An Integrative Framework to Guide Social Engagement Interventions and Technology Design for Persons With Mild Cognitive Impairment.
Social isolation and loneliness in older adults are associated with poor health outcomes and have been linked to an increased risk of cognitive impairment and incident dementia. Social engagement has been identified as a key factor in promoting positive health behaviors and quality of life and preventing social isolation and loneliness. Studies involving cognitively healthy older adults have shown the protective effects of both in-person and technology-based social engagement. However, the benefits of social engagement for people who are already at-risk of developing dementia, namely those with mild cognitive impairment (MCI), have yet to be elucidated. We present a narrative review of the literature, summarizing the research on social engagement in MCI. First, we identified social networks (quality, size, frequency, and closeness) and social activities (frequency, format, purpose, type, and content) as two overarching dimensions of an integrative framework for social engagement derived from literature examining typical cognitive aging. We then used this framework as a lens to examine studies of social engagement in MCI to explore (i) the relationship between in-person and technology-based social engagement and cognitive, emotional, and physical health, and (ii) interventions that target social engagement including technology-based approaches. Overall, we found that persons with MCI (PwMCI) may have different levels of social engagement than those experiencing typical cognitive aging. Moreover, in-person social engagement can have a positive impact on cognitive, emotional, and physical health for PwMCI. With respect to activity and network dimensions in our framework, we found that cognitive health has been more widely examined in PwMCI relative to physical and emotional health. Very few intervention studies have targeted social engagement, but both in-person and technology-based interventions appear to have promising health and well-being outcomes. Our multidimensional framework of social engagement provides guidance for research on characterizing the protective benefits of social engagement for PwMCI and informs the development of novel interventions including technology-based approaches.


2q23.1 microdeletion identified by array comparative genomic hybridisation: an emerging phenotype with Angelman-like features?
Genome-wide screening of patients with mental retardation using array comparative genomic hybridisation (CGH) has identified several novel imbalances. With this genotype-first approach, the 2q22.3q23.3 deletion was recently described as a novel microdeletion syndrome. The authors report two unrelated patients with a de novo interstitial deletion mapping in this genomic region and presenting similar "pseudo-Angelman" phenotypes, including severe psychomotor retardation, speech impairment, epilepsy, microcephaly, ataxia, and behavioural disabilities. The microdeletions were identified by array CGH using oligonucleotide and bacterial artificial chromosome (BAC) arrays, and further confirmed by fluorescence in situ hybridisation (FISH) and semi-quantitative polymerase chain reaction (PCR). The boundaries and sizes of the deletions in the two patients were different but an overlapping region of about 250 kb was defined, which mapped to 2q23.1 and included two genes: MBD5 and EPC2. The SIP1 gene associated with the Mowat-Wilson syndrome was not included in the deleted genomic region. Haploinsufficiency of one of the deleted genes (MBD5 or EPC2) could be responsible for the common clinical features observed in the 2q23.1 microdeletion syndrome, and this hypothesis needs further investigation.


Toxoplasma encephalitis in an HIV-infected patient on highly active antiretroviral therapy despite sustained immune response.
Toxoplasma encephalitis (TE) is usually diagnosed in advanced stages of HIV infection when the CD4+ count is <100-200 cells/µl. A 55-year-old woman with HIV/AIDS, well controlled on antiretroviral therapy (ART), CD4+ count in the 300 cells/μl range for >1 year presented with acute onset of headache, nausea and vomiting. She had been on her current ART regimen consisting of raltegravir, co-formulated emtricitabine/tenofovir and etravirine for three years and had been off Pneumocystis prophylaxis for 10 months (trimethoprim-sulfamethoxazole). Brain MRI showed multiple ring-enhancing, supratentorial and infra-tentorial parenchymal lesions suspicious for metastases. She had no other evidence of metastatic disease in her body. The possibilities of TE and primary CNS lymphoma were considered but deemed unlikely given the high CD4+ count. A brain biopsy demonstrated Toxoplasma tachyzoites. There was no evidence of lymphoma or carcinoma. Anti-toxoplasma treatment yielded good initial clinical and radiographic responses. While on TE maintenance therapy, she developed similar symptoms. Repeat MRI showed progression of lesions. Further work-up including CSF Epstein-Barr virus PCR and SPECT Th 201 imaging was not conclusive for CNS lymphoma. The patient's clinical condition deteriorated and she died. We postulate that functional immunological dysfunction is a possible mechanism by which our patient developed TE despite demonstrating sustained immune response on ART.


Apoptosis induced by the Tibetan herbal remedy PADMA 28 in the T cell-derived lymphocytic leukaemia cell line CEM-C7H2.
The Tibetan herbal remedy PADMA 28 revealed promising results to support treatment of atherosclerosis, Charot syndrome (intermittent claudication), chronic active hepatitis and infection of the respiratory tract. The remedy was confirmed to be closely linked with anti- and pro-oxidative properties in vitro. In this study, apoptogenic and survival effects of PADMA 28 were investigated in the T cell-derived lymphocytic leukaemia cell line CEM-C7H2. PADMA 28 led to a concentration-dependent inhibition of cell proliferation accompanied by the accumulation of CEM-C7H2 cells in subG1 phase, fragmentation of poly (ADP-ribose) polymerase (PARP) and nuclear body formation. Treatment with PADMA 28 rescued to some extent cells over-expressing Bcl-2 from apoptosis. This finding suggests that the mechanism of action of PADMA 28 may be via interference with Bcl-2 triggered survival pathways.


Ex vivo MRI evaluation of breast tumors: a novel tool for verifying resection of nonpalpable only MRI detected lesions.
A fundamental question in surgery of only magnetic resonance imaging (MRI)-detected breast lesions is to ensure their removal when they are not palpable by clinical examination and surgical exploration. This is especially relevant in the case of small tumors, carcinoma in situ or lobular carcinoma. Thirty-nine patients were enrolled in the study, 21 patients with breast lesions detected by both conventional imaging and breast MRI (bMRI) and 18 patients with bMRI findings only. Preoperative bMRI allowed staging the disease and localizing the lesion. In the operating theater, contrast medium was injected 1 minute before skin incision. After removal, surgical specimens were submitted to ex vivo MRI, performed using a dedicated surface coil and Spair inversion recovery sequences for suppression of fat signal intensity. All MRI enhancing lesions were completely included within the surgical specimen and visualized by ex vivo MRI. In the first 21 patients, bMRI was able to visualize branching margins or satellite nodules around the core lesion, and allowed for better staging of the surrounding in situ carcinoma; in the last 18 patients, eight of whom were breast cancer type 1 susceptibility protein (BRCA) mutation carriers, bMRI identified 12 malignant tumors, otherwise undetectable, that were all visualized by ex vivo MRI. This is the first description of a procedure that re-enhances breast lesions within a surgical specimen, demonstrating the surgical removal of nonpalpable breast lesions diagnosed only with bMRI. This new strategy reproduces the morphology and the entire extension of the primary lesion on the specimen, with potentially better local surgical control, reducing additional unplanned surgery.


Bioprosthetic valve fracture: Predictors of outcome and follow-up. Results from a multicenter study.
To evaluate outcome and its predictors of bioprosthetic valve fracture (BVF) in patients undergoing valve-in-valve transcatheter aortic valve replacement (VIV-TAVR). BVF is feasible and reduces transvalvular gradients in VIV-TAVR-procedures, but follow-up-data and information on factors influencing the outcome are missing. The 81 cases of BVF-VIV-TAVR were collected from 14 international centers. Predominantly transcatheter heart valve (THV) was implanted first, followed by BVF. VARC-2 defined device success was 93%, most failures were attributed to residual high gradients. Mean gradients decreased from 37 ± 13 mmHg to 10.8 ± 5.9 mmHg (p < 0.001). BVF reduced the gradient by 16 mmHg. During follow-up (FU, 281 ± 164 days) mean gradient remained stable (10.8 ± 5.9 mmHg at discharge, 12.4 ± 6.3 mmHg at FU, p = ns). In-hospital major adverse events occurred in 3.7%. Event-free survival at 276 ± 237.6 days was 95.4%. The linear mixed model identified balloon-expandable valves (BEV), Mitroflow surgical valve, stenotic surgical bioprostheses and balloon only 1 mm larger than the true internal diameter of the surgical valve as predictors for higher gradients. BVF is safe and can significantly reduce gradients, which remain stable at FU. BEV, Mitroflow surgical valve, stenotic bioprostheses and balloon larger than the true internal diameter of the surgical valve of only 1 mm are predictors for higher final gradients.


Impact of a Copayment Reduction Intervention on Medication Persistence and Cardiovascular Events in Hospitals With and Without Prior Medication Financial Assistance Programs.
Background Hospitals commonly provide a short-term supply of free P2Y12 inhibitors at discharge after myocardial infarction, but it is unclear if these programs improve medication persistence and outcomes. The ARTEMIS (Affordability and Real-World Antiplatelet Treatment Effectiveness After Myocardial Infarction Study) trial randomized hospitals to usual care versus waived P2Y12 inhibitor copayment costs for 1-year post-myocardial infarction. Whether the impact of this intervention differed between hospitals with and without pre-existing medication assistance programs is unknown. Methods and Results In this post hoc analysis of the ARTEMIS trial, we examined the associations of pre-study free medication programs and the randomized copayment voucher intervention with P2Y12 inhibitor persistence (measured by pharmacy fills and patient report) and major adverse cardiovascular events using logistic regression models including a propensity score. Among 262 hospitals, 129 (49%) offered pre-study free medication assistance. One-year P2Y12 inhibitor persistence and major adverse cardiovascular events risks were similar between patients treated at hospitals with and without free medication programs (adjusted odds ratio 0.93, 95% CI, 0.82-1.05 and hazard ratio 0.92, 95% CI, 0.80-1.07, respectively). The randomized copayment voucher intervention improved persistence, assessed by pharmacy fills, in both hospitals with (53.6% versus 44.0%, adjusted odds ratio 1.45, 95% CI, 1.20-1.75) and without (59.0% versus 48.3%, adjusted odds ratio 1.46, 95% CI, 1.25-1.70) free medication programs (Pinteraction=0.71). Differences in patient-reported persistence were not significant after adjustment. Conclusions While hospitals commonly report the ability to provide free short-term P2Y12 inhibitors, we did not find association of this with medication persistence or major adverse cardiovascular events among patients with insurance coverage for prescription medication enrolled in the ARTEMIS trial. An intervention that provided copayment assistance vouchers for 1 year was successful in improving medication persistence in hospitals with and without pre-existing short-term medication programs. Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02406677.


[Vulnerability and suffering in the work of a community health agent in the family health program].
This qualitative research was aimed at investigating the representations and significations that a group of community health agents (CHAs) has concerning the vulnerabilities for suffering in their work to which they are exposed to, as well as the manifestations of this suffering as they perform their actions in the Family Health Program (PSF, in the Portuguese language acronym). The semistructured interview with the group of agents explored the meaning of being a CHA and their perception of their work organization; the analysis was based on the hermeneutics theoretical-methodology referential and on the theories related to labor psychodynamics. The findings show the existence of considerable suffering vulnerability, generated by an idealized ideation of the practice and by the scarce perspective for rearranging the constitutive ingredients of work organization, since these professionals depend on factors that are beyond their grasp, which include the limitations of the assistential model proposed by the PSF.


Evaluating the effect of hydraulic retention time on fouling development and biomass characteristics in an algal membrane photobioreactor treating a secondary wastewater effluent.
Coupling algal biomass growth to wastewater treatment is a promising alternative for the simultaneous removal and recovery of nutrients. This study aims to evaluate the effects of the Hydraulic Retention Time (HRT) on the fouling behavior and biomass characteristics of C. Vulgaris in a Membrane Photobioreactor (MPBR), fed with a secondary synthetic wastewater effluent. The changes in the algal cell characteristics and in their metabolic products were assessed at three different HRTs (12 h, 24 h and 36 h). Experimental results showed that higher loading rates led to a broader Particle Size Distribution (PSD) resulting from looser and less stable algal flocs. In contrast, bigger and homogeneously distributed particles observed at lower loading rates, led to a porous layer with lower fouling rates and organic removal. The presence of smaller particles and dissolved organics resulted in a more compact and less porous layer that increased the removal of small-MW organics.


Adolescents Engaged in Radicalisation and Terrorism: A Dimensional and Categorical Assessment.
Since 2010 and the founding of the Islamic State, the radicalisation phenomenon in Europe has involved more adolescents and converts to Islam than in previous Islamist terrorist group movements (e.g., Al-Qaeda). In most cases, these adolescents are "homegrown terrorists," a challenging difference, as they are in confrontation with their home and societal environment. As a new and emerging phenomenon, radicalisation leads to many questions. Are empathic capacities altered? Are they presenting psychiatric pathologies or suicidal tendencies that explain why they put themselves in serious dangers? Are they just young delinquents who simply met a radical ideology? In January 2018, by special Justice Department authorisation, we contacted all minors (N = 31) convicted in France for "criminal association to commit terrorism." We assessed several sociodemographic, clinical and psychological variables, including empathy and suicidality, in half of them (N = 15) and compared them with 101 teenagers convicted for non-terrorist delinquency who were placed in Closed Educational Centres (CEC). The results show that adolescents engaged in radicalisation and terrorism do not have a significant prevalence of psychiatric disorders, suicidal tendencies or lack of empathy. It also appears that they have different psychological profiles than delinquent adolescents. "Radicalised" adolescents show better intellectual skills, insight capacities and coping strategies. In addition, the manifestation of their difficulties is less externalised than adolescents from the CEC, having committed very few delinquent acts.


Three-dimensional imaging of the internal auditory canal in patients with acoustic neuroma.
Three-dimensional imaging of the internal auditory canal (IAC) was carried out in 21 patients with acoustic neuromas using helical computed tomography. The IAC was widened in 20 patients, but no irregularities of the canal walls were seen. In addition, the shape of the enlarged IAC corresponded to that of the tumor on magnetic resonance imaging. The data suggest that widening of the IAC in acoustic neuroma patients is due to enlargement of the tumor. Other mechanisms, for example, tumor invasion or destruction caused by release of a specific mediator from the tumor, are unlikely to explain these findings; however, further investigation is needed.


Polymorphonuclear leukocyte elastase activity is increased by bacterial lipopolysaccharide: a response inhibited by glucocorticoids.
Human neutrophil elastase is thought to play an important role in connective tissue destruction in diseases such as emphysema and arthritis. In this article, it is demonstrated that the elastase activity of mature human peripheral blood neutrophils can be rapidly increased in vitro by treatment of the cells with lipopolysaccharide from E. coli and that this increase is inhibited by corticosteroid pretreatment of the cells and by inhibitors of protein synthesis. Alterations in intracellular enzyme content of the mature polymorph in response to bacterial products or other stimuli may be important for amplification of the inflammatory response.


Ginsenoside Rg3 Reduces Epithelial-Mesenchymal Transition Induced by Transforming Growth Factor-β1 by Inactivation of AKT in HMrSV5 Peritoneal Mesothelial Cells.
BACKGROUND Ginsenosides, including ginsenoside Rg3, are components of Panax ginseng C.A. Meyer (Araliaceae) used in traditional Chinese medicine. Long-term peritoneal dialysis induces peritoneal fibrosis that impairs ultrafiltration and is associated with epithelial-mesenchymal transition (EMT) of peritoneal cells. This study aimed to investigate the effects of ginsenoside Rg3 on EMT induced by transforming growth factor-ß1 (TGF-ß1) in HMrSV5 human peritoneal mesothelial cells. MATERIAL AND METHODS The cell counting kit-8 (CCK-8) assay measured HMrSV5 cell viability. The expression of EMT markers, E-cadherin, vimentin, and alpha-smooth muscle actin (alpha-SMA) were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The wound-healing assay determined cell migration. The S-phase of the cell cycle was assessed by 5-ethynyl-2'-deoxyuridine (EdU) labeling, and expression of phosphorylated AKT was measured by Western blot. The effect of ginsenoside Rg3 and the AKT activator SC79 on the TGF-ß1-induced EMT of HMrSV5 cells were evaluated. RESULTS Low concentration of ginsenoside Rg3 did not effect cell viability of HMrSV5 cells. TGF-ß1 treatment decreased the expression of E-cadherin, and increased the expression of vimentin and alpha-SMA and promoted cell migration of HMrSV5 cells. However, co-treatment of ginsenoside Rg3 and TGF-ß1 significantly reduced TGF-ß1-induced EMT in HMrSV5 cells. TGF-ß1 increased the phosphorylation of AKT and increased the expression of Smurf2. Ginsenoside Rg3 reduced TGF-ß1-induced activation of AKT and Smurf2. SC79 reversed the effects of ginsenoside Rg3 on TGF-ß1-induced EMT in HMrSV5 cells. CONCLUSIONS Ginsenoside Rg3 inhibited EMT induced by TGF-ß1 in HMrSV5 human peritoneal mesothelial cells by inhibiting the activation of AKT.


Sustainability Standards in Pediatric Anesthesia: Quality Initiative to Reduce Costly Environmentally Harmful Volatile Anesthetics.
The emission and entrapment of greenhouse gases (GHG) inside the atmosphere is one of the leading causes of global warming. Commonly administered anesthetics have global warming potential up to 2,000 times greater than carbon dioxide. This Quality Improvement (QI) initiative aimed to develop a set of sustainability standards to reduce volatile anesthetic GHG emissions and costs at a children's hospital. In January 2020, the QI project team implemented education sessions for clinical staff on the environmental impact of volatile anesthetics, bedside clinical reminders, resource guides on sustainable anesthesia practices, preset low-flow gas levels on anesthesia machines, relocated and reduced the number of available vaporizers, and implemented policies to standardize clinical practice. Using hospital pharmacy purchase order data between 2018 and 2022, GHG emissions and costs from three commonly used volatile anesthetics (Isoflurane, Sevoflurane, and Desflurane) were compared using metric ton carbon dioxide equivalents. During 3 years, GHG emissions from volatile anesthetics were significantly reduced by 77%, with most of the reduction attributed to the reduced use and eventual elimination of Desflurane. Purchase costs were also significantly reduced during this period by 41%. This QI project successfully decreased GHG emissions over 3 years by simultaneously reducing the use of costly and environmentally harmful volatile anesthetic, Desflurane, and increasing the use of low-flow anesthesia. This study addresses our anesthesia practices and healthcare system's impact on the pediatric population and proposes simple interventions to mitigate the negative consequences of current practices.


Faciocervical Group B Streptococcal Necrotising Fasciitis: a Multidisciplinary Approach Management.
Neonatal necrotising fasciitis secondary to Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is a rare, life-threatening entity with approximately 40 cases reported in the literature.1 GBS soft tissue infection in infancy most commonly affects the face, likely originating from the colonised oral cavity.2 In cases unresponsive to medical management alone, early surgical debridement can be life-saving. We present a case of faciocervical GBS necrotising fasciitis in a male neonate requiring multiple surgical debridements. The resultant soft tissue defect healed with topical negative pressure therapy and eventual placement of a double-layer dermal substitute. Due to his prematurity, the patient was not skin grafted to limit donor site morbidity. After recovering from his life-threatening infection, the patient had intensive scar therapy leading to a favourable cosmetic result with no evidence of function-limiting contracture. Our report draws focus to the need for a multidisciplinary approach incorporating therapy-led scar management early in the postsurgical recovery plan.


Robotic gastrointestinal surgery: learning curve, educational programs and outcomes.
The use of the robotic platform for gastrointestinal surgery was introduced nearly 20 years ago. However, significant growth and advancement has occurred primarily in the last decade. This is due to several advantages over traditional laparoscopic surgery allowing for more complex dissections and reconstructions. Several randomized controlled trials and retrospective reviews have demonstrated equivalent oncologic outcomes compared to open surgery with improved short-term outcomes. Unfortunately, there are currently no universally accepted or implemented training programs for robotic surgery and robotic surgery experience varies greatly. Additionally, several limitations to the robotic platform exist resulting in a distinct learning curve associated with various procedures. Therefore, implementation of robotic surgery requires a multidisciplinary team approach with commitment and investment from clinical faculty, operating room staff and hospital administrators. Additionally, there is a need for wider distribution of educational modules to train more surgeons and reduce the associated learning curve. This article will focus on the implementation of the robotic platform for surgery of the pancreas, stomach, liver, colon and rectum with an emphasis on the associated learning curve, educational platforms to develop proficiency and perioperative outcomes.


Enhancement of doxorubicin cytotoxicity of human cancer cells by tyrosine kinase inhibition of insulin receptor and type I IGF receptor.
The type I insulin-like growth factor receptor (IGF1R) contributes to cancer cell biology. Disruption of IGF1R signaling alone or in combination with cytotoxic agents has emerged as a new therapeutic strategy. Our laboratory has shown that sequential treatment with doxorubicin (DOX) and anti-IGF1R antibodies significantly enhanced the response to chemotherapy. In this study, we examined whether inhibition of the tyrosine kinase activity of this receptor family would also enhance chemotherapy response. Cis-3-[3-(4-methyl-piperazin-l-yl)-cyclobutyl]-1-(2-phenyl-quinolin-7-yl)-imidazo[1,5-a]pyrazin-8-ylamine (PQIP) inhibited IGF1R and insulin receptor (InsR) kinase activity and downstream activation of ERK1/2 and Akt in MCF-7 and LCC6 cancer cells. PQIP inhibited both monolayer growth and anchorage-independent growth in a dose-dependent manner. PQIP did not induce apoptosis, but rather, PQIP treatment was associated with an increase in autophagy. We examined whether sequential or combination therapy of PQIP with DOX could enhance growth inhibition. PQIP treatment together with DOX or DOX followed by PQIP significantly inhibited anchorage-independent growth in MCF-7 and LCC6 cells compared to single agent alone. In contrast, pre-treatment with PQIP followed by DOX did not enhance the cytotoxicity of DOX in vitro. Furthermore, OSI-906, a PQIP derivative, inhibited IGF-I signaling in LCC6 xenograft tumors in vivo. When given once a week, simultaneous administration of OSI-906 and DOX significantly enhanced the anti-tumor effect of DOX. In summary, these results suggest that timing and duration of the IGF1R/InsR tyrosine kinase inhibitors with chemotherapeutic agents should be evaluated in clinical trials. Long-term disruption of IGF1R/InsR may not be necessary when combined with cytotoxic chemotherapy.


Matrix loading: assembly of extracellular matrix collagen fibrils during embryogenesis.
Nothing in biology stimulates the imagination like the development of a single fertilized egg into a newborn child. Consequently, a major focus of biomedical research is aimed at understanding cell differentiation, proliferation, and specialization during child health and human development. However, the fact that the increase in size and shape of the growing embryo has as much to do with the extracellular matrix (ECM) as with the cells themselves, is largely overlooked. Cells in developing tissues are surrounded by a fiber-composite ECM that transmits mechanical stimuli, maintains the shape of developing tissues, and functions as a scaffold for cell migration and attachment. The major structural element of the ECM is the collagen fibril. The fibrils, which are indeterminate in length, are arranged in different tissues in exquisite supramolecular architectures, including parallel bundles, orthogonal lamellae, and concentric weaves. This article reviews our current understanding of the synthesis and assembly of collagen fibrils, and discusses challenging questions about how cells assemble an organized ECM during embryogenesis.


[Mechanisms of the development of recurrences of endogenous psychoses. The duration of remission in schizophrenia].
The distribution of the period of schizophrenia remissions is depicted by the exponential law. Having carried out an expensive epidemiological study, the authors have shown that such a depiction may turn adequate only in the design of the distribution in time intervals of the order of one year. In minor time intervals (weekly or approximating ones), the distribution acquires a wavy appearance indicating periodic fluctuations of relapse risk at the basis of which there lies a certain rhythmical process. The data are provided in favour of polyrhythmic pattern of that process, with the rhythms having a period of 5-6, 8-9, 12-13 and 21-22 weeks being the most permanent ones. The correlation between the exponential and polyrhythmic models of schizophrenia relapsing is discussed.


Impact of an inpatient geriatric consultative service on outcomes for cognitively impaired patients.
Impact of geriatric consultative services (GCS) on hospital readmission and mortality outcomes for cognitively impaired (CI) patients is not known. Evaluate impact of GCS on hospital readmission and mortality among CI inpatients. Secondary data analysis of a prospective trial of a computerized decision support system between July 1, 2006 and May 30, 2008. Study conducted at Eskenazi hospital, Indianapolis, Indiana, a 340-bed, public hospital with over 2300 yearly admissions of patients ages 65 years or older. There were 415 inpatients aged 65 years and older with CI enrolled from July 2006 to March 2008. Thirty-day and 1-year mortality and hospital readmission following the index admission. Cox proportional hazard models were used to determine the association between receiving GCS, readmission, or mortality while adjusting for demographics, discharge destination, delirium, Charlson Comorbidity Index, and prior hospitalizations. The propensity score method was used to adjust for the nonrandom assignment of GCS. Patients receiving GCS were older (79 years old, 8.1 standard deviation [SD] vs 76 years old, 7.8 SD; P < 0.001) with higher incidence of delirium (49% vs 29%; P < 0.001). No significant differences were found between the groups for hospital readmission (hazard ratio [HR] = 1.19; 95% confidence interval = 0.89-1.59) and mortality at 12 months of index admission (HR = 0.91; 95% confidence interval = 0.59-1.40). However, a significant increase in readmissions was observed for the GCS group (HR = 1.75; 95% confidence interval = 1.06-2.88) at 30 days postdischarge. One-year postdischarge outcomes of CI patients who received GCS were not different from patients who did not receive the service. New models of care are needed to improve postdischarge readmission and mortality among hospitalized patients with CI.


Fibrogenic fibroblast-selective near-infrared phototherapy to control scarring.
Rationale: Fibroblasts, the predominant cell type responsible for tissue fibrosis, are heterogeneous, and the targeting of unique fibrogenic population of fibroblasts is highly expected. Very recently, elevated glycolysis is demonstrated to play a pivotal role in the determination of fibrogenic phenotype of fibroblasts. However, it is lack of specific strategies for targeting and elimination of such fibrogenic populations. In this study, a novel strategy to use the a near-infrared (NIR) dye IR-780 for the targeting and elimination of a fibrogenic population of glycolytic fibroblasts to control the cutaneous scarring is developed. Methods: The identification and cell properties test of fibrogenic fibroblasts with IR-780 were conducted by using fluorescence activated cell sorting, transplantation experiments, in vivo imaging, RNA sequencing in human cell experiments and mouse and rat wound models. The uptake of IR-780 in fibroblasts mediated by HIF-1α/SLCO2A1 and the metabolic properties of IR-780H fibroblasts were investigated using RNA interference or signaling inhibitors. The fibrogenic fibroblast-selective near-infrared phototherapy of IR-780 were evaluated in human cell experiments and mouse wound models. Results: IR-780 is demonstrated to recognize a unique glycolytic fibroblast lineage, which is responsible for the bulk of connective tissue deposition during cutaneous wound healing and cancer stroma formation. Further results identified that SLCO2A1 is involved in the preferential uptake of IR-780 in fibrogenic fibroblasts, which is regulated by HIF-1α. Moreover, with intrinsic dual phototherapeutic activities, IR-780 significantly diminishes cutaneous scarring through the targeted ablation of the fibrogenic population by photothermal and photodynamic effects. Conclusion: This work provides a unique strategy for the targeted control of tissue scarring by fibrogenic fibroblast-selective near-infrared phototherapy. It is proposed that IR-780 based theranostic methodology holds promise for translational medicine aimed at regulation of fibrogenic behavior.


Depolarizing agents induce oscillations in canine bronchial smooth muscle membrane potential: possible mechanisms.
Tetraethylammonium (TEA) 925 mM), 4-aminopyridine (4-AP) (5 mM) and carbachol (3 X 10(-7) M) elicited membrane depolarization (approximately 20 mV) and oscillation (0.5-1.0 Hz; up to 25 mV in amplitude) in canine bronchi (3rd to 5th order). BaCl2 (1 mM) also elicited large depolarizations but not oscillations. The oscillations were antagonized by nitrendipine (NT) (10(-8) M) or atropine (10(-6) M) and were unaffected by phentolamine, propranolol or apamin (all 10(-7) M). TEA- or 4-AP-induced membrane depolarizations were partially reversed by atropine. After replacement of extracellular Ca++ with Sr++, oscillations elicited by carbachol or TEA were considerably slower (although amplitudes were similar to those seen in Ca++). Excitatory junction potentials were not altered by NT, were inhibited by 4-AP or replacement of extracellular Ca++ with Sr++, were potentiated by Ba++ and were variably affected by TEA. Contractile responses to acetylcholine were supported by Ca++ or Sr++ (with reduced efficacy), and only the latter were sensitive to NT. Our data suggest that, in canine bronchi (3rd to 5th order), 1) there are K+ channels and Ca++ channels (not L-type) on the cholinergic nerve endings, which modulate neurotransmitter release, 2) there are voltage-dependent K+ channels on the smooth muscle, which regulate membrane potential and suppress excitatory activity, and 3) membrane depolarization leads to alternating opening and closing of voltage-dependent (L-type) Ca++ channels on the smooth muscle, producing oscillations in membrane potential.(ABSTRACT TRUNCATED AT 250 WORDS)


[Ethnopsychiatry. The guardians of culture. Effects of geographic migration in late adulthood].
If one considers going through life as a temporal migration, one can observe that passing from one stage of life to the other is marked by certain rites (rites of passage or transition). The act of retirement is such a rite. This event involves individual and collective role changes (losses and gains). Within the context of stress produced at that particular time of temporal migration, the author examines the effects of physical (spatial) migration. Four cases are presented to illustrate this kind of situation. They are separated into two groups: multigenerational migration with and without the participation of aged parents. The use of an ethnological model--the concept of "Guardians of Culture"--allows for the study of the problem from the point of view of a reassessment of self in terms of a cultural role. This ethnopsychiatric approach attempts to assume a preventive role in that it deals with the detection of early signs of stress which could have serious repercussions on the health of the elderly population.


Continuous learning of emergent behavior in robotic matter.
One of the main challenges in robotics is the development of systems that can adapt to their environment and achieve autonomous behavior. Current approaches typically aim to achieve this by increasing the complexity of the centralized controller by, e.g., direct modeling of their behavior, or implementing machine learning. In contrast, we simplify the controller using a decentralized and modular approach, with the aim of finding specific requirements needed for a robust and scalable learning strategy in robots. To achieve this, we conducted experiments and simulations on a specific robotic platform assembled from identical autonomous units that continuously sense their environment and react to it. By letting each unit adapt its behavior independently using a basic Monte Carlo scheme, the assembled system is able to learn and maintain optimal behavior in a dynamic environment as long as its memory is representative of the current environment, even when incurring damage. We show that the physical connection between the units is enough to achieve learning, and no additional communication or centralized information is required. As a result, such a distributed learning approach can be easily scaled to larger assemblies, blurring the boundaries between materials and robots, paving the way for a new class of modular "robotic matter" that can autonomously learn to thrive in dynamic or unfamiliar situations, for example, encountered by soft robots or self-assembled (micro)robots in various environments spanning from the medical realm to space explorations.


Why did Danish women's life expectancy stagnate? The influence of interwar generations' smoking behaviour.
The general health status of a population changes over time, generally in a positive direction. Some generations experience more unfavourable conditions than others. The health of Danish women in the interwar generations is an example of such a phenomenon. The stagnation in their life expectancy between 1977 and 1995 is thought to be related to their smoking behaviour. So far, no study has measured the absolute effect of smoking on the mortality of the interwar generations of Danish women and thus the stagnation in Danish women's life expectancy. We applied a method to estimate age-specific smoking-attributable number of deaths to examine the effect of smoking on the trends in partial life expectancy of Danish women between age 50 and 85 from 1950 to 2012. We compared these trends to those for women in Sweden, where there was no similar stagnation in life expectancy. When smoking-attributable mortality was excluded, the gap in partial life expectancy at age 50 between Swedish and Danish women diminished substantially. The effect was most pronounced in the interwar generations. The major reason for the stagnation in Danish women's partial life expectancy at age 50 was found to be smoking-related mortality in the interwar generations.


HA-g-CS Implant and Moderate-intensity Exercise Stimulate Subchondral Bone Remodeling and Promote Repair of Osteochondral Defects in Mice.
Background: Substantial evidence shows that crosstalk between cartilage and subchondral bone may play an important role in cartilage repair. Animal models have shown that hydroxyapatite-grafted-chitosan implant (HA-g-CS) and moderate-intensity exercise promote regeneration of osteochondral defects. However, no in vivo studies have demonstrated that these two factors may have a synergistic activity to facilitate subchondral bone remodeling in mice, thus supporting bone-cartilage repair. Questions: This study was to clarify whether HA-g-CS and moderate-intensity exercise might have a synergistic effect on facilitating (1) regeneration of osteochondral defects and (2) subchondral bone remodeling in a mouse model of osteochondral defects. Methods: Mouse models of osteochondral defects were created and divided into four groups. BC Group was subjected to no treatment, HC Group to HA-g-CS implantation into osteochondral defects, ME group to moderate-intensity treadmill running exercise, and HC+ME group to both HA-g-CS implantation and moderate-intensity exercise until sacrifice. Extent of subchondral bone remodeling at the injury site and subsequent cartilage repair were assessed at 4 weeks after surgery. Results: Compared with BC group, HC, ME and HC+ME groups showed more cartilage repair and thicker articular cartilage layers and HC+ME group acquired the best results. The extent of cartilage repair was correlated positively to bone formation activity at the injured site as verified by microCT and correlation analysis. Histology and immunofluorescence staining confirmed that bone remodeling activity was increased in HC and ME groups, and especially in HC+ME group. This bone formation process was accompanied by an increase in osteogenesis and chondrogenesis factors at the injury site which promoted cartilage repair. Conclusions: In a mouse model of osteochondral repair, HA-g-CS implant and moderate-intensity exercise may have a synergistic effect on improving osteochondral repair potentially through promotion of subchondral bone remodeling and generation of osteogenesis and chondrogenesis factors. Clinical Relevance: Combination of HA-g-CS implantation and moderate-intensity exercise may be considered potentially in clinic to promote osteochondral defect repair. Also, cartilage and subchondral bone forms a functional unit in an articular joint and subchondral bone may regulate cartilage repair by secreting growth factors in its remodeling process. However, a deeper insight into the exact role of HA-g-CS implantation and moderate-intensity exercise in promoting osteochondral repair in other animal models should be explored before they can be applied in clinic in the future.


Immunosuppressant from group A streptococci.
A cytoplasmic component of group A streptococci suppresses both 19S and 7S antibody responses of mice to sheep erythrocytes. Partial purification is achieved by differential centrifugation and gel filtration. When the direct and indirect hemolytic plaque techniques are used, a single injection of this group A material given before injection of erythrocytes produces more than 90-percent suppression of either primary or secondary immune response.


Timing of Palliative Care Consultation and the Impact on Thirty-Day Readmissions and Inpatient Mortality.
Inpatient palliative care consultation (PCC) may reduce 30-day readmissions and inpatient mortality among seriously ill patients. To evaluate the impact of timing of PCC on 30-day readmissions and inpatient mortality. Retrospective, observational study comparing risk-adjusted, observed-to-expected (O/E) 30-day readmissions and inpatient mortality among patients receiving inpatient PCC to all other inpatients. Adult patients with hospital length of stay (LOS) <30 days, primary diagnoses of circulatory, infectious, respiratory, neoplasms, injury/poisoning, and digestive system were included from eight hospitals in a single health care system. Compared with non-PCC patients (n = 43,463), PCC patients (n = 6043) had a greater proportion of African Americans, Medicare, LOS ≥7 days, intensive care unit stays, discharges to skilled nursing facility and hospice, primary diagnoses of infections and neoplasms, comorbidities of congestive heart failure, cancer, and dementia, Charlson comorbidity score ≥8 (p < 0.001), and fewer males (p = 0.03). Adjusted readmission reduction attributed to PCC among 0-2-, 3-6-, and 7-30-day subgroups was 14.1%, 19.2%, and 16.4%, respectively (usual care O/E = 0.904 vs. subgroup O/Es = 0.764, 0.713, 0.741, respectively). Adjusted mortality reductions attributed to PCC among the 0-2- and 3-6-day subgroups were 19.4% and 19.1%, respectively. A 12% mortality increase was observed in the 7-30-day subgroup (usual care O/E = 0.738 vs. subgroup O/Es = 0.544, 0.547, 0.858, respectively). Inpatient PCC reduces 30-day readmissions and inpatient mortality with the greatest impact demonstrated within six days of hospital admission. Early PCC should be encouraged for eligible patients.


Effect of 4-hydroxyandrostenedione on murine Leydig tumor cell steroidogenesis.
The murine Leydig cell tumor (M5480A) possesses high levels of estrogen receptor and is known to produce estrogens. In these studies we examined the effects of the potent aromatase inhibitor 4-hydroxyandrostenedione (4-OHA) on Leydig tumor cell steroidogenesis both in vitro and in vivo. The addition of 4-OHA to Leydig tumor cells in primary culture resulted in a dose- and a time-dependent decrease in media progesterone levels. The observed decrease was most likely due to impaired synthesis of progesterone, inasmuch as no alteration in progesterone metabolism was seen when progesterone levels were diminishing. However, 4-OHA inhibited progesterone conversion to testosterone following 1 h of incubation, but this effect disappeared coincident with 4-OHA metabolism. Analysis of pregnenolone production revealed a biphasic dose-dependent effect of 4-OHA. At low doses (0.01-0.1 microM), 4-OHA was found to decrease pregnenolone concentrations, while at higher doses (1-10 microM) pregnenolone levels were elevated. Therefore, the actions of 4-OHA on Leydig cell steroidogenesis in vitro appear to be multifocal. Other experiments were performed to evaluate the effects of 4-OHA on tumor-bearing male mice in vivo. In these studies, the predominant effects of 4-OHA were to act as an aromatase inhibitor and to inhibit progesterone production. Thus, while 4-OHA is a potent aromatase inhibitor, we have found that this compound may alter steroidogenesis in Leydig tumor cells at several sites prior to aromatization.


LoRaWANSim: A Flexible Simulator for LoRaWAN Networks.
Among the low power wide area network communication protocols for large scale Internet of Things, LoRaWAN is considered one of the most promising, owing to its flexibility and energy-saving capabilities. For these reasons, during recent years, the scientific community has invested efforts into assessing the fundamental performance limits and understanding the trade-offs between the parameters and performance of LoRaWAN communication for different application scenarios. However, this task cannot be effectively accomplished utilizing only analytical methods, and precise network simulators are needed. To that end, this paper presents LoRaWANSim, a LoRaWAN simulator implemented in MATLAB, developed to characterize the behavior of LoRaWAN networks, accounting for physical, medium access control and network aspects. In particular, since many simulators described in the literature are deployed for specific research purposes, they are usually oversimplified and hold a number of assumptions affecting the accuracy of their results. In contrast, our simulator has been developed for the sake of completeness and it is oriented towards an accurate representation of the LoRaWAN at the different layers. After a detailed description of the simulator, we report a validation of the simulator itself and we then conclude by presenting some results of its use revealing notable and non-intuitive trade-offs present in LoRaWAN. Assuming the acceptance of the paper, the simulator will be made available via open access to the research community.


Efficacy of Biomist 30:30 and Aqua Reslin against Anopheles quadrimaculatus in Arkansas.
Aqua Reslin and Biomist 30:30 technical permethrin and piperonyl butoxide were applied via ground ultra-low volume at a rate of 237 ml/min and 0.00196 kg active ingredient/ha against wild-caught adult Anopheles quadrimaculatus. The 2 formulations did not differ significantly at 31 m from the spray path (P < or = 0.05). However, at 61 and 91 m, percent mortality for 30:30 was significantly higher than for Aqua Reslin at each time after treatment (P < or = 0.05). Between 12 and 24 h, about 8% recovery was observed in mosquitoes treated with Aqua Reslin at 31 m.


Concomitant carotid endarterectomy and cardiac surgery does not decrease postoperative stroke rates.
The timing of operative revascularization for patients with concomitant carotid artery stenosis and coronary artery disease remains controversial. We examined the Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database to evaluate the association of combined carotid endarterectomy (CEA) and coronary artery bypass grafting (CABG) with postoperative outcomes. All patients undergoing CABG with known carotid stenosis of >80% were identified from 2011 to 2016. Individuals were stratified by use of cardiopulmonary bypass and whether a concomitant CEA was performed at the time of CABG. Multivariate logistic regression was used to model the probability of combined CABG and CEA. The resulting propensity scores were used to match individuals on the basis of clinical and operative characteristics to evaluate primary (30-day mortality and in-hospital transient ischemic attack and stroke) and secondary (STS morbidity composite events and length of stay) end points, with P < .05 required to declare statistical significance. After propensity score matching, 994 off-pump CABG patients (497 CABG only and 497 CABG-CEA) and 5952 on-pump CABG patients (2976 CABG only and 2976 CABG-CEA) were identified. For patients who received on-pump operations, those undergoing CABG-CEA had no observed difference in rate of in-hospital stroke (odds ratio [OR], 0.93; 95% confidence interval [CI], 0.72-1.21; P = .6), higher incidence of STS morbidity composite events (OR, 1.15, 95% CI, 1.01-1.31; P = .03), longer length of stay (7.0 [interquartile range, 5.0-9.0] days vs 6.0 [interquartile range, 5.0-9.0] days; P < .005), and no observed difference in 30-day mortality (OR, 1.28; 95% CI, 0.97-1.69; P = .08) compared with those undergoing CABG only. For off-pump procedures, CABG-CEA patients had no observed difference in rate of in-hospital stroke (OR, 0.80; 95% CI, 0.37-1.69; P = .56) compared with those undergoing CABG only. Whereas the differences are relatively small, these data suggest that a combined CABG-CEA approach is unlikely to provide significant stroke reduction benefit compared with CABG only. However, comparison with staged approaches merits further investigation.


Antenatal betamethasone associates with transient immunodepression in very low birth weight infants.
Antenatal betamethasone (BM) treatment for mothers at risk for premature delivery is effective in reducing neonatal morbidity. Immunodepression, defined as monocyte human leukocyte antigen (HLA)-DR expression <60%, is common in patients in intensive care. In very low birth weight (VLBW) infants, immunodepression correlates with gestational age and may predispose to infections. To evaluate whether timing of antenatal BM associates with immunodepression in VLBW infants. We determined monocyte HLA-DR expression by flow cytometry and measured 13 cytokines, cortisol, and BM in plasma from 56 VLBW infants. We calculated total glucocorticoid index as the sum of BM and cortisol at the ratio 33.3:1. HLA-DR expression both in cord (R(2) = 0.175, p = 0.033, n = 26) and on day 1 (R(2) = 0.125, p = 0.011, n = 51) showed an association with timing of BM. A short interval from BM to birth induced more pronounced and prolonged immunodepression, with lower HLA-DR% on postnatal day 7. On day 3, 25 infants (45%) met the criteria of immunodepression. HLA-DR expression correlated negatively with total glucocorticoid index (cord: R(2) = -0.573, p = 0.003, n = 13; day 1: R(2) = -0.213, p = 0.008, n = 32). Elapsed time from maternal BM correlated positively with concentrations of cytokines IL-6 and IL-10 on day 1. In VLBW infants, antenatal BM associated with transient immunodepression in a time-dependent manner. Suppression of both anti- and proinflammatory cytokines occurred. These effects may lead to an increased risk for later infections.


Prehospital management of uncontrolled bleeding in trauma patients: nearing the light at the end of the tunnel.
The management of uncontrolled bleeding in trauma patients is difficult in the prehospital setting, especially when transfer time to a care facility is prolonged. The goal of treatment is to stabilize the patient until surgery can be performed. In modem practice, the major aspects of optimal patient stabilization are the timing and volume of resuscitation and the use of blood products. The main problems are the logistics of handling the blood products as well as achieving the appropriate endpoint of resuscitation, while balancing the need to maintain blood pressure with the need to avoid deleterious coagulopathy. This work reviews current therapeutic modalities for prehospital management of uncontrolled bleeding trauma patients, namely low volume resuscitation, packed red blood cells, hemoglobin solutions, perfluorocarbons, hypertonic saline solutions, and recombinant activated factor VII.


Shallow whole genome sequencing for robust copy number profiling of formalin-fixed paraffin-embedded breast cancers.
Pathology archives with linked clinical data are an invaluable resource for translational research, with the limitation that most cancer samples are formalin-fixed paraffin-embedded (FFPE) tissues. Therefore, FFPE tissues are an important resource for genomic profiling studies but are under-utilised due to the low amount and quality of extracted nucleic acids. We profiled the copy number landscape of 356 breast cancer patients using DNA extracted FFPE tissues by shallow whole genome sequencing. We generated a total of 491 sequencing libraries from 2 kits and obtained data from 98.4% of libraries with 86.4% being of good quality. We generated libraries from as low as 3.8 ng of input DNA and found that the success was independent of input DNA amount and quality, processing site and age of the fixed tissues. Since copy number alterations (CNA) play a major role in breast cancer, it is imperative that we are able to use FFPE archives and we have shown in this study that sWGS is a robust method to do such profiling.


AMP-activated protein kinase at the nexus of therapeutic skeletal muscle plasticity in Duchenne muscular dystrophy.
Recent studies have highlighted the potential of adenosine monophosphate-activated protein kinase (AMPK) to act as a central therapeutic target in Duchenne muscular dystrophy (DMD). Here, we review the role of AMPK as an important integrator of cell signaling pathways that mediate phenotypic plasticity within the context of dystrophic skeletal muscle. Pharmacological AMPK activation remodels skeletal muscle towards a slower, more oxidative phenotype, which is more pathologically resistant to the lack of dystrophin. Moreover, recent studies suggest that AMPK-activated autophagy may be beneficial for myofiber structure and function in mice with muscular dystrophy. Thus, AMPK may represent an ideal target for intervention because clinically approved pharmacological agonists exist, and because benefits can be derived via two independent yet, complementary biological pathways. The availability of several AMPK activators could therefore lead to the rapid development and implementation of novel and highly effective therapeutics aimed at altering the relentless progression of DMD.


Immunohistochemical analysis of hSNF5/INI1 distinguishes renal and extra-renal malignant rhabdoid tumors from other pediatric soft tissue tumors.
Malignant rhabdoid tumor (MRT) is a highly aggressive neoplasm that occasionally demonstrates phenotypic overlap with other soft tissue malignancies. Molecular genetic analysis of MRT frequently demonstrates deletion or mutation of the hSNF5/INI1 gene, with corresponding reduced expression at the protein level. INI1 immunohistochemistry was performed to determine the utility of this method in assessing loss of INI1 expression in rhabdoid tumors. Twenty-seven MRTs with molecular analysis (19 renal, 8 extra-renal) were evaluated. Seventeen additional MRT (10 renal, 7 extra-renal) without INI1 molecular analysis were also analyzed. Loss of INI1 expression was observed in the tumor cells in all 44 cases. To determine the specificity of this assay, a variety of 45 pediatric soft tissue tumors, some of which occasionally display rhabdoid differentiation, were investigated. These included Ewing's sarcoma, Wilms' tumor, desmoplastic small round cell tumor, clear cell sarcoma, congenital mesoblastic nephroma, synovial sarcoma, undifferentiated sarcoma, rhabdomyosarcoma, and epithelioid sarcoma. Positive nuclear staining was found in all nonrhabdoid tumors examined. Of interest, synovial and epithelioid sarcomas exhibited variable and/or focal staining. INI1 antibody immunohistochemistry is useful in confirming the histologic diagnosis of renal or extra-renal rhabdoid tumor, especially for cases with indeterminate histologic features, equivocal immunophenotypic profiles, or uninformative molecular studies.


[Color discrimination in humans during vestibular stimulation following exposure to intense light].
Manned studies have demonstrated that eye exposure to light of 2.5 X 10(3) -- 50.0 X 10(3) nit leads to transient color blindness, decrease in the central color, bright contrast sensitivity and decline in functional stability of color discrimination. Pre-exposure to light luminosity of 50.0 X 10(3) nit enhances the decrease in functional stability of color discrimination due to vestibular stimulation. This is accompanied by a decline in vestibular tolerance. Mechanisms of the changes in color discrimination and resistance to vestibular stimulation are discussed.


The Effect of Body Acupressure on Blood Pressure and Fatigue Levels in Individuals Suffering From Hypotension During Hemodialysis: A Randomized Controlled Trial.
Since hypotension is one of the most common complications experienced during hemodialysis (HD), and there are studies indicating that stimulation of the P6 (Neiguan) acupuncture point affects blood pressure, this study examines the effect of acupressure performed on this point on blood pressure regulation as well as its effect on symptoms such as hypotension-associated fatigue and pain. This randomized controlled trial was conducted in order to determine the effect of 12-session body acupressure, performed by electrostimulation device, on blood pressure, headache, and fatigue level in individuals suffering from hypotension during hemodialysis. The study was conducted with a total of 135 patients, including 67 patients in the intervention group and 68 patients in the placebo group at four hemodialysis centers located in two city centers. The data were gathered using a questionnaire, visual analog scale (VAS) for pain and fatigue, and the Piper fatigue scale. The forms were administered at the beginning of the application (first follow-up) and four weeks later (second follow-up). In the intervention group, the electrostimulation device was attached to the Neiguan (p6) acupuncture point and operated at the third hour of each dialysis session three times a week for one month. In the placebo group, the device was attached to the same acupuncture point but its batteries were removed and it was not operated. At the end of the four-week application, the forms were administered again. One-way analysis of variance, t test, Student-Newman-Keuls test, Pearson correlation analysis, Chi-square, McNemar test and McNemar Bowker test were used to assess the data. It was found that systolic and diastolic blood pressure levels were higher in all sessions in the intervention group compared to the placebo group (P < .05). In the first follow-up, no difference was observed between the groups in terms of the scores of VAS pain, VAS fatigue, and Piper fatigue scale (P > .05); whereas, in the second follow-up, it was determined that VAS pain scores, VAS fatigue scores, and affective, sensory, and total scores of the Piper fatigue scale decreased in the intervention group compared to the placebo group (P < .05). As a conclusion; it was found that body acupressure, which was performed on the Neiguan (P6) acupuncture point using electrostimulation device, provided the systolic and diastolic blood pressure regulation and decreased VAS pain severity, VAS fatigue severity, and total score and subscale mean Piper fatigue scale scores.


The Influence of trisomy 21 on facial form and variability.
Triplication of chromosome 21 (trisomy 21) results in Down syndrome (DS), the most common live-born human aneuploidy. Individuals with DS have a unique facial appearance that can include form changes and altered variability. Using 3D photogrammatic images, 3D coordinate locations of 20 anatomical landmarks, and Euclidean Distance Matrix Analysis methods, we quantitatively test the hypothesis that children with DS (n = 55) exhibit facial form and variance differences relative to two different age-matched (4-12 years) control samples of euploid individuals: biological siblings of individuals with DS (n = 55) and euploid individuals without a sibling with DS (n = 55). Approximately 36% of measurements differ significantly between DS and DS-sibling samples, whereas 46% differ significantly between DS and unrelated control samples. Nearly 14% of measurements differ significantly in variance between DS and DS sibling samples, while 18% of measurements differ significantly in variance between DS and unrelated euploid control samples. Of those measures that showed a significant difference in variance, all were relatively increased in the sample of DS individuals. These results indicate that faces of children with DS are quantitatively more similar to their siblings than to unrelated euploid individuals and exhibit consistent, but slightly increased variation with most individuals falling within the range of normal variation established by euploid samples. These observations provide indirect evidence of the strength of the genetic underpinnings of the resemblance between relatives and the resistance of craniofacial development to genetic perturbations caused by trisomy 21, while underscoring the complexity of the genotype-phenotype map.


Partial nucleotide sequence similarity within species of Mycoplasma and Acholeplasma.
The nucleotide sequence relationships between 18 species of Mycoplasma and 3 species of Acholeplasma were examined by solution DNA hybridization. Radiolabeled DNAs from strains representing 13 Mycoplasma and 2 Acholeplasma species were used as hybridization probes. The mycoplasmas were heterogeneous but displayed a low degree of conserved information of the order of 3 to 5% of the genome. However, several species within each genus showed 13 to 15% homology. There was no detectable homology between species from the two genera, and M. pneumoniae and M. neurolyticum appeared to be unrelated to any of the other Mycoplasma species or to each other. These results suggest that it may be possible to isolate genes common to most, if not all, Mycoplasma and Acholeplasma species.


Is humidified better than non-humidified low-flow oxygen therapy? A systematic review and meta-analysis.
To determine the effects of low-flow oxygen therapy with humidified or non-humidified oxygen in adult patients. Although non-humidified oxygen in low-flow oxygen therapy is recommended by many guidelines, humidifying oxygen regardless of oxygen flow has been routinely performed in China and Japan and further studies are needed to evaluate the evidence. A systematic review and meta-analysis that comply with the recommendations of the Cochrane Collaboration were conducted. Studies (1980-2016) were identified by searching PUBMED, EMBASE, Science Direct, Cochrane library, CNKI and Wanfang Database. We performed a comprehensive, systematic meta-analysis of randomized controlled trials on the efficacy of humidified and non-humidified low-flow oxygen therapy. Summary risk ratios or weighted mean differences with 95% confidence intervals were calculated using a fixed- or random-effects model. Twenty-seven randomized controlled trials with a total number of 8,876 patients were included. Non-humidified oxygen offers more benefits in reducing the bacterial contamination of humidifier bottles, as shown by the mean operating time for oxygen administration and the respiratory infections compared with humidified oxygen therapy. No significant differences were found in dry nose, dry nose and throat, nosebleed, chest discomfort, the smell of oxygen and SpO2 changes. The routine humidification of oxygen in low-flow oxygen therapy is not justifiable and non-humidified oxygen tends to be more beneficial. However, considering that the quality of most included studies is poor, rigorously designed, large-scale randomized controlled trials are still needed to identify the role of non-humidified oxygen therapy.


Role of topoisomerase mutations and efflux in fluoroquinolone resistance of Bacteroides fragilis clinical isolates and laboratory mutants.
Twelve laboratory mutants and 32 ciprofloxacin-resistant isolates of Bacteroides fragilis were examined for the mechanism(s) of fluoroquinolone resistance. Five mutants had mutations in gyrA. One mutant and two clinical isolates contained a mutation in gyrB. Eight mutants and five clinical isolates accumulated significantly less ciprofloxacin than did wild-type isolates; the mutants and clinical isolates were restored to wild-type characteristics when carbonyl cyanide m-chlorophenylhydrazone was used.


Case Report: Antibodies to the N-Methyl-D-Aspartate Receptor in a Patient With Multiple Sclerosis.
The association between multiple sclerosis and anti-N-Methyl-D-Aspartate receptor encephalitis is limited to merely a few case reports, and the exploration of the pathogenic mechanisms underlying the overlap of these two disease entities is very limited. Therefore, case reports and literature review on N-Methyl-D-aspartate receptor antibody in patients with multiple sclerosis are unusual and noteworthy. A young female had the first episode of paresthesia and motor symptoms with positive anti-N-Methyl-D-Aspartate receptor antibody and recovered after immunotherapy, and at the first relapse, the patient developed disorders of consciousness with positive anti-N-Methyl-D-Aspartate receptor antibody, findings of magnetic resonance imaging showed features of autoimmune encephalitis, which was also controlled by immunotherapy. At the second relapse, anti-N-Methyl-D-Aspartate receptor antibody turned negative while oligoclonal bands presented positive, and findings of magnetic resonance imaging showed features of multiple sclerosis. Afterwards, we followed the patient after receiving disease modifying treatment to monitor the efficacy and safety of teriflunomide. Based on literature review, demyelinating diseases patients with anti-neuronal antibody have complex, diverse and atypical symptoms; therefore, high attention and increased alertness are necessary for neurologists. Conclusively, anti-neuronal antibody may present in many neuroinflammatory conditions, and diagnostic criteria should be used with caution if the clinical presentation is atypical, and neurologists should not rely excessively on laboratory tests to diagnose neurological diseases. Timely and comprehensive examination and consideration as well as early standardized treatment are the key factors to reduce patient recurrence and obtain a good prognosis.


Prognosis in human glioblastoma based on expression of ligand growth hormone-releasing hormone, pituitary-type growth hormone-releasing hormone receptor, its splicing variant receptors, EGF receptor and PTEN genes.
Glioblastoma (GB) is the most frequent brain tumor. Despite recent improvement in therapeutic strategies, the prognosis of GB remains poor. Growth hormone-releasing hormone (GHRH) may act as a growth factor; antagonists of GHRH have been successfully applied for experimental treatment of different types of tumors. The expression profile of GHRH receptor, its main splice variant SV1 and GHRH have not been investigated in human GB tissue samples. We examined the expression of GHRH, full-length pituitary-type GHRH receptor (pGHRHR), its functional splice variant SV1 and non-functional SV2 by RT-PCR in 23 human GB specimens. Epidermal growth factor receptor (EGFR) and phosphatase and tensin homolog gene (PTEN) expression levels were also evaluated by quantitative RT-PCR. Correlations between clinico-pathological parameters and gene expressions were analyzed. Expression of GHRH was found to be positive in 61.9 % of samples. pGHRH receptor was not expressed in our sample set, while SV1 could be detected in 17.4 % and SV2 in 8.6 % of the GB tissues. In 65.2 and 78.3 % of samples, significant EGFR over-expression or PTEN under-representation could be detected, respectively. In 47.8 % of cases, EGFR up-regulation and PTEN down-regulation occurred together. Survival was significantly poorer in tumors lacking GHRH expression. This worse prognosis in GHRH negative group remained significant even if SV1 was also expressed. Our study shows that GHRH and SV1 genes expressed in human GB samples and their expression patterns are associated with poorer prognosis.


The HIV Continuum of Care for Adolescents and Young Adults Attending 13 Urban US HIV Care Centers of the NICHD-ATN-CDC-HRSA SMILE Collaborative.
Almost one-quarter of all new HIV diagnoses in the United States occur among persons aged 13-24 years. These youths have the poorest HIV care continuum (HCC) outcomes, yet few empirical youth-specific data are available. The Strategic Multisite Initiative for the Identification, Linkage, and Engagement in Care of HIV-infected youth (SMILE) helped HIV-infected (mostly newly diagnosed) youth, aged 12-24 years, link to youth-friendly care, and evaluated each milestone of the HCC (October 2012-September 2014). Numbers of HIV-infected youth referred, linked, engaged, and retained in care were recorded, along with sociodemographics. Viral suppression (VS) was defined as ≥1 HIV viral load (VL) below the level of detection on study. Correlates of VS were examined using Cox proportional hazards models. Among 1411 HIV-infected youth, 1053 (75%) were linked, 839 (59%) engaged, and 473 (34%) retained in care at adolescent health care sites. Antiretroviral therapy was initiated among 474 (34%), and 166 (12%) achieved VS. Predictors of VS included lower VL at baseline [aHR 1.56 (95% CI: 1.32-1.89), P < 0.0001], recent antiretroviral therapy receipt [aHR 3.10 (95% CI: 1.86-5.18), P < 0.0001], and shorter time from HIV testing until referral to linkage coordinator [aHR 2.52 (95% CI: 1.50-4.23), P = 0.0005 for 7 days to 6 weeks and aHR 2.08 (95% CI: 1.08-4.04), P = 0.0294 for 6 weeks to 3 months compared with >3 months]. Although this large national sample of predominately newly diagnosed youths linked to care at similar rates as adults, they achieved disproportionately lower rates of VS. Prompt referral to youth-friendly linkage services was an independent predictor of VS. Youth-focused interventions are urgently needed to improve their HCC outcomes.


Submicron tip breakage and silanization control improve ion-selective microelectrodes.
Probable causes of failure of otherwise well-constructed liquid ion-exchanger (LIE) micro-electrodes of average tip size less than 0.15 micron were examined. The problem could be attributed to two major variables, both localized at the tip: partial tip occlusion during fabrication prevents the generation of an electromotive force (small or absent slope and/or selectivity, high resistance); or poor hydrophobicity of the tip permits water to displace the resin from the tip (small or absent slope and/or selectivity and low electrode resistance). Controlled dry tip breakage on paper coated with glassine to final tip sizes well below 0.5 micron (confirmed by scanning electron microscopy) improves the yield of usable electrodes severalfold. Adequate silanization of the tip and consequent retention of resin at the tip can be predicted from the contact angles observed at the glass-LIE-backfilling solution interface. Satisfactory silanization can be achieved despite high ambient humidity. No evidence of shunting of Na+-LIE microelectrodes by the glass wall was seen. In the isolated perfused proximal tubule of Ambystoma tigrinum, the mean intracellular Na+ activity recorded by broken-tip electrodes (13.7 +/- 1.9 meq, n = 4) was similar to that recorded by intact electrodes (15.5 +/- 1.1 meq, n = 31).


Inhibitor of Differentiation 1 (ID1) Facilitates the Efficacy of Sorafenib in Non-Small Cell Lung Cancer Cells through Suppressing Epithelial to Mesenchymal Transition.
BACKGROUND Sorafenib, which is a multitargeted kinase inhibitor, has shown some antitumor effects in patients with non-small cell lung cancer (NSCLC). However, the potential target of sorafenib's antitumor activity is largely unknown. Moreover, definitive predictive biomarkers of benefit have rarely been reported. MATERIAL AND METHODS The alteration in inhibitor of differentiation 1 (ID1) expression in NSCLC cells with sorafenib treatment was detected by western blotting. The sensitivity of NSCLC cells to sorafenib was observed by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium) assay. Loss-of-function and gain-of-function experiments were performed to observe the role of ID1 expression in epithelial to mesenchymal transition (EMT) progression. RESULTS Initially, we observed that ID1 was downregulated in NSCLC cells treated with sorafenib. The response of NSCLC cells to sorafenib was inhibited by the transfection of small interfering RNAs (siRNAs) targeting ID1. In contrast, the transfection of ID1-overexpressing plasmids improved the response of NSCLC cells to sorafenib. Further experiments indicated that ID1 is expressed at high levels in epithelial H460 cells and expressed at low levels in mesenchymal H358 cells. Loss-of-function and gain-of-function experiments suggested that ID1 negatively regulates EMT in NSCLC. CONCLUSIONS The expression of ID1 is dose-dependently inhibited by sorafenib, and the overexpression of ID1 contributes to the antitumor activity of sorafenib by suppressing EMT development. Our results indicate that ID1 might be a potential target for the antitumor activity of sorafenib in NSCLC and that targeting ID1 is a feasible strategy to improve the sensitivity of NSCLC cells to sorafenib.


Conjugated bilirubin triggers anemia by inducing erythrocyte death.
Hepatic failure is commonly associated with anemia, which may result from gastrointestinal bleeding, vitamin deficiency, or liver-damaging diseases, such as infection and alcohol intoxication. At least in theory, anemia during hepatic failure may result from accelerated clearance of circulating erythrocytes. Here we show that bile duct ligation (BDL) in mice leads to severe anemia despite increased reticulocyte numbers. Bilirubin stimulated suicidal death of human erythrocytes. Mechanistically, bilirubin triggered rapid Ca(2+) influx, sphingomyelinase activation, formation of ceramide, and subsequent translocation of phosphatidylserine to the erythrocyte surface. Consistent with our in vitro and in vivo findings, incubation of erythrocytes in serum from patients with liver disease induced suicidal death of erythrocytes in relation to their plasma bilirubin concentration. Consistently, patients with hyperbilirubinemia had significantly lower erythrocyte and significantly higher reticulocyte counts compared to patients with low bilirubin levels. Bilirubin triggers suicidal erythrocyte death, thus contributing to anemia during liver disease.


High frequency stimulation of the subthalamic nucleus has beneficial antiparkinsonian effects on motor functions in rats, but less efficiency in a choice reaction time task.
Chronic subthalamic nucleus high frequency stimulation (STN HFS) improves motor function in Parkinson's disease. However, its efficacy on cognitive function and the mechanisms involved are less known. The aim of this study was to assess the effects of STN HFS in hemiparkinsonian awake rats performing different specific motor tests and a cognitive operant task. Unilateral STN HFS applied in unilaterally DA-depleted rats decreased the apomorphine-induced circling behaviour and reduced catalepsy induced by the neuroleptic haloperidol. DA-depleted rats exhibited severe deficits in the operant task, among which the inability to perform the task was not alleviated by STN HFS. However, in a few animals showing less impairment, STN HFS significantly reduced the contralateral neglect induced by the lesion. These results are the first to demonstrate a beneficial effect of STN HFS applied in awake rats on basic motor functions. However, STN HFS appears to be less effective on impaired cognitive functions.


Chemical and biological versatility of pyrazolo[3,4-d]pyrimidines: one scaffold, multiple modes of action.
Plain language summary Pyrazolo[3,4-d]pyrimidines are chemical compounds possessing remarkable versatility and significance in both biological and chemical contexts. These compounds are composed of specific arrangements of atoms, forming a unique ring structure, which is able to form bonds in a similar way as purines do. In the realm of chemistry, pyrazolo[3,4-d]pyrimidines showcase impressive flexibility due to their ability to easily react with various molecules, opening avenues for the creation of novel compounds with diverse properties for potential applications in medicinal chemistry. In a biological context, pyrazolo[3,4-d]pyrimidines play a crucial role due to their interaction with proteins such as enzymes. In fact, these compounds can impact various biological processes, including cancer cell proliferation, oxidative stress and inflammation. This has led to investigations into their potential as therapeutic agents: by designing pyrazolo[3,4-d]pyrimidines with specific biological targets in mind, new drugs can be developed for the effective treatment of a range of medical conditions. Finally, novel administration tools (e.g., nanomaterials and functionalized liposomes) are being studied as effective ways to overcome the main unwanted characteristics of pyrazolo[3,4-d]pyrimidines (scarce solubility and off-target side effects), thereby increasing their efficacy and specificity toward cell targets. In conclusion, pyrazolo[3,4-d]pyrimidines are fascinating molecules with a dual role in chemistry and biology. Their adaptability in chemical reactions makes them valuable building blocks for designing new compounds with diverse applications. Additionally, their interaction with biological molecules holds promise for the development of innovative medicines. Ongoing research into the properties and behaviors of these compounds could lead to significant advancements in both scientific fields.


Validity of using bovine teeth as a substitute for human counterparts in adhesive tests.
Shear and tensile bond strengths of 40 human and 40 bovine teeth were compared. Teeth were randomly assigned to group I, which received light-cured composite resin, or group II, which received light-cured resin-reinforced glass ionomer cement. The groups were subdivided for shear and tensile bond strength tests, which were conducted on a universal testing machine installed to a computer transducer. Statistical analysis revealed a highly significant difference between shear and tensile bond strengths of human and bovine enamel; however, regression prediction equations support the use of bovine teeth as a reliable substitute to human counterparts in bonding studies of orthodontic adhesion.


Age-dependent effects on the treatment response of natalizumab in MS patients.
Natalizumab is approved for treatment of active forms of relapsing-remitting multiple sclerosis (MS) based on a pivotal phase III study comprising patients aged 18-50 years. The effect of natalizumab has not been specifically studied in older patients. We analyzed age-dependent effects on treatment-related outcome measures in 1872 patients, 189 of whom were aged 50 or more, included in the Swedish post-marketing natalizumab surveillance program. In three MS centers registry data for patients aged >50 years were validated. At baseline older patients had longer disease duration, higher Expanded Disability Status Scale (EDSS) and lower Symbol Digit Modality Test (SDMT) scores than younger patients. The influence from natalizumab on outcome measures was significantly reduced and 18.7% of patients >50 years stopped treatment for lack of effect compared to 7.7% in the younger age group. At baseline, the cerebrospinal fluid levels of the chemokine CXCL13 and the leukocyte cell count were negatively correlated with age in a smaller subgroup of patients. These results were in agreement with previous findings suggesting that inflammation is more pronounced in younger patients and therefore the beneficial effects of potent anti-inflammatory treatments are subsiding with older ages.


Diabetic patients could do as well as non-diabetic patients without inflammation on peritoneal dialysis.
Diabetic patients on peritoneal dialysis (PD) have lower survival and are more likely complicated with inflammation than their non-diabetic counterparts. Here, we explored the interaction effects between diabetes and inflammation on the survival of PD patients. Overall, 2,264 incident patients were enrolled from a retrospective cohort study in China. Patients were grouped according to the baseline levels of high-sensitive C-reactive protein (hsCRP, ≤3 mg/L or >3 mg/L) or serum albumin (SA, ≥38 g/L or <38 g/L). Then, several multivariable adjusted stratified Cox regression models were constructed for these groups to explore the predicted role of diabetes on all-cause or cardiovascular death under inflammatory or non-inflammatory conditions. Diabetics on PD were more likely to have inflammation than non-diabetics on PD, and they presented with elevated hsCRP (52.7% vs. 47.3%, P = 0.03) or decreased SA (77.9% vs. 62.7%, P < 0.001) levels. After stratification by size of center and controlling for confounding factors, diabetes was found to predict all-cause death in patients with hsCRP >3 mg/L or SA <38 g/L but not in patients with hsCRP ≤3 mg/L or SA ≥38 g/L. Similarly, the presence of diabetes was an indication of cardiovascular death in patients with hsCRP >3 mg/L or SA <38 g/L. However, if further adjusted by baseline cardiovascular disease, the predicted role of diabetes on death related to cardiovascular disease in patients with SA <38 g/L disappeared. Diabetic patients could do as well as non-diabetic patients without inflammation on peritoneal dialysis. Active strategies should be implemented to improve inflammation status in diabetic patients on PD.


Processes to Preserve Spice and Herb Quality and Sensory Integrity During Pathogen Inactivation.
Selected processing methods, demonstrated to be effective at reducing Salmonella, were assessed to determine if spice and herb quality was affected. Black peppercorn, cumin seed, oregano, and onion powder were irradiated to a target dose of 8 kGy. Two additional processes were examined for whole black peppercorns and cumin seeds: ethylene oxide (EtO) fumigation and vacuum assisted-steam (82.22 °C, 7.5 psia). Treated and untreated spices/herbs were compared (visual, odor) using sensory similarity testing protocols (α = 0.20; β = 0.05; proportion of discriminators: 20%) to determine if processing altered sensory quality. Analytical assessment of quality (color, water activity, and volatile chemistry) was completed. Irradiation did not alter visual or odor sensory quality of black peppercorn, cumin seed, or oregano but created differences in onion powder, which was lighter (higher L* ) and more red (higher a* ) in color, and resulted in nearly complete loss of measured volatile compounds. EtO processing did not create detectable odor or appearance differences in black peppercorn; however visual and odor sensory quality differences, supported by changes in color (higher b* ; lower L* ) and increased concentrations of most volatiles, were detected for cumin seeds. Steam processing of black peppercorn resulted in perceptible odor differences, supported by increased concentration of monoterpene volatiles and loss of all sesquiterpenes; only visual differences were noted for cumin seed. An important step in process validation is the verification that no effect is detectable from a sensory perspective.


Profile of polycyclic aromatic hydrocarbons in digested sewage sludge.
One of the methods of sludge disposal in cities is its use as an amendment in adjoining agricultural soil. Contaminants in sludge can, however, nullify the benefits. Polycyclic aromatic hydrocarbons (PAHs) are a class of persistent organic pollutants, if present, can pose health risks by virtue of their carcinogenic potential and persistence in soil. The present study deals with profile analysis of PAHs in digested sewage sludge of a megacity, Delhi. Mean concentration of the sum of 16 PAHs in the sludge from 5 sewage treatment plants (STPs) was 20.67 ± 4.14 mg/kg, dry weight (dw). Carcinogenic PAHs represented ∼47% of the total PAHs. Benzo[g,h,i]perylene recorded the highest mean concentration followed by dibenzo[a,h]anthracene. Low molecular weight PAHs and high molecular weight PAHs contributed 19% and 81% to total PAHs content respectively. Principal component analysis identified the major sources of PAHs in sludge as coal and natural gas combustion. Wood combustion, oil and oil derivatives are the other identified sources. The observed PAH levels in sludge from selected STPs of Delhi were found to violate the limit values proposed by the European Union and the US legislation for application in agriculture.


[Polonium: the radioactive killer from tobacco smoke].
Among all carcinogenic substances contained in tobacco smoke, Polonium 210 (Po-210), with a half-life of 138 days, is one of the most dangerous, by exerting a devastating, chronic, slow and progressive carcinogenesis activity. The main source of Po-210 in tobacco is represented by fertilizers (polyphosphates) containing radium-226 (Ra-222) which decades to plumb 210 (Pb-210). Through the thricomes Pb-210 is concentrated in the tobacco leaves, where it turns to Po-210, which at the cigarette combustion temperature (800-900 degrees C) reaches the gaseous state and it is absorbed by the micro particles released into tobacco smoke. Thus, smoke becomes radioactive in both its gaseous and corpuscular components and reaches the airways, where, particularly at the branches level and together with other substances, it exerts its carcinogenic activity, especially in those subjects with impaired respiratory mucosal clearance. The carcinogenic risk/one year lifetime of a smoker of 20 cigarettes per day is equivalent to that of undertaking 300 chest x-rays. It is calculated that Po-210 may be independently responsible of 4 lung cancers every 10,000 smokers. During cigarette's combustion, tobacco smoke is also released in the air, contributing to serious health risks for those exposed to passive smoke.


US acculturation and poor sleep among an intergenerational cohort of adult Latinos in Sacramento, California.
Acculturation may shape the disproportionate burden of poor sleep among Latinos in the United States. Existing studies are limited by unidimensional acculturation proxies that are incapable of capturing cultural complexities across generations. Understanding how acculturation relates to sleep may lead to the identification of modifiable intervention targets. We used multivariable regression and latent class methods to examine cross-sectional associations between a validated multidimensional scale of US acculturation and self-reported poor sleep measures. We analyzed an intergenerational cohort: first-generation (GEN1) older Latinos (Sacramento Area Latino Study on Aging; N = 1,716; median age: 69.5) and second-generation (GEN2) middle-aged offspring and relatives of GEN1 (Niños Lifestyle and Diabetes Study; N = 670; median age: 54.0) in Sacramento, California. GEN1 with high US acculturation, compared with high acculturation towards another origin/ancestral country, had less restless sleep (prevalence ratio [PR] [95% confidence interval (CI)]: 0.67 [0.54, 0.84]) and a higher likelihood of being in the best sleep class than the worst (OR [95% CI]: 1.62 [1.09, 2.40]), but among nonmanual occupations, high intergenerational US acculturation was associated with more general fatigue (PR [95% CI: 1.86 [1.11, 3.10]). GEN2 with high intergenerational US acculturation reported shorter sleep (PR [95% CI]: 2.86 [1.02, 7.99]). High US acculturation shaped sleep differentially by generation, socioeconomic context, and intergenerational acculturative status. High US acculturation was associated with better sleep among older, lower socioeconomic Latinos, but with shorter sleep duration among middle-aged, higher socioeconomic Latinos; results also differed by parental acculturation status. Upon replication, future studies should incorporate prospective and intergenerational designs to uncover sociobehavioral pathways by which acculturation may shape sleep to ultimately inform intervention efforts.


Carotid endarterectomy in octogenarians: comparison with patient characteristics and outcomes in younger patients.
Carotid endarterectomy has been shown to be of clear benefit to selected patients. However, recent trials of carotid endarterectomy versus best medical therapy have excluded octogenarians, and some authors have suggested that carotid endarterectomy would have an unfavorable cost-benefit relationship in octogenarians. We compared patients and results for carotid endarterectomy in octogenarians and younger patients. We reviewed the results for 582 primary carotid endarterectomies (90 in octogenarians and 492 in younger patients) performed in 528 patients between February 1, 1985, and January 31, 1998 (all data were collected prospectively for the most recent 301 carotid endarterectomies). Conventional surgical technique was used with general anesthesia, selective shunting, and selective patching. Main outcome measures were perioperative and late ipsilateral stroke and death. The two groups were similar with respect to indications for carotid endarterectomy and patient characteristics, except that octogenarians were more likely to have histories of congestive heart failure or hypertension and less likely to have histories of smoking or chronic lung disease. Carotid endarterectomy was performed for asymptomatic disease in 27% of the octogenarians and 33% of the younger patients (P =.31). Stenosis was >/=80% in 90% of the octogenarians and 78% of the younger patients (P =.014). Perioperative strokes, all of which were ipsilateral, occurred in one octogenarian (1.1%) and eight younger patients (1.6%, P = 1.00). No octogenarians and two younger patients died within 30 days of surgery (P = 1.00). Length of stay and direct costs associated with carotid endarterectomy were similar for octogenarians and younger patients. Late strokes occurred in two octogenarians (one ipsilateral) and four younger patients (two ipsilateral). Life table estimates of freedom from ipsilateral stroke at 2 years were 98% and 97% for octogenarians and younger patients, respectively (log-rank P =.69), and life table estimates of patient survival at 4 years were 81% and 89% for octogenarians and younger patients, respectively (P =.11). Octogenarians represented an increasing fraction of the carotid endarterectomies performed during the study period. Octogenarians selected for carotid endarterectomy were similar to younger patients with respect to indications for carotid endarterectomy and comorbidities. Early mortality, early and late neurologic outcome, complications, and resource utilization were similar for the two groups, and more than 75% of octogenarians survived 4 years after undergoing carotid endarterectomy. Cost-benefit analyses for carotid endarterectomy, which are highly sensitive to expected patient survival, might not be pertinent to individual patient situations. Intellectually intact octogenarians without unusually severe comorbidities are good candidates for and should be offered the benefits of carotid endarterectomy.


Quantum simulation of a Fermi-Hubbard model using a semiconductor quantum dot array.
Interacting fermions on a lattice can develop strong quantum correlations, which are the cause of the classical intractability of many exotic phases of matter. Current efforts are directed towards the control of artificial quantum systems that can be made to emulate the underlying Fermi-Hubbard models. Electrostatically confined conduction-band electrons define interacting quantum coherent spin and charge degrees of freedom that allow all-electrical initialization of low-entropy states and readily adhere to the Fermi-Hubbard Hamiltonian. Until now, however, the substantial electrostatic disorder of the solid state has meant that only a few attempts at emulating Fermi-Hubbard physics on solid-state platforms have been made. Here we show that for gate-defined quantum dots this disorder can be suppressed in a controlled manner. Using a semi-automated and scalable set of experimental tools, we homogeneously and independently set up the electron filling and nearest-neighbour tunnel coupling in a semiconductor quantum dot array so as to simulate a Fermi-Hubbard system. With this set-up, we realize a detailed characterization of the collective Coulomb blockade transition, which is the finite-size analogue of the interaction-driven Mott metal-to-insulator transition. As automation and device fabrication of semiconductor quantum dots continue to improve, the ideas presented here will enable the investigation of the physics of ever more complex many-body states using quantum dots.


Alcohol use and associated risk factors among female sex workers in low- and middle-income countries: A systematic review and meta-analysis.
Due to its widespread use in the sex work industry, female sex workers (FSWs) in low- and middle-income countries (LMICs) are at high risk of harmful alcohol use and associated adverse health outcomes. Factors associated with harmful alcohol use include violence, mental health problems, drug use, sexual risk behaviors and HIV/STIs. To our knowledge, there has been no quantitative synthesis of FSW alcohol use data to date. This systematic review and meta-analysis aims to provide an estimate of the prevalence of harmful alcohol use among FSWs in LMICs and to examine associations with common health and social concerns. The review protocol was registered with PROSPERO, number CRD42021237438. We searched three electronic databases for peer-reviewed, quantitative studies from inception to 24th February 2021. Studies were selected for inclusion that reported any measure of prevalence or incidence of alcohol use among FSWs aged 18 or older from countries defined as LMIC in accordance with the World Bank income groups 2019. The following study designs were included: cross-sectional survey, case-control study, cohort study, case series analysis, or experimental study with baseline measures for alcohol use. Study quality was assessed with the Center for Evidence-Based Management (CEBMa) Critical Appraisal Tool. Pooled prevalence estimates were calculated for (i) any hazardous/harmful/dependent alcohol use, (ii) harmful/dependent alcohol use only, both overall and by region and (iii) daily alcohol use. Meta-analyses examined associations between harmful alcohol use and violence, condom use, HIV/STIs, mental health problems and other drug use. In total, 435 papers were identified. After screening, 99 papers reporting on 87 unique studies with 51,904 participants from 32 LMICs met the inclusion criteria. Study designs included cross-sectional (n = 89), cohort (n = 6) and experimental (n = 4). Overall, 5 scored as high quality, 79 studies scored as moderate and 15 scored as weak quality. Twenty-nine papers reporting on 22 unique studies used validated alcohol use tools including AUDIT, CAGE and WHO CIDI. The pooled prevalence of any hazardous/harmful/dependent alcohol use was 41% (95% CI: 31-51%), and of daily alcohol use was 26% (95% CI: 17-36%). There was variation in harmful alcohol use by global region (Sub-Saharan Africa: 38%; South Asia/Central Asia/ East Asia and Pacific: 47% and Latin America and the Caribbean:44%). Harmful alcohol use was significantly associated with inconsistent condom use (pooled unadjusted RR: 1.65; 95% CI: 1.01-2.67), STIs (pooled unadjusted OR: 1.29; 95% CI 1.15-1.46); and other drug use (pooled unadjusted OR of 2.44; 95% CI 1.24-4.80), but not with HIV, violence or mental health problems. We found a high prevalence of problem alcohol use and daily alcohol use among FSWs in LMICs. Harmful drinking was associated with important HIV risk factors such as inconsistent condom use, STIs and other drug use. Major limitations included heterogeneity in tools and cut-off scores to measure alcohol use and other common risk factors, and a paucity of longitudinal studies. There is an urgent need for tailored interventions for FSWs in LMICs that address alcohol use as well as the associated sex work risk environment.


[Comparison of the molecular and genetic map of the 2B6-2B7-8 of Drosophila melanogaster X-chromosome].
Molecular and genetic data were compared for the 2B6-2B7-8 region of the Drosophila melanogaster X chromosome. This region contains the dor (deep orange) and swi (single wing) genes influencing ecdysterone-dependent gene expression. Genes which had not been identified previously by genetic methods were shown to be present in this region. Two novel loci, designated a6 and b6, were characterized in detail. Both genes are expressed throughout Drosophila embryogenesis. The product of b6 has a homology with mammalian pentraxins. This is the first Drosophila gene found to contain the pentraxin motif.


An in vitro model for dissecting distraction osteogenesis.
Distraction osteogenesis (DO) is a mechanotransduction process capable of generating viable osseous tissue by the gradual separation of osteotomized bone edges. Several variables are implicated in DO: magnitude of mechanical strain, distraction rate, and type of distracted bone. The combination of these factors acts on different types of cells inducing apoptosis, cell proliferation, and differentiation. The elucidation of the molecular mechanisms has important clinical implications because it may facilitate the use of recombinant proteins or gene therapy to accelerate bone regeneration. Previous reports have analyzed several molecules such as extracellular matrix proteins, cytokines, bone morphogenetic proteins, hormones, and angiogenic factors. Moreover, a single protein can have multifunctional roles. With such a huge number of mechanical, histologic, cellular, and molecular variables, there is the need to have a cell culture model that enables the selection of the effect of a specific strength to a single cell type at different time points and with or without cytokines. The analysis of the genetic profiling of a cell line cultured on an equibiaxial stretch device has such characteristic. Because there is a recruitment and commitment of preosteoblastic cells during bone lengthening and no previous report has focus on them, the authors used a preosteoblast MC3T3-E1 cell line to detect the early molecular effects of distraction on mesenchymal cells. By using DNA microarrays containing 15,000 clones, the authors identified several genes the expression of which was significantly up- or down-regulated. The differentially expressed genes cover a broad range of biological processes: cell growth, metabolism, morphogenesis, cell communication, response to stress, and cell death. The data reported are the first genetic portrait of stretched preosteoblasts. They can be relevant in the better understanding of the molecular mechanism of DO and as a model for comparing the effect of distraction on different cell lines and primary cultures, rate and strength of distraction, and with or without cytokines.