 615 men were treated at the Fox Chase Cancer Center between April 1989 and December 1995 with three-dimensional conformal radiotherapy alone (median dose 73 Gy). The median follow-up was 64 months (range 2-135). Kaplan-Meier methods were used to estimate the rates of biochemical control, freedom from distant metastasis (FDM), and cause-specific survival. Multivariate predictors of outcome were assessed using stepwise Cox regression analysis. Multivariate analyses demonstrated that the predictors of improved biochemical control were a lower PSA nadir (p <0.0001), lower pretreatment PSA level (p <0.0001), Gleason score of 2-6 (p = 0.001), Stage T1-T2a tumors (p = 0.03), and higher RT dose (p = 0.02). The predictors of improved FDM were a lower PSA nadir (p <0.0001), longer interval to nadir from start of treatment (p = 0.0002), Gleason score of 2-6 (p = 0.005), androgen deprivation for biochemical failure (p = 0.001), and Stage T1-T2a tumors (p = 0.01). The predictors of improved cause-specific survival were a lower PSA nadir (p = 0.006) and longer interval to nadir from the start of treatment (p = 0.03). The 8-year FDM rate was 96%, 89%, and 61% for PSA nadir values of <or=1.0, 1.1-2.0, and >2.0 ng/mL (p <0.0001), respectively. The 8-year cause-specific survival rate was 97%, 96%, and 78% for posttreatment PSA nadir values of <or=1.0, 1.1-2.0, and >2.0 ng/mL (p <0.0001), respectively. For patients with sufficient PSA follow-up for PSADT calculations (n = 136), multivariate analysis of FDM from the time of biochemical failure demonstrated that androgen deprivation (p = 0.001), longer PSADT (p = 0.003), lower PSA nadir (p = 0.02), and longer interval to nadir from start of treatment (p = 0.04) were independent predictors of improved FDM. This is the first study, to our knowledge, to demonstrate the overwhelming predictive power of posttreatment PSA nadir for distant failure and death from prostate cancer. It is also the first study, to our knowledge, to demonstrate a strong association between posttreatment PSADT and distant failure. The results provide new information regarding disease progression as a function of posttreatment PSA profiles (time to achieve nadir from start of treatment, nadir, and PSADT) and the timing of androgen deprivation for biochemical relapse. This study may be used for the early identification of patients at high risk of distant metastasis and who may be directed to applicable systemic treatment clinical trials.


The Mother-Infant Transaction Program. The content and implications of an intervention for the mothers of low-birthweight infants.
A brief, economic neonatal intervention based on the transactional model of development and influenced predominantly by the conceptual design of the Neonatal Behavioral Assessment Scale was implemented in an intensive care nursery with the mothers of a group of low-birthweight infants. The development of the intervention group was compared with that of a similar group of low-birthweight infants who did not receive the intervention and contrasted with that of a group of normal-birthweight infants. The intervention had a significant effect on maternal adjustment and perception of the infant at 6 months. No significant effect on infant cognitive development was apparent until 36 months (that is, 31 months after the intervention had ceased). The intervention effect was even more significant at 48 months. It appeared that the two low-birthweight groups had progressively diverged after 12 months, the intervention group rising until it approximated the normal-birthweight group in cognitive development, whereas the low-birthweight control group deteriorated. The economical nature of the MITP, its unique (although delayed) benefits, and the apparent durability of the intervention effect, suggest that this intervention program has important theoretical and practical implications and potentially far-reaching applications.


Surgical treatment of spinal deformities in spinal muscular atrophy: a single-center experience from China.
To report the clinical characteristics and surgical outcomes of scoliosis in patients with spinal muscular atrophy (SMA) from Mainland China. Nineteen patients were retrospectively analyzed. Demographic, anthropometric and respiratory parameters were collected preoperatively. Surgical program was analyzed. Radiographic data were measured perioperatively. Motor status, ventilation support, sitting ability and respiratory symptoms were evaluated preoperatively and at final follow-up. Age at surgery was 17.08 (12.83, 20.08) years. More than 40% of patients were diagnosed with low weight. Pulmonary dysfunction was observed in all patients. All patients received posterior spinal fusion (PSF). Sacroiliac fixation with sacral-2 alar iliac technique was used in 16 patients. Major curve correction rate was 54.87 ± 16.14%. Pelvic obliquity correction rate was 63.84 ± 23.70%. T1-T12 height, space-available-for-lung ratio and thoracic transverse diameter were increased (p < 0.001). Percentage of patients capable of sitting independently increased from 26.32% preoperatively to 73.68% at final follow-up. Cumulative scores of sitting-related items in muscular dystrophy spine questionnaire improved from 19.11 ± 5.40 preoperatively to 26.21 ± 5.20 at final follow-up. Total scores of symptomatic domains in St. George's Respiratory Questionnaire decreased from 4 (2, 12) preoperatively to 1 (0, 3) at final follow-up. SMA patients in China always present severe scoliosis at late adolescence, accompanied with high proportion of low weight and pulmonary dysfunction. PSF is effective for the correction of scoliosis and pelvic obliquity and the improvement of thoracic morphology. Sitting ability and respiratory symptoms were improved postoperatively.


The effects of incremental speed-dependent treadmill training on postural instability and fear of falling in Parkinson's disease.
To detect the effectiveness of incremental speed-dependent treadmill training on postural instability, dynamic balance and fear of falling in patients with idiopathic Parkinson's disease. Randomized controlled trial. Ankara Education and Research Hospital, 2nd PM&R Clinic, Cardiopulmonary Rehabilitation Unit. Fifty-four patients with idiopathic Parkinson's disease in stage 2 or 3 of the Hoehn Yahr staging entered, and 31 patients (21 training, 10 control) had outcome data. Postural instability of patients with Parkinson's disease was assessed using the motor component of the Unified Parkinson's Disease Rating Scale (UPDRS), Berg Balance Test, Dynamic Gait Index and Falls Efficacy Scale. Twenty-one patients with Parkinson's disease participated in an eight-week exercise programme using incremental speed-dependent treadmill training. Before and after the training programme, balance, gait, fear of falling and walking distance and speed on treadmill were assessed in both Parkinson's disease groups. Walking distance and speed on treadmill, UPDRS, Berg Balance Test, Dynamic Gait Index and Falls Efficacy Scale. Initial total walking distance of the training group on treadmill was 266.45 +/- 82.14 m and this was progressively increased to 726.36 +/- 93.1 m after 16 training session (P < 0.001). Tolerated maximum speed of the training group on treadmill at baseline was 1.9 +/- 0.75 km/h and improved to 2.61 +/- 0.77 km/h (P < 0.001). Berg Balance Test, Dynamic Gait Index and Falls Efficacy Scale scores of the training group were improved significantly after the training programme (P < 0.01). There was no significant improvement in any of the outcome measurements in the control group (P > 0.05). Specific exercise programmes using incremental speed-dependent treadmill training may improve mobility, reduce postural instability and fear of falling in patients with Parkinson's disease.


Bisphenol A and its effects on the systemic organs of children.
For the past two decades, growing research has been pointing to multiple repercussions of bisphenol A (BPA) exposure to human health. BPA is a synthetic oestrogen which primarily targets the endocrine system; however, the compound also disturbs other systemic organ functions, in which the magnitude of impacts in those other systems is as comparable to those in the endocrine system. To date, the discoveries on the association between BPA and health outcomes mainly came from animal and in vitro studies, with limited human studies which emphasised on children's health. In this comprehensive review, we summarised studies on human, in vivo and in vitro models to understand the consequences of pre-, post- and perinatal BPA exposure on the perinatal, children and adult health, encompassing cardiovascular, neurodevelopmental, endocrine and reproductive effects.Conclusion: Evidence from in vitro and animal studies may provide further support and better understanding on the correlation between environmental BPA exposure and its detrimental effects in humans and child development, despite the difficulties to draw direct causal relations of BPA effects on the pathophysiology of the diseases/syndromes in children, due to differences in body system complexity between children and adults, as well as between animal and in vitro models and humans. What is known: • Very limited reviews are available on how BPA adversely affects children's health. • Previous papers mainly covered two systems in children. What is new: • Comprehensive review on the detrimental effects of BPA on children health outcomes, including expectations on adult health outcomes following perinatal BPA exposure, as well as covering a small part of BPA alternatives. • Essentially, BPA exposure during pregnancy has huge impacts on the foetus in which it may cause changes in foetal epigenetic programming, resulting in disease onsets during childhood as well as adulthood.


Economic evaluation of regular transfusions for cerebral infarct recurrence in the Silent Cerebral Infarct Transfusion Trial.
In 2020, the American Society of Hematology published evidence-based guidelines for cerebrovascular disease in individuals with sickle cell anemia (SCA). Although the guidelines were based on National Institutes of Health-sponsored randomized controlled trials, no cost-effectiveness analysis was completed for children with SCA and silent cerebral infarcts. We conducted a cost-effectiveness analysis comparing regular blood transfusion vs standard care using SIT (Silent Cerebral Infarct Transfusion) Trial participants. This analysis included a modified societal perspective with direct costs (hospitalization, emergency department visit, transfusion, outpatient care, and iron chelation) and indirect costs (special education). Direct medical costs were estimated from hospitalizations from SIT hospitals and unlinked aggregated hospital and outpatient costs from SIT sites by using the Pediatric Health Information System. Indirect costs were estimated from published literature. Effectiveness was prevention of infarct recurrence. An incremental cost-effectiveness ratio using a 3-year time horizon (mean SIT Trial participant follow-up) compared transfusion vs standard care. A total of 196 participants received transfusions (n = 90) or standard care (n = 106), with a mean age of 10.0 years. Annual hospitalization costs were reduced by 54% for transfusions vs standard care ($4929 vs $10 802), but transfusion group outpatient costs added $22 454 to $137 022 per year. Special education cost savings were $2634 over 3 years for every infarct prevented. Transfusion therapy had an incremental cost-effectiveness ratio of $22 025 per infarct prevented. Children with preexisting silent cerebral infarcts receiving blood transfusions had lower hospitalization costs but higher outpatient costs, primarily associated with the oral iron chelator deferasirox. Regular blood transfusion therapy is cost-effective for infarct recurrence in children with SCA. This trial is registered at www.clinicaltrials.gov as #NCT00072761.


Independent regulation of primary dendritic and axonal growth by maturing astrocytes in vitro.
Whereas axon growth is limited in the mature mammalian central nervous system (CNS), dendritic remodeling occurs throughout life. Since glia can regulate neurite growth during development, we tested whether glia from the mature CNS differ in their ability to support axon and dendrite growth. Cortical neurons were co-cultured with neonatal or mature astroglial, and dendrite and axon outgrowth quantified after 5DIV using immunohistochemical techniques. Primary dendritic growth was supported equally well by mature and immature astrocytes. By contrast, mature astrocytes demonstrated a reduced ability to support axon growth. We propose that the independent regulation of axon and dendrite growth by astrocytes provides a means by which the mature nervous system may adjust its function to activity and the environment.


Effect of weaning on serum lipoprotein(a) concentration: the STRIP baby study.
Risk for coronary heart disease is increased in adult Caucasians with high serum lipoprotein(a) [Lp(a)] concentration. In adults the concentration is mainly regulated by genetic factors. Our previous study suggests that breast milk has a beneficial effect on serum Lp(a) concentration in infants. Now we analyzed the influence of weaning by measuring serum Lp(a) and cholesterol in 414 infants at 7, 13, 24, and 36 mo of age. At 7 mo the infants received, in addition to solid food, only breast milk (n = 148), breast milk and formula (n = 74), or formula only (n = 191). Median (range) serum Lp(a) concentrations were then 25 (< or = 12-743) mg/L, 35 (< or = 12-1188) mg/L, and 45 (< or = 12-577) mg/L in the three feeding groups, respectively (p = 0.0013). Breast milk and formula were changed to cow's milk in all infants before 12 mo of age. At 13 mo serum Lp(a) concentration had increased more in infants who were weaned from breast milk than in those who had been fed both breast milk and formula, or formula only (median increases 37, 26, and 20 mg/L, respectively; p = 0.0062). Thus the serum Lp(a) concentration was similar in all feeding groups at 13 mo. This finding was also observed at 24 and 36 mo. The increase in serum Lp(a) concentration was independent of the baseline Lp(a) level, apolipoprotein E phenotype, gender, and weight gain of the infants between 7 and 13 mo.(ABSTRACT TRUNCATED AT 250 WORDS)


Novel Application of Localized Nanodelivery of Anti-Interleukin-6 Protects Organ Transplant From Ischemia-Reperfusion Injuries.
Ischemia-reperfusion injury (IRI) evokes intragraft inflammatory responses, which markedly augment alloimmune responses against the graft. Understanding the mechanisms underlying these responses is fundamental to develop therapeutic regimens to prevent/ameliorate organ IRI. Here, we demonstrate that IRI results in a marked increase in mitochondrial damage and autophagy in dendritic cells (DCs). While autophagy is a survival mechanism for ischemic DCs, it also augments their production of interleukin (IL)-6. Allograft-derived dendritic cells (ADDCs) lacking autophagy-related gene 5 (Atg5) showed higher death rates posttransplantation. Transplanted ischemic hearts from CD11cCre/Atg5 conditional knockout mice showed marked reduction in intragraft expression of IL-6 compared with controls. To antagonize the effect of IL-6 locally in the heart, we synthesized novel anti-IL-6 nanoparticles with capacity for controlled release of anti-IL-6 over time. Compared with systemic delivery of anti-IL-6, localized delivery of anti-IL-6 significantly reduced chronic rejection with a markedly lower amount administered. Despite improved allograft histology, there were no changes to splenic T cell populations, illustrating the importance of local IL-6 in driving chronic rejection after IRI. These data carry potential clinical significance by identifying an innovative, targeted strategy to manipulate organs before transplantation to diminish inflammation, leading to improved long-term outcomes.


Effect of Different Obturation Techniques on Sealer Penetration in Teeth with Artificial Internal Root Resorption: a Confocal Laser Microscope Analysis.
To investigate the efficacy of different obturation techniques on sealer penetration in teeth with internal root resorption using confocal laser microscopy. An artificial internal resorption cavity (3 mm deep and 1.2 mm in diameter) was formed in the round-shaped root canals of 45 single-rooted teeth at a distance of 7 mm from the apex, then roots were instrumented (size 40/.06). The samples were divided into three groups (n = 15) according to the obturation technique: lateral compaction (LC), warm vertical compaction (WVC) and carrier-based (CB). In the resorption regions, the sealer penetration depth in the CB and LC groups was significantly higher than that in the WVC group (P < 0.05). Within the limitations of this study, the penetration depth of the sealer in the resorption region was higher in the CB and LC groups as compared to that in the WVC group.


Prescribed fire alters nematode communities in an old-field grassland.
Fire is a common disturbance in many biomes, with both beneficial and detrimental effects on soil biology, which largely depend on fire intensity. However, little is known about the impact of fire on soil nematode communities in terrestrial ecosystem. In the present study, we investigated the effects of short-term prescribed fire on soil nematode communities and soil properties in an old-field grassland in Northern China. The results showed that burning significantly increased soil nematode abundance by 77% and genus richness by 49% compared to the control. Burning also decreased taxon dominance by 45% (Simpson's D) and increased nematode diversity by 31% (Shannon-Weaver H'). However, burning increased plant parasites (particularly genera Cephalenchus and Pratylenchus) and shifted community to more bacterial-feeding genera (i.e., decreased Channel Index). Generally, burning increased soil bio-available nitrogen (NH4 +-N and NO3 --N) content, which would be the main drivers causing nematode community to flourish via a "bottom-up" effect. These results suggest that prescribed fire increases nematode diversity and alters community composition toward more plant parasites and bacterial feeders. Our findings highlight the importance of prescribed fire management in shaping short-term nematode community structure and function, but the long-term effects and impacts of these changes on soil nutrient and carbon cycling remain unknown.


Health care professionals' views of sharing information with families who have a child with a genetic condition.
The purpose of this study was to examine health care professionals' views and strategies for individualizing information sharing in families who have a child with a genetic condition. The sample consisted of 37 health professionals from three clinical sites in the greater metropolitan area of a large Midwestern city. Qualitative content thematic analysis was used to analyze data from the health professionals' semi-structured interviews. Four themes captured how health care professionals work with families around information management: Sharing Information with Parents, Taking into Account Parental Preferences, Understanding of the Condition, and Helping Parents Inform Others. These findings contribute to understanding the processes that health professionals use in sharing information with parents who have children with a genetic condition, and they provide guidance for clinical practice, professional training, and future research.


Continuous enriched environment improves learning and memory in adult NMRI mice through theta burst-related-LTP independent mechanisms but is not efficient in advanced aged animals.
Effects of 3-month continuous environmental enrichment (EE) on cognitive abilities and on theta burst-related synaptic plasticity of CA1 hippocampal neuronal networks have been assessed in 6- and 20-month old NMRI female mice. EE decreased anxiety-like behavior and improved learning and memory performances in adult but not in aged mice. Electrophysiological results in CA1 hippocampal slices showed that basal synaptic transmission was not affected by EE in adult mice whereas it was partially improved in aged animals, even though not sufficient to rescue the decrease related to aging. Besides, no effect of EE on N-methyl-d-aspartate receptor activation and theta-burst-induced long-term potentiation was found in adult or aged animals. These results indicate that continuous EE is able to improve cognitive abilities in adult NMRI female mice, that does not correlate with changes in theta burst-related synaptic plasticity within neuronal networks. In addition, the lack of effects in aged animals suggests the existence of a critical delay for the beneficial effects of EE on cognitive aging.


In-situ anodic precipitation process for highly efficient separation of aluminum alloys.
Electrorefining process has been widely used to separate and purify metals, but it is limited by deposition potential of the metal itself. Here we report in-situ anodic precipitation (IAP), a modified electrorefining process, to purify aluminium from contaminants that are more reactive. During IAP, the target metals that are more cathodic than aluminium are oxidized at the anode and forced to precipitate out in a low oxidation state. This strategy is fundamentally based on different solubilities of target metal chlorides in the NaAlCl4 molten salt rather than deposition potential of metals. The results suggest that IAP is able to efficiently and simply separate components of aluminum alloys with fast kinetics and high recovery yields, and it is also a valuable synthetic approach for metal chlorides in low oxidation states.


Oxidative degradation of p-chlorophenol by the persulfate-doped Fe-Mn bimetallic hydroxide, the parametrical significance, and systematical optimization.
Aqueous Fe(II)-catalyzed activation commonly deteriorates the oxidation performance of persulfate (PS) to the treatment of organic contaminants. In this study, a PS-doped layered bimetallic hydroxide (Fe-Mn hydroxide) was synthesized to construct a heterogeneously catalytic system to solve the issue brought by homogeneity. The molar ratio of Fe(II) to Mn(II) and the mass ratio of PS to Fe-Mn hydroxide both had a significant impact on the catalytic degradation of p-CP. Reaction temperatures engaged in the most essential role in influencing the degradation and removal of p-chlorophenol (p-CP). The optimal combination of factors for the preparation of PS-hydroxide and the treatment of p-CP was finally determined by significance analysis. The degradation process was appropriately fitted by the pseudo-first-order kinetic model. The benzene ring in p-CP was broken by PS-hydroxide during the adsorption. The surface modification of PS-hydroxide caused by the valence transition of Mn was beneficial to the adsorption and catalytic degradation of p-CP.


Developmental and regional studies of the metabolism of inositol 1,4,5-trisphosphate in rat brain.
Coupling of CNS receptors to phosphoinositide turnover has previously been found to vary with both age and brain region. To determine whether the metabolism of the second messenger inositol 1,4,5-trisphosphate also displays such variations, activities of inositol 1,4,5-trisphosphate 5'-phosphatase and 3'-kinase were measured in developing rat cerebral cortex and adult rat brain regions. The 5'-phosphatase activity was relatively high at birth (approximately 50% of adult values) and increased to adult levels by 2 weeks postnatal. In contrast, the 3'-kinase activity was low at birth and reached approximately 50% of adult levels by 2 weeks postnatal. In the adult rat, activities of the 3'-kinase were comparable in the cerebral cortex, hippocampus, and cerebellum, whereas much lower activities were found in hypothalamus and pons/medulla. The 5'-phosphatase activities were similar in cerebral cortex, hippocampus, hypothalamus, and pons/medulla, whereas 5- to 10-fold higher activity was present in the cerebellum. The cerebellum is estimated to contain 50-60% of the total inositol 1,4,5-trisphosphate 5'-phosphatase activity present in whole adult rat brain. The localization of the enriched 5'-phosphatase activity within the cerebellum was examined. Application of a histochemical lead-trapping technique for phosphatase indicated a concentration of inositol 1,4,5-trisphosphate 5'-phosphatase activity in the cerebellar molecular layer. Further support for this conclusion was obtained from studies of Purkinje cell-deficient mutant mice, in which a marked decrement of cerebellar 5'-phosphatase was observed. These results suggest that the metabolic fate of inositol 1,4,5-trisphosphate depends on both brain region and stage of development.


Anti -TNFα agents in preventing the postoperative recurrence of Crohn's disease: Do they still play a role in the biological era?
Approximately half of patients with Crohn's disease (CD) may inevitably receive surgical intervention as the disease progress. However, about 75% of CD patients will experience postoperative recurrence (POR). Biologics are appealing alternatives for the prevention of POR; however, it is still unclear which biological agents are more efficient. This meta-analysis aimed to investigate the efficacy of biologics for POR prevention and to compare the superiority of different biologics. We conducted a thorough search of online databases and screened for studies on the efficacy of biologics in preventing POR (clinical, endoscopic, or histological) that were published until January 2021. The results were presented as forest plots and odds ratios (ORs) with 95% confidence intervals (CIs). We included 26 studies with 2,136 participants. Overall, biologics were more efficient over non-biological treatments in preventing endoscopic, severe endoscopic, and clinical POR without increasing the frequency of adverse events. Among the various types of biologics, anti-TNFα agents were better than vedolizumab in preventing endoscopic POR. Moreover, infliximab had a similar curative effect to adalimumab in preventing endoscopic, severe endoscopic, and clinical recurrence. Biologics, especially anti-TNFα agents, still play a vital role in preventing POR in the biological era.


Coupled use of Fe-impregnated biochar and urea-hydrogen peroxide to simultaneously reduce soil-air emissions of fumigant and improve crop growth.
Reducing the emissions of soil fumigants such as 1,3-dichloropropene (1,3-D) is essential to protecting air quality. Although biochar is useful in reducing such emissions, biochar-adsorbed fumigants may desorb and cause secondary air pollution. This study investigated the degradation of 1,3-D on iron (Fe)-impregnated biochar (FBC) amended with urea-hydrogen peroxide (UHP). The results indicated the degradation rate of trans-1,3-D on FBC-UHP was 54-fold higher than that on pristine biochar (PBC). Electron paramagnetic resonance (EPR) combined with other characterization methods revealed that the presence of semiquinone-type radicals in FBC effectively accelerated the Fe(III)/Fe(II) cycleto maintain enough Fe(IIII) for UHP activation and ·OH generation. ·OH, rather than ·O2-, was the dominant active oxidant. Soil column tests showed that application of FBC to the soil surface reduced cumulative 1,3-D emissions from 34.80 % (bare soil) to 0.81%. After the column experiment, the mixing of the FBC with UHP resulted in the residual cis-isomers decreasing from 32.5% to 10.5%. Greenhouse bioassays showed that mixing post-1,3-D degradation FBC-UHP with soil significantly promoted lettuce growth relative to PBC. The findings of this study provide a new approach for biochar application, especially for the emission reduction of hazardous volatile organic compounds from soil.


Complete genome sequence of Marinomonas arctica BSI20414, a giant antifreeze protein-producing bacterium isolated from Arctic sea ice.
Sea ice in the polar oceans is a dynamic and challenging environment for life to survive, with extreme gradients of temperature, salinity and nutrients etc., as well as formation of ice crystals. Bacteria surviving in sea ice attract broad attention from academia and industry, due to fascinating mechanisms for adaptation. Here we described the complete genome sequence of Marinomonas arctica BSI20414, isolated from Arctic sea ice. The strain tolerated high salinity and low temperature. Genetic features commonly related to adaptation to oxidative stress, osmotic stress and cold stress were detected in the genome. In addition, a large adhesion protein containing a putative antifreeze protein (AFP) domain was detected in the genome, similar with the giant AFP MpIBP from M. primoryensis. The presence of the putative AFP could facilitate M. arctica BSI20414 to bind to sea ice for favorable conditions and protect it from freezing. The genome sequence and the AFP reported here can provide insights into adaptation to sea ice and can be explored further for biotechnological applications.


Comparison among the efficacy of interventions for the return rate to receive the pap test report: randomized controlled clinical trial.
to test the effects of a behavioral, an educative and a comparative intervention on women's adherence to the return appointment to receive the pap test report. randomized controlled clinical trial at a Primary Health Care Service, involving three groups: EG (educative session and test demonstration), BG (recall ribbon) and standard intervention (card containing the return appointment - graphical reminder), called comparative group here (CG). To select the sample, the following was established: having started sexual activity and undergoing the pap smear during the study, resulting in 775 women. among the 775 women, 585 (75.5%) returned to receive the test result within 65 days. The educative group presented the highest return rate (EG=82%/CG=77%/BG=66%), statistically significant only when compared to the behavioral group (p=0.000). The educative group obtained the smallest interval (p<0.05) concerning the mean number of days of return to receive the test result (EG:M=43days/BG:M=47.5days/CG:M=44.8 days). the educative group reached higher return rates and the women returned earlier, but the behavioral intervention showed to be the least effective. Brazilian Clinical Trial Register: RBR-93ykhs. testar los efectos de una intervención comportamental (GCP), educativa (GE) y otra comparativa (GCA) en la adhesión de las mujeres a la consulta de retorno para recibir el laudo de citología vaginal. estudio experimental aleatorizado controlado en una Unidad de Atención Primaria de Salud con tres grupos: GE (sesión educativa y demonstración del examen), GCP (cinta recuerdo) e intervención estándar (tarjeta con la fecha de la consulta de retorno - recuerdo gráfico), llamado de grupo comparativo (GCA). Para seleccionar la muestra, fue establecido: haber iniciado actividad sexual y hacer la citología vaginal durante el estudio, resultando en 775 mujeres. entre las 775 mujeres, 585 (75,5%) regresaron para recibir el resultado del examen con hasta 65 días. El grupo educativo presentó el mayor porcentaje de retorno (GE=82%/GCA=77%/GCP=66%), con significancia estadística sólo cuando comparado al comportamental (p=0,000). El grupo educativo alcanzó menor intervalo (p<0,05) del promedio de días de retorno para recibir el resultado del examen (GE:M=43 días/GCP:M=47,5 días/GCA:M=44,8 días). el grupo educativo alcanzó proporciones mayores de retorno, y las mujeres regresaron más precozmente, pero la intervención comportamental se mostró la menos eficaz. Registro Brasileño de Ensayo Clínico: RBR-93ykhs. testar os efeitos de uma intervenção comportamental (GCP), educativa (GE) e outra de comparação (GCA) na adesão das mulheres à consulta de retorno para receber o laudo do exame colpocitológico. estudo experimental randomizado controlado em uma Unidade de Atenção Primária à Saúde com três grupos: GE (sessão educativa e demonstração do exame), GCP (fita lembrança) e intervenção-padrão (cartão contendo a data da consulta de retorno - lembrete gráfico), aqui denominado de grupo de comparação (GCA). Para a seleção da amostra, estabeleceu-se: ter iniciado atividade sexual e realizar o exame colpocitológico durante o estudo, resultando em 775 mulheres. dentre as 775 mulheres, 585 (75,5%) retornaram para receber, o resultado do exame com até 65 dias. O grupo educativo apresentou o maior percentual de retorno (GE=82%/GCA=77%/GCP=66%), com significância estatística apenas quando comparado ao comportamental (p=0,000). O grupo educativo obteve menor intervalo (p<0,05) da média de dias de retorno para receber o resultado do exame (GE:M=43dias/GCP:M=47,5dias/GCA:M=44,8 dias) . o grupo educativo atingiu proporções maiores de retorno, e as mulheres retornaram mais precocemente, porém a intervenção comportamental mostrou-se a menos eficaz. Registro Brasileiro de Ensaio Clínico: RBR-93ykhs.


Early changes in foveal thickness in eyes with central serous chorioretinopathy.
To investigate when and how fast the foveal thinning occurs in central serous chorioretinopathy. Outer nuclear layer (ONL) thickness was measured in 60 eyes of 60 patients with active central serous chorioretinopathy. Patients were divided into 3 groups based on the duration of symptoms; within 1 month (Group A, 25 eyes), 1 to 6 months (Group B, 17 eyes), and >6 months (Group C, 18 eyes). Outer nuclear layer thickness and visual acuity were compared between each group. Some of the patients underwent several examinations and serial changes were analyzed. The ONL thickness was correlated with the duration of symptoms (R = -0.61, P < 0.001). Visual acuity was worse in Group C compared with Group A (P = 0.003). The mean ONL thickness of each group and healthy contralateral eyes was 82.4, 70.2, 53.5, and 89.3 μm, respectively. Comparisons between each group showed statistical significances. Seventeen eyes in Group A were re-examined between 3 and 6 months after the first visit. The mean ONL thickness significantly decreased from 81.9 μm to 75.0 μm (P = 0.020). In central serous chorioretinopathy, ONL thinning starts in the early stage and may continue as long as the subretinal fluid persists.


Estimating the Theoretical Cost Implications of Funding New Drugs Considered Not to Be Cost-Effective.
This study aims to estimate the theoretical excess expenditure that would be incurred by the Irish state-payer, should drugs be reimbursed at their original asking ("list") price rather than at a price at which the drug is considered cost-effective. In Ireland, all new drugs are evaluated by the National Centre for Pharmacoeconomics. For this study, drugs that were submitted by pharmaceutical companies from 2012 to 2017 and considered not cost-effective at list price were reviewed. A total of 43 such drugs met our inclusion criteria, and their pharmacoeconomic evaluations were further assessed. The price at which the drug could be considered cost-effective (cost-effective price) at the upper cost-effectiveness threshold used in Ireland (€ 45 000/quality adjusted life-year) was estimated for 18 drugs with an available cost-effectiveness model. Then, for each drug, the list price and cost-effective price (both per unit) were both individually applied to 1 year of national real-world drug utilization data. This allowed the estimation of the expected expenditures under the assumptions of list price paid and cost-effective price paid. The resulting theoretical excess expenditure, the expenditure at list price minus the expenditure at the cost-effective price, was estimated to be €108.2 million. This estimate is theoretical because of the confidentiality of actual drug prices. The estimation is calculated using the list price and likely overestimates the actual excess expenditure, which would reduce to zero if cost-effective prices are agreed. Nevertheless, this estimate illustrates the importance of a process to assess the value of new drugs so that potential excess drug expenditure is identified.


Overview of the innervation of the lung.
The autonomic nervous system controls many aspects of airway function, including regulation of airway smooth-muscle tone, mucus secretion from submucosal glands and surface epithelial goblet cells, vascular permeability and blood flow. Recent data suggest that enhanced neural activity may play a key role in the symptomatology and pathophysiology of airway inflammatory diseases.


Protein release from electrospun nonwovens: improving the release characteristics through rational combination of polyester blend matrices with polidocanol.
Nonwoven scaffolds consisting of poly-ε-caprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA) and polidocanol (PD), and loaded with lysozyme crystals were prepared by electrospinning. The composition of the matrix was varied and the effect of PD content in binary mixtures, and of PD and PLGA content in ternary mixtures regarding processability, fiber morphology, water sorption, swelling and drug release was investigated. Binary PCL/PD blend nonwovens showed a PD-dependent increase in swelling of up to 30% and of lysozyme burst release of up to 45% associated with changes of the fiber morphology. Furthermore, addition of free PD to the release medium resulted in a significant increase of lysozyme burst release from pure PCL nonwovens from approximately 2-35%. Using ternary PCL/PD/PLGA blends, matrix degradation could be significantly improved over PCL/PD blends, resulting in a biphasic release of lysozyme with constant release over 9 weeks, followed by constant release with a reduced rate over additional 4 weeks. Based on these results, protein release from PCL scaffolds is improved by blending with PD due to improved lysozyme desorption from the polymer surface and PD-dependent matrix swelling.


Effect of aeromonas salmonicida (furunculosis) infection on the incorporation of [1-14C]acetate into lipids of trout liver.
[1-(14)C]acetate is incorporated into lipids more rapidly by liver from Aeromonas salmonicida-infected trout than by normal trout liver, both in vitro and in vivo. The increase was, in general, about twofold to less than threefold.


[Effect of PADI4 on the Expression of Inflammatory Cytokines During NB4 Cells Differentiation].
To investigate the expression of peptidylarginine deiminase 4 (PADI4) during the process of differentiation into granulocyte of NB4 cells induced by all-trans-retinoic acid (ATRA) and whether PADI4 is involved in the inflammatory cytokines expression. Granulocyte differentiation model of NB4 cells induced by ATRA was established. The cell morphology changes were observed by Wright-Giemsa staining. The expression of cell differentiation marker CD11b was analyzed by flow cytometry. The mRNA and protein expression of PADI4 was detected by RT-PCR and Western blot, respectively. The expression of tumor necrosis factor (TNF) α and interleukin (IL) 1β was analyzed by ELISA, and also examined with the knockdown of PADI4 expression by siRNA. After NB4 cells induced by ATRA, the cytoplasm increased and the ratio of nuclear to cytoplasmic was reduced. Nuclear dented, and rod-shaped nucleus, lobulated phenomenon increased (P<0.05). Flow cytometry analysis results showed that the cell surface molecule CD11b expression increased (P<0.01). RT-PCR and Western blot showed the expression of PADI4 increased at both transcriptional and translational levels during the process of the differentiation. ELISA showed TNF-α and IL-1β secretion increased in differentiated macrophages, while they could be inhibited by PADI4-specific siRNA. During the differentiation into granulocyte of NB4 cells induced by ATRA, PADI4 expression increased. Furthermore, PADI4 appeared to play a critical role in inflammatory cytokines secretion.


Identification and further differentiation of subendocardial and transmural myocardial infarction by fast strain-encoded (SENC) magnetic resonance imaging at 3.0 Tesla.
To investigate whether subendocardial and transmural myocardial infarction can be identified and differentiated using the peak circumferential and longitudinal strains measured by fast strain-encoded (SENC). Nineteen patients with ischemic heart diseases underwent imaging with fast SENC and late gadolinium enhancement (LGE) MRI at 3 T. Fast SENC measurements were performed in three short-axis slices (basal, mid-ventricular and apical levels) and one long-axis view (four-chamber) to assess peak longitudinal and circumferential systolic strains. All patients showed myocardial infarction with an average of 7 positive LGE segments. A total of 304 segments for longitudinal strains (LS) and 114 segments for circumferential strains (CS) could be analysed. Positive LGE segments showed lower peak CS and LS compared with the no LGE segments (P < 0.0001 for both). Segments with subendocardial infarction showed reduced CS and LS compared with the no LGE segments (P < 0.0001 for both). There was a significant difference in CS between subendocardial and transmural infarct segments (P = 0.03), but no significant difference in LS between them (P = 0.64). Fast SENC can identify old myocardial infarction and differentiate subendocardial from transmural infarction.


Mixed exposure effect of seminal metals on semen quality, mediation of total antioxidant capacity, and moderation of GSTM1/GSTT1 gene deletion in Chinese reproductive-aged men.
The effects of metal exposure on semen quality and the role of oxidative damage in this process remain unclear. We recruited 825 Chinese male volunteers, and 12 seminal metals (Mn, Cu, Zn, Se, Ni, Cd, Pb, Co, Ag, Ba, Tl, and Fe), the total antioxidant capacity (TAC), and reduced glutathione were measured. Semen parameters and GSTM1/GSTT1-null genotypes were also detected. Bayesian kernel machine regression (BKMR) was applied to evaluate the effect of the mixed exposure to metals on semen parameters. The mediation of TAC and moderation of GSTM1/GSTT1 deletion were analyzed. Most seminal metal concentrations were correlated with each other. The BKMR models revealed a negative association between the semen volume and metal mixture, with Cd (cPIP = 0.60) and Mn (cPIP = 0.10) as the major contributors. Compared to fixing all scaled metals at their median value (50th percentiles), fixing the scaled metals at their 75th percentiles decreased the TAC by 2.17 units (95%CI: -2.60, -1.75). Mediation analysis indicated that Mn decreased the semen volume, with 27.82% of this association mediated by TAC. Both the BKMR and multi-linear models showed that seminal Ni was negatively correlated with sperm concentration, total sperm count, and progressive motility, which was modified by GSTM1/GSTT1. Furthermore, Ni and the total sperm count showed a negative association in GSTT1 and GSTM1 null males (β[95%CI]: 0.328 [-0.521, -0.136]) but not in males with GSTT1 and/or GSTM1. Although Fe and the sperm concentration and total sperm count were positively correlated, they showed inverse "U" shapes in univariate analysis. Exposure to the 12 metals was negatively associated with semen volume, with Cd and Mn as the major contributors. TAC may mediate this process. GSTT1 and GSTM1 can modify the reduction in the total sperm count caused by seminal Ni exposure.


A locking rod and tube connector.
Two methods for interlocking the segments of fixed splints are advocated: (1) solderless joints where the connector occurs between adjacent abutment teeth and (2) a locking rod and tube attachment when the connector occurs in a pontic space. The locking rod and tube attachment was described. It allows complete independence of each segment. If problems occur in any segment of the splint, only that segment must be removed to make a repair. Other splinting techniques were presented along with their advantages and disadvantages.


Time to non-adherence to iron and folic acid supplementation and associated factors among pregnant women in Hosanna town, South Ethiopia: Cox-proportional hazard model.
Micronutrient deficits in women of reproductive age have been linked to poor pregnancy outcomes. The most common micronutrient deficits in women are iron and folate. The World Health Organization recommends daily oral iron and folic acid supplementation (IFAS) as part of routine antenatal care to lower the risk of maternal anemia and adverse pregnancy outcomes. However, the effectiveness of the supplementation relies on client's strict adherence. The aim of this study was to determine time- to- non-adherence to IFAS and associated factors among pregnant women in Hosanna Town, South Ethiopia. A community based cross sectional study design was employed from May 15-June11, 2021. Data were entered into Epi-Data version 3.1 and exported to SPSS version 23 for analysis. The Cox regression hazard model was applied. The threshold of statistical significance was declared at a p-value <0.05 and adjusted hazard ratios (AHRs) with corresponding 95% confidence intervals were used to report. The median time-to-non-adherence was 74 days (95 percent CI: 65.33-82.67). After adjusting for the confounders, age (AHR = 1.05, 95% CI: 1.01-1.09), education status (AHR = 2.43 95%CI 1.34-4.40, AHR 3.00, 95% CI: 2.09-4.31, AHR 1.91, 95% CI: 1.32-2.77), household's wealth index (AHR = 1.73, 95% CI: 1.19-2.51, AHR = 1.64, 95% CI:1.15-2.35), and counseling at service delivery (AHR = 2.53, 95% CI: 1.88-3.41) were independent predictors of time to non-adherence to IFAS among pregnant women. The median time to non-adherence was short and women became non-adherent before the recommended duration. Improving women's education and counseling pregnant women on IFAS during pregnancy would make a change.


Obesity research in Canada: literature overview of the last 3 decades.
To identify research published on obesity in Canada, to explore the range of areas studied, and to identify gaps and areas that merit future research attention. Medline and International Pharmaceutical Abstracts databases were searched from 1970 onwards. Original articles were identified and categorized by areas of interest. A total of 1186 relevant articles were identified: 17, 136, 687, and 346 articles during the 1970s, 1980s, 1990s, and 2000 to 2003, respectively. Of the articles, 816 were considered original studies and accepted for this analysis. Twelve research areas were identified: basic science involving animal experiments (29%), human experiments (16%), populations surveys (14%), obesity-related comorbidities (13%), diagnostic/surgical issues (11%), nonpharmacological approaches (7%), drug-related issues (4%), anthropometrics (2%), impact of weight loss (2%), cost/healthcare use (1%), attitudes/perceptions (0.9%), and models/procedures (0.5%). Two-thirds of all research was conducted in Quebec (34%) and Ontario (33%). Given the multifactorial nature of obesity, Canadian obesity research covers a broad range of areas with a predominance of basic science but lesser emphasis on community and primary care studies. Furthermore, there was a paucity of research on either clinical management of medical conditions in obese patients or clinical aspects that go beyond weight loss. Thus, although Canada appears well represented in basic research, more attention to exploration of clinical issues and healthcare delivery for obese patients appears warranted.


γδTDEs: An Efficient Delivery System for miR-138 with Anti-tumoral and Immunostimulatory Roles on Oral Squamous Cell Carcinoma.
In this study, we sought to investigate the potential application of γδ T cell-derived extracellular vesicles (γδTDEs) as drug delivery system (DDS) for miR-138 in the treatment of oral squamous cell carcinoma (OSCC). Our data showed that overexpression of miR-138 in γδ T cells obtained miR-138-rich γδTDEs accompanying increased expansion and cytotoxicity of γδ T cells. γδTDEs inherited the cytotoxic profile of γδ T cells and could efficiently deliver miR-138 to OSCC cells, resulting in synergetic inhibition on OSCC both in vitro and in vivo. The pre-immunization by miR-138-rich γδTDEs inhibited the growth of OSCC tumors in immunocompetent C3H mice, but not in nude mice, suggesting an immunomodulatory role by miR-13-rich γδTDEs. γδTDEs and miR-138 additively increased the proliferation, interferon-γ (IFN-γ) production, and cytotoxicity of CD8+ T cells against OSCC cells. Only delivered by γδTDEs can miR-138 efficiently target programmed cell death 1 (PD-1) and CTLA-4 in CD8+ T cells. We conclude that γδTDEs delivering miR-138 could achieve synergetic therapeutic effects on OSCC, which is benefited from the individual direct anti-tumoral effects on OSCC and immunostimulatory effects on T cells by both γδTDEs and miR-138; γδTDEs could serve as an efficient DDS for microRNAs (miRNAs) in the treatment of cancer.


Predicting Amyloid Pathology in Mild Cognitive Impairment Using Radiomics Analysis of Magnetic Resonance Imaging.
Noninvasive identification of amyloid-β (Aβ) is important for better clinical management of mild cognitive impairment (MCI) patients. To investigate whether radiomics features in the hippocampus in MCI improve the prediction of cerebrospinal fluid (CSF) Aβ42 status when integrated with clinical profiles. A total of 407 MCI subjects from the Alzheimer's Disease Neuroimaging Initiative were allocated to training (n = 324) and test (n = 83) sets. Radiomics features (n = 214) from the bilateral hippocampus were extracted from magnetic resonance imaging (MRI). A cut-off of <192 pg/mL was applied to define CSF Aβ42 status. After feature selection, random forest with subsampling methods were utilized to develop three models with which to predict CSF Aβ42: 1) a radiomics model; 2) a clinical model based on clinical profiles; and 3) a combined model based on radiomics and clinical profiles. The prediction performances thereof were validated in the test set. A prediction model using hippocampus volume was also developed and validated. The best-performing radiomics model showed an area under the curve (AUC) of 0.674 in the test set. The best-performing clinical model showed an AUC of 0.758 in the test set. The best-performing combined model showed an AUC of 0.823 in the test set. The hippocampal volume model showed a lower performance, with an AUC of 0.543 in the test set. Radiomics models from MRI can help predict CSF Aβ42 status in MCI patients and potentially triage the patients for invasive and costly Aβ tests.


Preliminary experience & rationale of primary allo Simple Limbal Epithelial Transplantation (SLET) following surgical excision of Ocular Surface Tumors.
To report the preliminary outcomes and elucidate the possible rationale of alloSLET for primary ocular surface reconstruction following excision of extensive ocular surface tumors. Retrospective interventional case series with a minimum postoperative follow up of 1 year. AlloSLET was performed along with wide surgical excision and cryotherapy in 3 eyes. Of the 2 eyes with extensive OSSN and one with an extensive pigmented lesion, there was no occurrence of symblepharon in all 3 eyes. No features suggestive of LSCD was noted in 2 eyes. In the child with xeroderma pigmentosum and OSSN, early peripheral vascularization was noted at 1 year of follow up with reduced vision secondary to amblyopia. Primary alloSLET could be an alternative to primary autoSLET in eyes with extensive ocular surface tumors, commonly seen with ocular surface squamous neoplasia (OSSN) and pigmented lesions. This facilitates ocular surface reconstruction with reduced occurrence of symblepharon formation as well as limbal stem cell deficie4ncy (LSCD). It possibly, is the only option in eyes with OSSN with coexistent bilateral limbal insufficiency. It may obviate the need for autoSLET, primary or secondary in eyes with adequate residual limbus.


Perianal thrombosis: no need for surgery.
There is little evidence for the best therapy for perianal thrombosis. No prospective trials exist. Even quality of retrospective data is low, due to low patient numbers or vague follow-up data. Six hundred nineteen patients with thrombosis of internal or external hemorrhoids who presented in our clinic between March 2017 and August 2018 were enrolled in the study. All patients were treated conservatively, with sitz baths and oral pain medication, if needed. No surgery was performed. Follow-up data was obtained by personal examination. Data was gathered prospectively, and data analysis was retrospective. Five hundred four patients had perianal thrombosis (81.4%), and 115 patients had thrombosed hemorrhoids. Mean pain on a numerical rating scale (0-10) was 3.8 for perianal thrombosis and 5.2 for thrombosed hemorrhoids. Five hundred forty-eight patients (88.5%) did not need a sick leave. On follow-up, patients stated that their pain had largely resolved after 5 days and completely disappeared after 10 days. Local recurrence rate after perianal thrombosis was 6.3%. Perianal thrombosis and thrombosed hemorrhoids heal well without surgery. There is no evidence for advantages surgical therapy could offer.


Detection of the EBV-determined nuclear antigen (EBNA) in Burkitt's lymphoma and nasopharyngeal carcinoma biopsies by the acid fixed nuclear binding (AFNB) technique.
Epstein-Barr virus (EBV) carrying biopsies of Burkitt lymphoma (BL) and nasopharyngeal carcinoma (NPC) were used to examine the question whether the EBV-associated nuclear antigen (EBNA) can be demonstrated by the acid fixed nuclear binding (AFNB) technique, developed previously for the demonstration of EBNA in cultured cell lines [11]. Extracts of 5 BL and 5 NPC biopsies gave a brilliant, EBNA specific fluorescence after binding to acid fixed chicken red cells. Similar extracts of 3 other African tumors that are not known to carry the EBV-genome were negative, in spite of the fact that they were derived from EBV-seropositive patients with relatively high anti-EBV (VCA) antibody titers. Crude extraction and DNA-cellulose purification gave equally active extracts, provided that incubation was carried out at 4 degrees C. These results show that the acid fixed nuclear binding technique can be applied to biopsy material. This may be helpful in searching for EBNA carrying cells in heterogeneous normal and tumor tissues in vivo where the direct in situ ACIF staining for EBNA is known to meet great difficulties.


Complex transcriptional organization regulates an Escherichia coli locus implicated in lipopolysaccharide biogenesis.
The Escherichia coli yrbG-lptB locus (yrbG kdsD kdsC lptC lptA lptB) encodes genes for outer membrane biogenesis, namely, kdsC and kdsD for biosynthesis of the lipopolysaccharide inner core sugar Kdo, and lptA, lptB, and lptC for lipopolysaccharide transport to the outer membrane. Three promoters (yrbGp, kdsCp and the σ(E)-dependent lptAp) have been previously identified by genetic analysis. In this work, we show that transcription of this locus generates an array of overlapping mRNAs and we characterize the two intralocus promoter regions. In the kdsCp region, we identified three promoters (kdsCp1, kdsCp2, and kdsCp3) scattered within about 600 nt in the 3'-coding region of kdsD. The lptAp region is composed of two closely spaced promoters, lptAp1 and lptAp2. The former had been previously identified as a σ(E)-dependent promoter. Interestingly, lptAp1 is not activated by several stressful conditions that normally induce the σ(E)-dependent envelope stress response, whereas it seems to respond to conditions affecting lipopolysaccharide biogenesis, thus implying a specialized σ(E)-dependent LPS stress signaling pathway.


Long-term outcomes of single-incision versus multiport laparoscopic totally extra-peritoneal inguinal hernia repair: a single-institution experience of 186 consecutive cases.
This retrospective study was conducted to compare the long-term outcomes of single-incision totally extraperitoneal (S-TEP) inguinal hernia repair and conventional multiport totally extraperitoneal (M-TEP) inguinal hernia repair. The study population included 186 consecutive patients (S-TEP, n = 149; M-TEP, n = 37) who underwent elective surgery for inguinal hernia at Osaka Police Hospital between 2011 and 2013. No significant between-group difference was found in patient or hernia characteristics or in perioperative outcomes, with the exception of age (S-TEP group vs. M-TEP group: median 69 [IQR 60-75] years vs. 64 [55-69] years, respectively; P = 0.019). Furthermore, no significant between-group difference was found in follow-up time (5.5 [3.0-5.8] vs. 5.4 [3.1-5.7] years, P = 0.839), recurrence rate (0.6 vs. 2.4%, P = 0.358), chronic pain (1.2 vs. 0%, P = 1.000), feeling the mesh (2.3 vs. 7.1%, P = 0.142), or movement limitation (0.6 vs. 0%, P = 1.000). All chronic symptoms were "mild but not bothersome." A metachronous contralateral inguinal hernia developed in 8.1% of patients. The long-term outcomes of S-TEP repair were comparable to those of M-TEP, with rates of recurrence, chronic pain, feeling the mesh, and movement limitation falling within acceptable limits.


An antibacterial bilayer hydrogel modified by tannic acid with oxidation resistance and adhesiveness to accelerate wound repair.
Bacterial infection and oxidative stress remain critical problems for wound closure because they frequently trigger severe complications and delay wound healing. In addition, maintaining a moist microenvironment can promote skin regeneration. In this study, a bilayer hydrogel modified with tannic acid (TA) was constructed to accelerate wound repair. The bilayer hydrogel, composed of a layer with large pores to absorb the fluids and allow gas exchange and small pores to maintain the wound moist and prevent bacterial invasion, was initially developed. Thereafter, TA was introduced into the hydrogel to form a dual crosslinked network and endowed the hydrogel with adhesiveness, antibacterial, and oxidation resistance. In addition, the TA@bilayer hydrogel exhibited shape memory behaviour and self-healing ability due to the hydrogen bonds formed between TA and the bilayer hydrogel. As a result, the TA@bilayer hydrogel significantly promoted wound closure by accelerating collagen deposition, reducing tumour necrosis factor-α (TNF-α) levels, and facilitating the expression of vascular endothelial growth factor (VEGF).


Fungal-associated NO is involved in the regulation of oxidative stress during rehydration in lichen symbiosis.
Reactive oxygen species (ROS) are normally produced in respiratory and photosynthetic electron chains and their production is enhanced during desiccation/rehydration. Nitric oxide (NO) is a ubiquitous and multifaceted molecule involved in cell signaling and abiotic stress. Lichens are poikilohydrous organisms that can survive continuous cycles of desiccation and rehydration. Although the production of ROS and NO was recently demonstrated during lichen rehydration, the functions of these compounds are unknown. The aim of this study was to analyze the role of NO during rehydration of the lichen Ramalina farinacea (L.) Ach., its isolated photobiont partner Trebouxia sp. and Asterochloris erici (Ahmadjian) Skaloud et Peksa (SAG 32.85 = UTEX 911). Rehydration of R. farinacea caused the release of ROS and NO evidenced by the fluorescent probes DCFH₂-DA and DAN respectively. However, a minimum in lipid peroxidation (MDA) was observed 2 h post-rehydration. The inhibition of NO in lichen thalli with c-PTIO resulted in increases in both ROS production and lipid peroxidation, which now peaked at 3 h, together with decreases in chlorophyll autofluorescence and algal photobleaching upon confocal laser incidence. Trebouxia sp. photobionts generate peaks of NO-endproducts in suspension and show high rates of photobleaching and ROS production under NO inhibition which also caused a significant decrease in photosynthetic activity of A. erici axenic cultures, probably due to the higher levels of photo-oxidative stress. Mycobiont derived NO has an important role in the regulation of oxidative stress and in the photo-oxidative protection of photobionts in lichen thalli. The results point to the importance of NO in the early stages of lichen rehydration.


Zinc concentrations in human tissues. Liver zinc in carcinoma and severe liver disease.
In 58 unselected necropsies, zinc (Zn) in specimens of liver (mean +/- s = 280 +/- 178 micrograms/g d.w./4.28 +/- 2.72 mumol/g d.w.), kidney (170 +/- 57 micrograms/g d.w./2.60 +/- 0.87 mumol/g d.w.), spleen (69 +/- 13 micrograms/g d.w./1.05 +/- 0.20 mumol/g d.w.), and lung (64 +/- 16 micrograms/g d.w./0.98 +/- 0.24 mumol/g d.w.) were analysed by means of flameless atomic absorption spectrometry. In the examined range from 25 to 92 years of age, the Zn concentrations in all tissues measured did not show age or sex-dependency. There was a high correlation between the tissue concentration of Zn and Mg in lung, liver, and spleen, between Zn, Mg, and Pb in liver as well as between Zn and Pb and Zn and Cd in kidney. All hepatic cirrhosis cases had very low Zn conc. in liver tissue, the tumor cases generally increasing Zn conc. in liver tissue with progressive stage of regional invasion and distant metastasis.


Embryo blastulation and quality between days 5 and 6 of extended embryo culture.
This study aims to know what proportion of culture day 5 pre-blastocyst-stage embryos develop into blastocysts by culture day 6 and what patient and cycle characteristics are associated with delayed blastocyst formation. A retrospective observational cohort analysis was performed including a total of 9886 embryos from 1008 IVF cycles in 835 patients, who underwent treatment between January 1, 2016, and December 31, 2018. Autologous fresh in vitro fertilization (IVF) cycles at a single academic center were included in the analysis. Embryos were group-cultured using single-step culture media. Blastulation was defined as the presence of a new blastocyst. Usable blastulation was defined as the presence of a new good or excellent quality, expanded, hatching, or hatched blastocysts. The mean blastulation rate between days 5 and 6 of extended embryo culture was 30.9%. The mean percentage of embryos developing into usable blastocyst-stage embryos was 19.8%. The factors associated with blastulation on day 6 included the total number of embryos and the number of pre-blastocysts on day 5, as well as the use of ICSI. Age, the number of total embryos, those remained in culture and pre-blastocysts, as well as the blastulation rate on day 5 were associated with usable blastulation. It is important to know the usable blastocyst development rate between culture days 5 and 6 in order to adequately counsel patients debating whether to proceed with fresh ET on day 5 or forego ET with the expectation that embryos will be biopsied for PGT and/or cryopreserved on culture day 6. Our findings provide evidence to help guide patients in this difficult decision.


Total neoadjuvant treatment and organ preservation strategies in the management of localized rectal cancer: A narrative review and evidence-based algorithm.
The multimodal approach with total mesorectal excision preceded by neoadjuvant (chemo)radiotherapy represented the mainstay treatment for locally advanced rectal cancer (LARC) for a long time. However, the benefit of adjuvant chemotherapy in terms of distant relapse reduction is limited. Recently, chemotherapy regimens administered before surgery and incorporated with (chemo)radiotherapy in total neoadjuvant treatment protocols have been established as new options in the management of LARC. Meanwhile, patients with clinical complete response to neoadjuvant treatment can benefit from organ preservation strategies, aimed at sparing surgery and long-term post-operative morbidities, while preserving an adequate disease control. However, the introduction of a non-operative management in clinical practice is a matter of debate with some concerns regarding the risk of local recurrence and long-term outcomes. In this review, we discuss how these recent advances are reshaping the multimodal management of localized rectal cancer and propose an algorithm to place them in the clinical practice.


Effect of superior cervical ganglionectomy on the ultrastructure of the pinealocyte in the cotton rat (Sigmodon hispidus).
The ultrastructure of pinealocytes was examined morphometrically in superior cervical ganglionectomized and sham-operated cotton rats. Following denervation, the pinealocytes decreased in size. Reduced areas of the nucleoli, Golgi apparatus, granular endoplasmic reticulum, mitochondria, and vacuoles containing a flocculent material as well as a decreased number of dense-core vesicles were noted. In contrast, the numbers of "synaptic" ribbons and ribbon fields increased. The nature of ultrastructural changes observed in the cotton rat pinealocyte after sympathectomy may indicate a diminution of the presumptive secretory processes of this cell. The presence of a small number of myelinated and unmyelinated axons in the pineal gland of the cotton rat following superior cervical ganglionectomy suggests that the sympathetic nerve fibers from the superior cervical ganglia do not comprise the only source of innervation to the pineal. Additionally, the presence of striated muscle fibers has been observed in the present study in the pineal gland of the cotton rat which heretofore has not been reported in this species.


Evaluation of radiomics and machine learning in identification of aggressive tumor features in renal cell carcinoma (RCC).
The purpose of this study was to evaluate the use of CT radiomics features and machine learning analysis to identify aggressive tumor features, including high nuclear grade (NG) and sarcomatoid (sarc) features, in large renal cell carcinomas (RCCs). CT-based volumetric radiomics analysis was performed on non-contrast (NC) and portal venous (PV) phase multidetector computed tomography images of large (> 7 cm) untreated RCCs in 141 patients (46W/95M, mean age 60 years). Machine learning analysis was applied to the extracted radiomics data to evaluate for association with high NG (grade 3-4), with multichannel analysis for NG performed in a subset of patients (n = 80). A similar analysis was performed in a sarcomatoid rich cohort (n = 43, 31M/12F, mean age 63.7 years) using size-matched non-sarcomatoid controls (n = 49) for identification of sarcomatoid change. The XG Boost Model performed best on the tested data. After manual and machine feature extraction, models consisted of 3, 7, 5, 10 radiomics features for NC sarc, PV sarc, NC NG and PV NG, respectively. The area under the receiver operating characteristic curve (AUC) for these models was 0.59, 0.65, 0.69 and 0.58 respectively. The multichannel NG model extracted 6 radiomic features using the feature selection strategy and showed an AUC of 0.67. Statistically significant but weak associations between aggressive tumor features (high nuclear grade, sarcomatoid features) in large RCC were identified using 3D radiomics and machine learning analysis.


Effect of impaired cardiac conduction after alcohol septal ablation on clinical outcomes: insights from the Euro-ASA registry.
We analysed the impact of bundle branch block (BBB) and pacemaker (PM) implantation on symptoms and survival after alcohol septal ablation (ASA) in patients with hypertrophic cardiomyopathy (HCM). Among 1416 HCM patients from the Euro-ASA registry, 58 (4%) patients had a PM and 64 (5%) patients had an implantable cardioverter-defibrillator (ICD) before ASA. At latest follow-up (5.0 ± 4.0 years) after ASA, 118 (8%) patients had an ICD and 229 (16%) patients had a PM. In patients without an implantable device prior to ASA 13% had a PM and 5% had an ICD implanted following ASA. New onset BBB was present in 44% (right BBB in 31%) of patients without previous BBB. At latest follow-up, we found no associations between BBB and New York Heart Association (NYHA) Class 3-4 [odds ratio (OR) 0.98, 95% confidence interval (CI) 0.63-1.51; P = 0.91] or Canadian Cardiovascular Society (CCS) Class 3-4 (OR 1.5, CI 0.32-6.7; P = 0.62), respectively, and no associations between PM and NYHA Class 3-4 (OR 1.2, CI 0.70-2.0; P = 0.52) or CCS 3-4 (OR 1.3, CI 0.24-6.6; P = 0.79), respectively. The survival after ASA was not reduced in patients with BBB [hazard ratio (HR) 0.73, CI 0.53-1.01; P = 0.06] or PM (HR 0.78, CI 0.52-1.17; P = 0.24). Development of BBB or need for a PM after ASA in patients with obstructive HCM was not associated with inferior symptomatic outcome or reduced survival, thus concerns for the negative impact of impaired cardiac conduction on the clinical outcome after ASA were not confirmed.


Keratoconus associated with congenital stationary night blindness type 1.
A 35-year-old man presented with keratoconus; his best corrected visual acuities were -18.00/+10.00 ×180 (6/60) oculus dexter and -10.00/+8.00 ×5 (6/36) oculus sinister. Bilateral steep central corneal thinning, paracentral ectasia and Vogts striae were present. Normal fundi. Corneal topography disclosed 7.4 dioptres of irregular astigmatism in the central 3 mm with thinning (335 μm). Electroretinography (ERG) showed no response. There were no medical or environmental influences for his keratoconus. Occurrence of keratoconus and congenital stationary night blindness (CSNB) in the patient may represent a chance association, but keratoconus has not been previously linked with CSNB1 either as a chance or true association though both show genetic predisposition.