Tight Control Research Articles

Single cell dual-omic atlas of the human developing retina

The development of the retina is under tight temporal and spatial control. To gain insights into the molecular basis of this process, we generate a single-nuclei dual-omic atlas of the human developing retina with approximately 220,000 nuclei from 14 human embryos and fetuses aged between 8 and 23-weeks post-conception with matched macular and peripheral tissues. This atlas captures all major cell classes in the retina, along with a large proportion of progenitors and cell-type-specific precursors. Cell trajectory analysis reveals a transition from continuous progression in early progenitors to a hierarchical development during the later stages of cell type specification. Both known and unrecorded candidate transcription factors, along with gene regulatory networks that drive the transitions of various cell fates, are identified. Comparisons between the macular and peripheral retinae indicate a largely consistent yet distinct developmental pattern. This atlas offers unparalleled resolution into the transcriptional and chromatin accessibility landscapes during development, providing an invaluable resource for deeper insights into retinal development and associated diseases.

Direct measurement of self-diffusiophoretic force generated by active colloids of different patch coverage using optical tweezers

Hypothesis: Synthetic micro/nanomotors are gaining extensive attention for various biomedical applications (especially in drug delivery) due to their ability to mimic the motion of biological micro/nanoscale swimmers. The feasibility of these applications relies on tight control of propulsion speed, direction, and type of motion (translation, circular, etc.) along with the exerted self-propulsive force. We propose to exploit the variation of both self-propulsion speed and force of active colloids with different patch coverages (with and without supporting layer) for engineering diffusiophoretic micro/nanomotors.Experiments: The microswimmers were designed at various patch coverages (10°, 30°, and 90°) with (Ti/Pt) and without (Pt) an adhesion layer for the catalytic patch through glancing angle metal deposition (GLAD) technique. Mean-square displacement (MSD) analysis was performed to obtain the self-propulsion parameters like speed and angular speed. Using optical tweezers (OT), the self-propulsive force was measured from the force power spectral density.Findings: The findings of our experiments suggest the non-requirement of any adhesion layer preceding the catalyst deposition since the Pt 10° colloidal batch had the maximal self-propulsion speed (4.61±0.3μm/s) and force (345±57fN) for 5% w/v H2O2 fuel concentration. Moreover, the self-propulsion speed and force decreased with increasing patch size, contrary to theoretical estimates. Also, the self-propulsive force obtained from MSD is 2 to 4 times lower in magnitude than the OT based force values. We believe that the self-propelling motion of the micromotors is possibly hindered due to interactions with the surface of the quartz cuvette during the optical microscopic analysis. Further, the MSD is limited to the self-propulsive motion in two dimensions. On the other hand, OT based force measurement involve trapping the particles in the bulk of the solution entirely avoiding the particle–substrate interactions. Hence, OT based force measurements are better than the propulsion velocity based stokes drag force estimates. We believe that this study can lay the foundation in designing efficient micro/nanomotors for translational biomedical applications.

Autoinhibition and relief mechanisms for MICAL monooxygenases in F-actin disassembly

MICAL proteins represent a unique family of actin regulators crucial for synapse development, membrane trafficking, and cytokinesis. Unlike classical actin regulators, MICALs catalyze the oxidation of specific residues within actin filaments to induce robust filament disassembly. The potent activity of MICALs requires tight control to prevent extensive damage to actin cytoskeleton. However, the molecular mechanism governing MICALs’ activity regulation remains elusive. Here, we report the cryo-EM structure of MICAL1 in the autoinhibited state, unveiling a head-to-tail interaction that allosterically blocks enzymatic activity. The structure also reveals the assembly of C-terminal domains via a tripartite interdomain interaction, stabilizing the inhibitory conformation of the RBD. Our structural, biochemical, and cellular analyses elucidate a multi-step mechanism to relieve MICAL1 autoinhibition in response to the dual-binding of two Rab effectors, revealing its intricate activity regulation mechanisms. Furthermore, our mutagenesis study of MICAL3 suggests the conserved autoinhibition and relief mechanisms among MICALs.

MATERIAL PROPERTIES OF THE EMBRYONIC SMALL INTESTINE DURING BUCKLING MORPHOGENESIS.

During embryonic development, tissues undergo dramatic deformations as functional morphologies are stereotypically sculpted from simple rudiments. Formation of healthy, functional organs therefore requires tight control over the material properties of embryonic tissues during development, yet the biological basis of embryonic tissue mechanics is poorly understood. The present study investigates the mechanics of the embryonic small intestine, a tissue that is compactly organized in the body cavity by a mechanical instability during development, wherein differential elongation rates between the intestinal tube and its attached mesentery create compressive forces that buckle the tube into loops with wavelength and curvature that are tightly conserved for a given species. Focusing on the intestinal tube, we combined micromechanical testing with histologic analyses and enzymatic degradation experiments to conclude that elastic fibers closely associated with intestinal smooth muscle layers are responsible for the bending stiffness of the tube, and for establishing its pronounced mechanical anisotropy. These findings provide insights into the developmental role of elastic fibers in controlling tissue stiffness, and raise new questions on the physiologic function of elastic fibers in the intestine during adulthood.

Central Bank Operations Under Foreign Exchange Accumulation: The Case of the Macedonian Central Bank (2005–2022)

ABSTRACT The present article analyses the balance sheet composition and the evolution of the operational framework of the Macedonian central bank. It shows that the compensating movements on its balance sheet could not be attributed exclusively to domestic liquidity management operations, as in the absence of substantial foreign currency inflows, the central bank has increased foreign reserves through the proceeds arising from the issuance of government bonds denominated in foreign currency on international financial markets. Despite retaining some of the characteristics of a currency board, the absence of a strict commitment to such a regime has allowed the central bank to employ a range of instruments of domestic liquidity management and to maintain relatively tight control over its policy rate. The level of the policy rate under a rigidly fixed exchange rate parity meant to be sustained over time, would however continue to depend on the ability of the authorities to ensure a sufficient level of foreign exchange reserves.

Chaperone BiP controls ER stress sensor Ire1 through interactions with its oligomers.

The complex multistep activation cascade of Ire1 involves changes in the Ire1 conformation and oligomeric state. Ire1 activation enhances ER folding capacity, in part by overexpressing the ER Hsp70 molecular chaperone BiP; in turn, BiP provides tight negative control of Ire1 activation. This study demonstrates that BiP regulates Ire1 activation through a direct interaction with Ire1 oligomers. Particularly, we demonstrated that the binding of Ire1 luminal domain (LD) to unfolded protein substrates not only trigger conformational changes in Ire1-LD that favour the formation of Ire1-LD oligomers but also exposes BiP binding motifs, enabling the molecular chaperone BiP to directly bind to Ire1-LD in an ATP-dependent manner. These transient interactions between BiP and two short motifs in the disordered region of Ire1-LD are reminiscent of interactions between clathrin and another Hsp70, cytoplasmic Hsc70. BiP binding to substrate-bound Ire1-LD oligomers enables unfolded protein substrates and BiP to synergistically and dynamically control Ire1-LD oligomerisation, helping to return Ire1 to its deactivated state when an ER stress response is no longer required.

Hygrothermal Performance of Enclosures in a Storage Room and Energy Efficiency in Environmental Control

ABSTRACT This study aims to provide energy-efficient strategies for collections care in the face of financial and environmental challenges. Focusing on paper-based enclosures in storage rooms, the research proposes strategies to enhance energy efficiency by relaxing tight environmental controls. The five-stage process began with a standard test of hygrothermal properties and buffering capacity of the enclosures. In the second stage, a computer model was developed using the first stage results. This model was used in a series of specially designed tests simulating the transient heat, air, and moisture transfer between the room and enclosure to determine an acceptable room environment in which the enclosure conditions could meet collections care standards. The modelling results were used, in the third stage, to develop an AI model that predicted the enclosure conditions using room temperature and relative humidity (RH) inputs. In the final stage, a model for energy consumption of air-conditioning system operations was developed to predict across various control accuracies. Results indicate that the tight maintenance of room RH levels can be relaxed from 47–53% to 33–65%, with a corresponding reduction in energy consumption of approximately 16–18%. This relaxation, while maintaining enclosure conditions in line with conservation standards, was demonstrated through a simulation case at the National Library of Scotland. This study underscores the broader applicability of the developed procedure, asserting its relevance for cultural institutions seeking energy-saving potential through customized enclosure models.

A Retrospective Analysis of Pinnaplasty Outcomes: The Welsh Experience.

Prominent ears (PEs) are the most frequent congenital external ear deformity, occurring in ∼5% of the population. Although the deformity does not usually cause functional difficulties, it can significantly affect the patient's psychological and social health. The authors aim to present the Welsh experience of pinnaplasty, reviewing our outcomes and complications. A retrospective cross-sectional study was performed of all patients undergoing pinnaplasty in Morriston Hospital, Swansea, Wales. We represent the tertiary plastic surgery referral unit across Wales. We included all patients undergoing pinnaplasty between 2015 and 2022 inclusive. We excluded patients undergoing revision procedures or those who had no follow-up. Over the 7-year period, 236 pinnaplasties were performed and 203 were included in the analysis. Ninety-six percent of cases were performed using a cartilage-sparing approach, which represents the mainstay in our unit. The mean follow-up length for our cases was 12 months. Revision procedures were required in 4% of cases. Three hematomas (1.5%) and one (0.5%) wound dehiscence due to infection were recorded and required a return to the operating room. Suture extrusion was noted in 5% of cases (10 patients); 4.5% (9) cases were affected by either hypertrophic or keloid scarring. Across the United Kingdom, cosmetic procedures have come under scrutiny, namely, because of a difficult economic climate. In the era of tight fiscal control in health care, it is pertinent to analyze the outcomes and performance metrics of our operations regularly, thus aiding in the development of an established evidence base to advocate for our respective patients.

Zygotic spindle orientation defines cleavage pattern and nuclear status of human embryos

The first embryonic division represents a starting point for the development of a new individual. In many species, tight control over the first embryonic division ensures its accuracy. However, the first division in humans is often erroneous and can impair embryo development. To delineate the spatiotemporal organization of the first mitotic division typical for normal human embryo development, we systematically analyzed a unique timelapse dataset of 300 IVF embryos that developed into healthy newborns. The zygotic division pattern of these best-quality embryos was compared to their siblings that failed to implant or arrested during cleavage stage. We show that division at the right angle to the juxtaposed pronuclei is preferential and supports faithful zygotic division. Alternative configurations of the first mitosis are associated with reduced clustering of nucleoli and multinucleation at the 2-cell stage, which are more common in women of advanced age. Collectively, these data imply that orientation of the first division predisposes human embryos to genetic (in)stability and may contribute to aneuploidy and age-related infertility.

Metal-Organic Framework on Fullerene (MOFOF) as a Hierarchical Composite by the Integration of Coordination Chemistry and Supramolecular Chemistry.

There is a synergy between coordination chemistry and supramolecular chemistry that has led to the development of innovative hierarchical composites with diverse functionalities. Here, we present a novel approach for the synthesis and characterization of a metal-organic framework on fullerene (MOFOF) composites, achieved through the integration of coordination chemistry and supramolecular chemistry principles. The hierarchical nature of the MOFOF harnesses the inherent properties of metal-organic frameworks and fullerenes. The two-step synthesis procedure involves controlled assembly of fullerenes as tube-like nanostructures (fullerene nanotube: FNT), their surface functionalization, and the on-surface growth of the MOF (in this case, ZIF-67). The method permits the precise tuning of morphology, effective distribution of MOF-on-FNT, and tight compositional control. The materials were comprehensively structurally characterized using electron microscopy, spectroscopic techniques, and other methods to elucidate the unique features and interactions within the MOFOF composites. The main findings reveal that the novel synthesis and characterization of MOFOF composites demonstrate the successful integration of coordination chemistry and supramolecular chemistry for the designing and fabricating of advanced hierarchical composites with tailored properties, including micro- and mesopore channels, interfacial facets, and defect sites. These properties are expected to lead to numerous potential applications such as gas storage and separation, catalysis, sensing, energy storage, and environmental remediation. However, only the capability of acid vapor sensing was tested and is described here.

Local and systemic transcriptome and spliceome reprogramming induced by the root-knot nematode Meloidogyne incognita in tomato.

Root-knot nematodes (Meloidogyne spp.) are widely spread root parasites that infect thousands of vascular plant species. These highly polyphagous nematodes engage in sophisticated interactions with host plants that results in the formation of knot-like structures known as galls whose ontogeny remains largely unknown. Here, we determined transcriptome changes and alternative splicing variants induced by Megalaima incognita in galls and neighboring root cells at two distinct infective stages. M. incognita induced substantial transcriptome changes in tomato roots both locally in galls and systemically in neighboring cells. A considerable parallel regulation of gene expression in galls and neighboring cells were detected, indicative of effective intercellular communications exemplified by suppression of basal defense responses particularly during the early stage of infection. The transcriptome analysis also revealed that M. incognita exerts a tight control over the cell cycle process as a whole that results in an increase of ploidy levels in the feeding sites and accelerated mitotic activity of the gall cells. Alternative splicing analysis indicated that M. incognita significantly modulates pre-mRNA splicing as a total of 9064 differentially spliced events from 2898 genes were identified where intron retention and exon skipping events were largely suppressed. Furthermore, a number of differentially spliced events were functionally validated using transgenic hairy root system and found to impact gall formation and nematode egg mass production. Together, our data provide unprecedented insights into the transcriptome and spliceome reprogramming induced by M. incognita in tomato with respect to gall ontogeny and nematode parasitism.

Membrane vectorial lipidomic features of coral host cells’ plasma membrane and lipid profiles of their endosymbionts Cladocopium

The symbiotic relationships between coral animal host and autotrophic dinoflagellates are based on the mutual exchange and tight control of nutritional inputs supporting successful growth. The corals Sinularia heterospiculata and Acropora aspera were cultivated using a flow-through circulation system supplying seawater during cold and warm seasons of the year, then sorted into host cells and symbionts and subjected to phylogenetic, morphological, and advanced lipid analyses. Here we show, that the lipidomes of the dinoflagellates Cladocopium C1/C3 and acroporide-specific Cladocopium hosted by the corals, are determined by lipidomic features of different thermosensitivity and unique betaine- and phospholipid molecular species. Phosphatidylserines and ceramiaminoethylphosphonates are not detected in the symbionts and predominantly localized on the inner leaflet of the S. heterospiculata host plasma membrane. The transmembrane distribution of phosphatidylethanolamines of S. heterospiculata host changes during different seasons of the year, possibly contributing to mutualistic nutritional exchange across this membrane complex to provide the host with a secure adaptive mechanism and ecological benefits.

Low-cost, portable, easy-to-use kiosks to facilitate home-cage testing of nonhuman primates during vision-based behavioral tasks.

Nonhuman primates (NHPs), especially rhesus macaques, have significantly contributed to our understanding of the neural computations underlying human vision. Besides the established homologies in the visual brain areas between these species and our ability to probe detailed neural mechanisms in monkeys at multiple scales, NHPs' ability to perform human-like visual behavior makes them an extremely appealing animal model of human vision. Traditionally, such behavioral studies have been conducted in controlled laboratory settings, offering experimenters tight control over variables like luminance, eye movements, and auditory interference. However, in-lab experiments have several constraints, including limited experimental time, the need for dedicated human experimenters, additional lab space requirements, invasive surgeries for headpost implants, and extra time and training for chairing and head restraints. To overcome these limitations, we propose adopting home-cage behavioral training and testing of NHPs, enabling the administration of many vision-based behavioral tasks simultaneously across multiple monkeys with reduced human personnel requirements, no NHP head restraint, and monkeys' unrestricted access to experiments. In this article, we present a portable, low-cost, easy-to-use kiosk system developed to conduct home-cage vision-based behavioral tasks in NHPs. We provide details of its operation and build to enable more open-source development of this technology. Furthermore, we present validation results using behavioral measurements performed in the lab and in NHP home cages, demonstrating the system's reliability and potential to enhance the efficiency and flexibility of NHP behavioral research.NEW & NOTEWORTHY Training nonhuman primates (NHPs) for vision-based behavioral tasks in a laboratory setting is a time-consuming process and comes with many limitations. To overcome these challenges, we have developed an affordable, open-source, wireless, touchscreen training system that can be placed in the NHPs' housing environment. This system enables NHPs to work at their own pace. It provides a platform to implement continuous behavioral training protocols without major experimenter intervention and eliminates the need for other standard practices like NHP chair training, collar placement, and head restraints. Hence, these kiosks ultimately contribute to animal welfare and therefore better-quality neuroscience in the long run. In addition, NHPs quickly learn complex behavioral tasks using this system, making it a promising tool for wireless electrophysiological research in naturalistic, unrestricted environments to probe the relation between brain and behavior.

When Usual Care Is Not So Usual: Protocol Violations and Generalizability in a Treat-to-Target Strategy Trial in Patients With Axial Spondyloarthritis.

The objective of this study was to evaluate the impact of protocol violations in the treat-to-target group in the Tight Control in Spondyloarthritis (TICOSPA) trial and to compare the proportion of patients optimally treated according to the Assessment of Spondyloarthritis International Society (ASAS)/EULAR 2016 recommendations for patients with axial spondyloarthritis (axSpA) between the treat-to-target versus usual care (UC) arms. This study was a cluster-randomized, controlled 48-week trial including patients with axSpA who fulfilled the ASAS criteria, had an Axial Spondyloarthritis Disease Activity Score >2.1, and were biologic disease-modifying antirheumatic drug naive. Eighteen axSpA expert centers were randomly allocated to one treatment arm: (a) treat-to-target prespecified management strategy (four-week visits), and (b) UC treatment decisions at the rheumatologist's discretion (12-week visits). Protocol violations in the treat-to-target arm and the fulfillment of the 2016 ASAS/EULAR recommendations in both arms were evaluated at every visit. ASAS Health Index (ASAS-HI) and disease activity outcomes at 48 weeks were compared between treat-to-target violators versus nonviolators. Patients treated according to the ASAS/EULAR recommendations were compared between both arms. A total of 160 patients initiated the trial (80 patients with treat to target; 80 patients with UC). In the treat-to-target arm, 51.2% patients violated the protocol at least once (62.2% of violations resulting in maintenance/reduction of treatment against protocol). After 48 weeks, treat-to-target violators versus nonviolators showed similar ratios of ASAS-HI improvement. The proportion of patients managed according to the ASAS/EULAR recommendations after the first 12 weeks were 63.9% versus 61.8% for the treat-to-target and UC arms, respectively. Protocol violations in the treat-to-target arm in the TICOSPA trial were frequent, although they did not have an impact on the rate of the primary outcome. The groups with UC was optimally treated, partly explaining the nonachievement of the primary objective in the TICOSPA trial.

The Effect of Oxidative Stress and Antioxidants Treatment on Gestational Diabetes Mellitus Outcome: A Scoping Review.

Diagnosing a pregnant woman's glucose intolerance is referred to as gestational diabetes mellitus (GDM). Diabetes has been linked to enhanced oxidative stress. In this condition, oxidative stress may damage nucleic acids, fats, and proteins, which in turn affects cell and tissue functions. The present study highlights the relationship between oxidative stress and GDM, with a particular focus on the role of hyperglycemia-induced processes during reactive oxygen species (ROS) oversupply, followed by it discusses the oxidative stress biomarkers and assesses the effects of antioxidant supplements on glycemic control, inflammatory processes, and oxidative stress among individuals with GDM. Two reviewers conducted a comprehensive literature search utilizing the PubMed®, Web of Science™, and Scopus® databases. Only items published in the English language up until June 2024 were taken into account. We conducted a thorough search of research databases to identify articles that had the terms "oxidative stress" or "antioxidant" and "GDM". From this search, we selected 55 relevant papers to be included in this narrative review. Pregnancy-induced hypertension, postpartum bleeding, lower birth weight, a higher risk of hyperbilirubinemia in their neonates, fetal growth retardation, and birth asphyxia were revealed to be outcomes of women enduring major oxidative stress during pregnancy. Furthermore, tight glycemic control both before and throughout pregnancy as well as oxidative stress treatment may help women highly prone to GDM.

D and Ds decay constants in Nf = 2 + 1 QCD with Wilson fermions

We present results for the leptonic decay constants of the D and Ds mesons from Nf = 2 + 1 lattice QCD. We employ a set of 49 high statistics gauge ensembles generated by the Coordinated Lattice Simulations (CLS) effort utilising non-perturbatively improved Wilson fermions and the tree-level Symanzik improved gauge action at six values of the lattice spacing in the range a = 0.098 fm down to a = 0.039 fm, with pion masses varying from around 420 MeV down to below the physical point. The ensembles lie on three trajectories in the quark mass plane, two trajectories intersecting close to the physical quark mass point and the third one approaching the SU(3) chiral limit, enabling tight control of the light and strange quark mass dependence. We obtain fDs\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ {f}_{{\ extrm{D}}_{\ extrm{s}}} $$\\end{document} = 246.8(1.3) MeV, fD = 208.4(1.5) MeV and fDs\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$ {f}_{{\ extrm{D}}_{\ extrm{s}}} $$\\end{document}/fD = 1.1842(36), where the precision of our results is mostly limited by the determination of the scale.

Decline in use of high-risk agents for tight glucose control among older adults with diabetes in New York City: 2017-2022.

This study aimed to examine the prevalence of inappropriate tight glycemic control in older adults with type 2 diabetes and other chronic conditions in New York City, and to identify factors associated with this practice. We conducted a retrospective cohort study using the INSIGHT Clinical Research Network. The study population included 11,728 and 15,196 older adults in New York City (age ≥ 75 years) with a diagnosis of type 2 diabetes, and at least one other chronic medical condition, in 2017 and 2022, respectively. The main outcome of interest was inappropriate tight glycemic control, defined as HbA1c <7.0% (<53 mmol/mol) with prescription of at least one high-risk agent (insulin or insulin secretagogue). The proportion of older adults with inappropriate tight glycemic control decreased by nearly 19% over a five-year period (19.4% in 2017 to 15.8% in 2022). There was a significant decrease in insulin (27.8% in 2017; 24.3% in 2022) and sulfonylurea (29.4% in 2017; 21.7% in 2022) medication prescription, and increase in use of GLP-1 agonists (1.8% in 2017; 11.4% in 2022) and SGLT-2 inhibitors (5.8% in 2017; 25.1% in 2022), among the total population. Factors associated with inappropriate tight glycemic control in 2022 included history of heart failure (adjusted odds ratio [aOR] 1.38), chronic kidney disease ([aOR] 1.93), colorectal cancer ([aOR] 1.38), acute myocardial infarction ([aOR] 1.28), "other" ([aOR] 0.72) or "unknown" ([aOR] 0.72) race, and a point increase in BMI ([aOR] 0.98). We found an encouraging trend toward less use of high-risk medication strategies for older adults with type 2 diabetes and multiple chronic conditions. However, one in six patients in 2022 still had inappropriate tight glycemic control, indicating a need for continued efforts to optimize diabetes management in this population.

Chemokine CX3CL1 (Fractalkine) Signaling and Diabetic Encephalopathy.

Diabetes mellitus (DM) is the most common metabolic disease in humans, and its prevalence is increasing worldwide in parallel with the obesity pandemic. A lack of insulin or insulin resistance, and consequently hyperglycemia, leads to many systemic disorders, among which diabetic encephalopathy (DE) is a long-term complication of the central nervous system (CNS), characterized by cognitive impairment and motor dysfunctions. The role of oxidative stress and neuroinflammation in the pathomechanism of DE has been proven. Fractalkine (CX3CL1) has unique properties as an adhesion molecule and chemoattractant, and by acting on its only receptor, CX3CR1, it regulates the activity of microglia in physiological states and neuroinflammation. Depending on the clinical context, CX3CL1-CX3CR1 signaling may have neuroprotective effects by inhibiting the inflammatory process in microglia or, conversely, maintaining/intensifying inflammation and neurotoxicity. This review discusses the evidence supporting that the CX3CL1-CX3CR1 pair is neuroprotective and other evidence that it is neurotoxic. Therefore, interrupting the vicious cycle within neuron-microglia interactions by promoting neuroprotective effects or inhibiting the neurotoxic effects of the CX3CL1-CX3CR1 signaling axis may be a therapeutic goal in DE by limiting the inflammatory response. However, the optimal approach to prevent DE is simply tight glycemic control, because the elimination of dysglycemic states in the CNS abolishes the fundamental mechanisms that induce this vicious cycle.

Evaluation of Cardiovascular Risk in People with Type 1 Diabetes: A Comprehensive and Specific Proposed Practical Approach.

People living with type 1 diabetes (T1D) have an increased risk of cardiovascular disease (CVD), and it is the leading cause of morbidity and mortality in this population. CVD risk increases with each uncontrolled risk factor, even in individuals with good glycaemic control. Recommendations for assessing CVD risk in the T1D population are extended from those for type 2 diabetes (T2D) even though the physiopathology and underlying mechanisms of atherosclerosis in T1D are poorly understood and differ from those in T2D. Unlike the assessment of microvascular complications, which is well established in T1D, this is far from being the case for the comorbidities and risk associated with CVD. Aside from classical cardiovascular comorbidities, carotid ultrasound can be useful to stratify CVD risk. The utilization of specific risk scales such as the Steno Type 1 Risk Engine can help to more accurately classify cardiovascular risk in these individuals. The cornerstones of the management of cardiovascular risk in T1D are the promotion of the Mediterranean diet, tight glycaemic control (glycated haemoglobin (HbA1c) < 7%), blood pressure < 130/80mmHg in most patients, and low-density lipoprotein (LDL) cholesterol < 100mg/dL in moderate-risk individuals, < 70mg/dL in high-risk individuals, and < 55mg/dL in very high-risk individuals. Conventional medical follow-up of patients with T1D should be individualized (approximately 2-3 visits per year), and a carotid ultrasound evaluation is recommended every 5 years in the absence of significant preclinical atherosclerosis or more often in those with severe preclinical atherosclerosis. Antithrombotic therapy is recommended in those receiving secondary prevention, those with stenosis > 50% in any arterial bed, and those with an impaired ankle-brachial index. This document is a proposal of a practical approach for the evaluation, classification, and management of CVD risk in individuals living with T1D.

The Demand for Real Money Balances in Zimbabwe: An Error Correction Estimation

Purpose: The purpose of the study is to examine the stability of the money demand function in Zimbabwe. Understanding, the money demand function is a prerequisite for effective monetary policy formulation and understanding the monetary transmission process and shocks propagation in the economy. Materials and Methods: The study employs the error correction modeling methodology to investigate the money demand function for Zimbabwe using quarterly data from 2017q2 – 2023q2. The analysis is expanded to characterize the monetary transmission mechanism following a shock to the price level and how the demand for real money balances responds to both single period and multiple shocks. Findings: The findings confirm a stable long run money demand function that is subject to short run dynamics. In addition, real money demand responds positively to real GDP (Scale factor) and inversely related to the price level (inflation). Short term dynamics (particularly inflation expectations) compound real money demand collapse in response to rising inflation. Implications to Theory, Practice and Policy: Monetary Policy must aim to collapse inflation expectations through a tight monetary control program and a functioning interbank market for foreign exchange to avoid surging parallel market activity.