Hydrogel Membranes from Chitosan-Fish Gelatin-Glycerol for Biomedical Applications: Chondroitin Sulfate Incorporation Effect in Membrane Properties.

Chondroitin sulfate (ChS), chitosan (Chi), and fish gelatin (FG), which are byproducts of a fish-treatment small enterprise, were incorporated with glycerol (Gly) to obtain dense hydrogel membranes with reduced brittleness, candidates for dressing in wound healing applications. The mechanical properties of all samples were studied via Dynamic Mechanical Analysis (DMA) and tensile tests while their internal structure was characterized using Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy (ATR-FTIR) and X-ray Diffraction (XRD) instruments. Their surface morphology was analyzed by ThermoGravimetric Analysis (TGA) method, while their water permeability was estimated via Water Vapor Transmission Rate (WVTR) measurements. Wettability and degradation rate measurements were also carried out. Characterization results indicated that secondary interactions between the natural polymers and the plasticizer create the hydrogel membranes. The samples were amorphous due to the high concentration of plasticizer and the amorphous nature of the natural polymers. The integration of ChS led to decreased decomposition temperature in comparison with the glycerol-free sample, and all the materials had dense structures. Finally, the in vitro endothelial cell attachment studies indicate that the hydrogel membranes successfully support the attachment and survival of primary on the hydrogel membranes and could be appropriate for external application in wound healing applications as dressings.

CTH/MPST double ablation results in enhanced vasorelaxation and reduced blood pressure via upregulation of the eNOS/sGC pathway.

Hydrogen sulfide (H2S), a gasotransmitter with protective effects in the cardiovascular system, is endogenously generated by three main enzymatic pathways: cystathionine gamma lyase (CTH), cystathionine beta synthase (CBS) and 3-mercaptopyruvate sulfurtransferase (MPST) enzymes. CTH and MPST are the predominant sources of H2S in the heart and blood vessels, exhibiting distinct effects in the cardiovascular system. To better understand the impact of H2S in cardiovascular homeostasis, we generated a double Cth/Mpst knockout (Cth/Mpst -/- ) mouse and characterized its cardiovascular phenotype. CTH/MPST-deficient mice were viable, fertile and exhibited no gross abnormalities. Lack of both CTH and MPST did not affect the levels of CBS and H2S-degrading enzymes in the heart and the aorta. Cth/Mpst -/- mice also exhibited reduced systolic, diastolic and mean arterial blood pressure, and presented normal left ventricular structure and fraction. Aortic ring relaxation in response to exogenously applied H2S was similar between the two genotypes. Interestingly, an enhanced endothelium-dependent relaxation to acetylcholine was observed in mice in which both enzymes were deleted. This paradoxical change was associated with upregulated levels of endothelial nitric oxide synthase (eNOS) and soluble guanylate cyclase (sGC) α1 and ß1 subunits and increased NO-donor-induced vasorelaxation. Administration of a NOS-inhibitor, increased mean arterial blood pressure to a similar extent in wild-type and Cth/Mpst -/- mice. We conclude that chronic elimination of the two major H2S sources in the cardiovascular system, leads to an adaptive upregulation of eNOS/sGC signaling, revealing novel ways through which H2S affects the NO/cGMP pathway.

Recent advances in understanding and managing pituitary adenomas.

Pituitary adenomas (PAs) are common intracranial tumors. Despite their benign nature, PAs may cause a significant burden of disease, leading to either hormonal disturbances or local compression. A subset of PAs presents an aggressive behavior that remains difficult to predict, and in rare cases they metastasize. Therefore, early diagnosis and treatment are important. Advances in molecular pathology have improved the understanding of their pathogenesis and offer opportunities to identify and target novel pathways. Improved imaging and functional molecular techniques precisely detect even very small tumors and guide targeted treatment. Transsphenoidal surgery is the first-line treatment for the majority of PAs, and advances in the field of endoscopic neurosurgery offer excellent outcomes. Dopamine agonists (DAs) are traditionally the first-line treatment for prolactinomas. For patients with acromegaly, first- and second-generation somatostatin analogues (SSAs) are applied when surgery is not successful or not indicated. For Cushing's disease (CD), drugs targeting adrenal steroidogenesis, somatostatin receptors in the pituitary, and glucocorticoid receptors are used to treat hypercortisolism in patients with persistent or recurrent CD, for those who are not good surgical candidates, and as a bridge treatment for those who have undergone radiation treatment until cortisol levels are controlled. Temozolomide (TMZ) is the first-line chemotherapy for aggressive PAs, but new experimental therapies, like the anti-vascular endothelial growth factor (anti-VEGF) therapy, mechanistic target of rapamycin (mTOR) inhibitors, tyrosine kinase inhibitors, and cell cycle and checkpoint inhibitors, are now available. Radiotherapy is offered to patients with residual, recurrent, or progressive tumors. Modern techniques in radiotherapy planning and delivery are able to deliver high doses to the target tissue while sparing vital structures. As we familiarize ourselves with the biological behavior of PAs and our therapeutic armamentarium expands, the next goal is to tailor and personalize treatment to each individual patient so as to achieve the best outcome.

Translational control in neurovascular brain development.

The human brain carries out complex tasks and higher functions and is crucial for organismal survival, as it senses both intrinsic and extrinsic environments. Proper brain development relies on the orchestrated development of different precursor cells, which will give rise to the plethora of mature brain cell-types. Within this process, neuronal cells develop closely to and in coordination with vascular cells (endothelial cells (ECs), pericytes) in a bilateral communication process that relies on neuronal activity, attractive or repulsive guidance cues for both cell types and on tight-regulation of gene expression. Translational control is a master regulator of the gene-expression pathway and in particular for neuronal and ECs, it can be localized in developmentally relevant (axon growth cone, endothelial tip cell) and mature compartments (synapses, axons). Herein, we will review mechanisms of translational control relevant to brain development in neurons and ECs in health and disease.

Embryonic stem cells are devoid of macropinocytosis, a trafficking pathway for activin A in differentiated cells.

Ligand-receptor complexes formed at the plasma membrane are internalised via various endocytic pathways that influence the ultimate signalling output by regulating the selection of interaction partners by the complex along the trafficking route. We report that, in differentiated cells, activin A-receptor complexes are internalised via clathrin-mediated endocytosis (CME) and macropinocytosis (MP), whereas in human embryonic stem cells (hESCs) internalisation occurs via CME. We further show that hESCs are devoid of MP, which becomes functional upon differentiation towards endothelial cells through mesoderm mediators. Our results reveal, for the first time, that MP is an internalisation route for activin A in differentiated cells, and that MP is not active in hESCs and is induced as cells differentiate.

Acute Respiratory Distress Syndrome Induced by Parathyroid Storm.

Hypercalcemic crisis associated with the development of acute respiratory distress syndrome (ARDS) has been rarely documented in the literature. Most cases have been described in patients suffering from malignancies or renal failure with the presence of metastatic calcifications being a prominent feature. Only three cases of ARDS have been reported to date in patients with hypercalcemic crisis due to primary hyperparathyroidism (PHPT). Herein, we report a 72-year-old patient with PHPT that presented with severe hypercalcemic crisis and developed ARDS. He had mild chronic kidney disease and at presentation he had extremely high levels of serum calcium (22.5 mg/dl) and parathormone (3822 pg/ml). After receiving medical treatment for hypercalcemia and the initiation of hemodialysis, he developed ARDS with a fatal outcome, without the presence of pancreatitis, sepsis or heart failure. Although very rare, ARDS should be taken into account as a possible complication of parathyroid crisis, especially in patients with excessive calcium and parathormone levels.

Blood Pressure-Lowering Effect of Newer Antihyperglycemic Agents (SGLT-2 Inhibitors, GLP-1 Receptor Agonists, and DPP-4 Inhibitors).

The prevalence of arterial hypertension is high in patients with diabetes mellitus (DM). When DM and hypertension coexist, they constitute a dual cardiovascular threat and should be adequately controlled. Novel antihyperglycemic agents, including sodium-glucose co-transporter 2 (SGLT-2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and dipeptidyl peptidase-4 (DPP-4) inhibitors, have recently been used in the treatment of DM. Beyond their glucose-lowering effects, these drugs have shown beneficial pleiotropic cardiovascular effects, including lowering of arterial blood pressure (BP), as acknowledged in the 2019 European Society of Cardiology/European Association for the Study of Diabetes guidelines on diabetes, prediabetes, and cardiovascular diseases. The purpose of this review was to summarize the available information on the BP-reducing effects of these new glucose-lowering drug classes and provide a brief report on underlying pathophysiological mechanisms. We also compare the three drug classes (SGLT-2 inhibitors, GLP-1 RAs, and DPP-4 inhibitors) in terms of their BP-lowering effect and show that the greater BP reduction seems to be achieved with SGLT-2 inhibitors, whereas DPP-4 inhibitors have probably the mildest antihypertensive effect.

Evaluating the knowledge level, attitudes, and therapeutic approaches of Greek dentists for traumatic dental injuries.

BACKGROUND/AIM: Greek dentists are facing a new era of a globally continuous effort to improve the first-aid management and long-term treatment outcome of traumatic dental injuries (TDI). In Greece, where the basic and clinical research in the field of dental trauma has been limited until recently, assessing the attitudes and therapeutic strategies of Greek dentists for dental trauma is of great importance. The aim of this study was to evaluate the knowledge attitudes and therapeutic approaches of Greek dentists in different clinical scenarios of TDI. MATERIALS AND METHODS: A cross-sectional study was conducted among 448 dentists. A questionnaire-based survey of demographic characteristics, attitudes, and a scenario-based knowledge test, of TDI, which was used to formulate a "Dental Trauma Knowledge Score" with a 0-8 score range, was administered. Mann-Whitney U tests (for two categories variables) and Kruskal-Wallis tests (for more than two categories variables) were performed. RESULTS: The median knowledge score was 5.0 (IQR: 4-7), a level considered as "Acceptable." Knowledge scores were found to significantly differ by age group, with the younger dentists presenting the highest scores. Dentists with a self-evaluation as "Acceptable" had significantly higher scores. Most of the dentists would refer for CBCT in severe trauma cases. A significant association was found between younger ages and on awareness of the mobile application ToothSOS. Female dentists had significantly higher scores compared to males when asked about avulsion management. CONCLUSION: An acceptable level of knowledge on TDI management was revealed among dentists in Greece. Higher knowledge scores were observed among younger dentists.

Assessment of Cone-beam Computed Tomographic Referral Reasons and the Impact of Cone-beam Computed Tomographic Evaluation on Decision Treatment Planning Procedure in Endodontics.

INTRODUCTION: The aim of the present study was to assess the number of cone-beam computed tomographic (CBCT) referral cases from a private endodontic practice during a 1-year observation period and to investigate if preoperative use of CBCT imaging has an impact on the final diagnosis and decision treatment planning. METHODS: The data of the patients who attended a private endodontic office in Athens, Greece, seeking endodontic treatment from January 2018 to December 2018 were scanned to retrieve all the cases that were further referred for CBCT evaluation. Two qualified (University of Athens) and experienced (more than 10 years of daily practicing) endodontists referred the cases for CBCT imaging. All CBCT cases were evaluated to collect information about the number of cases, the reason for referral, the diagnosis before and after CBCT interpretation, and the treatment planning decision and management of each case. Descriptive statistics were used to describe the clinical characteristics of the study sample. Logistic regression was used to estimate the odds ratios and their 95% confidence intervals. RESULTS: Of a total of 1029 patients (1269 teeth) referred for endodontic treatment, 86 patients were further referred for CBCT imaging (8.35% of the patients). A total of 104 teeth (8.2% of the teeth) were scanned. The most frequent reason for CBCT referral was surgical treatment planning. In 18 of 104 (17.3%) cases, there has been a change of the initial diagnosis after CBCT interpretation. Posterior and endodontically treated teeth without lesions presented 4.35 and 6.6 times times higher odds, respectively, of having a change in the initial diagnosis after CBCT evaluation. CONCLUSIONS: A small percentage of patients referred for endodontic treatment or retreatment are further referred by specialists for CBCT imaging. CBCT scanning was considered necessary both for all surgical treatment planning cases and the evaluation of inflammatory resorptive defects.

Tissue Engineering Using Vascular Organoids From Human Pluripotent Stem Cell Derived Mural Cell Phenotypes.

Diffusion is a limiting factor in regenerating large tissues (100-200 µm) due to reduced nutrient supply and waste removal leading to low viability of the regenerating cells as neovascularization of the implant by the host is a slow process. Thus, generating prevascularized tissue engineered constructs, in which endothelial (ECs) and mural (MCs) cells, such as smooth muscle cells (SMCs), and pericytes (PCs), are preassembled into functional in vitro vessels capable of rapidly connecting to the host vasculature could overcome this obstacle. Toward this purpose, using feeder-free and low serum conditions, we developed a simple, efficient and rapid in vitro approach to induce the differentiation of human pluripotent stem cells-hPSCs (human embryonic stem cells and human induced pluripotent stem cells) to defined SMC populations (contractile and synthetic hPSC-SMCs) by extensively characterizing the cellular phenotype (expression of CD44, CD73, CD105, NG2, PDGFRß, and contractile proteins) and function of hPSC-SMCs. The latter were phenotypically and functionally stable for at least 8 passages, and could stabilize vessel formation and inhibit vessel network regression, when co-cultured with ECs in vitro. Subsequently, using a methylcellulose-based hydrogel system, we generated spheroids consisting of EC/hPSC-SMC (vascular organoids), which were extensively phenotypically characterized. Moreover, the vascular organoids served as focal starting points for the sprouting of capillary-like structures in vitro, whereas their delivery in vivo led to rapid generation of a complex functional vascular network. Finally, we investigated the vascularization potential of these vascular organoids, when embedded in hydrogels composed of defined extracellular components (collagen/fibrinogen/fibronectin) that can be used as scaffolds in tissue engineering applications. In summary, we developed a robust method for the generation of defined SMC phenotypes from hPSCs. Fabrication of vascularized tissue constructs using hPSC-SMC/EC vascular organoids embedded in chemically defined matrices is a significant step forward in tissue engineering and regenerative medicine.

Suprasellar extension independently predicts preoperative pituitary hormone deficiencies in patients with nonfunctioning pituitary macroadenomas: a single-center experience.

PURPOSE: Nonfunctioning pituitary adenomas (NFPAs) are among the commonest benign tumors of the pituitary. Hypopituitarism is frequently present at the time of diagnosis, and this has been attributed to stalk portal vessel compression and/or destruction of normal anterior pituitary cells. The aim of our study was to examine possible factors at diagnosis associated with the presence of hypopituitarism. METHODS: We retrospectively evaluated the records of patients with nonfunctioning pituitary macroadenomas from the database of our department. The inclusion criterion was the availability of imaging data regarding the extension of the lesion. RESULTS: A total of 148 patients (89 men, 60.1%) with nonfunctioning macroadenomas and available imaging data were identified. Mean age at diagnosis was 56.0 ± 14.5 years, and hypopituitarism was found in 66.2%. The maximum diameter of the adenoma, the patient's age at diagnosis, and compression of the optic chiasm were significant factors predicting the presence of hypopituitarism (OR 1.077, p = 0.006; OR 1.025, p = 0.045; and OR 2.893, p = 0.042, respectively). Suprasellar adenomas with extension to adjacent sinuses, although larger than those with only suprasellar extension, did not differ as to the degree of hypopituitarism. Moreover, in suprasellar adenomas, prolactin levels, albeit not independently, were also related to hypopituitarism (OR 1.035, p = 0.045). CONCLUSIONS: In patients with NFPAs, prognostic factors related to increased risk of hypopituitarism are age at diagnosis, size of the adenoma, and most importantly the presence of suprasellar extension. These data accentuate the necessity for surgical decompression in case of suprasellar extension, in order, apart from saving visual acuity, to possibly avoid or reverse hypopituitarism.

A questionnaire-based survey for the evaluation of the knowledge level of primary school teachers on first-aid management of traumatic dental injuries in Athens, Greece.

BACKGROUND/AIM: School teachers can play an important role in improving the prognosis of traumatized teeth of school children through immediate onsite management or on time referral to healthcare providers. In Greece where the research in the field of dental traumatology is very limited, this issue is of utmost importance. The aim of this study was to evaluate the knowledge level of Greek primary school teachers and their attitude with regard to emergency first-aid management of traumatic dental injuries (TDI) occurring in schools. MATERIAL AND METHODS: A cross-sectional descriptive study among 276 school teachers was undertaken in Athens, Greece. This was done through a two-part questionnaire-based survey including demographic characteristics, attitude, and knowledge of first-aid management of TDI. Data were analyzed using non-parametric tests for differences. Log Poisson regression analysis was used to estimate relative risks of low or high knowledge of first-aid management. RESULTS: The risk of lower knowledge score was almost double in teachers with <10 years of teaching experience and almost threefold higher in those reporting that they are not interested in being informed about dental trauma. In the case of luxation injury, 69.9% of the participants would not take any immediate action and would refer the child to a dentist. In case of permanent tooth avulsion, 52.2% knew that the tooth can be replanted in the socket, whereas only 17% believed that this should be performed within 30 minutes. Most of the participants would send the child to their own/family dentist, whereas only 4.7% would refer to an Endodontist. CONCLUSION: The knowledge of primary school teachers in Greece about first-aid management of TDI is limited. However, a clear positive association was found between knowledge of first-aid management and teaching experience. Reliable information about dental trauma may result in improving the knowledge level of Greek primary school teachers.

Medium-term Electrophysiologic Effects of a Cellularized Scaffold Implanted in Rats After Myocardial Infarction.

Background Cardiac repair strategies are being evaluated for myocardial infarctions, but the safety issues regarding their arrhythmogenic potential remain unresolved. By utilizing the in-vivo rat model, we have examined the medium-term electrophysiologic effects of a biomaterial scaffold that has been cellularized with spheroids of human adipose tissue, derived from mesenchymal stem cells and umbilical vein endothelial cells. Methods Mesenchymal stem cells, which exhibit adequate differentiation capacity, were co-cultured with umbilical vein endothelial cells and were seeded on an alginate based scaffold. After in-vitro characterization, the cellularized scaffold was implanted in (n=15) adult Wistar rats 15 min post ligation of the left coronary artery, with an equal number of animals serving as controls. Two weeks thereafter, monophasic action potentials were recorded and activation-mapping was performed with a multi-electrode array. An arrhythmia score for inducible ventricular tachyarrhythmias was calculated after programmed electrical stimulation. Results The arrhythmia score was comparable between the treated animals and controls. No differences were detected in the local conduction at the infarct border and in the voltage rise in monophasic action potential recordings. Treatment did not affect the duration of local repolarization, but tended to enhance its dispersion. Conclusions The fabricated bi-culture cellularized scaffold displayed favorable properties after in-vitro characterization. Medium-term electrophysiologic assessment after implantation in the infarcted rat myocardium revealed low arrhythmogenic potential, but the long-term effects on repolarization dispersion will require further investigation.

Preventing the development and progression of diabetic kidney disease: Where do we stand?

Diabetic kidney disease (DKD) is a major factor associated with increased cardiovascular (CV) and all-cause mortality and morbidity in patients with diabetes. Current standard therapy includes intensive management of hyperglycemia and blood pressure control with renin-angiotensin-aldosterone system (RAAS) blockers. Despite the implementation of this strategy, DKD remains the leading cause of end-stage renal disease (ESRD), mainly because of the increasing burden of diabetes mellitus. The aim of this review is to evaluate the available evidence, focusing on the benefit of current treatment in the development and progression of DKD.

Mechanical stress affects methylation pattern of GNAS isoforms and osteogenic differentiation of hAT-MSCs.

Mechanical stress exerts a substantial role on skeletal-cell renewal systems, whereas accumulating evidence suggests that epigenetic mechanisms induce changes and differential gene expression. Although the underlying mechanisms remain to be fully elucidated, our study suggests that the influence of the long term mechanical stimulation elicits epigenetic modifications controlling osteogenic differentiation of human adipose tissue multipotential stromal cells (hAT-MSCs) and contributes to an accelerating in vitro osteogenesis. GNAS imprinting gene acts as a critical regulator of osteoblast differentiation and is implicated in human genetic disorders with pathological formation of ectopic-skeletal bone. Investigating a wide variety of stimuli, we showed that daily mechanical stretch on hAT-MSCs of 7th and 15th days' intervals induced a significant down-regulation in DNA methylation status of critical CpG sites of NESP and GNASXL isoforms, accompanied by up-regulation of the corresponding gene transcripts, and osteogenic differentiation earlier in culture. Importantly, methylation analysis of differentiating bone marrow-derived MSCs revealed similar methylation patterns. Bioinformatic analysis further showed that all CpG islands exhibiting significant methylation alterations encompassed transcriptional repressor CTCF binding sites. We hereby emphasize the need to investigate the epigenetic alterations on hAT-MSCs during environmental mechanical forces and to consider how the knowledge gained through these studies may foster new means of symptoms prevention and management of ectopic bone formation in the clinic.

Individual and area-level risk factors for suicidal ideation and attempt in people with severe depression.

INTRODUCTION: Previous research has identified several risk factors that are strongly associated with suicidal behavior in patients with severe depression. However, the effects of area-level characteristics on suicidal ideation and attempt in this population remain unclear. METHODS: The Clinical Record Interactive Search (CRIS) database was used to identify 2587 patients with severe depression who received secondary mental health services from the Camden & Islington NHS Foundation Trust. Stepwise multivariable logistic regression models were used to examine associations between socio-demographic characteristics, clinical variables, area-level measures, and suicidal ideation and attempt as separate outcomes. RESULTS: Both suicidal ideation and attempts were common among this cohort of severely depressed individuals (70.5% and 37.7%, respectively). While several individual socio-demographic and clinical characteristics were associated with both outcomes, particularly past psychiatric admission (suicidal ideation: adjusted OR=2.86, 95% CI: 2.26-3.62; suicide attempt: adjusted OR=4.00, 95% CI: 3.30-4.89), neither social deprivation nor ethnic density (measured at the area-level) was associated with risk for either outcome. LIMITATIONS: Data were not collected specifically for research purposes and hence information on some potential confounders was not available. Additionally, information was restricted to individuals who accessed secondary mental health services in a defined catchment area and period. The study therefore does not take into account individuals who did not access mental health services. CONCLUSIONS: The variation in risk for suicidal ideation and attempt among severely depressed individuals is explained by differences in individual socio-demographic and clinical characteristics, most notably past psychiatric admission and substance misuse, and not by area-level measures.

Twenty-Four-Hour Urine α1 -Microglobulin as a Marker of Hypertension-Induced Renal Impairment and Its Response on Different Blood Pressure-Lowering Drugs.

The purpose of this study was to assess the role of urine α1 -microglobulin as a marker of hypertension-induced renal damage compared with estimated glomerular filtration rate, (eGFR), urine albumin, and urine albumin-to-creatinine ratio (ACR). Its response on different blood pressure (BP)-lowering drugs was also studied. Sixty never-treated hypertensive patients (65.0% men, 46.9 years, BP 141.4/94.0 mm Hg) were randomized to an irbesartan (an angiotensin receptor blocker [ARB]) or a diltiazem (a nondihydropyridine calcium channel blocker [CCB])-based regimen. Patients with diabetes or established cardiovascular, renal, or liver disease were excluded. Blood samples and 24-hour urine were analyzed at baseline and 6 months after pharmaceutical BP normalization. Serum creatinine was measured and eGFR was calculated. Urine albumin, creatinine, and α1 -microglobulin were measured and ACR was calculated. Minor changes (P=not significant [NS]) in eGFR were noted during follow-up in both groups (from 111.0 mL/min/1.73 m2 to 108.4 mL/min/1.73 m2 in the ARB group and from 111.3 mL/min/1.73 m2 to 114.0 mL/min/1.73 m2 in the CCB group). Twenty-four-hour urine indices were all significantly improved (P<.01) in the ARB group (albumin from 19.4 mg/L to 8.2 mg/L, ACR from 21.5 mg/g to 10.0 mg/g, α1 -microglobulin from 5.06 mg/L to 3.64 mg/L) but not (P=NS) in the CCB group (albumin from 15.6 mg/L to 13.9 mg/L, ACR from 17.6 mg/g to 17.1 mg/g, α1 -microglobulin from 4.94 mg/L to 4.79 mg/L). These differences between groups remained significant (P<.05) after adjusting for office heart rate and BP. α1 -Microglobulin was significantly correlated (P<.05) with albumin and ACR both at baseline (r=0.283 and 0.299, respectively) and at the end of follow-up (r=0.432 and 0.465, respectively) but not (P=NS) with eGFR. It was also significantly related (P<.05) to cardiovascular risk scores (Framingham and HeartScore) both at baseline (r=0.264 and 0.436, respectively) and at the end of follow-up (r=0.308 and 0.472, respectively). Urine α1 -microglobulin emerges as a potentially usable marker of hypertension-induced renal impairment. Its excretion rate and its response to treatment appears similar to that of albumin. Irbesartan but not diltiazem seems to be associated with reduced excretion of α1 -microglobulin in urine.

Beginning at the beginning: Recall order and the number of words to be recalled.

When participants are asked to recall a short list of words in any order that they like, they tend to initiate recall with the first list item and proceed in forward order, even when this is not a task requirement. The current research examined whether this tendency might be influenced by varying the number of items that are to be recalled. In 3 experiments, participants were presented with short lists of between 4 and 6 words and instructed to recall 1, 2, 3, or all of the items from the lists. Data were collected using immediate free recall (IFR, Experiment 1), immediate serial recall (ISR, Experiment 2), and a variant of ISR that we call ISR-free (Experiment 3), in which participants had to recall words in their correct serial positions but were free to output the words in any order. For all 3 tasks, the tendency to begin recall with the first list item occurred only when participants were required to recall as many items from the list as they could. When participants were asked to recall only 1 or 2 items, they tended to initiate recall with end-of-list items. It is argued that these findings show for the first time a manipulation that eliminates the initial tendency to recall in forward order, provide some support for recency-based accounts of IFR and help explain differences between single-response and multiple-response immediate memory tasks. (PsycINFO Database Record

Correlation of 24-Hour Blood Pressure and Heart Rate Variability to Renal Function Parameters in Hypertensive Patients. The Effect of Smoking.

Intrarenal hemodynamics depend on blood pressure (BP), heart rate (HR), and smoking. Although BP levels have been associated with kidney function, the effect of HR levels, BP, and HR variability on renal function are less well clarified. This cross-sectional study sought to determine the association of 24-hour BP and HR variability with kidney function in hypertensive patients, stratified by smoking. The study comprised 9600 nondiabetic, never-treated hypertensive individuals without evident renal impairment examined from 1985 to 2014 (aged 53.3±13.4 years, 55.3% males). The 24-hour systolic BP (SBP) and HR variability were estimated via their coefficient of variation (CV =standard deviation×100/mean value) derived from ambulatory recording. The CV SBP-to-CV HR ratio (CV R) was used as a marker of the interplay between 24-hour SBP and HR variability. Renal function was estimated via 24-hour urine creatinine clearance (CrCl), estimated glomerular filtration rate (eGFR), albumin-to-creatinine ratio (ACR), and 24-hour urine α1 -microglobulin. After adjustment for age, sex, and smoking, CV SBP was found to be weakly correlated to eGFR (r=-0.017, P=.1) and somewhat more strongly to CrCl, ACR, and α1 -microglobulin (r=-0.032, 0.072, and 0.065; P=.002, <.001 and <.001, respectively). CV HR was much better related to renal function, with stronger adjusted correlations to CrCl, eGFR, ACR, and α1 -microglobulin (r=0.185, 0.134, -0.306, -0.247; all P<.001, respectively). CV R also showed equally good adjusted correlations (r=-0.175, -0.125, 0.336, 0.262; all P<.001, respectively). Most adjusted correlations for CV HR and CV R were even better in smokers (r=0.213, 0.158, -0.332, -0.272 and -0.183, -0.118, 0.351, 0.275, respectively; all P<.001). CV HR and CV R emerge as better related to kidney function than CV SBP, especially in smokers. The correlation of CV HR and CV SBP to renal function is inverse to each other. ACR and α1 -microglobulin are better related to variability indices than CrCl and eGFR. However, causal relations cannot be proved.