[Shared Decision Making (SDM) - Patient and Physician as a Team].
The article provides an overview on Shared Decision Making (SDM), which is considered as the ideal form of physician-patient-interaction by many stakeholders of the health care system. SDM is distinguished from other models of physician-patient-interaction such as the paternalistic model and the information model. Besides the degree of acceptance of SDM in the general population and among physicians, barriers for its implementation will be reported. Indications for SDM as well as strategies and support material for its use in individual consultations will be discussed and illustrated by an oncological case study. Effects of SDM for patients as well as for clinicians will be highlighted. After background information on origins of SDM, its significance with regard to health policy in Germany is discussed.


Evidence for altered regulation of I kappa B alpha degradation in human colonic epithelial cells.
The nuclear factor kappaB (NF-kappaB) regulates the transcription of genes bearing the kappaB consensus motif. Transmigration of NF-kappaB from the cytoplasm to the nucleus is regulated by the IkappaB family of inhibitory NF-kappaB-binding proteins. Dissociation of the NF-kappaB-IkappaB complex requires both phosphorylation and degradation of IkappaBs. We demonstrate that IL-1beta induces complete IkappaB alpha degradation in Caco-2 cell lines but not in HT-29, T84, SW-480 transformed cell lines, or native colonic epithelial cells. A similar lack of IkappaB alpha degradation in HT-29 cells followed TNF-alpha and bacterial polymer stimulation. IL-1beta stimulated NF-kappaB nuclear translocation and NF-kappaB-dependent IL-1beta and IL-8 expression in both Caco-2 and HT-29 cells as assayed by electrophoretic mobility shift assay, immunofluorescence, kappaB-luciferase transfection, reverse transcriptase-PCR analysis and ELISA. In HT-29 cells stimulated with IL-1beta, IkappaB alpha was phosphorylated and when cycloheximide blocked new protein synthesis, IkappaB alpha was partially degraded. NF-kappaB cytoplasmic to nuclear transmigration was incomplete and preceded IkappaB alpha degradation in 9T-29 cells, in contrast to complete coordinated NF-kappaB nuclear translocation and IkappaB alpha degradation in Caco-2 cells. Greater sensitivity of HT-29 cells to a calpain inhibitor, as measured by IL-8 secretion, suggested enhanced resistance to IkappaB alpha proteolysis. These data show that IL-1beta induces NF-kappaB activity and expression of NF-kappaB-dependent genes in colonic epithelial cells and suggest altered regulation of IkappaB alpha degradation compared with other cell lineages, which may result in their increased responsiveness to therapeutic blockade.


A practical guide to active colloids: choosing synthetic model systems for soft matter physics research.
Synthetic active colloids that harvest energy stored in the environment and swim autonomously are a popular model system for active matter. This emerging field of research sits at the intersection of materials chemistry, soft matter physics, and engineering, and thus cross-talk among researchers from different backgrounds becomes critical yet difficult. To facilitate this interdisciplinary communication, and to help soft matter physicists with choosing the best model system for their research, we here present a tutorial review article that describes, in appropriate detail, six experimental systems of active colloids commonly found in the physics literature. For each type, we introduce their background, material synthesis and operating mechanisms and notable studies from the soft matter community, and comment on their respective advantages and limitations. In addition, the main features of each type of active colloid are summarized into two useful tables. As materials chemists and engineers, we intend for this article to serve as a practical guide, so those who are not familiar with the experimental aspects of active colloids can make more informed decisions and maximize their creativity.


Low serum IgA and airway injury in World Trade Center-exposed firefighters: a 17-year longitudinal study.
Serum IgA ≤70 mg/dL (low IgA) is associated with exacerbations of chronic obstructive pulmonary disease. The association of low IgA with longitudinal lung function is poorly defined. This study included 917 World Trade Center (WTC)-exposed firefighters with longitudinal spirometry measured between September 2001 and September 2018 and IgA measured between October 2001 and March 2002. Low IgA, compared with IgA >70 mg/dL, was associated with lower forced expiratory volume in 1 s (FEV1) % predicted in the year following 11 September 2001 (94.1% vs 98.6%, p<0.001), increased risk of FEV1/FVC <0.70 (HR 3.8, 95% CI 1.6 to 8.8) and increased antibiotic treatment (22.5/100 vs 11.6/100 person-years, p=0.002). Following WTC exposure, early IgA ≤70 mg/dL was associated with worse lung function and increased antibiotic treatment.


Interplay between N-WASP and CK2 optimizes clathrin-mediated endocytosis of EGFR.
Clathrin-mediated endocytosis (CME) involves spatially and temporally restricted molecular dynamics, to which protein kinases and actin contribute. However, whether and how these two elements merge to properly execute CME remains unknown. Here, we show that neural Wiskott-Aldrich syndrome protein (N-WASP) and casein kinase 2 (CK2) form a complex and localize to clathrin-coated vesicles. N-WASP binds to and is phosphorylated by CK2, thereby reducing the kinase activity of CK2. By contrast, N-WASP-promoted actin polymerization is decreased upon both phosphorylation and binding of CK2. Knockdown of CK2 and N-WASP, either alone or in combination, causes a similar inhibition in the initial rate of CME of epidermal growth factor receptor (EGFR) and its accumulation at the plasma membrane. Increased levels of EGFR at the cell surface can only be efficiently rescued by reconstituting the N-WASP-CK2 complex with either wild-type or phosphorylation-mimicking N-WASP and wild-type CK2. Notably, perturbation of N-WASP-CK2 complex function showed that N-WASP controls the presence of F-actin at clathrin-coated structures. In summary, the N-WASP-CK2 complex integrates in a single circuit different activities contributing to CME.


Hypertrophic Interstitial Neuropathy of the Trigeminal Nerve: Case Report and Literature Review.
Hypertrophic interstitial neuropathy (HIN) is an uncommon, non-neoplastic lesion typically affecting peripheral nerves. Cranial nerve (CN) involvement is exceedingly rare. We present a case of isolated trigeminal nerve HIN manifesting with V3 distribution neuralgia. A 50-yr-old male presented with left sided trigeminal neuralgia refractory to medical management. The patient underwent retromastoid craniectomy for possible microvascular decompression. Intra-operatively, the trigeminal nerve appeared to be focally enlarged with a sausage-like configuration. We selectively resected 1 fascicle which was predominantly involved. Histopathological examination revealed onion bulb formations composed of Schwann cells around centrally placed axons. A diagnosis of HIN was made. Postoperatively, the patient experienced complete resolution of symptoms. This is the third case of isolated trigeminal nerve HIN in the literature. We performed a selective resection in a patient presenting with trigeminal neuralgia, resulting in complete resolution of symptoms. It is reported here with intraoperative microscope images, along with a review and analysis of this topic as it related to CN.


Evaluation of a new immunoassay for therapeutic drug monitoring of tacrolimus in adult liver transplant recipients.
Therapeutic drug monitoring is necessary when using tacrolimus (FK) due to the associated side effects. The aim of this study was to compare the chemiluminescent assay (CMIA) system with the previously established Abbott IMx Tacrolimus II microparticle enzyme immunoassay (MEIA) in liver transplant recipients and evaluate its accuracy. Between March and June 2008, all blood samples from the liver transplant recipients at the hospital were tested for FK trough level using 2 different methods, CMIA and MEIA. The posttransplant time, hematocrit, and other clinical parameters during the study period were recorded. FK trough level was analyzed in 398 samples from 57 liver transplant recipients by CMIA and MEIA. The correlation in FK level between the 2 methods was excellent (r(2) = 0.941). However, the FK level was underestimated in MEIA by more than 23% in samples with an FK level of less than 3.5 ng/mL and by 6.8% in those with an FK level between 3.5 and 5 ng/mL. CMIA is superior to MEIA in measuring low FK level, allowing the FK level to be maintained at less than 5 ng/mL in selected liver transplant recipients. The effects of maintaining low levels of FK should be evaluated in liver transplant recipients.


Synthesis of [beta-(4-pyridyl-1-oxide)-L-alanine4]-angiotensin I as a potential suicide substrate for protein-tyrosine kinases.
An asymmetric synthesis of [beta-(4-pyridyl-1-oxide)-L-alanine4]-angiotensin I (1a), which is a potential suicide substrate (mechanism-based inhibitor) for protein-tyrosine kinases, has been performed. Deprotonation of 6 with n-butyllithium in THF gave the anion 7, which was alkylated with 4-(chloromethyl)pyridine-1-oxide to afford intermediate 9 as a crystalline solid. Hydrolysis of 9 afforded a mixture of 11 and 12 in a ratio of 96:4 as estimated by conversion to the diastereomeric dipeptides 13 and 14 followed by HPLC analysis. The 96:4 mixture of 11 and 12 was used in the solid phase synthesis of the target angiotensin analog 1a and its diastereomer 1b, which were separated and tested for inhibitory activity against two thymocyte protein-tyrosine kinases: p40 and p56lck. Neither peptide displayed significant inhibitory activity toward p40 and both served as weak competitive inhibitors of p56lck.


Does Motor Control Exercise Restore Normal Morphology of Lumbar Multifidus Muscle in People with Low Back Pain? - A Systematic Review.
Aberrant morphological changes in lumbar multifidus muscle (LMM) are prevalent among patients with low back pain (LBP). Motor control exercise (MCE) aims to improve the activation and coordination of deep trunk muscles (eg, LMM), which may restore normal LMM morphology and reduce LBP. However, its effects on LMM morphology have not been summarized. This review aimed to summarize evidence regarding the (1) effectiveness of MCE in altering LMM morphometry and decreasing LBP; and (2) relations between post-MCE changes in LMM morphometry and LBP/LBP-related disability. Cumulative Index to Nursing and Allied Health Literature, MEDLINE, Cochrane Central Register of Controlled Trials, the Physiotherapy Evidence Database, EMBASE and SPORTDiscus were searched from inception to 30 September 2020 to identify relevant randomized controlled trials. Two reviewers independently screened articles, extracted data, and evaluated risk of bias and quality of evidence. Four hundred and fifty-one participants across 9 trials were included in the review. Very low-quality evidence supported that 36 sessions of MCE were better than general physiotherapy in causing minimal detectable increases in LMM cross-sectional areas of patients with chronic LBP. Very low- to low-quality evidence suggested that MCE was similar to other interventions in increasing resting LMM thickness in patients with chronic LBP. Low-quality evidence substantiated that MCE was significantly better than McKenzie exercise or analgesics in increasing contracted LMM thickness in patients with chronic LBP. Low-quality evidence corroborated that MCE was not significantly better than other exercises in treating people with acute/chronic LBP. Low-quality evidence suggested no relation between post-MCE changes in LMM morphometry and LBP/LBP-related disability. Collectively, while MCE may increase LMM dimensions in patients with chronic LBP, such changes may be unrelated to clinical outcomes. This raises the question regarding the role of LMM in LBP development/progression.


[The practice guideline 'Anemia' from the Dutch College of General Practitioners; a response from the perspective of general practice medicine].
The practice guideline 'Anaemia' from the Dutch College of General Practitioners will certainly be a support for the Dutch general practitioner. The inclusion of an algorithm to make a more precise diagnosis is an experiment that needs to be evaluated in the near future. However, many general practitioners will regard it as too complex for use in daily practice and specialists will find it to be of limited use, as it does not cover all cases. Consultation between the general practitioner and the specialist will give the best answer in complicated cases. Patients who complain about tiredness or dizziness will expect their general practitioner to take a blood sample for a haemoglobin test. The general practitioner will consider the risk of false-positive test results in interpreting the patient's haemoglobin level. A few concrete remarks: the guideline does not mention that vegetarianism and a low meat intake can increase the risk of vitamin B12 deficiency, and iron suppletion is advised in premenopausal women with profuse vaginal blood loss, whereas there are several treatable disorders that may cause menorrhagia.


Steering valley-polarized emission of monolayer MoS2 sandwiched in plasmonic antennas.
Monolayer transition metal dichalcogenides have intrinsic spin-valley degrees of freedom, making it appealing to exploit valleytronic and optoelectronic applications at the nanoscale. Here, we demonstrate that a chiral plasmonic antenna consisting of two stacked gold nanorods can modulate strongly valley-polarized photoluminescence (PL) of monolayer MoS2 in a broad spectral range at room temperature. The valley-polarized PL of the MoS2 using the antenna can reach up to ~47%, with approximately three orders of PL magnitude enhancement within the plasmonic nanogap. Besides, the K and K' valleys under opposite circularly polarized light excitation exhibit different emission intensities and directivities in the far field, which can be attributed to the modulation of the valley-dependent excitons by the chiral antenna in both the excitation and emission processes. The distinct features of the ultracompact hybrid suggest potential applications for valleytronic and photonic devices, chiral quantum optics, and high-sensitivity detection.


'Smoking': use of cigarettes, cigars and blunts among Southeast Asian American youth and young adults.
Increased use of cigars has been noted among youth, as well as use of blunts (hollowed-out cigars filled with marijuana). Three types of relationships have been previously hypothesized between use of tobacco and marijuana in substance use progression. We aimed to assess these relationships for Southeast Asian American youth and adults in an urban population. We conducted in-person interviews with 164 Southeast Asians, smokers and non-smokers, in two low-income urban communities in Northern California, collecting both quantitative and qualitative data. Analysis of the quantitative data indicated distinct use patterns for blunts, cigars and other forms of marijuana in terms of associations with generation in the United States. The use of these items was also found to be related: ever having smoked cigarettes or blunts increased the risk of ever having smoked the other three items. Qualitative data found indications of all three hypothesized relationships between tobacco and marijuana for youths but not for older adults. For youths in the study, 'smoking' was found to constitute a social construct within which use of cigarettes, cigars and blunts were somewhat interchangeable. Youths in similar settings may initiate into and progress through smoking as an activity domain rather than any one of these items.


Acute leukemia incidence and patient survival among children and adults in the United States, 2001-2007.
Since 2001, the World Health Organization classification for hematopoietic and lymphoid neoplasms has provided a framework for defining acute leukemia (AL) subtypes, although few population-based studies have assessed incidence patterns and patient survival accordingly. We assessed AL incidence rates (IRs), IR ratios (IRRs), and relative survival in the United States (2001-2007) in one of the first population-based, comprehensive assessments. Most subtypes of acute myeloid leukemia (AML) and acute lymphoblastic leukemia/lymphoma (ALL/L) predominated among males, from twice higher incidence of T-cell ALL/L among males than among females (IRR = 2.20) to nearly equal IRs of acute promyelocytic leukemia (APL; IRR = 1.08). Compared with non-Hispanic whites, Hispanics had significantly higher incidence of B-cell ALL/L (IRR = 1.64) and APL (IRR = 1.28); blacks had lower IRs of nearly all AL subtypes. All ALL/L but only some AML subtypes were associated with a bimodal age pattern. Among AML subtypes, survival was highest for APL and AML with inv(16). B-cell ALL/L had more favorable survival than T-cell ALL/L among the young; the converse occurred at older ages. Limitations of cancer registry data must be acknowledged, but the distinct AL incidence and survival patterns based on the World Health Organization classification support biologic diversity that should facilitate etiologic discovery, prognostication, and treatment advances.


Geographical traceability of Italian white truffle (Tuber magnatum Pico) by the analysis of volatile organic compounds.
Results are presented that were obtained on the geographic traceability of the white truffle Tuber magnatum Pico. Solid-phase microextraction coupled to gas chromatography/mass spectrometry (SPME-GC/MS) was employed to characterize the volatile profile of T. magnatum white truffle produced in seven geographical areas of Italy. The main components of the volatile fraction were identified using SPME-GC/MS. Significant differences in the proportion of volatile constituents from truffles of different geographical areas were detected. The results suggest that, besides genetic factors, environmental conditions influence the formation of volatile organic compounds. The mass spectra of the volatile fraction of the samples were used as fingerprints to characterize the geographical origin. Next, stepwise factorial discriminant analysis afforded a limited number of characteristic fragment ions that allowed a geographical classification of the truffles studied.


To what degree patient-reported symptoms of central sensitization, kinesiophobia, disability, sleep, and life quality associated with 24-h heart rate variability and actigraphy measurements?
Chronic musculoskeletal pain is associated with decreased parasympathetic and increased sympathetic activity in the autonomic nervous system. The objective of this study was to determine the associations between objective measures of heart rate variability (a measure of autonomic nervous system function), actigraphy (a measure of activity and sleep quality), respiration rates, and subjective patient-reported outcome measures (PROMs) of central sensitization, kinesiophobia, disability, the effect of pain on sleep, and life quality. Thirty-eight study subjects were divided into two subgroups, including low symptoms of central sensitization (n = 18) and high symptoms of central sensitization (n = 20), based on patient-reported scores on the Central Sensitization Inventory (CSI). Heart rate variability (HRV) and actigraphy measurements were carried out simultaneously in 24 h measurement during wakefulness and sleep. A decrease in HRV during the first 2 h of sleep was stronger in the low CSI subgroup compared to the high CSI subgroup. Otherwise, all other HRV and actigraphy parameters and subjective measures of central sensitization, disability, kinesiophobia, the effect of pain on sleep, and quality of life showed only little associations. The high CSI subgroup reported significantly more severe symptoms of disability, kinesiophobia, sleep, and quality of life compared to the low CSI subgroup. However, there were only small and nonsignificant trend in increased sympathetic nervous system activity and poorer sleep quality on the high central sensitization subgroup. Moreover, very little differences in respiratory rates were found between the groups.


Adipose-derived Stromal Vascular Fraction Injection in a Competitive High-level Athlete Affected by Insertional Achilles Tendinopathy.
Achilles tendinopathy is one of the most common ankle and foot overuse injuries, especially among athletes. Despite this, the management of this injury lacks an evidence-based support, and patients are at risk of long-term morbidity with unpredictable clinical outcome. Recently, injective approach has gained more and more attention, and in particular the intratendinous injection with adipose-derived stromal vascular fraction. We report a case of an insertional Achilles tendinopathy in a high-level professional athlete, who was treated avoiding surgical treatment in favor of this innovative biological approach. Patient's satisfaction and return to play was prospectively evaluated for a period of 6 months of follow-up. An improvement of all functional scores was yet appreciated after 1 month from the treatment, with a crescent trend until the last 6-month follow-up. The patient was able to return to train after 34 days, and returned to match after 68 days, playing 20 minutes. She returned to the complete full game 72 days after treatment. However subsequent ultrasound and MRI evaluations failed to show any substantial changes in the characteristics of the lesion from the preoperative images. This case report opens a new window for the treatment of insertional Achilles tendinopathy in competitive athletes. The current outcome deserves further investigation with higher quality studies in order to confirm the validity of this fascinating therapeutic option.


Prediction and network modelling of self-harm through daily self-report and history of self-injury.
Self-harm is a significant public health issue, and both our understanding and ability to predict adverse outcomes are currently inadequate. The current study explores how preventative efforts could be aided through short-term prediction and modelling of risk factors for self-harm. Patients (72% female, Mage = 40.3 years) within an inpatient psychiatric facility self-reported their psychological distress, interpersonal circumstances, and wish to live and die on a daily basis during 3690 unique admissions. Hierarchical logistic regressions assessed whether daily changes in self-report and history of self-harm could predict self-harm, with machine learning used to train and test the model. To assess interrelationships between predictors, network and cross-lagged panel models were performed. Increases in a wish to die (β = 1.34) and psychological distress (β = 1.07) on a daily basis were associated with increased rates of self-harm, while a wish to die on the day prior [odds ratio (OR) 3.02] and a history of self-harm (OR 3.02) was also associated with self-harm. The model detected 77.7% of self-harm incidents (positive predictive value = 26.6%, specificity = 79.1%). Psychological distress, wish to live and die, and interpersonal factors were reciprocally related over the prior day. Short-term fluctuations in self-reported mental health may provide an indication of when an individual is at-risk of self-harm. Routine monitoring may provide useful feedback to clinical staff to reduce risk of self-harm. Modifiable risk factors identified in the current study may be targeted during interventions to minimise risk of self-harm.


Understanding Barriers to Implementing and Managing Therapeutic Diets for People Living with Chronic Kidney Disease in Remote Indigenous Communities.
Indigenous peoples in Canada, and globally, experience a disproportionate burden of chronic kidney disease (CKD) and end-stage renal disease (ESRD) ESRD patients in remote Indigenous communities might experience significant challenges in adhering to dietary guidelines. Much research has documented the poor quality, high cost, and limited availability of healthy foods in remote, Indigenous communities. Food quality and availability are poor in remote communities, indicating that persons with ESRD and CKD might have limited ability to adhere to dietary guidelines. This article reports on research designed to understand food-access barriers in remote First Nations for persons living with stage 4 and 5 CKD/ESRD. The study involved semi-structured interviews with 38 patients in remote communities. It concludes with some reflections on the significance of this issue in the context of dietetic practice.


The use of high resolution magnetic resonance on 3.0-T system in solid/multicystic ameloblastoma surgical planning. Case report.
The solid/multicystic ameloblastoma is a slowly growing, locally invasive epithelial odontogenic tumour. In 80% of cases this lesion occurs in the mandible, mainly in the posterior region, and it is characterized by the involvement of the inferior alveolar nerve. A panoramic radiograph of a 43-year-old man with chronic deep pain in the posterior area of the mandible showed a multilocular radiolucent lesion with scalloped borders in the left mandibular ramus. After the execution of a computed tomography of the jaws, to accurately determine the limits of the lesion and the relationship with the the inferior alveolar nerve, the magnetic resonance imaging was used. The spatial relationship between the lesion and the inferior alveolar nerve was defined comparing different imaging methods: panoramic radiography, computed tomography and magnetic resonance imaging. T1-weighted fast spoiled gradient-recalled echo, T1-weighted fast imaging employing steady-state acquisition, T2-weighted interactive decomposition of water and fat with echo asymmetry least-squares estimation and Diffusion weighted imaging acquisition sequences were used on a 3.0 T unit. Regarding the inferior alveolar nerve course and its spatial relationship with the mandibular lesion, magnetic resonance imaging provided more detailed spatial and structural information than other imaging methods. The described acquisition sequences allowed us to highlight the diagnostic efficacy of the magnetic resonance in the morpho-structural characterization of a maxillofacial lesion and showed the importance of this imaging method as an additional technique to the computerized tomography in the maxillofacial surgical planning, resulting in a risk reduction of the inferior alveolar nerve surgical injury. Ameloblastoma, Mandibular Nerve, Magnetic Resonance Imaging, Tomography X-Ray Computed.


Properties of Caulobacter ribonucleic acid bacteriophage phi Cb5.
The ribonucleic acid (RNA) bacteriophage phiCb5, which specifically infects only one form of the dimorphic stalked bacterium Caulobacter crescentus, has been obtained in high yield. Since the phage is extremely salt-sensitive, a purification procedure was devised which avoided contact with solutions of high ionic strength. Phage phiCb5 was studied with respect to the physical and chemical properties of both the phage and its RNA. In an electron microscope, the phage particles appear as small polyhedra, 23 nm in diameter. The phage is similar to the Escherichia coli RNA phages in that it (i) sediments at an S(20, w) of 70.6S, (ii) is composed of a single molecule of single-stranded RNA and a protein coat, (iii) contains two structural proteins, and (iv) apparently contains the genetic capacity to code for a coat protein subunit, a maturation-like protein, and an RNA polymerase. Phage phiCb5 differs from the E. coli RNA phages in (i) host specificity, (ii) salt sensitivity, and (iii) the presence of histidine, but not methionine, in the coat protein.


Heart Disease Mortality in Cancer Survivors: A Population-Based Study in Japan.
Data on the risk of cardiovascular-related mortality in patients with cancer are limited. This retrospective cohort study used data from the Osaka Cancer Registry and vital statistics in Japan between 1985 and 2013. The causes of death were investigated, and the risk of fatal heart disease was analyzed. Standardized mortality ratios were calculated to compare the risk of fatal heart disease between patients with cancer and the general population. Fine and Gray competing risk regression models were used to assess the risk of fatal heart disease among patients with cancer. In total, 682 886 patients with cancer were included in the analysis, and 335 635 patients died during the study period. Heart disease was the leading cause of noncancer deaths, with 10 686 deaths. Among the patients who died of heart disease, 5017 had ischemic heart disease, 3598 had heart failure, 356 had hypertensive disease, and 1715 had other heart diseases. The standardized mortality ratio for heart disease was 2.80 (95% CI, 2.74-2.85). The standardized mortality ratio for ischemic heart disease, heart failure, and hypertensive disease were 3.26 (95% CI, 3.17-3.35), 2.69 (95% CI, 2.60-2.78), and 5.97 (95% CI, 5.38-6.63), respectively. The risk of fatal heart disease increased over time after cancer diagnosis. Men were more likely to die of heart disease than women (subdistribution hazard ratio, 1.08 [95% CI, 1.02-1.16]). The risk of fatal heart disease among cancer survivors has decreased in recent years. Cancer survivors have a higher risk of fatal heart disease than the general population.


Comparison of different TiO2 photocatalysts for the gas phase oxidation of volatile organic compounds.
Gas-solid photocatalyzed oxidation of air contaminants is being explored more and more for possible application to decontamination, purification and deodorization of enclosed atmospheres. Indoor air is characterized by a huge number of pollutants at low concentrations. Volatile organic compounds (VOC) represent the main indoor air pollutants category, and are of great concern since some of them can act negatively on human health. Several treatments exist to reduce VOC concentrations in gaseous effluents, but photocatalytic oxidation appears to be the most appropriate regarding indoor air specific constraints. It is then necessary to develop photocatalysts, which can possibly be used in an application such as indoor air-quality improvement. In the present work, three different TiO2-based materials were studied and compared for the photocatalytic oxidation of a typical pollutant of indoor air: methyl ethyl ketone. Kinetic studies were performed for each material in dry and humid air conditions, and the Langmuir-Hinshelwood model was satisfactorily applied in almost every case. A second approach consisted of determining methyl ethyl ketone degradation by-products. Acetaldehyde was found to be the main gaseous intermediate, and could be taken into account in the general Langmuir-Hinshelwood modeling.


[Overview and therapy update Crohn's disease].
Crohn's disease (CD) is a chronic inflammatory bowel disease that can affect the entire gastrointestinal tract. The pathophysiology of CD includes a disrupted interplay of intestinal bacteria, the intestinal immune system and the intestinal surface in genetically susceptible individuals, which remains incompletely understood. Conventional therapies include steroids, but numerous advanced therapies are also available. Three tumor necrosis factor (TNF) inhibitors (infliximab, adalimumab and certolizumab pegol (Switzerland)) have been approved for MC. Additional treatment options include the interleukin (IL)-12/23 inhibitors ustekinumab and the integrin inhibitors vedolizumab. With risankizumab, a first selective IL-23 inhibitor for CD has been approved by the EMA in 2022. Moreover, the Janus kinase-1 inhibitor upadacitinib has been available for the treatment of CD in the EU since 2023. For localized CD, elective surgical resection also remains a valid option with good long-term outcomes. Perianal and fistulizing CD are difficult to treat and require a close interdisciplinary collaboration between gastroenterologists and colorectal surgeons. Surgical fistula treatment with curative intent should only be performed in well-controlled CD. The recent increase in therapeutic options in CD is encouraging, since more safe and effective therapies are now available to patients. Nevertheless, CD remains an incurable disease and so far, for all existing treatments only a fraction of patients responds to the therapy. Therefore, the development of new therapies should continue.


In vitro assessment of the biological activity of basic fibroblast growth factor released from various polymers and biomatrices.
The kinetics of controlled release of basic fibroblast growth factor (bFGF) from polymers (sutures, polycarbonate, Hydron, and Elvax), biopolymers (alginate), and biomatrices (lens capsules), and conditions for storage of bFGF (temperature, plastic type, heparin) were evaluated in vitro. Tissue culture proliferation bioassays with 3T3 fibroblasts, showed that only lens capsules with bFGF had a sustained release of bFGF for up to three weeks. The other materials released all of the 'bound' bFGF with two hours or produced an inflammatory response in vivo. Therefore, the lens tissue had the most potential for controlled long-term delivery of bFGF in vivo. These studies emphasise the importance of in vitro analysis of release kinetics of growth factors from a range of materials as a basis for potential in vivo applications.


In vitro activity and resistance profile of samatasvir, a novel NS5A replication inhibitor of hepatitis C virus.
The hepatitis C virus (HCV) nonstructural 5A (NS5A) protein is a clinically validated target for drugs designed to treat chronic HCV infection. This study evaluated the in vitro activity, selectivity, and resistance profile of a novel anti-HCV compound, samatasvir (IDX719), alone and in combination with other antiviral agents. Samatasvir was effective and selective against infectious HCV and replicons, with 50% effective concentrations (EC50s) falling within a tight range of 2 to 24 pM in genotype 1 through 5 replicons and with a 10-fold EC50 shift in the presence of 40% human serum in the genotype 1b replicon. The EC90/EC50 ratio was low (2.6). A 50% cytotoxic concentration (CC50) of >100 μM provided a selectivity index of >5 × 10(7). Resistance selection experiments (with genotype 1a replicons) and testing against replicons bearing site-directed mutations (with genotype 1a and 1b replicons) identified NS5A amino acids 28, 30, 31, 32, and 93 as potential resistance loci, suggesting that samatasvir affects NS5A function. Samatasvir demonstrated an overall additive effect when combined with interferon alfa (IFN-α), ribavirin, representative HCV protease, and nonnucleoside polymerase inhibitors or the nucleotide prodrug IDX184. Samatasvir retained full activity in the presence of HIV and hepatitis B virus (HBV) antivirals and was not cross-resistant with HCV protease, nucleotide, and nonnucleoside polymerase inhibitor classes. Thus, samatasvir is a selective low-picomolar inhibitor of HCV replication in vitro and is a promising candidate for future combination therapies with other direct-acting antiviral drugs in HCV-infected patients.


Doenjang, a Korean fermented soy food, exerts antiobesity and antioxidative activities in overweight subjects with the PPAR-γ2 C1431T polymorphism: 12-week, double-blind randomized clinical trial.
We examined the antiobesity and antioxidant effects of supplementation with doenjang, a fermented soybean paste, in overweight Koreans with the PPAR-γ2 C1431T polymorphism. Sixty overweight subjects were randomly assigned to consume either 9.8 g/day of doenjang or placebo for 12 weeks. Before and after the intervention, anthropometric and metabolic parameters, along with abdominal fat distribution and PPAR-γ2 polymorphisms, were measured. Fifty-one subjects completed the study, doenjang (n=26) and placebo (n=25) groups. Relative frequencies of the PPAR-γ2 genotypes CC, TC, and TT were 70% (n=41), 25.9% (15), and 3.4% (2), whereas those of the PPAR-γ2 alleles C and T were 81.6% and 18.4%. Visceral fat area (VFA) was significantly decreased by doenjang supplementation in subjects with a mutant T allele of PPAR-γ2 compared to those with a C allele after adjusting for age, sex, and body mass index. Plasma free fatty acid, insulin, and homeostatic model assessment insulin resistance (HOMA-IR) levels were also significantly increased in the doenjang group. Doenjang pills significantly activated radical clearance capacity (ORAC and DNA tail length) in subjects with the C allele. The catalase (CAT) activity was increased twofold in the doenjang-treated group with the C allele, but this phenomenon was reversed in those with the T allele. Doenjang-treated subjects tended to have low dietary carbohydrate and sodium intakes compared with those given placebo. We found that doenjang supplementation decreased visceral fat accumulation and aging most effectively in subjects with PPAR-γ polymorphisms. This study suggests that doenjang has antiobesity and antioxidative effects in overweight individuals with mutant alleles of PPAR-γ2.


Oscillatory vagal maneuvers produce ventricular entrainment in patients with atrial fibrillation.
Atrial fibrillation (AF) is the most common sustained dysrhythmia and appears to be an independent predictor of sudden cardiac death. The irregular ventricular rhythm contains both linear and non-linear patterns; however, it remains unclear whether vagally mediated effects are present within these patterns. We sought to determine if (1) power spectral analysis of heart rate can detect changes in vagal activity in patients with AF and (2) if the vagus modulates ventricular response during AF. Time and frequency domain parameters of heart rate variability (HRV) were calculated during forced vagal oscillations at 0.125 and 0.25 Hz imposed by neck suction and deep breathing in five AF patients. There was a significant increase in SDRRI during deep breathing/neck suction combined compared to baseline (p=0.01) and deep breathing (p=0.03). Neck suction significantly increased SDRRI compared to baseline (p=0.03). Deep breathing/neck suction significantly increased spectral power compared to baseline (p=0.02) and deep breathing (p=0.03). Neck suction significantly increased spectral power compared to baseline (p=0.03). Deep breathing did not significantly increase HRV compared to baseline (p>0.20). In addition, SDRRI and spectral power were significantly correlated during deep breathing (r=0.91, p=0.03) and deep breathing/neck suction combined (r=0.92, p=0.02). These data suggest that (1) power spectral analysis can detect vagal influences on heart rate in AF patients, and (2) oscillatory vagal maneuvers produce ventricular entrainment during AF.


Dual effect of fetal bovine serum on early development depends on stage-specific reactive oxygen species demands in pigs.
Despite the application of numerous supplements to improve in vitro culture (IVC) conditions of mammalian cells, studies regarding the effect of fetal bovine serum (FBS) on mammalian early embryogenesis, particularly in relation to redox homeostasis, are lacking. Herein, we demonstrated that early development of in vitro-produced (IVP) porcine embryos highly depends on the combination of FBS supplementation timing and embryonic reactive oxygen species (ROS) requirements. Interestingly, FBS significantly reduced intracellular ROS levels in parthenogenetically activated (PA) embryos regardless of the developmental stage. However, the beneficial effect of FBS on early embryogenesis was found only during the late phase (IVC 4-6 days) treatment group. In particular, developmental competence parameters, such as blastocyst formation rate, cellular survival, total cell number and trophectoderm proportion, were markedly increased by FBS supplementation during the late IVC phase. In addition, treatment with FBS elevated antioxidant transcript levels during the late IVC phase. In contrast, supplementation with FBS during the entire period (1-6 days) or during the early IVC phase (1-2 days) greatly impaired the developmental parameters. Consistent with the results from PA embryos, the developmental competence of in vitro fertilization (IVF) or somatic cell nuclear transfer (SCNT) embryos were markedly improved by treatment with FBS during the late IVC phase. Moreover, the embryonic stage-specific effects of FBS were reversed by the addition of an oxidant and were mimicked by treatment with an antioxidant. These findings may increase our understanding of redox-dependent early embryogenesis and contribute to the large-scale production of high-quality IVP embryos.


The effectiveness of current informative material in improving awareness and opinion of undergraduate students towards organ donation: a comparative, randomized survey study.
Despite the contribution of awareness campaigns to the rise of organ donation rates in Brazil, younger folks are subject to few awareness actions. Records on the effect of informative campaigns at improving opinion and knowledge of undergraduates about organ donation are scarce. This study aimed to assess the effect of informative material about organ donation on changes in the trend of answers to a questionnaire compared to the answers of a control group. Two randomized groups were compared, receiving the same standardized questionnaire. One group was supplied informative material on the subject, while the other was not. The questionnaire was sent to undergraduate students from two Brazilian universities. Statistical analysis was performed using Student's t-test, Chi-square test and multinomial regression tests. Adopted significance was 5%. There were 739 responses to the questionnaire. Mean age was 22 years, with a majority of women. Six of 14 questions displayed a change in the answer pattern of the experimental group compared to controls (p<0.05). Opinion on organ donation had changes in 2 of 7 analyzed questions (p<0.05). Knowledge on the subject had a shift in answer patterns in 4 of 7 questions. Regression demonstrated 3 items that were not influenced by respondents' age. There is controversy regarding the benefit of exposure to informative material. Negative changes were noted in the trust in transplantation as a safe treatment. Positive results regarding technical knowledge were obtained. Better results may be obtained by designing informative material tailored towards the student's specific concerns.


Dietary intake and body composition of prepubescent female aesthetic athletes.
The purpose of this study was to assess dietary intake and body composition of prepubescent girls competing in 3 aesthetic sports (artistic and rhythmic gymnastics and ballet). Because physiological demands of ballet training are similar to those in other aesthetic sports, ballet dancers were, for the purpose of this study, regarded as athletes. The sample consisted of 39 athletes (median age, 11 years, range 9-13) and 15 controls (median age, 11 years, range 10-12). Dietary intake was assessed using a quantitative food frequency questionnaire, and body composition, by means of anthropometry. There was no significant difference in total energy intake between groups, but there was a significant difference in energy substrate distribution. Artistic gymnasts reported significantly higher carbohydrate and lower fat contribution to total energy (57% +/- 6% and 29% +/- 5%, respectively) than rhythmic gymnasts (48% +/- 6% and 36% +/- 5%), ballet dancers (51% +/- 4% and 34% +/- 3%), or controls (51% +/- 5% and 34% +/- 4%). Relative to body weight, artistic gymnasts reported higher intake of carbohydrates (9.1 +/- 4.2 g/kg) than rhythmic gymnasts (5.6 +/- 3.1 g/kg), ballet dancers (6.6 +/- 2.5 g/kg), or controls (5.4 +/- 1.9 g/kg). Artistic gymnasts also had the lowest body-fat percentage among the groups. In all the groups mean reported daily intakes of most nutrients were higher than the current daily recommended intakes. The exceptions were dietary fiber and calcium. The proportion of athletes with an inadequate reported intake was highest for phosphorus (33%), followed by vitamin A and niacin (18%) and zinc (13%).


Essential fatty acids in mothers and their neonates.
Essential fatty acids (EFAs) and their long-chain polyenes (LCPs) are indispensable for human development and health. Because humans cannot synthesize EFAs and can only ineffectively synthesize LCPs, EFAs need to be consumed as part of the diet. Consequently, the polyunsaturated fatty acid (PUFA) status of the developing fetus depends on that of its mother, as confirmed by the positive relation between maternal PUFA consumption and neonatal PUFA status. Pregnancy is associated with a decrease in the biochemical PUFA status, and normalization after delivery is slow. This is particularly true for docosahexaenoic acid (DHA) because, on the basis of the current habitual diet, birth spacing appeared to be insufficient for the maternal DHA status to normalize completely. Because of the decrease in PUFA status during pregnancy, the neonatal PUFA status may not be optimal. This view is supported by the lower neonatal PUFA status after multiple than after single births. The neonatal PUFA status can be increased by maternal PUFA supplementation during pregnancy. For optimum results, the supplement should contain both n-6 and n-3 PUFAs. The PUFA status of preterm neonates is significantly lower than that of term infants, which is a physiologic condition. Because the neonatal DHA status correlates positively with birth weight, birth length, and head circumference, maternal DHA supplementation during pregnancy may improve the prognosis of preterm infants. In term neonates, maternal linoleic acid consumption correlates negatively with neonatal head circumference. This suggests that the ratio of n-3 to n-6 PUFAs in the maternal diet should be increased. Consumption of trans unsaturated fatty acids appeared to be associated with lower maternal and neonatal PUFA status. Therefore, it seems prudent to minimize the consumption of trans fatty acids during pregnancy.


MicroRNAs in the miR-17 and miR-15 families are downregulated in chronic kidney disease with hypertension.
In older adults (aged 70-74 years), African-Americans have 4-fold higher risk of developing hypertension-attributed end-stage renal disease (ESRD) than European-Americans. A hypothesized mechanism linking hypertension and progressive chronic kidney disease (CKD) is the innate immune response and inflammation. Persons with CKD are also more susceptible to infection. Gene expression in peripheral blood can provide a view of the innate immune activation profile. We aimed to identify differentially expressed genes, microRNAs, and pathways in peripheral blood between cases with CKD and high blood pressure under hypertension treatment versus controls without CKD and with controlled blood pressure in African Americans. Case and control pairs (N = 15x2) were selected from those without diabetes and were matched for age, sex, body mass index, APOL1 risk allele count, and hypertension medication use. High blood pressure under hypertension treatment was defined as hypertension medication use and systolic blood pressure (SBP) ≥ 145 mmHg. CKD was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2. Cases were selected from those with CKD and high blood pressure under hypertension treatment, and controls were selected from those without CKD (eGFR: 75-120 mL/min/1.73m2 and urine albumin-to-creatinine ratio < 30mg/g) and with blood pressure controlled by hypertension medication use (SBP < 135 mmHg and D(diastolic)BP < 90 mm Hg). We perform RNA sequencing of mRNA and microRNA and conducted differential expression and co-expression network analysis. Of 347 miRNAs included in the analysis, 14 were significantly associated with case status (Benjamini-Hochberg adjusted p-value [BH p] < 0.05). Of these, ten were downregulated in cases: three of each belong to the miR-17 and miR-15 families. In co-expression network analysis of miRNA, one module, which included 13 of the 14 significant miRNAs, had significant association with case status. Of the 14,488 genes and 41,739 transcripts included in the analysis, none had significant association with case status. Gene co-expression network analyses did not yield any significant associations for mRNA. We have identified 14 differentially expressed miRNAs in the peripheral blood of CKD cases with high blood pressure under hypertension treatment as compared to appropriate controls. Most of the significant miRNAs were downregulated and have critical roles in immune cell functions. Future studies are needed to replicate our findings and determine whether the downregulation of these miRNAs in immune cells may influence CKD progression or complications.


SPARCL1 Promotes Excitatory But Not Inhibitory Synapse Formation and Function Independent of Neurexins and Neuroligins.
Emerging evidence supports roles for secreted extracellular matrix proteins in boosting synaptogenesis, synaptic transmission, and synaptic plasticity. SPARCL1 (also known as Hevin), a secreted non-neuronal protein, was reported to increase synaptogenesis by simultaneously binding to presynaptic neurexin-1α and to postsynaptic neuroligin-1B, thereby catalyzing formation of trans-synaptic neurexin/neuroligin complexes. However, neurexins and neuroligins do not themselves mediate synaptogenesis, raising the question of how SPARCL1 enhances synapse formation by binding to these molecules. Moreover, it remained unclear whether SPARCL1 acts on all synapses containing neurexins and neuroligins or only on a subset of synapses, and whether it enhances synaptic transmission in addition to boosting synaptogenesis or induces silent synapses. To explore these questions, we examined the synaptic effects of SPARCL1 and their dependence on neurexins and neuroligins. Using mixed neuronal and glial cultures from neonatal mouse cortex of both sexes, we show that SPARCL1 selectively increases excitatory but not inhibitory synapse numbers, enhances excitatory but not inhibitory synaptic transmission, and augments NMDAR-mediated synaptic responses more than AMPAR-mediated synaptic responses. None of these effects were mediated by SPARCL1-binding to neurexins or neuroligins. Neurons from triple neurexin-1/2/3 or from quadruple neuroligin-1/2/3/4 conditional KO mice that lacked all neurexins or all neuroligins were fully responsive to SPARCL1. Together, our results reveal that SPARCL1 selectively boosts excitatory but not inhibitory synaptogenesis and synaptic transmission by a novel mechanism that is independent of neurexins and neuroligins.SIGNIFICANCE STATEMENT Emerging evidence supports roles for extracellular matrix proteins in boosting synapse formation and function. Previous studies demonstrated that SPARCL1, a secreted non-neuronal protein, promotes synapse formation in rodent and human neurons. However, it remained unclear whether SPARCL1 acts on all or on only a subset of synapses, induces functional or largely inactive synapses, and generates synapses by bridging presynaptic neurexins and postsynaptic neuroligins. Here, we report that SPARCL1 selectively induces excitatory synapses, increases their efficacy, and enhances their NMDAR content. Moreover, using rigorous genetic manipulations, we show that SPARCL1 does not require neurexins and neuroligins for its activity. Thus, SPARCL1 selectively boosts excitatory synaptogenesis and synaptic transmission by a novel mechanism that is independent of neurexins and neuroligins.


Increasing the potency of neutralizing single-domain antibodies by functionalization with a CD11b/CD18 binding domain.
Recombinant single domain antibodies (nanobodies) constitute an attractive alternative for the production of neutralizing therapeutic agents. Their small size warrants rapid bioavailability and fast penetration to sites of toxin uptake, but also rapid renal clearance, which negatively affects their performance. In this work, we present a new strategy to drastically improve the neutralizing potency of single domain antibodies based on their fusion to a second nanobody specific for the complement receptor CD11b/CD18 (Mac-1). These bispecific antibodies retain a small size (~30 kDa), but acquire effector functions that promote the elimination of the toxin-immunocomplexes. The principle was demonstrated in a mouse model of lethal toxicity with tetanus toxin. Three anti-tetanus toxin nanobodies were selected and characterized in terms of overlapping epitopes and inhibition of toxin binding to neuron gangliosides. Bispecific constructs of the most promising monodomain antibodies were built using anti Mac-1, CD45 and MHC II nanobodies. When co-administered with the toxin, all bispecific antibodies showed higher toxin-neutralizing capacity than the monomeric ones, but only their fusion to the anti-endocytic receptor Mac-1 nanobody allowed the mice to survive a 10-fold lethal dose. In a model of delayed neutralization of the toxin, the anti- Mac-1 bispecific antibodies outperformed a sheep anti-toxin polyclonal IgG that had shown similar neutralization potency in the co-administration experiments. This strategy should have widespread application in the development of nanobody-based neutralizing therapeutics, which can be produced economically and more safely than conventional antisera.


A difference in perception of quality of life in chronically ill children was found between parents and pediatricians.
Quality of life measurements can help to estimate the well-being of chronically ill patients, and disclose discrepancies in perception between physicians and patients that might otherwise interfere with the effectiveness of treatment. The objective was to investigate the differences in perception of quality of life between parents of chronically ill children and pediatricians. A cross-sectional study was conducted in four tertiary pediatric care centers in The Netherlands. The Health Utilities Index mark 3 (HUI3) was used by 37 pediatricians and 279 parents of patients (children aged 1 to 17 years) with cystic fibrosis admitted either in daycare or for a pneumonia, or patients with newly diagnosed acute lymphoblastic leukemia, juvenile idiopathic arthritis, or asthma. Differences in perception of quality of life between parents and pediatricians appeared to be dependent of the disease. In patients with acute lymphoblastic leukemia (OR 7.4; [95% CI 2.88-18.97], juvenile idiopathic arthritis (4.7; [95% CI 2.00-11.22]), and asthma (2.3; [95% CI 1.13-4.69]) a difference in perception was more likely to occur than in patients with cystic fibrosis admitted in daycare. At the onset of a chronic disease, the parents of pediatric patients may be misunderstood by health care professionals, especially in subjective attributes. Assessment of quality of life may contribute to better understanding between pediatricians and parents, and thus may even enhance compliance and treatment effects.


Standardization of milk mid-infrared spectrometers for the transfer and use of multiple models.
An increasing number of models are being developed to provide information from milk Fourier transform mid-infrared (FT-MIR) spectra on fine milk composition, technological properties of milk, or even cows' physiological status. In this context, and to take advantage of these existing models, the purpose of this work was to evaluate whether a spectral standardization method can enable the use of multiple equations within a network of different FT-MIR spectrometers. The piecewise direct standardization method was used, matching "slave" instruments to a common reference, the "master." The effect of standardization on network reproducibility was assessed on 66 instruments from 3 different brands by comparing the spectral variability of the slaves and the master with and without standardization. With standardization, the global Mahalanobis distance from the slave spectra to the master spectra was reduced on average from 2,655.9 to 14.3, representing a significant reduction of noninformative spectral variability. The transfer of models from instrument to instrument was tested using 3 FT-MIR models predicting (1) the quantity of daily methane emitted by dairy cows, (2) the concentration of polyunsaturated fatty acids in milk, and (3) the fresh cheese yield. The differences, in terms of root mean squared error, between master predictions and slave predictions were reduced after standardization on average from 103 to 17 g/d, from 0.0315 to 0.0045 g/100 mL of milk, and from 2.55 to 0.49 g of curd/100 g of milk, respectively. For all the models, standard deviations of predictions among all the instruments were also reduced by 5.11 times for methane, 5.01 times for polyunsaturated fatty acids, and 7.05 times for fresh cheese yield, showing an improvement of prediction reproducibility within the network. Regarding the results obtained, spectral standardization allows the transfer and use of multiple models on all instruments as well as the improvement of spectral and prediction reproducibility within the network. The method makes the models universal, thereby offering opportunities for data exchange and the creation and use of common robust models at an international level to provide more information to the dairy sector from direct analysis of milk.


Effect of synthetic ovine corticotropin-releasing factor: prolonged duration of action and biphasic response of plasma adrenocorticotropin and cortisol.
The duration of the response to synthetic ovine corticotropin-releasing factor (CRF) was studied in 13 healthy male volunteer subjects. Placebo or CRF (0.3, 3, or 30 micrograms/kg BW) was administered as an iv bolus or, in the case of the largest dose, a 30-sec infusion in single blind fashion in the late afternoon. Basal plasma immunoreactive ACTH (IR-ACTH) and IR-cortisol were 10.8 +/- 7.7 pg/ml and 5.0 +/- 1.8 micrograms/dl (mean +/- SD), respectively. IR-ACTH rose rapidly after CRF, reached an initial peak at 15 min, fell rapidly until 1.5 h after CRF, and then either fell more slowly (after the lowest dose) or rose to a second major peak at 2-3 h before falling back to baseline. After 0.3, 3, and 30 micrograms/kg CRF, IR-ACTH remained elevated for 4, 7, and 8 h, respectively. The effect on plasma IR-cortisol was similar, but more prolonged. The magnitude of both peaks of IR-ACTH, the duration of the response, and the area under the curve all appeared dose dependent. The same was true for IR-cortisol, except that the first peak height was similar after all three doses. The duration of CRF's action is probably due to its long circulating half-life. The biphasic response curve may reflect initial secretion of a readily releasable pool of ACTH, followed by later secretion of a second pool of newly synthesized and/or matured peptide. The next morning's normal circadian rise in both IR-ACTH and IR-cortisol was delayed and diminished after 3 micrograms/kg CRF; there was no increase in IR-ACTH after 30 micrograms/kg CRF, and the IR-cortisol level was diminished. Inhibition of the normal circadian rise may reflect inhibition of ACTH secretion by the sustained high plasma cortisol levels.


Changes in anxiety and depression during the COVID-19 pandemic in the European population: A meta-analysis of changes and associations with restriction policies.
Early studies of common mental disorders (CMDs) during the COVID-19 pandemic mainly report increases; however, more recent findings have been mixed. Also, studies assessing the effects of restriction measures on CMDs show varied results. The aim of this meta-analysis was to assess changes in levels of CMDs from pre-/early to during the pandemic and the effects of restriction policies in the European population. We searched for studies assessing both pre-pandemic and peri-pandemic self-reported emotional distress and symptoms of depression or anxiety among nationally/regionally representative samples in Europe and collected microdata from those studies. Estimates of corona containment index were related to changes in CMDs using random-effects meta-regression. Our search strategy resulted in findings from 15 datasets drawn from 8 European countries being included in the meta-analysis. There was no evidence of change in the prevalence of emotional distress, anxiety, or depression from before to during the pandemic; but from early pandemic periods to later periods, there were significant decreases in emotional distress and anxiety. Increased school restrictions and social distancing were associated with small increases in self-reported emotional distress. Despite initial concerns of increased emotional distress and mental illness due to the COVID-19 pandemic, the results from this meta-analysis indicate that there was a decrease in emotional distress and no change in anxiety or depression in the general population in Europe. Overall, our findings support the importance of strong governance when implementing periodic and robust restriction measures to combat the spread of COVID-19.


Aortic neck attachment failure and the AneuRx graft: incidence, treatment options, and early results.
Some investigators have reported that proximal attachment failure is a long-term complication of endovascular abdominal aortic aneurysm repair (EVAR) with the AneuRx (Medtronic, Santa Rosa, CA) device. We evaluated the need for an intervention in patients with suboptimal proximal fixation as well as the feasibility and early success of a variety of treatment strategies. From October 1999 to October 2003, we performed 365 EVARs using the AneuRx graft. At a mean follow-up of 23.7 +/- 14.8 months, 20 patients (5.5%) with suboptimal outcomes (14 with a type I endoleak, one with a type III endoleak, and 5 with an inadequate seal zone <1 cm) were considered for treatment. Characteristics of each patient''s aortic neck anatomy that could be associated with proximal attachment failure were evaluated. Eighteen patients (90%) underwent successful treatment (9 AneuRx cuffs, 6 Talent cuffs, 5 aortic stents, one redo endograft, and two surgical conversions) without major perioperative complications, one patient had a persistent type I endoleak despite endovascular treatment, and one patient refused treatment, ultimately leading to aneurysm rupture. There have been no further endoleaks or graft migrations noted since the secondary intervention at a mean follow-up of 13.9 +/- 11.8 months. In our experience, proximal attachment failure associated with the AneuRx graft is relatively uncommon and usually associated with unfavorable neck anatomy. Despite this, most cases are treatable by endovascular means. Long-term follow-up is needed to assess the ultimate frequency of these combined device reconstructions.


[Adipocytokins, obesity and development of type 2 diabetes].
Normal metabolic balance is maintained by a complex homeostatic system involving multiple tissues and organs. Acquired or inherited defects associated to environmental factors in any part of this system can lead to metabolic disorders such as the syndrome X which is presently a frequent syndrome in industrialized countries. It is characterized by a cluster of risk factors of atherosclerosis including insulin resistance, hyperinsulinemia, impaired glucose tolerance or type 2 diabetes, hypertension, dyslipidemia, and coagulation abnormalities. Its pathophysiology is likely to involve insulin resistance at the level of both skeletal muscle and visceral adipose tissue and altered fluxes of metabolic substrates between these tissues that in turn impair liver metabolism. Therapeutic intervention favours at present diet and exercise prescriptions. In addition, if necessary, specific treatment of the metabolic disorders is required. In the treatment of insulin resistance, new promising drugs are likely to be used in the next future. In this regard, adipose tissue, once thought to function primarily as a passive depot for the storage of excess lipid, is now understood to play a much more active role in metabolic regulation, secreting a variety of metabolic hormones and actively functioning to prevent deleterious lipid accumulation in other tissues and to modulate the insulin resistance. Here, we review new advances in our understanding of mechanisms leading to insulin resistance and type 2 diabetes from the perspective of the role and interactions of recently identified adipocyte-specific chemical messengers, the adipocytokines, such as adiponectin, tumor necrosis factor-alpha, interleukin 6, and resistin.


Specific detection and semiquantitation of micro-organisms in tissue by nucleic acidhybridization. I. Characterization of the method and application to model systems.
On the basis of circumstantial evidence, a number of human diseases have been postulated to result from the presence of occult infection. To investigate this problem amethod of specifically detecting and semiquantitaing trace quantities of bacterial DNA in infected tissue has been devised. It is based on RNA-DNA hybridization using radiolabeled RNAcomplementary to the DNA of the organism being sought. The characteristics of the reaction are shown to conform to those expected for RNA-DNA hybridization and the sensitivity of the method is shown to correspond to approximately one organism per 50 mammalian cells. Specificity at this level of sensitivity is sufficient to clearly distinguish between infections with Listeria monocytogenes and Erysipelothrix insidiosa. This approach may have general applicability forthe study of diseases putatively caused by chronic infection not readily demonstrable bythe usual cultural or immunologic techniques. It may also be useful for helping distinguish contaminants from pathogens when isolates are obtained from diseases tissue. Unique to this approach is the value of negative information in excluding the presenceof an organism within its limits of sensitivity.


[Intratesticular hemorrhage mimicking a tumor].
The authors describe a case of painless swelling of the testis considered, both clinically and by echography, as a tumor, and which was submitted to an orchiectomy. The histopathological examination showed an extended, not organised, intratesticular haematoma. The review of the bibliography confirms the difficulties in the pre-operative diagnosis of testis tumours.


Occult constrictive pericardial disease. Diagnosis by rapid volume expansion and correction by pericardiectomy.
Significant pericardial disease can exist without overt manifestations. Occult constrictive pericardial disease (OCPD) is identified by normal baseline hemodynamics and normal left ventricular systolic function with a characteristic response to rapid volume infusion. Following the intravenous administration of 1000 ml of normal saline over six to eight minutes, striking elevations of filling pressures are seen; however, diagnosis depends specifically upon a) the development of typical pressure pulse morphology of constriction, b) loss or reversal or respiratory variation of right atrial pressure, and c) precise diastolic equilibration of intracardiac pressures. Nineteen patients with OCPD have been identified in a five year period. Unexplained fatigue, dyspnea and chest pain was the uniform pattern of presentation. Eleven have undergone pericardiectomy resulting in a dramatic symptomatic improvement in all. Each demonstrated gross and/or microscopic evidence of pericardial disease. Recatheterization with volume infusion in five patients following pericardiectomy has revealed return to normal or near normal hemodynamics. This study describes the method for diagnosis of OCPD and recommends pericardiectomy for the management of disabling symptoms.


Large-scale analysis of yeast filamentous growth by systematic gene disruption and overexpression.
Under certain conditions of nutrient stress, the budding yeast Saccharomyces cerevisiae initiates a striking developmental transition to a filamentous form of growth, resembling developmental transitions required for virulence in closely related pathogenic fungi. In yeast, filamentous growth involves known mitogen-activated protein kinase and protein kinase A signaling modules, but the full scope of this extensive filamentous response has not been delineated. Accordingly, we have undertaken the first systematic gene disruption and overexpression analysis of yeast filamentous growth. Standard laboratory strains of yeast are nonfilamentous; thus, we constructed a unique set of reagents in the filamentous Sigma1278b strain, encompassing 3627 integrated transposon insertion alleles and 2043 overexpression constructs. Collectively, we analyzed 4528 yeast genes with these reagents and identified 487 genes conferring mutant filamentous phenotypes upon transposon insertion and/or gene overexpression. Using a fluorescent protein reporter integrated at the MUC1 locus, we further assayed each filamentous growth mutant for aberrant protein levels of the key flocculence factor Muc1p. Our results indicate a variety of genes and pathways affecting filamentous growth. In total, this filamentous growth gene set represents a wealth of yeast biology, highlighting 84 genes of uncharacterized function and an underappreciated role for the mitochondrial retrograde signaling pathway as an inhibitor of filamentous growth.


Melatonin receptors in the brain and pituitary gland of hypothalamo-pituitary disconnected Soay rams.
In Soay rams in which the pituitary gland has been surgically separated from the hypothalamus, blood prolactin concentrations vary in response to changes in photoperiod and the administration of melatonin, as in intact animals, providing evidence that melatonin acts within the pituitary gland to control prolactin secretion. In this study the presence of potentially functional melatonin receptors in the pars tuberalis and zona tuberalis (PT/ZT) of hypothalamo-pituitary disconnected (HPD) Soay rams is confirmed using both in vitro autoradiography with the ligand 2-(125I)-iodomelatonin and in situ hybridization for the melatonin receptor. There was no effect of the HPD operation on the pattern and quantity of 2-(125I)iodomelatonin binding in the brain demonstrating that this binding is independent of hypothalamic regulation. The possibility that melatonin may control prolactin secretion directly via specific receptors on lactotrophs was investigated using dual in situ hybridization with a (35S) labelled probe for the ovine melatonin receptor (Mel 1a(b)) and a Digoxigenin labelled probe for ovine prolactin. Melatonin receptor gene expression was observed in the PT/ZT in both intact and HPD rams, however, there was no colocalization with prolactin gene expression; only in the ZT was there a close association between cells expressing the melatonin receptor and lactotrophs. The results provide strong support for the view that melatonin acts via the PT/ZT to mediate the effects of photoperiod on the seasonal cycle in prolactin secretion.


Pattern of glomerular disease in Nepal: A single-center experience.
Glomerulonephritis (GN) is the most common cause of end-stage renal disease in Nepal. The aim of the present study is to determine the clinical presentation and histological pattern of GN with and without immunofluorescence (IF). It is a retrospective analysis of all GN patients with kidney biopsy at the Bir Hospital from January 2000 to April 2009. The clinical presentation, blood pressure, urine analysis, 24-h urinary protein, biochemistry, hemoglobin, antinuclear antibody, anti-ds DNA, light microscopy (LM) and IF findings of kidney biopsies were computed from hospital records. SPSS package was used for analysis. A total of 398 patients [LM 204 (51%) and LM plus IF 194 (49%] were analyzed. The mean age of the study patients was 28 ± 13.6 years (range 7-74); males comprised 52.8% and females 47.2% of the patients; 51% were between 16 and 30 years of age. The common clinical presentations included nephrotic syndrome (NS), seen in 69% of the patients, followed by acute nephritic syndrome, seen in 14.4% of the patients. Kidney biopsy without IF showed mesangial proliferative GN (MesPGN) in 21.1%, membranoproliferative GN (MPGN) in 18.6%, membranous nephropathy (MN) in 14.2%, minimal change disease (MCD) in 12.3% and focal and segmental glomerulosclerosis (FSGS) in 9.8% of the cases. With IF, MCD was seen in 23.2%, FSGS in 18%, MN in 11.9%, IgA nephropathy in 9.8%, MesPGN in 8.2%, MPGN in 4.1% and crescentic GN in 3.1% of the cases. Lupus nephritis in the cases GN was most common in young adults, with the majority presenting with NS. MCD and FSGS were the most common glomerular lesions; over-diagnosis of MesPGN and MPGN by LM could be due to exclusion of IgA nephropathy.


[Discovery of natural variant strain of HIV1 in env gene C2-V3 encoded PND of membrane protein].
To sequence and analyze the env gene C2-V3 region of proviral genome from a HIV1 isolate(WWBH7) which was obtained from Huadong Area in China. The env gene C2-V3 DNA fragment was amplified by nested-primer PCR with genome DNA of eripheral blood mononuclear cells from a confirmed HIV1 infected individual as a template. The amplified DNA fragment was inserted into pGEM-T vector. The recombinant plasmid was confirmed by restriction enzyme analysis. The inserted DNA fragment was sequenced by ABI737 autosequencer and analyzed by PROSIS software. The HIV1 strain was the derivatives of HIV1 B subtype. But there was mutation of 192 bp fragment repeated insertion at env C2-V3 region of the HIV1 strain compared with standard HIV1 B subtype such as SF2 strain. The mutation brought about a double V3 region in gene encoded PND (principal neutralizing domains). The DNA sequence was registered in GenBank (AF220245). This was a natural mutated variant strain of HIV1 whose genome showed a 192 bp repeated insertion at C2-V3 region of env gene encoded PND of membrane protein.


Prenatal DES exposure in relation to breast size.
Prenatal DES exposure has been associated with increased risk of breast cancer, but the mechanisms are unknown. Larger bra cup size has also been associated with increased breast cancer risk, although not consistently. We investigated the relation of prenatal DES exposure to mammary gland mass, as estimated by bra cup size. In 2006, 3,222 DES-exposed and 1,463 unexposed women reported their bra cup size, band size (chest circumference), and weight at age 20. Prevalence ratios (PR) were calculated for DES exposure in relation to large bra cup size, with control for year of birth and study cohort. Primary analyses were carried out among women who reported a chest circumference of no more than 32 inches because their cup size would be less influenced by fat mass. Within this group, DES-exposed women had an estimated 45% increased prevalence (95% CI 0.97-2.18) of large cup size (C or greater) relative to unexposed women. The PR was further increased among women in this group who had a body mass index of < 21 at age 20: PR = 1.83 (95% CI 1.11-3.00). The PR for high-dose DES exposure relative to no exposure was 1.67, 95% CI 1.02-2.73, whereas there was no association of bra cup size with low-dose exposure. These results provide support for the hypothesis that in utero DES exposure may result in greater mammary gland mass. Taken together with previous research on bra size and breast cancer risk, these findings suggest a mechanism for a possible association of in utero DES exposure with increased risk of breast cancer.


Genetic Screening of Anderson-Fabry Disease in Probands Referred From Multispecialty Clinics.
Anderson-Fabry disease (AFD) is a rare X-linked lysosomal storage disease, caused by defects of the alpha-galactosidase A (GLA) gene. AFD can affect the heart, brain, kidney, eye, skin, peripheral nerves, and gastrointestinal tract. Cardiology (hypertrophic cardiomyopathy), neurology (cryptogenic stroke), and nephrology (end-stage renal failure) screening studies suggest the prevalence of GLA variants is 0.62%, with diagnosis confirmation in 0.12%. This study sought to expand screening from these settings to include ophthalmology, dermatology, gastroenterology, internal medicine, pediatrics, and medical genetics to increase diagnostic yield and comprehensively evaluate organ involvement in AFD patients. In a 10-year prospective multidisciplinary, multicenter study, we expanded clinical, genetic, and biochemical screening to consecutive patients enrolled from all aforementioned clinical settings. We tested the GLA gene and α-galactosidase A activity in plasma and leukocytes. Inclusion criteria comprised phenotypical traits and absence of male-to-male transmission. Screening was extended to relatives of probands harboring GLA mutations. Of 2,034 probands fulfilling inclusion criteria, 37 (1.8%) were carriers of GLA mutations. Cascade family screening identified 60 affected relatives; clinical data were available for 4 affected obligate carriers. Activity of α-galactosidase A in plasma and leukocytes was diagnostic in male subjects, but not in female subjects. Of the 101 family members harboring mutations, 86 were affected, 10 were young healthy carriers, and 5 refused clinical evaluation. In the 86 patients, involved organs or organ systems included the heart (69%), peripheral nerves (46%), kidney (45%), eye (37%), brain (34%), skin (32%), gastrointestinal tract (31%), and auditory system (19%). Globotriaosylceramide accumulated in organ-specific and non-organ-specific cells in atypical and classic variants, respectively. Screening probands with clinically suspected AFD significantly increased diagnostic yield. The heart was the organ most commonly involved, independent of the clinical setting in which the patient was first evaluated.


Endocrine side effects of cancer immunotherapy.
Immune checkpoint inhibitors have recently become a cornerstone for the treatment of different advanced cancers. These drugs, represented mainly by monoclonal antibodies anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4), anti-programmed cell death protein-1 (PD-1) and anti-PD-1 ligand molecules (PD-L1 and L2), have the ability to reactivate the immune system against tumor cells, but can also trigger a myriad of autoimmune side effects, termed immune-related adverse events (irAEs). In particular, there are a number of endocrine-related irAEs. Current data from clinical trials show increased incidence of hypophysitis with CTLA4 inhibition and thyroid dysfunction with PD-(L)1 blockade. In addition, a few cases of type 1 diabetes mellitus and primary adrenal insufficiency have been reported. We discuss the incidence, clinical manifestations, diagnosis and management of immune-related endocrinopathies in this highly complex context of oncological patients in need of immunotherapies.


Cerebrovascular disease and late-life depression.
Depression may occur as a result of vascular disease in a significant subpopulation of elderly persons. Indirect support for vascular disease as an underlying etiology of late-life depression includes the high rate of depression in patients with vascular disease, the frequency of "silent stroke" and white-matter hyperintensities in late-life depression, and the lower frequency of positive family histories of depression in such patients. The authors evaluate the associations of late-life depression with cerebrovascular disease by reviewing the existing pathophysiological, prognosis, and treatment-outcomes studies. Findings are based on review of the current literature systematically searched in electronic databases. Review of such studies indicates a high frequency of depression in older patients with cardiovascular and cerebrovascular diseases, and the possibility of a bidirectional relationship between depression and vascular disease. Studies examining patients with vascular depression have found that such patients have different symptom profiles, greater disability, and higher risk for poorer outcomes than those with nonvascular depression. Since the vascular depression hypothesis was proposed as a conceptual framework, evidence has accumulated that patients with vascular depression may have poorer outcomes that may be related in part to executive dysfunction and consequent disability. However, the association of vascular risk factors with geriatric depression has not been consistent in the studies to-date. Although an association between a subset of late-life depression and vascular disease is clear, significant gaps remain in our understanding. Further research is needed to establish the precise linkages and interactions between vascular disease and geriatric depression.


Antioxidant vitamins and mortality in older persons: findings from the nutrition add-on study to the Medical Research Council Trial of Assessment and Management of Older People in the Community.
Older persons are at risk of both poor nutrition and increased oxidative stress. Plasma ascorbate concentrations fall with increasing age, and concentrations of other antioxidants may also be reduced. The goal was to examine the association between antioxidants and mortality in older persons. We randomly selected persons aged 75-84 y from the lists of 51 British family practitioners taking part in a randomized trial of assessment of older persons. A total of 1214 participants provided a blood sample and were interviewed about their usual diet with the use of a food-frequency questionnaire. Statistical analyses were based on deaths after a median of 4.4 y of follow-up, and hazard ratios were estimated for quintiles of dietary or blood antioxidants. We found strong inverse trends for blood ascorbate concentrations with all-cause and cardiovascular disease mortality, which were only marginally reduced after adjustment for confounders or supplement use. Those in the lowest fifth (< 17 micromol/L) had the highest mortality, whereas those in the highest fifth (> 66 micromol/L) had a mortality risk nearly half that (hazard ratio = 0.54; 95% CI: 0.34, 0.84). Similar results were found after the exclusion of those subjects with cardiovascular disease or cancer at baseline (hazard ratio = 0.51; 0.28, 0.93). In fully adjusted models, there was no evidence for an influence of alpha-tocopherol, beta-carotene, or retinol on total mortality. Dietary antioxidants measured by the food-frequency questionnaire were not associated with all-cause or cardiovascular disease mortality. Low blood vitamin C concentrations in the older British population are strongly predictive of mortality.


Tecnologias educacionais utilizadas para promoção do autocuidado de pessoas com diabetes mellitus: revisão integrativa.
To summarize the scientific productions that used educational technologies to promote self-care for people with diabetes. Integrative review carried out from October 2022 to January 2023, in the databases: LILACS; Scopus; Embase; PubMed/MEDLINE and CINAHL. The search was paired, and the sample consisted of ten articles. The levels of evidence were analyzed by the Hierarchy of Evidence for Intervention Studies, and the results were synthesized for interpretation of the findings. The educational technologies identified to promote self-care were: mobile applications, interactive platforms, print, telemonitoring, video and simulation. The focus of the contents was on the promotion of foot care, prevention of neuropathy, self-management, knowledge, and expectation of people with diabetes and prevention of acute complications. The synthesis of knowledge about educational technologies to promote self-care for people with diabetes pointed to the need for robust evidence.


Effect of exercise intensity and volume on persistence of insulin sensitivity during training cessation.
The purpose of this study was to determine whether exercise prescriptions differing in volume or intensity also differ in their ability to retain insulin sensitivity during an ensuing period of training cessation. Sedentary, overweight/obese subjects were assigned to one of three 8-mo exercise programs: 1) low volume/moderate intensity [equivalent of approximately 12 miles/wk, 1,200 kcal/wk at 40-55% peak O(2) consumption (Vo(2peak)), 200 min exercise/wk], 2) low volume/vigorous intensity ( approximately 12 miles/wk, 1,200 kcal/wk at 65-80% Vo(2peak), 125 min/wk), and 3) high volume/vigorous intensity ( approximately 20 miles/wk, 2,000 kcal/wk at 65-80% Vo(2peak), 200 min/wk). Insulin sensitivity (intravenous glucose tolerance test, S(I)) was measured when subjects were sedentary and at 16-24 h and 15 days after the final training bout. S(I) increased with training compared with the sedentary condition (P < or = 0.05) at 16-24 h with all of the exercise prescriptions. S(I) decreased to sedentary, pretraining values after 15 days of training cessation in the low-volume/vigorous-intensity group. In contrast, at 15 days S(I) was significantly elevated compared with sedentary (P < or = 0.05) in the prescriptions utilizing 200 min/wk (low volume/moderate intensity, high volume/vigorous intensity). In the high-volume/vigorous-intensity group, indexes of muscle mitochondrial density followed a pattern paralleling insulin action by being elevated at 15 days compared with pretraining; this trend was not evident in the low-volume/moderate-intensity group. These findings suggest that in overweight/obese subjects a relatively chronic persistence of enhanced insulin action may be obtained with endurance-oriented exercise training; this persistence, however, is dependent on the characteristics of the exercise training performed.


Antiphosphotyrosine immunoprecipitation of an insulin-stimulated receptor phosphatase activity from FRTL5 cells.
Phosphotyrosine-containing proteins (PYPs) from FRTL5 epithelial cells were immunoprecipitated with Sepharose-linked phosphotyrosine antibody and phosphorylated in vitro with insulin and insulin-like growth factor-I (IGF-I) receptor kinases. Insulin preactivation of the kinases resulted in increased phosphorylation of a single 175,000 mol wt PYP (p175) beside insulin and IGF-I receptors. Phosphorylation of both p175 and receptors exhibited almost identical time courses and insulin dose responses, suggesting that p175 may serve as a substrate for the insulin and IGF-I receptor kinases. Preincubation of autophosphorylated receptors with PYPs derived from insulin-stimulated cells decreased 32P-labeled receptor precipitation by antiphosphotyrosine-Sepharose by 50-70% compared to that obtained upon preincubation with PYPs from unstimulated cells. This effect was not the result of PYP-receptor competition, was observed on both in vivo and in vitro phosphorylated receptors, and was almost completely blocked by 100 microM sodium vanadate, suggesting PYP copurification of a phosphotyrosine phosphatase. No phosphatase was recovered in lysates from insulin-unstimulated cells. Maximum activity was detected after 2 min of insulin stimulation, decreasing by more than 50% after 30 min. Antiphosphotyrosine recovery of p175 from cell lysates exhibited almost identical insulin dependency. Complete recovery of both p175 and phosphatase activity was obtained after receptor immunodepletion of the extracts. Thus, a receptor phosphatase activity from insulin-stimulated FRTL5 cells is retained on an antiphosphotyrosine affinity matrix and correlates with phosphorylation of the p175 substrate for the insulin and IGF-I receptor kinases.


Finite element modelling of dense and porous piezoceramic disc hydrophones.
The acoustic characteristics of dense and porous piezoceramic disc hydrophones have been studied by finite element modelling (FEM). The FEM results are validated initially by an analytical model for a simple disc of dense piezoceramic material and then it is extended to a porous piezoceramic disc replicating a foam-reticulated sample. Axisymmetric model was used for dense piezoceramic hydrophone due its regular geometric shape. 3-dimensional model was used for the porous piezoceramics, since the unit cell model is inadequate to fully represent transducers of finite lateral dimensions. The porous PZT discs have been synthesised by foam-reticulation technique. The electrical impedance and the receiving sensitivity of the hydrophones in water are evaluated in the frequency range 10-100 kHz. The model results are compared with the experimental data. The receiving sensitivity of piezocomposite hydrophones is found to be reasonably constant over the frequency range studied. The sharp resonance peaks observed for the dense piezoceramic hydrophone has broadened to a large extent for porous piezoceramic hydrophones, indicating higher losses. The flat frequency response suggests that the 3-3 piezocomposites are useful for wide-band hydrophone applications.


Carbon-13 and phosphorus-31 nuclear magnetic resonance studies of myocardial metabolism in live guinea pigs.
Myocardial metabolism in live guinea pigs was investigated by 13C and 31P nuclear magnetic resonance (NMR) at 20.18 and 32.5 MHz, respectively. 13C NMR studies allowed monitoring of myocardial glycogen synthesis during intravenous infusion of D-[1-13C]glucose and insulin. Anoxia resulted in degradation of the labeled glycogen within 6 min and appearance of 13C label in lactic acid. Infusion of sodium [2-13C]acetate resulted in incorporation of label into the C-4, C-2, and C-3 positions of glutamate, reflecting "scrambling" of the label expected from tricarboxylic-acid-cycle activity. 31P NMR spectra of heart in live guinea pigs were obtained continuously in 20.5-sec time blocks during 3 min of anoxia, during subsequent reoxygenation, and, in separate animals, during terminal anoxia. Reversible anoxia resulted in rapid degradation of phosphocreatine (t1/2 = 54.5 +/- 2.5 sec), which recovered fully during reoxygenation. Heart inorganic phosphate increased during anoxia and returned to basal levels after oxygen was restored. During 3 min of anoxia, no significant changes in ATP levels or pH were detected.


The health outcomes of human offspring conceived by assisted reproductive technologies (ART).
Concerns have been raised about the health and development of children conceived by assisted reproductive technologies (ART) since 1978. Controversially, ART has been linked with adverse obstetric and perinatal outcomes, an increased risk of birth defects, cancers, and growth and development disorders. Emerging evidence suggests that ART treatment may also predispose individuals to an increased risk of chronic ageing related diseases such as obesity, type 2 diabetes and cardiovascular disease. This review will summarize the available evidence on the short-term and long-term health outcomes of ART singletons, as multiple pregnancies after multiple embryos transfer, are associated with low birth weight and preterm delivery, which can separately increase risk of adverse postnatal outcomes, and impact long-term health. We will also examine the potential factors that may contribute to these health risks, and discuss underlying mechanisms, including epigenetic changes that may occur during the preimplantation period and reprogram development in utero, and adult health, later in life. Lastly, this review will consider the future directions with the view to optimize the long-term health of ART children.


Lung function decline in laboratory animal workers: the role of sensitisation and exposure.
Little is known about the relation between allergic sensitisation and subsequent long term lung function changes in working populations exposed to sensitising agents. To investigate whether exposure and work related sensitisation to laboratory animals are associated with lung function decline. The relation between exposure and sensitisation to laboratory animal allergens and changes in lung function was investigated in a longitudinal study (median follow up 2.0 years) among 319 laboratory animal workers. Subjects who had been working with laboratory animals for less than 4 years (n = 102) were analysed separately, since an earlier cross sectional analysis had suggested a strong healthy worker effect in more experienced workers. In multiple regression analyses both sensitisation and exposure appeared to contribute independently to lung function decline in subjects who had been working with laboratory animals for less than 4 years, adjusting for gender, age, smoking, and atopy. Lung function decline was most pronounced in sensitised subjects who continued to be in contact with the animals to which they were sensitised, with estimated average excess declines in FEV1, FVC, and MMEF of 83 ml/y (p < 0.05), 148 ml/y (p < 0.01), and 7 ml/s/y (p = 0.9). We conclude that exposure to laboratory animals is a significant risk factor for accelerated lung function decline, and that sensitised workers are especially at risk.


Comprehensive Phytochemical Analysis and Bioactivity Evaluation of Padina boergesenii: Unveiling Its Prospects as a Promising Cosmetic Component.
Marine macroalgae, such as Padina boergesenii, are gaining recognition in the cosmetics industry as valuable sources of natural bioactive compounds. This study aimed to investigate the biochemical profile of P. boergesenii and evaluate its potential as a cosmetic ingredient. Fourier-transform infrared (FTIR), gas chromatography-mass spectrometry (GCMS), and high-resolution liquid chromatography-mass spectrometry quadrupole time-of-flight (HRLCMS QTOF) analyses were employed to assess the functional groups, phycocompounds, and beneficial compounds present in P. boergesenii. Pigment estimation, total phenol and protein content determination, DPPH antioxidant analysis, and tyrosinase inhibition assay were conducted to evaluate the extracts' ability to counteract oxidative stress and address hyperpigmentation concerns. Elemental composition and amino acid quantification were determined using inductively coupled plasma atomic emission spectrometry (ICP-AES) and HRLCMS, respectively. FTIR spectroscopy confirmed diverse functional groups, including halo compounds, alcohols, esters, amines, and acids. GCMS analysis identified moisturizing, conditioning, and anti-aging compounds such as long-chain fatty alcohols, fatty esters, fatty acids, and hydrocarbon derivatives. HRLCMS QTOF analysis revealed phenolic compounds, fatty acid derivatives, peptides, terpenoids, and amino acids with antioxidant, anti-inflammatory, and skin-nourishing properties. Elemental analysis indicated varying concentrations of elements, with silicon (Si) being the most abundant and copper (Cu) being the least abundant. The total phenol content was 86.50 µg/mL, suggesting the presence of antioxidants. The total protein content was 113.72 µg/mL, indicating nourishing and rejuvenating effects. The ethanolic extract exhibited an IC50 value of 36.75 μg/mL in the DPPH assay, indicating significant antioxidant activity. The methanolic extract showed an IC50 value of 42.784 μg/mL. Furthermore, P. boergesenii extracts demonstrated 62.14% inhibition of tyrosinase activity. This comprehensive analysis underscores the potential of P. boergesenii as an effective cosmetic ingredient for enhancing skin health. Given the increasing use of seaweed-based bioactive components in cosmetics, further exploration of P. boergesenii's potential in the cosmetics industry is warranted to leverage its valuable properties.


Epinephrine injected into the basolateral amygdala affects anxiety-like behavior and memory performance in stressed rats.
The amygdala is known to mediate in moderating the impacts of emotional arousal and stress on memory. According to a growing body of research, the basolateral amygdala (BLA) is an important locus for integrating neuromodulator influences coordinating the retrieval of different types of memory and anxiety. This study aimed to investigate how the epinephrine in the BLA affects hippocampal fear memory, anxiety, and plasticity in control and stressed rats. For four days, male Wistar rats were exposed to electrical foot-shock stress. Animals received bilateral micro-injections of either vehicle or epinephrine (1 µg/side) into the BLA over four days (5 min before foot-shock stress). Behavioral characteristics (fear memory and anxiety-like behavior), histological features and electrophysiological parameters were investigated. Epinephrine injection into BLA resulted in a considerable impairment of fear memory in stressed rats. On the other hand, epinephrine effectively affected fear memory in control rats. Under stress conditions, epinephrine in the BLA is thought to increase anxiety-like behaviors. Treatment with epinephrine significantly increases the slope of fEPSP in the CA1 region of the hippocampus in the control and stress rats. In different groups, foot-shock stress had no effect on the apical and basal dendritic length in the CA1 region of the hippocampus. These results indicate that activating adrenergic receptors diminish fear memory and anxiety-like behaviors in the foot-shock stress, which this impact is independent of CA1 long-term potentiation induction.