PCL/Col I-based magnetic nanocomposite scaffold provides an osteoinductive environment for ADSCs in osteogenic cues-free media conditions.
The bone tissue engineering (BTE) approach has been introduced as an alternative to conventional treatments for large non-healing bone defects. Magnetism promotes stem cells' adherence to biocompatible scaffolds toward osteoblast differentiation. Furthermore, osteogenic differentiation media are expensive and any changes in its composition affect stem cells differentiation. Moreover, media growth factors possess a short half-life resulting in the rapid loss of their functions in vivo. With the above in mind, we fabricated a multilayered nanocomposite scaffold containing the wild type of Type I collagen (Col I) with endogenous magnetic property to promote osteogenesis in rat ADSCs with the minimum requirement of osteogenic differentiation medium. Fe3O4 NPs were synthesized by co-precipitation method and characterized using SEM, VSM, and FTIR. Then, a PCL/Col I nanocomposite scaffold entrapping Fe3O4 NPs was fabricated by electrospinning and characterized using SEM, TEM, AFM, VSM, Contact Angle, tensile stretching, and FTIR. ADSCs were isolated from rat adipose tissue and identified by flow cytometry. ADSCs were loaded onto PCL/Col I and PCL/Col I/Fe3O4-scaffolds for 1-3 weeks with/without osteogenic media conditions. The cell viability, cell adhesion, and osteogenic differentiation were evaluated using MTT assay, SEM, DAPI staining, ALP/ARS staining, RT-PCR, and western blotting, respectively. SEM, VSM, and FTIR results indicated that Fe3O4 was synthesized in nano-sized (15-30 nm) particles with spherical-shaped morphology and superparamagnetic properties with approved chemical structure as FTIR revealed. According to SEM images, the fabricated magnetic scaffolds consisted of nanofiber (500-700 nm). TEM images have shown the Fe3O4 NPs entrapped in the scaffold's fiber without bead formation. FTIR spectra analysis confirmed the maintenance of the natural structure of Col I, PCL, and Fe3O4 upon electrospinning. AFM data have shown that MNPs incorporation introduced stripe-like topography to nanofibers, while the depth of the grooves has decreased from 800 to 500 nm. Flow cytometry confirmed the phenotype of ADSCs according to their surface markers (i.e., CD29 and CD105). Additionally, Fe3O4 NP improved nanocomposite scaffold strength, wettability, porosity, biocompatibility and also facilitates the ALP activity, calcium-mineralization. Finally, magnetic nanocomposite scaffolds upregulated osteogenic-related genes or proteins' expression (e.g., Col I, Runx2, OCN, ON, BMP2) in seeded ADSCs with/without osteo-differentiation media conditions. Together, these results indicate that Fe3O4 NPs within the natural structure of Col I increase osteogenic differentiation in osteogenic cues-free media conditions. This effect could be translated in vivo toward bone defects healing. These findings support the use of natural ECM materials alongside magnetic particles as composite scaffolds to achieve their full therapeutic potential in BTE treatments.


In vitro selection by using mutated GCN4-bZIP peptides for analysis of peptide-DNA interactions.
In vitro selection has been used as a method to determine the optimal binding site for DNA-binding proteins. We report here in vitro selection of dsDNA sequences that bind to mutated-GCN4-bZIP peptides. The GCN4-bZIP peptide mutated from alanine to histidine on a position-14 that contacts with DNA bound to different sequence from a binding site of wild type peptide.


Unified Analysis of Multiple ChIP-Seq Datasets.
High-throughput sequencing technologies are increasingly used in molecular cell biology to assess genome-wide chromatin dynamics of proteins bound to DNA, through techniques such as chromatin immunoprecipitation sequencing (ChIP-seq). These techniques often rely on an analysis strategy based on identifying genomic regions with increased sequencing signal to infer the binding location or chemical modifications of proteins bound to DNA. Peak calling within individual samples has been well described, however relatively little attention has been devoted to the merging of replicate samples, and the cross-comparison of many samples. Here, we present a generalized strategy to enable the unification of ChIP-seq datasets, enabling enhanced cross-comparison of binding patterns. The strategy works by merging peak data between different (even unrelated) samples, and then using a local background to recalculate enrichment. This strategy redefines the peaks within each experiment, allowing for more accurate cross-comparison of datasets.


Ayurvedic management of idiopathic small fibre neuropathy- A case report.
Small fibre neuropathy (SFN) is a subgroup of peripheral neuropathy which is characterized by a disorder of the thin myelinated A-δ and unmyelinated C-fibres. With a prevalence of 52.95 per 100,000 population per year, the reported etiology of SFN has remained unclear in 23-93% of investigated patients and hence termed idiopathic small fibre neuropathy (iSFN). Pain is the most common symptom which is often described as burning. Conventional pain management is the only treatment option for iSFN, which is only modestly effective and associated with adverse events which lead to reduced drug compliance. It also affects the overall quality of life. This case report discusses the effect of Ayurvedic interventions in the management of iSFN. The patient was a 37-year-old male, who presented with severe pain, burning, and tingling sensation of B/L lower limbs and hands with decreased sleep for 5 years (visual analogue scale (VAS) was 10 and neuropathic pain scale (NPS) score was 39). Considering the signs and symptoms, the disease was diagnosed under the Vata Vyadhi (disease/syndrome caused by Vata Dosha) spectrum. The treatment included an initial OPD-based Shamana (treatment that pacifies the aggravated doshas) treatment with Drakshadi Kwatha, Sundibaladwaya Ksheera Kwatha, Kalyanaka Gritha, and Ashwagandhadi Churna. As the symptoms persisted, Shodhana (treatment in which aggravated doshas are expelled from the body) treatment was adopted which included Mridu (mild) Shodhana, Nasya (medicine administered through nasal route) and Basti (administration of medicine through the procto-colonic route). The intervention resulted in significant clinical improvement as evidenced by the reduction in VAS and NPS scores to zero and five respectively. The patient's quality of life also showed significant improvement. This case report signifies the pivotal role of Ayurvedic intervention in the management of iSFN and encourages further research in this area. Integrative therapeutic approaches can be developed which may offer a promising strategy for managing iSFN and improving patient outcomes.


The effect of an oral gold preparation on the gastrointestinal tract motility in two species of experimental animals.
The oral gold preparation, auranofin, used in rheumatoid arthritis has been reputed to cause chronic diarrhea. To investigate this the G.I. tract motility was measured before auranofin therapy and after 1, 3, and 5 weeks of therapy using scintigraphy following indium-111-labeled meals in three beagle dogs. The gastric emptying times of the dogs accelerated throughout the duration of the experiment, although the large bowel transit times did not seem to be affected. The affect of auranofin on the stools of the baboon Papio ursinus was also noted. The baboon stools were observed for any change in consistency. Sigmoidoscopic examination including mucosal biopsies was carried out monthly over a 6-month period. The baboon's stools were noted to become very soft in consistency, but histology indicated no mucosal changes.


Efficacy and safety of oxybutynin chloride topical gel for women with overactive bladder syndrome.
This subgroup analysis of a phase-3 study evaluated the efficacy and safety of oxybutynin chloride topical gel (OTG) in women with overactive bladder syndrome (OAB). Women (n = 704) with urgency-predominant urinary incontinence received OTG or placebo for 12 weeks. The primary endpoint was change from baseline to last observation in number of daily incontinence episodes. Treatments were compared with the use of analysis of covariance. OTG significantly reduced the number (mean ± standard deviation) of daily incontinence episodes (OTG, -3.0 ± 2.8 episodes; placebo, -2.5 ± 3.0 episodes; P < .0001), reduced urinary frequency (P = .0013), increased voided volume (P = .0006), and improved select health-related quality-of-life domains (P ≤ .0161) vs placebo. Dry mouth was the only drug-related adverse event significantly more common with OTG (7.4%) than with placebo (2.8%; P = .0062). OTG was well tolerated and provided significant improvement in urinary symptoms and health-related quality of life in women with OAB.


Biobased contents of biodegradable poly(epsilon-caprolactone) composites polymerized and directly molded using aluminium triflate from caprolactone with cellulose and inorganic filler.
Poly(epsilon-caprolactone) (PCL) composite samples were prepared by polymerization and direct molding. The starting compound was epsilon-caprolactone monomer liquid combined with cellulose and inorganic fillers, using aluminium triflate as a catalyst at 80 degrees C, for 6 or 24 h. Cylinder-shaped PCL composite samples with a homogeneously dispersed cellulose filler were prepared with (-)M(n) = 4 600 ((-)M(w)/(-)M(n) = 2.9). The mechanical properties of the PCL composite samples were studied using compression test methods. The strength of a PCL composite with 50 wt.-% cellulose filler (10.8 MPa) was found to be lower than the PCL sample without fillers (19.2 MPa). The biobased content of the PCL composite with 50 wt.-% cellulose filler (51.67%) measured using accelerated mass spectrometry (AMS) was slightly higher than the carbon ratio of cellulose in the starting powder samples (41.3 mol-%). The biobased content of the polymer composite powders by AMS was found not to be affected by the presence of inorganic fillers, such as talc. The rate and extent of biodegradation, caused by Amano Lipase PS, of the PCL composite sample with cellulose filler (40% degradation in 4 d) was the same as that of a PCL sample without the cellulose filler.


Role of Serial Phlebotomy in the Management of Blunt Solid Organ Injury in Adults.
The management of blunt spleen and liver trauma has become increasingly nonoperative. There is no consensus on timing or duration of serial hemoglobin and hematocrit monitoring in this patient population. This study examined the clinical utility of serial hemoglobin and hematocrit monitoring. We hypothesized that most interventions occur early in the hospital course, based on hemodynamic instability or physical examination findings rather than serial monitoring. We conducted a retrospective cohort study of adult trauma patients with blunt spleen or liver injury from November 2014 through June 2019 at our Level II trauma center. Interventions were classified as no intervention, surgical intervention, angioembolization, or packed red blood cell transfusion. Demographics, length of stay, total blood draws, laboratory values, and clinical triggers preceding intervention were reviewed. A total of 143 patients were studied, of whom 73 (51%) received no intervention, 47 (33%) received an intervention within 4 hr of presentation, and 23 (16%) had interventions beyond 4 hr. Of these 23 patients, 13 received an intervention based on phlebotomy results alone. Most of these patients (n = 12, 92%) received blood transfusion without further intervention. Only one patient underwent operative intervention based on serial hemoglobin results on hospital day 2. The majority of patients with these injury patterns either require no intervention or declare themselves promptly after arrival. Serial phlebotomy after initial triage and intervention may add little value in the management of blunt solid organ injury.


[Self-perception of health status in people retired due to diabetes mellitus complications from Guadalajara, Mexico].
To evaluate self-perception of health status (APES by its Spanish acronym) of people retired due to complications of diabetes mellitus, and what socio-demographic, family, work and clinical characteristics are associated to these variables. Analytical, cross-sectional study in a universe of 240 pensioners who agreed to participate. The APES was evaluated with the EuroQol-5D questionnaire in Spanish, and socio-demographic, family, work and clinical variables were included. 240 pensioners with a mean age of 53.43 ± 8.16 years (94.29% male and 5.71% female) were studied. It was found that 53.4% reported regular, poor or very poor APES. A significant association between poor APES and work life ≤30 years (OR=6.00; 95%CI: 1.27, 28.26) and chronic renal failure (OR=7.00; 95%CI: 1.39, 35.35) was found. No explanatory models were found through logistic regression. No explanatory models were found by logistic regression. The frequency of poor APES was high in the sample of patients with diabetes. Studies with larger samples are required for better conclusions.


Effects of aromatherapy on agitation in patients with dementia in the community: A quasi-experimental study.
The behavioral and psychological symptoms of dementia (BPSD) are experienced by up to 90% of patients with dementia throughout dementia. This study aims to investigate the effect of aromatherapy on agitation in patients with dementia in the community. This prospective cohort study was conducted at a single day-care center for patients with dementia located in northern Taiwan with 2-week and 4-week follow-ups, comparing the severity of agitation between 3 measure points as the primary outcome. The aromatherapy was performed over 5 consecutive days for 4 weeks. Throughout the four-week observation were analyzed by GEE. Significant differences were found in the Chinese version of Cohen-Mansfield Agitation Inventory (CCMAI) total agitation score (ß=-3.622, p=0.037) and physically non-aggressive behavior subscale (ß=-4.005, p=0.004) between aromatherapy group and control group. The severity of dementia-related agitation, especially the severity of physically non-aggressive behavior in demented patients, could be significantly reduced by a four-week intervention of aromatherapy.


A single-file model for potassium transport in squid giant axon. Simulation of potassium currents at normal ionic concentrations.
A physical model for potassium transport in squid giant axon is proposed. The model is designed to explain the empirical data given by the Hodgkin-Huxley model and related experiments. It is assumed that K(+) moves across the axon membrane by single-file diffusion through narrow pores. In the model a pore has three negatively charged sites that can be occupied alternatively by K(+) or by a gating particle, GP(++), coming from the external surface. GP(++) is considered to be part of the membrane rather than a diffusible component of the surrounding solutions. A high activation barrier for GP(++) is supposed at the inner membrane border so that it cannot change over to the internal surface. Therefore potassium diffusion can be blocked by GP(++) penetrating into the pores. This mechanism controls the dynamic behaviour of the model. The time-dependent probabilities of the pore states are described by a system of differential equations. The rate constants in these equations depend on the ionic concentrations, the membrane voltage, and the electrostatic interaction between ions in a single pore. Detailed computational tests for normal composition of external and internal solutions show that the model agrees remarkably well with the stationary and dynamic behaviour of the Hodgkin-Huxley model. However, the hyperpolarization delay is not reproduced. A structural modification, concerning this delay and the way in which GP(++) is attached to the membrane, is proposed, and the qualitative behavior of the model at varied external and internal concentrations is discussed.


Post-transcriptional action of ACTH in the control of P450c17 expression in rabbit adrenal glands.
Stimulation of transcription of the CYP17 gene by ACTH has been demonstrated previously by others using cultures of adrenal tissue from several species. In the present investigations we have demonstrated from measurements in pooled rabbit adrenal glands that after 4 or 6 days of ACTH injections no difference in amounts of CYP17 mRNA per microgram of total adrenal RNA was observed between ACTH and control animals. While the total amount of CYP17 mRNA per adrenal increased 1.4- to 1.7-fold over the injected and non-injected controls due to an increase in total RNA in the ACTH-stimulated adrenals, Western analysis of adrenal microsomal protein demonstrated that the amount of adrenal P450c17 protein, the product of the CYP17 gene, increased over 50-fold. The data show that ACTH is acting at both transcriptional and post-transcriptional loci to increase the amount of rabbit adrenal P450c17 and that the greater effect is post-transcriptional.


Tonic endocannabinoid signaling supports sleep through development in both sexes.
Sleep is an essential behavior that supports brain function and cognition throughout life, in part by acting on neuronal synapses. The synaptic signaling pathways that mediate the restorative benefits of sleep are not fully understood, particularly in the context of development. Endocannabinoids (eCBs) including 2-arachidonyl glycerol (2-AG) and anandamide (AEA), are bioactive lipids that activate cannabinoid receptor, CB1, to regulate synaptic transmission and mediate cognitive functions and many behaviors, including sleep. We used targeted mass spectrometry to measure changes in forebrain synaptic eCBs during the sleep/wake cycle in juvenile and adolescent mice of both sexes. We find that eCBs lack a daily rhythm in juvenile mice, while in adolescents AEA and related oleoyl ethanolamide are increased during the sleep phase in a circadian manner. Next, we manipulated the eCB system using selective pharmacology and measured the effects on sleep behavior in developing and adult mice of both sexes using a noninvasive piezoelectric home-cage recording apparatus. Enhancement of eCB signaling through inhibition of 2-AG or AEA degradation, increased dark-phase sleep amount and bout length in developing and adult males, but not in females. Inhibition of CB1 by injection of the antagonist AM251 reduced sleep time and caused sleep fragmentation in developing and adult males and females. Our data suggest that males are more sensitive to the sleep-promoting effects of enhanced eCBs but that tonic eCB signaling supports sleep behavior through multiple stages of development in both sexes. This work informs the further development of cannabinoid-based therapeutics for sleep disruption.


Standardized Technique of Laparoscopic Adjustable Gastric Banded Plication with 4-Year Results.
No bariatric procedure is perfect, and a plethora of such procedures itself is a proof for the same. Laparoscopic adjustable gastric banding has a high safety profile, but also a high rate of re-operation has been reported (Schouten, Wiryasaputra, van Dielen et al. Obes Surg 20(12):1617-26, 2010). Laparoscopic sleeve gastrectomy (LSG) is becoming popular, but has its own set of complications and is irreversible. We introduced laparoscopic adjustable gastric banded plication (LAGBP) in 2009 (Huang, Lo, Shabbir et al. Surg Obes Relat Dis 8(1):41-5, 2012) In a case matched comparative study with LSG, LAGBP showed similar results at 2 years in terms of weight loss, comorbidity resolution, and complications. (Huang, Chhabra, Goel et al. Obes Surg 23(8):1319-23, 2013). Several authors have reported variations in their technique, bougie size, and suture material used to perform plication. (Ramos, Galvao Neto, Galvao et al. Obes Surg 20(7):913-8, 2010, (Mui, Lee, Lam et al. Obes Surg 23(2): 179-83, 2013, Brethauer, Harris, Kroh et al. Surg Obes Relat Dis 7(1):15-22, 2011) Our initial technique of placing the band first and then plicating the stomach resulted in higher incidence of gastric fundus herniation compared to that reported in a systematic review (Abdelbaki, Huang, Ramos et al. Obes Surg 22(10):1633-9, 2012). After the first 65 cases, we reversed the order by performing the gastric plication first which ensures proper plication of the fundus and a more uniformly placed plication line. This technique has become our standard, and the same is described in this video in a stepwise fashion. We performed LAGBP in 202 cases over the last 4 years and recorded the findings. Our standardized technique is shown in this video. The T-suspension technique was used for liver retraction. (Zachariah, Tai, Chang et al. J Laparoendosc Adv Surg Tech A 23(4):311-5, 2013) Gastric plication formula is shown in Fig. 1. Fig. 1 Gastric plication formula Two hundred two (69 male, 133 female) patients in over the last 4 years underwent LAGBP. Follow-up at 1 year was 168 patients, and 56 patients reached 4-year follow-up. Age was 16-60 years (mean = 31.1). Mean BMI was 39.5 ± 3.18 and body weight 110 kg ± 19.4. Mean operative time was 104 min ± 39 and length of hospital stay after surgery 2.1 ± 2.3 days. No mortality was recorded. Excess weight loss at 1 year was 57.84 % and at four years 68 %. LAGBP has been proven to be an effective bariatric procedure in the midterm results. Standardization with plication first and then placement of the band could be important to achieve best outcomes.


Follow the leader. Inspiring the next generation to become nurses.
There is a perception among the Indian and Pakistani communities that nursing is not an appropriate career for women. Aruna Dawda and her two nieces are breaking the mould.


Naked in the Old and the New World: Differences and Analogies in Descriptions of European and American herbae nudae in the Sixteenth Century.
The sixteenth century could be understand as a period of renaissance of interest in nature and as a period of development of natural history as a discipline. The spreading of the printing press was connected to the preparation of new editions of Classical texts and to the act of correcting and commenting on these texts. This forced scholars to confront texts with living nature and to subject it to more careful investigation. The discovery of America uncovered new horizons and brought new natural products, which were exotic and unknown to Classical tradition. The aim of this study is to compare strategies and categories, which were used in describing plants of the Old and the New World. Attention will be paid to the first reactions to the new flora, to the methods of naming and describing plants, to the ways of gaining knowledge about plants from local sources or by means of one's own observation. The confrontation with novelty puts naturalists in the Old World and in the New World in a similar situation. It reveals the limits of traditional knowledge based on Classical authorities. A closer investigation, however, brings to light not only the sometimes unexpected similarities, but also the differences which were due to the radical otherness of American plants.


Elevated red cell distribution width to platelet count ratio predicts poor prognosis in patients with breast cancer.
Red cell distribution width (RDW) to platelet ratio (RPR) is a prognosticator in acute pancreatitis and myocardial infarction; however, the prognostic values of RDW and RPR in breast cancer have not been studied. This retrospective analysis of 299 breast cancer patients investigated the association between RDW and RPR and clinicopathological characteristics and prognosis, compared to platelet distribution width to platelet count ratio (PDW/P) which is a known independent prognostic factor in patients with breast cancer. We found a significant correlation between RPR, and age and HER2 status. An elevated RPR significantly correlated with age and HER2 status. After a median follow-up duration of 48 months, tumour size, nuclear grade, PDW/P, and RPR were recgnized to be significantly associated with lower disease-free survival rates (tumour size: p < 0.01; nuclear grade, PDW/P, and RPR: p < 0.05) in univariate analysis. Tumour size and RPR were significant prognostic factors for lower disease-free survival rates, with hazard ratios of 4.31 (95% confidence interval: 1.76-10.53) (p < 0.01)] and 2.79 [95% confidence interval: 1.01-87.69) (p < 0.05)], respectively, in a multivariate analysis using the Cox proportional hazards model. This is the first study showing that an elevated RPR could independently predict poor prognosis in patients with breast carcinoma. Thus, RPR could be a novel biomarker for prognostic estimation.


Glioma Stem Cells Upregulate CD39 Expression to Escape Immune Response through SOX2 Modulation.
Ectonucleotidase CD39 hydrolyzing extracellular ATP (eATP) functions as a key modulator of immune response in the tumor microenvironment, yet the role of CD39 in contributing tumor stem cells in a more immunosuppressive microenvironment remains elusive. Here we report that the upregulation of CD39 is crucial for the decrease of extracellular ATP concentration around glioma stem cells (GSCs) to maintain an immunosuppressive microenvironment. Adriamycin (ADM) is able to promote the release of ATP, which recruits dendritic cells (DCs) to phagocytose GSCs. CD39 inhibition further increased extracellular ATP concentrations following ADM treatment and DCs phagocytosis. In addition, GSCs upregulated CD39 expression by SOX2-binding CD39 promotor. In mouse tumor models, the combination of ADM and CD39 blockade increased immune cell infiltration and reduced tumor size. These findings suggest that GSCs upregulate CD39 expression by their biological characteristics to maintain an immunosuppressive microenvironment, and CD39 inhibition supplies a favorable tumor microenvironment (TME) for immunotherapeutic intervention and enhances the immune response induced by chemotherapy.


State criminal justice policy context and opioid agonist treatment delivery among opioid treatment admissions, 2015.
Criminal justice referral to treatment is associated with reduced odds of receiving opioid agonist treatment (OAT), the gold-standard treatment for opioid use disorder. States vary substantially in the extent of criminal justice system involvement in opioid treatment; however, the effects on treatment provision are not clear. We examined whether state-level criminal justice involvement in the substance use treatment system modified the association between criminal justice referral to treatment and OAT provision among opioid treatment admissions. We conducted a random effects logistic regression to investigate how the effects of criminal justice referral to treatment on OAT provision differed in states with high vs. low state-level criminal justice involvement in opioid treatment, adjusting for individual and state-level covariates, among 22 states in the 2015 Treatment Episode Dataset-Admissions. Criminal justice referral to treatment was associated with an 85% reduction in the odds of receiving OAT, compared to other sources of treatment referral (OR = 0.15; 95% CI: 0.15, 0.16). Among opioid treatment admissions resulting from criminal justice referral in 2015, receiving treatment in high criminal justice involvement states was associated with a 63% reduction in the odds of OAT provision, compared to opioid treatment received in low criminal justice involvement states (interaction OR = 0.37, 95% CI: 0.11, 0.89). The effects of criminal justice referral to treatment on OAT provision varied by criminal justice involvement in opioid treatment at the state level. Targeted interventions should increase access to OAT in states that rely on the criminal justice system for opioid treatment referrals.


Cross-cultural considerations in custody and parenting plans.
Children are entitled to their cultural heritage and it is important to their development. Cultural considerations must be incorporated in devising custody and parenting plans. Several generalizations are useful. Children are capable of integrating highly diverse and even contradictory cultural and religious identity fragments. The more distinctly a child's cultural inheritance varies from that of the dominant society, the more it must be taken into account. The more bias or hostility that exists against an aspect of the child's cultural inheritance, the more that cultural component is to be considered. The value of culture to the child is best seen in a developmental context. We are limited in our ability to ensure children's rights to cultural inheritance by our own ethnocentrism or ignorance, by bureaucratic or legalistic definitions of cultural identity, by the desire of one parent to reduce the contribution of the other parent, and by a tendency to rely on consistency as a value in and of itself.


Cadmium alters heat shock protein pathways in SN56 cholinergic neurons, leading to Aβ and phosphorylated Tau protein generation and cell death.
Cadmium, a neurotoxic environmental compound, produces cognitive disorders, although the mechanism remains unknown. Cadmium induces a more pronounced cell death on cholinergic neurons from basal forebrain (BF), mediated, in part, by increase in Aβ and total and phosphorylated Tau protein levels, which may explain cadmium effects on learning and memory processes. Cadmium downregulates the expression of heat shock proteins (HSPs) HSP 90, HSP70 and HSP27, and of HSF1, the master regulator of the HSP pathway. HSPs proteins reduce the production of Aβ and phosphorylated Tau proteins and avoid cell death pathways induction. Thus, we hypothesized that cadmium induced the production of Aβ and Tau proteins by HSP pathway disruption through HSF1 expression alteration, leading to BF cholinergic neurons cell death. Our results show that cadmium downregulates HSF1, leading to HSP90, HSP70 and HSP27 gene expression downregulation in BF SN56 cholinergic neurons. In addition, cadmium induced Aβ and total and phosphorylated Tau proteins generation, mediated partially by HSP90, HSP70 and HSP27 disruption, leading to cell death. These results provide new understanding of the mechanisms contributing to cadmium harmful effects on cholinergic neurons.


Ophthalmic health care needs of children with disabilities.
Although vision care is crucial for pediatric eye health, research on vision care utilization by children with disabilities remains limited. Furthermore, no study has investigated the variations among various disability types and the interaction between disability status and age. All children with disabilities listed in the Taiwan National Disability Registry during the study period (2015-2019) were matched by age and sex at a 1:4 ratio with children without disabilities. Vision care needs were measured on the basis of (1) the number of outpatient ophthalmology visits, (2) total medical costs associated with outpatient ophthalmology visits, and (3) whether ophthalmic care was provided. Generalized estimating equation models were estimated to determine the relationships between utilization, disability status, and age. Significant differences in needs between various disability types were identified. Other than children with visual disability, children with facial disability and balance abnormalities also had considerable needs. Children with intellectual disabilities, which constituted the most common disability type (29.4% in 2019), had fewer visits (mean = 1.38, SD = 2.12) and lower medical costs, compared with the averages for all children with disabilities. Care utilization shared an inverted U-shaped relationship with age. Children with disabilities have higher vision care needs, which vary by disability type and age. Such needs are greater at younger ages and decreases after the ages of 9-10 years. Policies should be specific to disability type and age to ensure vision care needs are met.


Clinical efficacy of co-trimoxazole versus amoxicillin twice daily for treatment of pneumonia: a randomised controlled clinical trial in Pakistan.
To compare the clinical efficacy of twice daily oral co-trimoxazole with twice daily oral amoxicillin for treatment of childhood pneumonia. Randomised controlled, double blind, multicentre study in outpatient departments of seven hospitals and in one community health service. A total of 1471 children (aged 2-59 months) with non-severe pneumonia were randomly assigned to 25 mg/kg amoxicillin (n = 730) or 4 mg/kg trimethoprim plus 20 mg/kg sulphamethoxazole (co-trimoxazole) (n = 741). Both medicines were given orally twice daily for five days. Data from 1459 children were analysed: 725 were randomised to amoxicillin and 734 to co-trimoxazole. Treatment failure in the amoxicillin group was 16.1% compared to 18.9% in the co-trimoxazole group. Multivariate analysis showed that treatment failure was more likely in infants who had history of difficult breathing or those who had been ill for more than three days before presentation. Both amoxicillin and co-trimoxazole were equally effective in non-severe pneumonia. Good follow up of patients is essential to prevent worsening of illness.


Clinical Characteristics of Short-Stature Patients With an NPR2 Mutation and the Therapeutic Response to rhGH.
The natriuretic peptide receptor 2 gene (NPR2) is a causative gene of idiopathic short stature (ISS) with an incidence rate of 2% to 6%. The clinical characteristics of patients with NPR2 heterozygous mutations are atypical, and data on the efficacy of recombinant human growth hormone (rhGH) treatment in patients with NPR2 mutations are limited. This work reports 6 cases with NPR2 mutation and explores the characteristics of patients with an NPR2 mutation and their therapeutic response to rhGH. Six Chinese short-stature patients in our hospital with NPR2 mutations by whole-exome sequencing were included. We also searched all previously published NPR2 mutation cases as of August 10, 2020, and information about their medical history, mutations, and rhGH treatment were recorded and summarized. The clinical characteristics of patients with an NPR2 heterozygous mutation mainly included short stature, facial anomalies, and skeletal dysplasia. Skeletal dysplasia mainly included brachydactyly (56.2%), shortened metacarpals or metatarsals (particularly fourth to fifth; 26.1%), and clinodactyly (21.7%). rhGH treatment significantly improved the height SD score (SDS) of patients with NPR2 heterozygous mutations (median, -2.1 vs -2.9, P < .001), especially in girls. The height SDS change correlated negatively with initial age of treatment (r = -0.477; P = .034), and height SDS change of patients with NPR2 heterozygous mutations in the carboxyl-terminal guanylyl cyclase catalytic domain was significantly higher than that of the extracellular ligand-binding region domain (median, 1.9 vs 0.6, P = .019). ISS patients with skeletal deformities should be tested for an NPR2 mutation. rhGH treatment is beneficial for short-stature patients with NPR2 heterozygous mutations and needs further study.


Comparison of different regimens of a gonadotropin-releasing hormone analog during ovarian stimulation for in vitro fertilization.
Three treatment protocols were used in 156 in vitro fertilization cycles. Leuprolide acetate was begun on day 1 of the cycle in one group (n = 20), on day 3 in another (n = 48), and the third control group (n = 88) did not receive the gonadotropin-releasing hormone analog. Human menopausal gonadotropin was initiated on day 3 in all groups. Peak estradiol (E2) levels and the mean numbers of mature oocytes and embryos transferred per cycle were significantly greater in the day 3 group than in either the day 1 or control groups. Patients who received the day 3 protocol had significantly fewer cancelled cycles. A decline in E2 was observed on the third day of analog administration in certain patients, particularly those on the day 1 protocol. Follicle-stimulating hormone and luteinizing hormone (LH) levels increased two- to fivefold 24 hours after initiation of the analog. Thereafter the gonadotropin levels fell, but nevertheless remained above those of controls for most of the cycle. Hence, it appears that enhanced follicular growth attributed to the early transient rises in gonadotropins can be coupled to a suppression of endogenous LH surges in leuprolide-treated women. These beneficial effects seem to be more likely to occur if leuprolide is initiated on cycle day 3 rather than day 1.


A new approach for evaluating continuous and discontinuous pipeline deformation induced by soil tunnel excavation.
The deformation of the overlying pipeline caused by the soil tunnel excavation cannot be ignored in the case of the small spacing between the pipeline and the tunnel. Based on the rigid bar method, the pipeline-soil interaction model was established, with the simply supported beam as the basic system, and the loads acting on the pipeline by the soil are considered to be linearly distributed. Calculation methods for continuous and discontinuous pipeline deformations were established. The results calculated by the proposed method agree well with the experimental data of centrifuge tests and field data. Parametric study on the effect of the volume loss (η = 1%, 2%,3 %), rotational stiffness (β0 = 4.47 × 106N⋅m/rad, 4.47 × 108N⋅m/rad, 4.47 × 1010N⋅m/rad), ratio of pipeline section length to inflection point of soil settlement curve (L/is = 0.5, 1.0, 1.5, 2.0) and soil elastic modulus (E = 10 MPa, 30 MPa, 50 MPa) on the deflection and joint rotation angle of the discontinuous pipeline were carried out. Results show that: (1) the maximum pipeline deflection and the maximum rotation angle of the joint increase as η increases and decrease as β0 increases; (2) in the "odd" case, the maximum pipeline deflection and the maximum rotation angle of the joint first increase and then decrease as L/is increases, reaching a peak at L/is = 1.5, while in the "even" case, the maximum pipeline deflection decreases as L/is increases and the maximum rotation angle of the joint first increases and then decreases as L/is increases; (3) in the "odd" case, the maximum pipeline deflection and the maximum angle of rotation of the joint decrease as E increases, while the opposite trend is observed in the "even" case. Additionally, the maximum pipeline deflection and the maximum rotation angle of the joint are always greater in the "odd" case than that in the "even" case.


[Stability and virus-inhibiting effect of recombinant receptor toxins based on the human CD4 receptor and diphtheria toxin].
The causes of differences in the stability of CD4 receptor and diphtherial toxin based recombinant receptorotoxins synthesized in E.coli and differing by their primary structure were under study. Insertion of a CD4 receptor fragment, responsible for HIV binding, on the N terminus of hybrid protein was found to lead to a drastic reduction of the stability of the hybrid polypeptide in E.coli and to impossibility of obtaining full-size protein product. In vitro experiments on a model of human T lymphocyte culture demonstrated that recombinant receptorotoxin stably expressed in E.coli inhibited the cytopathic effect of type 1 HIV and the effect of syncytium formation induced by the virus.


[68Ga]Ga-DOTA-FAPI-04 PET/MR in patients with acute myocardial infarction: potential role of predicting left ventricular remodeling.
To assess predictive value of 68Ga-labeled fibroblast activation protein inhibitor-04 ([68Ga]Ga-DOTA-FAPI-04) PET/MR for late left ventricular (LV) remodeling in patients with ST-segment elevated myocardial infarction (STEMI). Twenty-six patients with STEMI were included in the study. [68Ga]Ga-DOTA-FAPI-04 PET/MR was performed at baseline and at average 12 months after STEMI. LV remodeling was defined as >10% increase in LV end-systolic volume (LVESV) from baseline to 12 months. The LV remodeling group demonstrated higher [68Ga]Ga-DOTA-FAPI-04 uptake volume (UV) at baseline than the non-LV remodeling group (p < 0.001). [68Ga]Ga-DOTA-FAPI-04 UV at baseline was a significant predictor (OR = 1.048, p = 0.011) for LV remodeling at 12 months after STEMI. Compared to clinical information, MR imaging and cardiac function parameters at baseline, [68Ga]Ga-DOTA-FAPI-04 UV demonstrated better predictive ability (AUC = 0.938, p < 0.001) for late LV remodeling, with sensitivity of 100.0% and specificity of 81.3%. [68Ga]Ga-DOTA-FAPI-04 PET/MR is an effective tool to non-invasively quantify myocardial fibroblasts activation, and baseline [68Ga]Ga-DOTA-FAPI-04 UV may have potential predictive value for late LV remodeling.


Formation of Ga2Te2 and M3Te3(M = Ga, In) rings from reactions of sodium ditelluroimidodiphosphinate with Group 13 halides.
Metathetical reactions of Na[N(iPr2PTe)2] with Group 13 metal halides produce the telluride complexes {Ga(mu-Te)[iPr2PNiPr2PTe]}2(2) and {M(mu-Te)[N(iPr2PTe)2]}3, M = In (3) and Ga (4), which contain central Ga2Te2 and M3Te3 rings, respectively.


Early prediction of implant failures in geriatric intertrochanteric fractures with single-screw cephalomedullary nailing fixation.
The implant failures of intertrochanteric fractures (ITF) after single-screw cephalomedullary nailing (CMN) were multifactorially associated with various related factors. However, a comprehensive scoring system for the early prediction of implant failures is still lacking. Thus, this study aims to establish a quantification scoring system (QSS) and verify whether the QSS is reliable for predicting implant failures in geriatric ITF patients. We established the QSS of geriatric ITF with single-screw cephalomedullary nailing within three days after surgery. The QSS included eight points totally at eight parameters, including bone quality, fracture type, reduction quality, and internal fixation placement. Then we retrospectively analyzed seventy-seven ITF (seventy-six patients) with surgical treatment between October 2016 and July 2020 in our hospital to verify whether the QSS scoring is suitable for predicting implant failures in ITF patients. Implant failures were in fifteen fractures (fifteen patients), including six cases of cut-out, eight of pending cut-out, and one of cut-through. There were three cases with 2 points in QSS, three with 3 points, five with 4 points, four with 5 points in these fifteen fractures. No fractures were with 1 point in QSS, and no implant failures when scoring over 5 points in QSS. Except for QSS scoring, no significant difference was in the collected data by binary logistic regression analysis. QSS scoring was significantly associated with implant failures (Adjusted odds ratio (OR) = 7.312; 95% confidence intervals (CI), 2.561 to 20.871; p < 0.001). In the analysis of Spearman's correlation, there was a strong correlation between QSS scoring and the occurrences of implant failures (RQSS = -0.964, p < 0.001). The ROC result indicated that QSS was reliable in predicting implant failures at the cut-off of 5 points (AUC (the area under the curve) = 0.944; 95% CI, 0.866 to 0.983; p < 0.001). The QSS is a useful early prediction of implant failures in geriatric ITF with cephalomedullary nailing fixation. QSS scoring more than 5 points can effectively reduce the risk of implant failures.


Reaching a genetic and molecular understanding of skeletal development.
In the last ten years, we have made considerable progress in our genetic and molecular understanding of all aspects of skeletal development, chondrogenesis, joint formation, and osteogenesis. This review addresses the role of the principal growth factors and transcription factors affecting these different processes and presents, in several cases, the genetic cascade leading to cell differentiation.


Composite films of sodium alginate and konjac glucomannan incorporated with tea polyphenols for food preservation.
At present, food waste has become a serious issue and the use of petroleum-based food packaging films has resulted in a series of potential hazards. Therefore, more attention has been focused on the development of new food packaging materials. The polysaccharide-based composite film loaded with active substances considered to be an excellent preservative material. A novel packaging film based on sodium alginate and konjac glucomannan (SA-KGM) blended with tea polyphenols (TP) was prepared in the present study. The excellent microstructure of films was shown by atomic force microscopy (AFM). It was indicated by FTIR spectra that the components could interact with each other through hydrogen bonds, which was also confirmed by molecular docking simulation. Meanwhile, the mechanical properties, barrier property, oxidation property, antibacterial activity, and stability of the structure of the TP-SA-KGM film were significantly improved. The AFM images and results of molecular docking simulation indicated that TP could affect the cell wall of bacteria by acting with peptidoglycan. Finally, the film showed excellent preservation effects in both beef and apples, which suggested that TP-SA-KGM film could be a novel bioactive packaging material with wide application potential in food preservation.


Echinostoma caproni in mice: shedding of antigens from the surface of an intestinal trematode.
The surface antigens, which induce a serum antibody response during infection of mice with the intestinal trematode Echinostoma caproni, were examined. It was demonstrated that antigens are shed from the surface of juvenile and 4-week old adult E. caproni during in vitro culture. SDS-PAGE and Western blot analysis of in vitro shed and detergent solubilized surface antigens indicated that the four major antigens released from the surface of adult parasites had molecular masses of approximately 26,000, 66,000, 75,000 and 88,000. A modified ELISA technique showed the in vitro turn-over rate of the surface antigens to be very high, with a half-life of 8-15 min in both juvenile and adult E. caproni trematodes. Transmission electron microscopy of the surface of adult parasites revealed a highly active secreting tegument which was densely packed with membrane-bound vesicles, reflecting the high rate of shedding of the surface antigens. An attempt to immunize mice with detergent solubilized adult surface antigens failed to induce resistance to infection with metacercariae of E. caproni.


[Value of computer assisted tomography in the exploration of the sellar and supra sellar structures (author's transl)].
The results obtained in 145 cases of space-occupying lesions in the sellar and suprasellar structures, after exploration with computer assisted tomography, were used to assess the technical and diagnostic value of this procedure. Precise details of the localization and extent of the lesion can be obtained, but not the nature of the lesion in many cases.


Tetrazole as a Carboxylic Acid Isostere and the Synthesis of All Amine-Based Polyampholytes.
A new family of polyampholytes (PAMs) is described in which both the basic and acidic groups are based on nitrogen functional groups. Reversible addition-fragmentation chain transfer-prepared poly(pentafluorophenyl acrylate) is quantitatively modified sequentially with 3-picolylamine and 5-aminotetrazole, yielding the new well-defined statistical PAMs. Successful formation of the PAMs is confirmed via a combination of 19 F and 13 C NMR spectroscopy and FTIR. Aqueous electrophoresis indicates isoelectric points (pI) between 2.9 and 4.4 depending on copolymer composition. However, the pI is somewhat insensitive to the copolymer composition, a feature attributed to the similarity of the pKa s of the acid tetrazole species and the conjugate acid of the pyridyl repeat units.


Dataset on the single nucleotide variation in diversity panel of 500 lettuce accessions genotyped with tunable genotyping-by-sequencing (tGBS) method.
Lettuce (Lactuca sativa L.) is an important leafy vegetable cultivated in moderate climates around the world. Based on phenotypic characteristics, such as formation and size of 'heads' (leaves arranged in a dense rosette), size, and texture of leaves, length of stems, and size and composition of seeds, lettuce cultivars can be classified into several distinct horticultural types (Batavia, butterhead, iceberg, Latin, leaf, oilseed, romaine, and stem). L. serriola, a wild progenitor of cultivated lettuce, is frequently utilized in breeding programs to introgress desirable genes and alleles (e.g., resistance to diseases) into lettuce gene pool. A diversity panel of ∼500 lettuce accessions was genotyped with tunable genotyping-by-sequencing (tGBS) method to identify single nucleotide polymorphism (SNP) sites. 115,261 SNPs were positioned on lettuce genome using the reference genome of cultivar Salinas. The described diversity panel together with the set of SNP markers can be used for mapping quantitative trait loci (QTL) and to develop marker assays for marker assisted selection (MAS). Identified SNP sites can also be used to identify F1 hybrids, genotype gene bank collections, and in other areas of lettuce genetics and breeding.


Secondary Traumatic Stress Disorder in the Surgical Profession.
The psychological impact of treating individuals who have undergone severely traumatic experiences is known as secondary traumatic stress (STS). It has been well characterized by mental health therapists and social workers. Analysis of STS in surgeons and medical students is limited to merely a handful of studies, with only 1 paper describing STS in trauma surgeons and two describing STS in medical students. This review aims to provide a comprehensive account of existing work on STS, identify gaps in knowledge of STS in surgeons and medical students, and distinguish STS from other similar phenomena that have been commonly misidentified by recent works. A review of the literature in English was conducted through PubMed. MeSH terms included "STS, compassion fatigue, vicarious traumatization, and secondary trauma." All papers referenced in the identified works were screened and assessed for relevance. Only two studies that directly assess STS in surgeons were identified. STS levels reported varied widely between the two. Similar studies were identified that focused on burnout, compassion fatigue, or post-traumatic stress disorder, which are similar but not identical. Only 1 study evaluated STS in trauma surgeons and found that 65% of those in the study had at least 1 symptom of STS. Only two studies were identified that studied STS in medical students, but with conflicting results on prevalence. It was identified that there are various measuring tools to assess for STS symptoms but no established standard of assessment that allows for cross-comparisons. Knowledge of STS is extremely limited in surgeons and medical students, not only due to a general lack of awareness of STS but also due to confusion and misuse of other related terms. This review calls for more efforts to identify and address STS in surgeons and medical students while also standardizing methodologies that screen for STS symptoms.


Patient dose reference levels for interventional radiology: a national approach.
A set of patient dose reference levels (RLs) for fluoroscopically guided interventional procedures was obtained in a survey launched by the National Society of Interventional Radiology (IR), involving 10 public hospitals, as recommended by the European Medical Exposures Directive. A sample of 1391 dose values (kerma area product [KAP]) was collected randomly during clinical procedures for seven of the most frequent procedures. Third quartiles of the KAP distributions were used to set the RLs. A regular quality control of the X-ray systems and a calibration of the dose meters were performed during the survey. The fluoroscopy time and total number of digital subtraction angiography images per procedure were also analyzed. The RL values proposed were 12 Gy cm(2) for fistulography (hemodialysis access; sample of 180 cases), 73 Gy cm(2) for lower limb arteriography (685 cases), 89 Gy cm(2) for renal arteriography (55 cases), 80 Gy cm(2) for biliary drainage (205 cases), 289 Gy cm(2) for hepatic chemoembolization (151 cases), 94 Gy cm(2) for iliac stent (70 cases), and 236 Gy cm(2) for uterine embolization (45 cases). The provisional national RL values are lower than those obtained in a similar survey carried out in the United States from 2002 to 2004. These new values could be used to improve the practice of centers consistently working with doses higher than the RLs. This national survey also had a positive impact, as it helped increase the awareness of the members of the National Society of IR on a topic as crucial as patient dose values and programs on radiation protection.


Composite resin microhardness: the influence of light curing method, composite shade, and depth of cure.
The aim of this study was to investigate the influence of light curing method, composite shade, and depth of cure on composite microhardness. Forty-eight specimens with 4 mm of depth were prepared with a hybrid composite (Filtek Z-100, 3M ESPE); 24 with shade A1 and the remaining with shade C2. For each shade, two light curing units (LCUs) were used: a quartz-tungsten-halogen (QTH) LCU (Optilight Plus - Gnatus) and a light emitting diode (LED) LCU (LEC 470 II - MM Optics). The LED LCU was tested using two exposure times (LED 40 seconds and LED 60 seconds). After 24-hour storage, three indentations were made at mm depth intervals using a Knoop indenter. Data were submitted to three-way analysis of variance (ANOVA) and Tukey's test (p<0.05). The three factors tested (light curing method, shade, and depth) had a significant influence on the composite microhardness (p<0.05). All groups presented similar hardness values in the first mm, except for composite shade C2 cured with LED for 40 seconds. The hardness decreased with depth, especially for shade C2 for 40 seconds. Increasing light-curing time with LED produced hardness values similar to the QTH. The light curing method including variations of time, the depth of cure, and the composite shade influence the composite microhardness. Clinicians should avoid thicker increments when working with composite restorations. Extended light-curing time might be indicated depending on the composite shade and on the light-curing device.


[Molecular epidemiology of ECHO 6 virus, the causative agent of the 2006 outbreak of serous meningitis in Khabarovsk].
A total of 3194 cases of enterovirus meningitis were notified in the Russian Federation in 2005, of them there were 1434 cases in the Khabarovsk Territory. Enteroviruses were isolated from 1020 out of the virologically studied 1362 patients from the Khabarovsk Territory. Viruses E6 and E30 were isolated in 80 and 14.7% of cases, respectively. E1, E3, E7, E33, Coxsackie virus B1, B4, B5, and A10 were sporadically detected. The E6 strains isolated in Komsomolsk-on-Amur were identical while E6 strains isolated in Khabarovsk belonged to two different genotypes and greatly differed from those isolated in Konsomolsk-on-Amur. The virus E30 strains isolated in Khabarovsk and Komsomolsk-on-Amur had a 1% difference in VP1 genome nucleotide sequence and belonged to E30 subtype that circulated in Russia and Kazakhstan in 2004-2005.


Neutrophil recruitment is inhibited by nicotinamide in experimental pleurisy in mice.
Several emerging lines of evidence support an anti-inflammatory role for nicotinamide and other vitamin B components. However, the mechanisms underlying their activity remain unclear. In the present study, we investigated the ability of nicotinamide to inhibit both neutrophil recruitment in IL-8-, LTB(4)- or carrageenan-induced pleurisy in mice and the rolling and adherence of neutrophils. Nicotinamide inhibited IL-8-, LTB(4)- and carrageenan-induced neutrophil migration, KC production and carrageenan-induced neutrophil rolling and adherence. We propose that the effects of nicotinamide in inhibiting neutrophil recruitment in carrageenan-induced pleurisy may be due to the ability of nicotinamide to inhibit the action of IL-8 and LTB(4), decrease KC production, and inhibit early events that regulate leukocyte migration from blood vessels into tissue.


Phosphorylation of EphA2 receptor and vasculogenic mimicry is an indicator of poor prognosis in invasive carcinoma of the breast.
The occurrence of vasculogenic mimicry (VM) and EphA2-mediated tumour progression are associated with poor prognosis in various solid tumours. Here, we aimed to investigate the prognostic implications of VM and its association with phosphorylated EphA2 receptor in invasive carcinoma of the breast. The patients were stratified based on CD-31/PAS dual staining and subsequently the expression status of phospho-EphA2 (S897), FAK, phospho-ERK1/2 and Laminin 5Ƴ2 was analysed by immunohistochemistry. Survival of patients was correlated within the stratified cohort. The pathologically defined VM phenotype and phospho-EphA2 (S897) expression status were significantly associated with lower disease-free survival (DFS) and overall survival (OS). Both the features were also found to be significantly associated with higher nodal status, poor Nottingham Prognostic Index (NPI) and were more prevalent in the triple-negative breast cancer (TNBC) group. Incidentally, there were no significant association between age of the patient, grade and size of the tumour with VM and phospho-EphA2 (S897). The effector molecules of phospho-EphA2 (S897) viz., Focal Adhesion Kinase (FAK), phospho-ERK1/2 and Laminin 5Ƴ2 were significantly upregulated in the VM-positive cohort. Survival analysis revealed that the VM and phospho-EphA2 (S897) dual-positive cohort had poorest DFS [mean time = 48.313 (39.992-56.633) months] and OS [mean time = 56.692 (49.055-64.328) months]. Individually, VM-positive [Hazard Ratio (HR) 6.005; 95% confidence interval (CI) 2.002-18.018; P = 0.001 for DFS and HR 11.654; 95% CI 3.195-42.508; P < 0.0001 for OS] and phospho-EphA2 (S897)-positive (HR 4.342; 95% CI 1.717-10.983; P = 0.002 for DFS and HR 5.853; 95% CI 1.663-20.602; P = 0.006 for OS) expression proved to be independent indicators of prognosis. This study evaluated tumour dependency on oncogenic EphA2 receptor regulation and VM in invasive carcinoma of the breast and their prognostic significance. Significant correlations between VM, phospho-EphA2 and several clinicopathologic parameters of breast cancer were found. Subsequently, the occurrence of VM or phospho-EphA2 expression proved to be major contributors for poor prognosis in patients with breast cancer but their simultaneous expression failed to be an independent risk factor.


Towards a classification of organic enrichment in marine sediments based on biogeochemical indicators.
A nomogram is developed to show that pH, redox potentials (Eh(NHE)) and measures of dissolved sulfides (H2S + HS(-) + S(2-))(total free S(2-)) can be used to classify organic enrichment impacts in marine sediments. The biogeochemical cycle of sulfur in marine sediments is described to show that changes in macrobenthic infauna community structure associated with high levels of organic matter supply result from stress due to oxygen deficiency (hypoxia and anoxia) and toxic effects of S(2-). The changes reflect enhancement of microbial sulfate reduction under conditions of high organic matter sedimentation and the progressive formation of hypoxic-anoxic conditions measured by decreased Eh NHE and increased concentrations of S(2-). The nomogram provides a basis for classification of the oxic status of marine sediments based on changes in inter-related biological and biogeochemical variables along an organic enrichment gradient.


"AV nodal" reentry: Part I: "AV nodal" reentry revisited.
This review is the first of a two-part series of articles on "atrioventricular [AV] nodal reentry." The early clinical literature as well as the experimental studies are reviewed, and more recent morphologic data are presented, with the aim of clarifying whether the reentrant circuit is confined to the AV node, or consists in part of extranodal components. Most of the evidence supports the concept that atrial tissue is an essential link in the reentrant pathway. Arguments will be presented to indicate that within the AV node, the separation between antegrade and retrograde pathways is functional, not anatomical, and that both pathways are in electrotonic contact.


Advanced botulinum toxin techniques against wrinkles in the upper face.
The use of botulinum toxin type A for facial rejuvenation is one of the most common procedure in esthetic medicine. Overall clinical and study experience with botulinum toxin type A for facial enhancement has confirmed that it is effective and safe even in the long term. The different injection techniques, the starting doses, the sex, the dilution, and the storing of the product, nevertheless, may influence the final result of the treatment. In this article we propose some recommendations including general principles as well as information about its specific use. Perhaps one of the most important perspectives is that, based on a well-established knowledge of the technique, individualized esthetic planning is the key to success. This depends on a precise understanding of the underlying anatomy and physiology of the individual muscles and their interactions, as well as on individual patient's characteristics, including goals and expectations.


Carcinogenesis promotion in oral squamous cell carcinoma: KDM4A complex-mediated gene transcriptional suppression by LEF1.
Oral squamous cell carcinoma (OSCC) is the most prevalent cancer of the mouth, characterised by rapid progression and poor prognosis. Hence, an urgent need exists for the development of predictive targets for early diagnosis, prognosis determination, and clinical therapy. Dysregulation of lymphoid enhancer-binding factor 1 (LEF1), an important transcription factor involved in the Wnt-β-catenin pathway, contributes to the poor prognosis of OSCC. Herein, we aimed to explore the correlation between LEF1 and histone lysine demethylase 4 A (KDM4A). Results show that the KDM4A complex is recruited by LEF1 and specifically binds the LATS2 promoter region, thereby inhibiting its expression, and consequently promoting cell proliferation and impeding apoptosis in OSCC. We also established NOD/SCID mouse xenograft models using CAL-27 cells to conduct an in vivo analysis of the roles of LEF1 and KDM4A in tumour growth, and our findings show that cells stably suppressing LEF1 or KDM4A have markedly decreased tumour-initiating capacity. Overall, the results of this study demonstrate that LEF1 plays a pivotal role in OSCC development and has potential to serve as a target for early diagnosis and treatment of OSCC.


The Warburg effect: a score for many instruments in the concert of cancer and cancer niche cells.
Although Warburg's discovery of intensive glucose uptake by tumors, followed by lactate fermentation in oxygen presence of oxygen was made a century ago, it is still an area of intense research and development of new hypotheses that, layer by layer, unravel the complexities of neoplastic transformation. This seemingly simple metabolic reprogramming of cancer cells reveals an intriguing, multi-faceted nature that may link various phenomena including cell signaling, cell proliferation, ROS generation, energy supply, macromolecules synthesis/biosynthetic precursor supply, immunosuppression, or cooperation of cancerous cells with cancer-associated fibroblasts (CAFs), known as reversed Warburg effect. According to the current perception of the causes and consequences of the Warburg effect, PI3K/Akt/mTOR are the main signaling pathways that, in concert with the transcription factors HIF-1, p53, and c-Myc, modulate the activity/expression of key regulatory enzymes, including PKM2, and PDK1 to tune in the most optimal metabolic setting for the cancer cell. This in turn secures adequate levels of biosynthetic precursors, NADPH, NAD+, and rapid ATP production to meet the increased demands of intensively proliferating tumor cells. The end-product of "aerobic glycolysis", lactate, an oncometabolite, may provide fuel to neighboring cancer cells, and facilitate metastasis and immunosuppression together enabling cancer progression. The importance and possible applicability of the presented issue are best illustrated by numerous trials with various agents targeting the Warburg effect, constituting a promising strategy in future anti-cancer regimens. In this review, we present the key aspects of this multifactorial phenomenon, depicting the mechanisms and benefits behind the Warburg effect, and also pointing to selected aspects in the field of anticancer therapy.


Variable gene expression and parasite load predict treatment outcome in cutaneous leishmaniasis.
Patients infected with Leishmania braziliensis develop chronic lesions that often fail to respond to treatment with antiparasite drugs. To determine whether genes whose expression is highly variable in lesions between patients might influence disease outcome, we obtained biopsies of lesions from patients before treatment with pentavalent antimony and performed transcriptomic profiling on these clinical samples. We identified genes that were highly variably expressed between patients, and the variable expression of these genes correlated with treatment outcome. Among the most variable genes in all the patients were components of the cytolytic pathway, and the expression of these genes correlated with parasite load in the skin. We demonstrated that treatment failure was linked to the cytolytic pathway activated during infection. Using a host-pathogen marker profile of as few as three genes, we showed that eventual treatment outcome could be predicted before the start of treatment in two separate cohorts of patients with cutaneous leishmaniasis (n = 21 and n = 25). These findings raise the possibility of point-of-care diagnostic screening to identify patients at high risk of treatment failure and provide a rationale for a precision medicine approach to drug selection in cutaneous leishmaniasis. This work more broadly demonstrates the value of identifying genes of high variability in other diseases to better understand and predict diverse clinical outcomes.


Neutrophils infiltrating bronchial epithelium in chronic obstructive pulmonary disease.
In order to characterize neutrophil and eosinophil presence in the airways of patients with chronic obstructive pulmonary disease (COPD), bronchoscopy with bronchial washings and bronchial biopsies was performed in 12 smoking stable COPD subjects and 18 normal non-smoking control subjects. Bronchial biopsies were examined by light microscopy using plastic embedding and histochemical techniques to identify different cell types. Bronchial washing fluid of COPD patients was characterized by a predominance of neutrophils (P = 0.001), and a slight, but significant (P = 0.03), increase of eosinophil fraction. Subjects with COPD had higher number of neutrophils in the epithelium (P = 0.01), and eosinophils in the lamina propria (P = 0.01) than did control subjects. The thickness of reticular basement membrane was increased for COPD patients in comparison to control subjects (P = 0.01). The present study provides evidence of neutrophil infiltration both in bronchial washing and bronchial epithelium of patients with COPD, suggesting that the source of neutrophils in airway lumen may be the bronchial mucosa. Although less common than in asthma, airways of COPD subjects reveal eosinophil presence and airway remodelling.


Synthesis of a biocompatible gelatin functionalized graphene nanosheets and its application for drug delivery.
A simple and environmentally friendly synthetic route for the preparation of gelatin functionalized graphene nanosheets (gelatin-GNS) was reported by using exfoliated graphene oxide as a precursor, in which gelatin acted as not only a reducing reagent but also a functionalization reagent to guarantee good dispersibility and stability of the GNS in distilled water and various physiological solutions. The obtained biocompatible gelatin-GNS attaching methotrexate (MTX) via strong π-π stacking interaction, exhibited a high drug loading capacity of MTX and excellent ability for controlled drug release. The pH-dependent release behavior of MTX from MTX@gelatin-GNS showed that the release amount under acid conditions is much higher than that under neutral conditions, which experienced a gelatin-mediated sustained release process. From the cytotoxicity assay, we can see that the MTX@gelatin-GNS showed remarkable toxicity while the gelatin-GNS showed nontoxic at appropriate concentration, both of them might be taken up by A549 cells through a nonspecific endocytosis process. The prepared nanohybrids system offers a novel formulation that combines the unique properties of a biodegradable material, gelatin, and graphene for biomedical applications. Therefore, the gelatin-GNS with good stability and biocompatibility can be selected as an ideal drug carrier to be applied in biomedicine studies.


ARCON: experience in 215 patients with advanced head-and-neck cancer.
"ARCON" combines accelerated radiotherapy to counteract tumor repopulation with carbogen breathing and nicotinamide to reduce chronic and acute hypoxia. The aim of this Phase II study was to assess the feasibility, toxicity, and potential effectiveness of ARCON for advanced head-and-neck cancer. The study included 215 patients with head-and-neck carcinoma distributed as follows: larynx, n = 100; hypopharynx, n = 50; oropharynx, n = 52; oral cavity, n = 13; Stage II, n = 8, Stage III, n = 71, and Stage IV, n = 136. Accelerated radiotherapy was given to a total dose of 64-68 Gy in 2-Gy fractions within 36-38 days. This was combined with carbogen breathing during irradiation and administration of nicotinamide (60-80 mg/kg) 1-1.5 h before irradiation. There was full compliance with carbogen breathing in 88% of the patients. A nicotinamide dose of 80 mg/kg produced severe nausea and vomiting, necessitating discontinuation of the drug, in 31% of the patients. Adjustment of the dose to 60 mg/kg and antiemesis prophylaxis reduced the discontinuation rate to 10%. Confluent mucositis was observed in 91% of the patients with a median duration of 6 weeks. Grade 4 late complications occurred in 5% of the patients. The actuarial 3-year local control rates were 80% for larynx, 69% for hypopharynx, 88% for oropharynx, and 37% for oral cavity tumors. For T3-4 tumors, the local control rates were 80% for larynx, 60% for hypopharynx, 87% for oropharynx, and 29% for oral cavity. Regional control rates were 100% for N0, 93% for N1, and 74% for N2 disease. ARCON yields high local and regional control rates in advanced head-and-neck carcinomas, and compliance is satisfactory and morbidity acceptable. The local control rate of 80% for T3 and T4 larynx carcinomas offers excellent possibilities for organ preservation.


Incidence of postoperative residual neuromuscular blockade - A multicenter, observational study in Portugal (INSPIRE 2).
Although the use of neuromuscular blocking agents (NMBAs) optimizes surgical conditions and facilitates tracheal intubation, it can lead to residual neuromuscular blockade (RNMB), with postoperative complications. This study aimed to assess RNMB incidence and management in Portugal. Prospective observational study of patients admitted for elective surgery requiring general anesthesia with nondepolarizing NMBAs between July 2018 and July 2019 at 10 Portuguese hospitals. The primary endpoint was the proportion of patients arriving at postanesthesia care unit (PACU) with a TOF ratio <0.9. A total of 366 patients were included, with a median age of 59 years, and 89.1% classified as ASA II or III. Rocuronium was the most used NMBA (99.5%). A total of 96.2% of patients received a reversal agent, 96.6% of which sugammadex and 3.4% neostigmine. Twenty patients displayed a TOF ratio <0.9 at PACU arrival, representing an RNMB incidence of 5.5% (95% CI, 3.1%-7.8%). Only two patients displayed a TOF ratio <0.7. RNMB incidence was 16.7% with neostigmine and 5.3% with sugammadex (P = .114). In patients with intraoperative neuromuscular blockade (NMB) monitoring, RNMB incidence was 5% (95% CI, 2%-8%), which varied significantly according to the type of monitoring (P = .018). Incidence of adverse events was 3.3% (2 severe and 10 moderate). The reported overall incidence of 5.5% is numerically lower than results from similar observational studies. An appropriate pharmacological neuromuscular reversal strategy, guided by quantitative neuromuscular monitoring, has the potential to achieve even better results, converting RNMB from an unusual to a very rare or even inexistent event.


Alcohol-induced damage to the fimbria/fornix reduces hippocampal-prefrontal cortex connection during early abstinence.
Alcohol dependence is characterized by a gradual reduction in cognitive control and inflexibility to contingency changes. The neuroadaptations underlying this aberrant behavior are poorly understood. Using an animal model of alcohol use disorders (AUD) and complementing diffusion-weighted (dw)-MRI with quantitative immunohistochemistry and electrophysiological recordings, we provide causal evidence that chronic intermittent alcohol exposure affects the microstructural integrity of the fimbria/fornix, decreasing myelin basic protein content, and reducing the effective communication from the hippocampus (HC) to the prefrontal cortex (PFC). Using a simple quantitative neural network model, we show how disturbed HC-PFC communication may impede the extinction of maladaptive memories, decreasing flexibility. Finally, combining dw-MRI and psychometric data in AUD patients, we discovered an association between the magnitude of microstructural alteration in the fimbria/fornix and the reduction in cognitive flexibility. Overall, these findings highlight the vulnerability of the fimbria/fornix microstructure in AUD and its potential contribution to alcohol pathophysiology. Fimbria vulnerability to alcohol underlies hippocampal-prefrontal cortex dysfunction and correlates with cognitive impairment.


Partial purification of a thylakoid-bound enzyme using temperature-induced phase partitioning.
Triton X-114 was used to partially purify broad bean polyphenol oxidase, a thylakoid membrane-bound enzyme, in latent form, free of phenolic compounds and chlorophylls, with a high recovery rate. The activation of the latent enzyme by detergents or trypsin was 10 times higher than that obtained when the enzyme was purified by other methods used in plant biochemistry, such as acetone powders and ammonium sulfate fractionation. The kinetic parameters of the latent and activated enzyme are also given.


Decreasing aspiration risk with enteral feeding.
Aspiration is a clinical concern in patients receiving enteral tube feeding. Aspiration can result in pneumonia leading to increases in the use of antibiotics, length of hospital stay, and the risk of mortality. Pneumonia caused by aspiration of gastric contents is of particular concern in patients who require mechanical ventilation and feeding by nasogastric tube. This article summarizes factors that might influence the development of aspiration pneumonia and minimize risk, such as the position of the patient's body, method of feeding, and size of the feeding tube.


Malignant lymphoma of the oral cavity and the maxillofacial region: overall survival prognostic factors.
To identify the overall survival and prognostic factors of malignant lymphoma of the oral cavity and the maxillofacial region. Clinical records data were obtained in order to determine overall survival at 2 and 5 years, the individual survival percentage of each possible prognostic factor with the actuarial technique, and the survival regarding the possible prognostic factors with the actuarial technique and the Log-rank and Cox's regression tests. Of 151 subjects, an overall survival was 60% at 2 years, and 45% at 5 years. The multivariate analysis demonstrated statistically significant differences for clinical stage (p=0.002), extranodal involvement (p=0.030), presence of human immunodeficiency virus (p=0.032), and presence of Epstein-Barr virus (p=0.010). The advanced clinical stage and the larger number of involved extranodular sites are related to a lower overall survival, as well as, the presence of previous infections such as the human immunodeficiency and the Epstein-Barr virus.


Prevalence and correlates of the proposed DSM-5 diagnosis of Chronic Depressive Disorder.
The draft proposal to add Chronic Depressive Disorder to DSM-5 will combine DSM-IV Dysthymic Disorder and Major Depressive Disorder, with chronic specifier, into a single diagnosis. The objective of this study is to estimate the prevalence and correlates of the proposed DSM-5 diagnosis of Chronic Depressive Disorder using unit record data from the 2007 Australian National Survey of Mental Health and Wellbeing. Secondary analysis of a nationally representative household survey. Urban and rural census tracts. One individual between the ages of 16 and 85 years from 8841 households was interviewed for the survey. Lifetime prevalence estimates for chronic and non-chronic depression were determined using data from the World Health Organization's Composite International Diagnostic Interview, version 3.0 (WMH-CIDI 3.0). Chronic depression of at least two years' duration had a lifetime prevalence of 4.6% (95% CI: 3.9-5.3%) and was found in 29.4% (95% CI: 25.6-33.3%) of individuals with a lifetime depressive disorder. Higher rates of psychiatric co-morbidity (OR=1.42; 95% CI=1.26-1.61), older age (OR=1.04; 95% CI=1.02-1.05), a younger age of onset (OR=0.97; 95% CI=0.95-0.98) and more frequent episodes of depression (OR=1.75; 95% CI=1.07-2.86) were found to be significant correlates of chronic depression. The first episode of depression for individuals with chronic depression often developed after the death of someone close (OR=2.38; 95% CI 1.16-5.79). Chronic depression is highly prevalent among community-residing persons and has a set of correlates that discriminate it from non-chronic depression. The distinction between chronic and non-chronic depression proposed for DSM-5, in the form of Chronic Depressive Disorder, seems to be warranted.


Renin-angiotensin system inhibition and outcome after coronary artery bypass grafting: A population-based study from the SWEDEHEART registry.
Renin-angiotensin system (RAS) inhibitors are recommended postoperatively to coronary artery bypass grafting (CABG) patients with reduced left ventricular function, diabetes, hypertension or previous myocardial infarction, but not to remaining patients. The aim of the study was to assess the long-term utilization of RAS inhibitors after CABG in patients with and without indication for treatment, and its association with outcome. All patients (n = 28,782) not meeting exclusion criterion in Sweden who underwent isolated first time CABG from 2006 to 2015 were included using nationwide registries. The association between treatment and outcome was assessed using adjusted Cox regression models with time-updated data on medications. The primary outcome was major adverse cardiovascular events (MACE), defined as all-cause mortality, stroke and/or myocardial infarction. At baseline 26,284 (91.3%) of the patients had at least one indication for RAS inhibition while 2498 (8.7%) had not. RAS inhibitors were dispensed to 77.0% and 29.7% of patients with and without indication respectively. Dispense declined over time. RAS inhibition was associated with a reduction in MACE in the whole study population (adjusted hazard ratio (aHR) 0.88, 95% confidence interval (95% CI) 0.83-0.93, p < 0.0001), and in patients with (aHR 0.87 95% CI: 0.82-0.93, p < 0.0001) and without indication (aHR 0.75, 95% CI: 0.58-0.98, p = 0.034). RAS inhibition is underutilized after CABG. The use of RAS inhibitors was associated with a reduction in MACE, both in patients with and without indication for treatment. The results suggest that RAS inhibition is beneficial for all CABG patients. Randomized controlled trials are necessary to confirm this hypothesis.


IRF3-binding lncRNA-ISIR strengthens interferon production in viral infection and autoinflammation.
Interferon regulatory factor 3 (IRF3) is an essential transductor for initiation of many immune responses. Here, we show that lncRNA-ISIR directly binds IRF3 to promote its phosphorylation, dimerization, and nuclear translocation, along with enhanced target gene productions. In vivo lncRNA-ISIR deficiency results in reduced IFN production, uncontrolled viral replication, and increased mortality. The human homolog, AK131315, also binds IRF3 and promotes its activation. More important, AK131315 expression is positively correlated with type I interferon (IFN-I) level and severity in patients with lupus. Mechanistically, in resting cells, IRF3 is bound to suppressor protein Flightless-1 (Fli-1), which keeps its inactive state. Upon infection, IFN-I-induced lncRNA-ISIR binds IRF3 at DNA-binding domain in cytoplasm and removes Fli-1's association from IRF3, consequently facilitating IRF3 activation. Our results demonstrate that IFN-I-inducible lncRNA-ISIR feedback strengthens IRF3 activation by removing suppressive Fli-1 in immune responses, revealing a method of lncRNA-mediated modulation of transcription factor (TF) activation.


Amelioration of cisplatin nephrotoxicity by genetic or pharmacologic blockade of prostaglandin synthesis.
Nephrotoxicity is a common complication of cisplatin chemotherapy that limits its clinical use. Here, we determined whether arachidonic acid metabolism has a role in the pathogenesis of cisplatin nephrotoxicity in mice. Three days following cisplatin injection, wild-type mice displayed renal functional and structural abnormalities consistent with nephrotoxicity accompanied by elevated circulating and renal levels of TNF-α and renal levels of IL-1β, subunits of NADPH oxidase, thiobarbituric acid-reactive substances, and PGE(2). These indices of kidney injury, inflammation, oxidative stress, and arachidonate metabolism were all diminished in microsomal prostaglandin E synthase-1 (mPGES-1) null mice; a phenotype recapitulated by treatment of wild-type mice with the COX-2 inhibitor celecoxib. Following cisplatin administration, there was paralleled induction of COX-2 and mPGES-1 in renal parenchymal cells. Interestingly, mPGES-1 null mice were not protected from acute kidney injury caused by ischemia-reperfusion or endotoxin. Hence, our results suggest the activation of COX-2/mPGES-1 pathway in renal parenchymal cells may selectively mediate cisplatin-induced renal injury. This may offer a novel therapeutic target for management of the adverse effect of cisplatin chemotherapy.


Selected problems with boron determination in water treatment processes. Part I: comparison of the reference methods for ICP-MS and ICP-OES determinations.
The aim of the study was to compare the two reference methods for the determination of boron in water samples and further assess the impact of the method of preparation of samples for analysis on the results obtained. Samples were collected during different desalination processes, ultrafiltration and the double reverse osmosis system, connected in series. From each point, samples were prepared in four different ways: the first was filtered (through a membrane filter of 0.45 μm) and acidified (using 1 mL ultrapure nitric acid for each 100 mL of samples) (FA), the second was unfiltered and not acidified (UFNA), the third was filtered but not acidified (FNA), and finally, the fourth was unfiltered but acidified (UFA). All samples were analysed using two analytical methods: inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma optical emission spectrometry (ICP-OES). The results obtained were compared and correlated, and the differences between them were studied. The results show that there are statistically significant differences between the concentrations obtained using the ICP-MS and ICP-OES techniques regardless of the methods of sampling preparation (sample filtration and preservation). Finally, both the ICP-MS and ICP-OES methods can be used for determination of the boron concentration in water. The differences in the boron concentrations obtained using these two methods can be caused by several high-level concentrations in selected whole-water digestates and some matrix effects. Higher concentrations of iron (from 1 to 20 mg/L) than chromium (0.02-1 mg/L) in the samples analysed can influence boron determination. When iron concentrations are high, we can observe the emission spectrum as a double joined and overlapping peak.


Entropy-enthalpy Compensation of Biomolecular Systems in Aqueous Phase: a Dry Perspective.
We survey thermodynamic measurements on processes involving biological macromolecules in aqueous solution, which illustrate well the ubiquitous phenomenon of entropy-enthalpy compensation. The processes include protein folding/unfolding and ligand binding/unbinding, with compensation temperatures varying by about 50 K around an average near 293 K. We show that incorporating both near-exact entropy-enthalpy compensation (due to solvent relaxation) and multi-excitation entropy (from vibrational quanta) leads to a compensation temperature in water of about 230 K. We illustrate a general procedure for subtracting solvent and environment-related terms to determine the bare Gibbs free energy changes of chemical processes.


The Perceptions of Nurses and Nursing Students Regarding Family Involvement in the Care of Hospitalized Adult Patients.
Over the past few decades, there have been concerns regarding the humanization of healthcare and the involvement of family members in patients' hospital care. The attitudes of hospitals toward welcoming families in this respect have improved. In Arab culture, the main core of society is considered to be the family, not the individual. The objective behind involving family in patient care is to meet patients' support needs. Consequently, this involvement affects nurses and their attitudes toward the importance of family involvement in patient care. To describe nurses' and nursing students' perceptions of family involvement in the care of hospitalized adult patients in Saudi Arabia. This study used a quantitative descriptive cross-sectional design. The data were collected using a convenience sampling survey via social media. A total of 270 participants (staff and students) took part in this study, including 232 (85.9%) females and 38 (14.1%) males. Moreover, a high percentage of participants (78.8%) acknowledged that family presence strongly affected the improvement of the patient's condition. However, 69.3% of participants thought that involving family members during special care processes or cardiopulmonary resuscitation (CPR) would be traumatizing for these individuals. Moreover, there was a significant diffidence between the attitudes of the nurses and nursing students toward family involvement and the number of years of employment (F = 3.60, p < 0.05). On the contrary, there were insignificant differences between the attitudes of the nurses and nursing students toward family involvement and their gender, nationality, age, education level, and years of work experience in Saudi Arabia (p > 0.05). Furthermore, the regression analysis showed a significant negative correlation between nurses' years of employment and their support of family involvement in patient care (ß = -0.20, SE = 0.08, t = -2.70, p = 0.01). Nurses with more experience showed no support for family involvement in patient care. We have to consider the clinical barriers that affect nurses' support for family involvement in patient-centered care, such as hospital polices, guidelines, and the model used for family-centered care integration in the hospital system to facilitate the interaction between healthcare providers and family members.


Primary adhered neutrophils increase JNK1-MARCKSL1-mediated filopodia to promote secondary neutrophil transmigration.
During inflammation, leukocytes extravasate the vasculature to areas of inflammation in a process termed transendothelial migration. Previous research has shown that transendothelial migration hotspots exist, areas in the vasculature that are preferred by leukocytes to cross. Several factors that contribute to hotspot-mediated transmigration have been proposed already, but whether one leukocyte transmigration hotspot can be used subsequently by a second wave of leukocytes and thereby can increase the efficiency of leukocyte transmigration is not well understood. Here, we show that primary neutrophil adhesion to the endothelium triggers endothelial transmigration hotspots, allowing secondary neutrophils to cross the endothelium more efficiently. Mechanistically, we show that primary neutrophil adhesion increases the number of endothelial apical filopodia, resulting in an increase in the number of adherent secondary neutrophils. Using fluorescence resonance energy transfer (FRET)-based biosensors, we found that neutrophil adhesion did not trigger the activity of the small GTPase Cdc42. We used kinase translocation reporters to study the activity of mitogen-activated protein (MAP) kinases and Akt in endothelial cells on a single-cell level with a high temporal resolution during the process of leukocyte transmigration and found that c-Jun N-terminal kinase (JNK) is rapidly activated upon neutrophil adhesion, whereas extracellular regulated kinase (ERK), p38, and Akt are not. Additionally, we show that short-term chemical inhibition of endothelial JNK successfully prevents the adhesion of neutrophils to the endothelium. Furthermore, we show that neutrophil-induced endothelial JNK1 but not JNK2 increases the formation of filopodia and thereby the adhesion of secondary neutrophils. JNK1 needs its downstream substrate MARCKSL1 to trigger additional apical filopodia and consequently neutrophil adhesion. Overall, our data show that primary neutrophils can trigger the endothelial transmigration hotspot by activating JNK1 and MARCKSL1 to induce filopodia that trigger more neutrophils to transmigrate at the endothelial hotspot area.


Eye discomfort and air pollution.
Discomfort eye syndrome (DES) comprises a series of 'minor' subjective symptoms in patients where no relevant clinical signs are observed suggesting ocular disease. Our study includes 100 DES patients, excluding video terminal users, selected from the First Aid Service of our Department over two peak periods in both winter and summer time. The Schirmer test I, ferning test, breakup time and conjunctival cytology (scraping and imprint) were performed and data were related to sex, age and air pollution indexes, recorded in the patients' living zones. Our results demonstrate that: (i) the ocular surface cytology and the analysis of tear film changes provide significant information in those patients where no other clinical signs are evident; (ii) DES symptoms are more frequent in women than in men (ratio about 2:1), both with ages over 51 years; (iii) DES is significantly associated with ocular surface inflammation, as detected by cytological methods, and (iv) ocular surface subclinical inflammation and ocular dryness are related to high concentrations of atmospheric polluters, in both sexes.


Fatal Hepatocellular Carcinoma in a Patient with Occult Hepatitis B Virus Infection following the Administration of R-CHOP for Diffuse Large B-Cell Lymphoma.
Occult hepatitis B (OBI) is caused by a persistent low-level replication of HBV. Like overt HBV infection, OBI can be associated with the integration of HBV sequences into the host genome and has a substantial clinical relevance for patients who are severely immunosuppressed for long durations. We present the case of a patient with a diffuse large B-cell non-Hodgkin lymphoma and OBI who developed a hepatocellular carcinoma with a fulminant clinical course following the administration of rituximab plus CHOP.


[Laparoscopic total prostatectomy in renal transplant recipients: a case report].
Despite increased screening in renal transplant recipients, the prostate cancer-renal transplantation association is not well-known. Treatment of localized forms must be curative. Total prostatectomy is performed according to the classically described incisions, either retropubic or perineal. The authors describe the technique and results of laparoscopic total prostatectomy in a renal transplant recipient.


Unusual tubular calcification of a nephrostomy tract.
Unusual tubular calcification occurred in the nephrostomy tract of a 30-year-old male, 6 months after percutaneous nephrostolithotomy. To our knowledge, this phenomena has not been previously reported. The main radiologic differential diagnoses are focal dystrophic calcification and vascular calcification. The etiology is unknown but may have been related to the patients' tendency to form renal calculi. The temporal sequence of events and the location of the nephrostomy catheter which correlated with the calcification suggests the correct diagnosis.


Can We Restore Vision? A Cadaveric Study Using Hyaluronidase for Retinal Artery Occlusion.
Supplemental Digital Content is available in the text.


The evaluation of uterine activity: a comparative analysis.
In this study a comparison is made between the most widely accepted method of expressing uterine activity, Montevideo units, and an automated on-line method expressed as uterine activity units. Although the actual numerical expression differs, the percentage of variation when the two values are compared is small at various phases of labor. The variation between the methods for uterine activity required to progress from 4 to 6 cm cervical dilatation and from 6 to 10 cm cervical dilatation is less than 5%. Both methods closely agree on the actual expression of uterine activity or uterine work.


In vivo confocal microscopy study of blebs after filtering surgery.
To analyze bleb structure after filtering surgery at the cellular level using a new generation in vivo confocal microscope. Observational case series. We retrospectively evaluated 17 filtering blebs of 13 patients after trabeculectomy. Ophthalmologic examinations included slit-lamp examination, applanation tonometry, and in vivo confocal microscopy (Heidelberg Retina Tomograph II, Rostock Cornea Module). Eyes were classified into 3 groups: (1) functioning blebs (6 eyes), (2) nonfunctioning blebs (6 eyes), and (3) functioning blebs after application of mitomycin C (5 eyes). Cellular patterns, morphologic appearance, and functional aspects of functioning and nonfunctioning blebs were compared in a masked manner. In vivo confocal microscopy images were analyzed for number of intraepithelial microcysts, density of subepithelial connective tissue, presence of blood vessels, or encapsulation. All functioning blebs had numerous intraepithelial optically-empty microcysts, whereas all nonfunctioning blebs had none or few. Subepithelial connective tissue was widely spaced in all functioning blebs, whereas the tissue was dense in 83.3% of nonfunctioning blebs. Functioning blebs with mitomycin C had numerous microcysts and loosely arranged subepithelial connective tissue as compared with nonfunctioning blebs. In vivo confocal microscopy study of blebs is an original method that agrees well with ex vivo histologic examination. The number of microcysts and the density of the subepithelial connective tissue observed with in vivo confocal microscopy are correlated with bleb function. By providing details of the structures of filtering blebs at the cellular level, in vivo confocal microscopy constitutes a new promising way to understand wound healing mechanisms after filtering surgery.


Mesenchymal stem cell-derived exosome: a promising alternative in the therapy of Alzheimer's disease.
Alzheimer's disease (AD) has been a devastating public health with the development of global aging. Approaches for reducing the current AD epidemic are becoming a primary focus of human healthcare due to the lack of achieved lasting and complete remission strategies to treat AD with the characteristics of heterogeneity and complexity. Exosomes, which is the new emerging approach to intercellular communication, provide novel perspective on identified therapeutic strategies of AD. Mesenchymal stem cell-derived exosomes (MSC-exos) are emerging to be an appealing therapeutic tool for AD, with the donor-derived properties and the characteristics of minimal immunogenicity, effortless storage, nature delivery vehicles, and low risks of tumor formation based on the previous researches. In this review, we elaborate the mechanism of MSC-exos in the treatment of AD and discuss limitations in the clinical application.