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Background: DDH is 1 of the most important causes of childhood disability. A diagnosis of instability can be made in the neonatal period via the Ortolani and Barlow manoeuvres. However, clinical examination, although highly specific, has poor sensitivity as compared to ultrasound. There is controversy between the necessity of universal screening for dysplasia of all newborns or selective screening reserved for those with clinical signs of instability or known risk factors of DDH.Aim: To analyse the risk factors of congenital hip dysplasia in a consecutive case series of children referred for diagnosis and treatment of DDH.Materials and methods: This was a cross-sectional study on infants consecutively examined between January 2000 and December 2019 at the Marino Ortolani Centre in Ferrara, Italy. The first 3 types on Graf’s classification were considered physiological (1A, 1B, 2A+), while the last 6 pathological (2A-, 2B, 2C, 2D, 3, 4).Results: 18,954 infants met the inclusion criteria and were therefore considered eligible for the study. Of these 18,954 infants, 56% (n= 10,629) were females and 44% (n= 8325) were males. According to Graf classification, 34.9% (n= 6621) were 1A, 52.7% (n= 9999) were 1B, 4.0% (n= 753) were 2A+, 2.5% (n= 478) were 2A-, 1.5% (n= 284) were 2B, 1% (n= 196) were 2C, 1.3% (n= 243) were 2D, 1% (n= 193) were 3 and 1.0% (n= 187) were 4. The most significant risk factor was the female gender (OR 5.36; 95% CI, 4.63–6.20) followed by a family history (OR 2.35; 95% CI, 2.08–2.65), then skeletal pathologies (OR 2.04; 95% CI, 1.21–3.42), oligohydramnios (OR 1.75; 95% CI, 1.44–2.13), and finally breech presentation (OR 1.42: 95% CI, 1.27–1.60).Conclusions: Based on our data, family history, musculoskeletal disease, oligohydramnios and breech presentation are the main risk factors for DDH development, as is the female sex.

The 100 Tm superconducting synchrotron SIS100 is the main accelerator of the international Facility for Antiproton and Ion Research (FAIR) currently under advanced construction in Darmstadt, Germany. The SIS100 dipole circuit which creates the magnetic field required to bend the beam, consists of 108 dipoles distributed over six arc sections of the ring. The magnetic field for the beam focusing is generated by three individual quadrupole circuits with total amount of 166 magnets located in both arc and straight sections of the ring. The dipole circuit is powered from two synchronized power converters and will be cycled up to 13.2 kA at 28 kA/s. The dipole magnet chain is not self-protecting. 12 energy extraction resistors are used to protect the superconducting coils and bus-bars against overheating and overvoltage in case of a quench. The largest quadrupole circuit consists of 83 magnets. The nominal current is 10.5 kA cycled up to 22 kA/s. Similarly to dipoles, the quadrupole circuit is not self-protecting. Four energy extraction units are used to discharge the circuit's energy in case of a quench or fast power abort. This work presents a customized Python software tool created to simulate electrical behavior of a superconducting magnet chain. The software is under development at GSI. However, certain modules strongly rely on the approach developed at CERN. The paper contains selected simulations of the SIS100 dipole and defocusing quadrupole circuits. Special attention is drawn to: transient effects during typical operation and during the fast power abort; the damping effect of vacuum chambers; voltage distribution in the circuits and basic failure modes.

AbstractAnalytical quality by design and Response Surface Methodology based UPLC procedure has been developed for the concurrent quantification of four oral anti-diabetic drugs Metformin, Vildagliptin, Dapagliflozin and Sitagliptin in bulk and tablets. ANOVA was applied for responses statistical analysis. Retention times and peak resolutions were selected as critical quality attributes. The Critical method parameters (CMPs) considered for the Response surface methodology were the organic composition of the mobile phase (%), pH of the buffer, and flow rate. CMPs of the UPLC procedure were optimized employing a 16-runs 53Central-composite design. The optimized procedure suggested by the desirability functions approach utilizing 49.3 volumes ethanol and 50.7 volumes pH 3.73, 0.1% Triethylamine buffer with 0.26 mL/min flow rate as mobile phase, Shield RP-18 (100 × 2.1 mm, 1.7 μm) column as a stationary phase with 4 min run time resulted in maximum desirability, 1.000. At 0.737 min, 1.425 min, 1.929 min and 2.645 min Metformin, Vildagliptin, Dapagliflozin and Sitagliptin retention times were observed respectively with acceptable resolution. The optimized procedure was validated and stress studies were executed following the ICHQ2(R1) and ICHQ1A, ICHQ1B guidelines respectively. The proposed technique was evaluated employing greenness assessment tool and 0.86 was the observed greenness score. In accordance with the literature, it is evident that this is the initially reported green UPLC procedure for Metformin, Vildagliptin, Dapagliflozin and Sitagliptin concurrent estimation.

AbstractIn this study, we developed a robust Quality by Design guided reverse phase high-performance liquid chromatographic method for quantifying daridorexant with simplicity, speed, sensitivity, reproducibility, and cost-effectiveness. Utilizing a Waters e2690 alliance HPLC system with Empower 2® software control and a SpursilTM C18 HPLC column, critical method parameters such as flow rate, % aqueous buffer and buffer pH were identified through preliminary trials and risk assessment studies. Optimization via central composite design as part of a Design of Experiments framework, with retention time and tailing factor as critical analytical attributes, resulted in optimized chromatographic conditions: 30:70 (% v/v) phosphate buffer (pH 3) and acetonitrile as mobile phase, flowing at 1.0 mL/min, with detection at 270 nm. The method exhibited linearity within a range of 2.0-10.0 μg/ mL (correlation coefficient: 0.9997) and detection, quantitation limits of 0.089 μg/mL and 0.271 μg/mL, respectively. Validation according to ICH Q2 (R1) guidelines confirmed the method’s robustness, precision, accuracy, sensitivity, and high linearity for daridorexant estimation in both bulk drug and marketed formulations.

This review aims to argue how using probiotics can improve anxiety and depressive behaviour without adverse effects, also exploring the impact of postbiotics on it. Specifically, probiotics have drawn more attention as effective alternative treatments, considering the rising cost of antidepressant and anti-anxiety drugs and the high risk of side effects. Depression and anxiety disorders are among the most common mental illnesses in the world's population, characterised by low mood, poor general interest, and cognitive or motor dysfunction. Thus, this study analysed published literature on anxiety, depression, and probiotic supplementation from PubMed and Scopus, focusing on the last twenty years. This study focused on the effect of probiotics on mental health as they have drawn more attention because of their extensive clinical applications and positive impact on various diseases. Numerous studies have demonstrated how the gut microbiota might be critical for mood regulation and how probiotics can affect host health by regulating the gut-brain axis. By comparing the different works analysed, it was possible to identify a strategy by which they are selected and employed and, at the same time, to assess how the effect of probiotics can be optimised using postbiotics, an innovation to improve mental well-being in humans.

The prevalence of chronic kidney disease (CKD) is increasing globally, especially in elderly patients. Uremic cardiomyopathy is a common cardiovascular complication of CKD, characterized by left ventricular hypertrophy (LVH), diastolic dysfunction, and fibrosis. Kisspeptins and their receptor, KISS1R, exert a pivotal influence on kidney pathophysiology and modulate age-related pathologies across various organ systems. KISS1R agonists, including kisspeptin-13 (KP-13), hold promise as novel therapeutic agents within age-related biological processes and kidney-related disorders. Our investigation aimed to elucidate the impact of KP-13 on the trajectory of CKD and uremic cardiomyopathy. Male Wistar rats (300–350 g) were randomized into four groups: (I) sham-operated, (II) 5/6 nephrectomy-induced CKD, (III) CKD subjected to a low dose of KP-13 (intraperitoneal 13 µg/day), and (IV) CKD treated with a higher KP-13 dose (intraperitoneal 26 µg/day). Treatments were administered daily from week 3 for 10 days. After 13 weeks, KP-13 increased systemic blood pressure, accentuating diastolic dysfunction’s echocardiographic indicators and intensifying CKD-associated markers such as serum urea levels, glomerular hypertrophy, and tubular dilation. Notably, KP-13 did not exacerbate circulatory uremic toxin levels, renal inflammation, or fibrosis markers. In contrast, the higher KP-13 dose correlated with reduced posterior and anterior wall thickness, coupled with diminished cardiomyocyte cross-sectional areas and concurrent elevation of inflammatory (Il6, Tnf), fibrosis (Col1), and apoptosis markers (Bax/Bcl2) relative to the CKD group. In summary, KP-13’s influence on CKD and uremic cardiomyopathy encompassed heightened blood pressure and potentially activated inflammatory and apoptotic pathways in the left ventricle.

Many women are affected by breast cancer, if not treated properly it can be fatal. This paper proposes a new dual band microstrip patch antenna with combination of hexogen and pentagon slots operating at 2.45 GHz and 4 GHz suitable for ISM and 5G application. The reflection magnitude S11 obtained at 2.45 GHz is -23.72 dB and at 4 GHz it is -15.04 dB. The proposed conformal antenna is printed on flexible 1mm thick PDMS substrate and can be applied for breast cancer detection. Simulations have been carried out with multiple antennas for tumour detection. The designed antenna has low SAR of 0.261 W/Kg with two antennas and 0.318 W/Kg with 6 antennas placed 5 mm off the body tested for 1 gm of tissue, well below the FCC specification of 1.6 W/Kg. The lower band antenna frequency can be used for detection of tumour and 5G bands suitable for faster transmission for further processing.

According to the mounting evidence in the literature, pro-inflammatory mediators/targets activate multiple signalling pathways to trigger illnesses that are ultimately responsible for acute pain, chronic inflammatory diseases, and several auto-immune disorders. Conventional drugs have been ruled out since proteolysis-targeting chimeras (PROTACs) are poised to overcome the limitations of traditional therapies. These heterobifunctional molecules help to degrade the targeted proteins of interest through ubiquitination. This review encompasses current and future aspects of PROTACs in inflammation-mediated and autoimmune targets. Different key points are highlighted and discussed, such as why PROTACs are preferred in this disease area, drawbacks and lessons learnt from the past, the role of linkers in establishing crucial degradation, in vitrofindings, pharmacokinetics, in silicoparameters, limitations of PROTACs in clinical settings, and future outcomes.

Inspection of tube networks is an important process in the manufacturing and maintenance of aircraft. Currently, borescopes are commonly used with limited success. To improve the inspection process, a prototype design based on a vertebra concept is introduced, analyzed, and optimized. The modular robotic inspection system (MoRIS) allows for a microsized camera to be driven noninvasively through a 3-m-long, 36-mm internal diameter tube network. MoRIS provides a complete view of the tube walls. Our system includes a localization algorithm that tracks the progress of the robot inside the tubes. This algorithm results in an experimentally validated error of 19.7 mm. Using MoRIS, operators can inspect tube networks that previously required hazardous disassembly of aircraft.

This article explores the design and experimental validation of an isolated half-bridge DC-DC converter customized for cryogenic environments, addressing the challenges posed by extreme low temperatures. The key contribution lies in the adoption of the isolated half-bridge topology which ensures exceptional output voltage stability with a simplified structure. By leveraging this innovative design, a rigorous design process for the selection of critical components is employed to ensure the stable performance and reliability at cryogenic environment. The performance of the designed isolated DC-DC converter and practical challenges are investigated experimentally at a cryogenic temperature. The results contribute valuable insights to the converter design in extreme temperature environments, promising advancements in the field of cryogenic power electronics.

Full-electric propulsion aircraft is attracting a lot of interests in recent years. To improve the power density of electric propulsion systems, superconducting power devices are attractive due to their high current density and high efficiency. Fault analysis and fault management techniques with the combination of superconducting power devices are critically needed to ensure the safety and reliability of electric propulsion systems. In this paper, pole-to-pole fault analysis is carried out for the dc network in electric aircraft. High temperature superconducting (HTS) cable modeling is taken into consideration for the fault characterization. A system-level pole-to-pole fault management strategy is proposed to detect and isolate the faults at different locations. The analytical results are verified by the simulation models using Matlab/Simscape. The studies in this paper provide valuable guidance for the design and setting of protection systems in electric aircraft.

Aiming to increase the power density of electrical systems and realize all-electric aircraft, research has been focused on immersing power electronics at cryogenic temperatures as they tend to have lower conduction and switching losses. To ensure proper switching of semiconductor devices at cryogenic temperature, their gate driver circuits should ideally be placed in close physical proximity and therefore in the same environment. Although some commercial off-the-shelf gate drivers have been tested at cryogenic temperatures, in this article we present a bespoke magnetically isolated gate driver for cryogenic temperatures. Experiments with the circuit immersed in liquid nitrogen verify the proposals of the article.

An efficient synthetic method was developed to access isoquinoline-derived diene esters from enynones and isoquinoline-N-oxides in an atom-economic manner. The isoquinoline-substituted diene esters were obtained in moderate to excellent yields via [3 + 2]-cycloaddition and isoxazole ring opening followed by a [1,5]-sigmatropic rearrangement reaction, which resulted in one C–C and two C–O bond formations. Further, quinolin-2(1H)-ylidene-substituted 1,5-diones were achieved by reaction of enynones with quinoline-N-oxides in very good to high yields.

This paper presents the design, kinematic, and nonlinear control algorithm of a 3 degrees of freedom (DOF) pneumatic haptic finger developed for elastographic imaging virtual palpation. This haptic interface allows for precise tracking of the index finger position and can provide directional force perception at the fingertip. Of the 4 DOF of the human finger, two are kinematically coupled (distal and proximal interphalangeal joints), one DOF of the metacarpophalangeal (MCP) joint is controlled independently, while the remaining MCP joint DOF is only measured. Relationships between the joint angles and actuator positions, as well as fingertip to actuator forces are derived in closed form. A sliding mode nonlinear pneumatic controller is implemented and experimental results are presented.

In den letzten Jahren wurden grundlegende Veränderungen hinsichtlich Geodatenressourcen deutlich. Die Etablierung von Gaming-Software und dazugehörigen webbasierten Austausch- und Kommunikationsplattformen bietet der Kartographie und den Geoinformationswissenschaften neue Potenziale an Geodaten, die − insbesondere im Bereich der 3D-Visualisierung − ein Umdenken erfordern. Die Ressourcen der amtlichen geodatenhaltenden Stellen und ersten VGI-Communities aus frühen Zeiten der Digitalisierung werden erweitert um Geodaten, die der 3D-Modellierung im Gaming entstammen und hohes Kreativpotenzial enthalten. Hier zeigt sich, bezogen auf die Verfügbarkeit von Geodatenressourcen, ein Wandel der Geodatenkultur − von einer Geodatenkultur der Abhängigkeit(ca. 1830–1980), über eine Geodatenkultur der Teilhabe(ca. 1980–2020) bis hin zu deren Weitentwicklung zu einer Geodatenkultur der Diversität(seit ca. 2020). Diese drei Paradigmen einer Geodatenkultur werden in diesem Aufsatz, nach einer Begriffsreflektion, die wissenschaftstheoretisch auf einem neopragmatischen Verständnis aufbaut, diskutiert. Verwendete Fallbeispiele basieren auf Virtual und Augmented Reality. Mit diesen Beispielen wird die Synthese der verschiedenen Geodatenressourcen für zielgerichtete 3D-kartographische Anwendungen hervorgehoben.

Amyloid-beta related angiitis (ABRA) is a rare central nervous system inflammatory and vasculitic process. It is seen in patients with cerebral amyloid angiopathy (CAA) and thought to be mediated by an autoimmune reaction against cerebrovascular β-amyloid. We describe the case of a patient with ABRA with clinical information and brain imaging over a 10-year period. The patient was hospitalized in 2018 for altered mental status, paranoia and hallucinations. Her symptoms started in 2009 with an episode of vertigo and loss of consciousness. From 2011-2019, she had multiple episodes of transient focal neurological deficits with overall cumulative progressive decline in cognition and functional status. Retrospective and comparative reviews of brain magnetic resonance imaging (MRI) from 2009-2019 showed waxing and waning vasogenic cerebral edema with overall progression of white matter hyperintensities and peripheral micro-hemorrhages consistent with inflammatory CAA. Re-examination of a brain biopsy from 2009 showed ABRA, and immunostaining was positive for β-amyloid. She was treated with intravenous steroids with minimal symptomatic improvement. She was lost to our follow-up after hospital discharge. We describe the temporal progression of ABRA through serial brain imaging over a 10-year period. To our knowledge, this is the longest published follow-up duration of ABRA. The patient in our case had severe cognitive impairment and disability despite treatment with steroids.

Gold(I)-catalyzed efficient synthetic transformation was achieved to access the tetrahydrobenzo[h]cyclopropa[c]chromenes from allyl-substituted 1,6-diynes. Cyclopropane-fused tetrahydrobenzochromenes were obtained regioselectively in ≤92% yields. In this atom-economic organic transformation, three new C–C bonds were formed sequentially in one pot.

AbstractTolpyralate is an herbicide that is usually mixed with atrazine for broad-spectrum weed control in corn. Previous research has provided information on the effective dose (ED) of tolpyralate applied alone and in a 1:33.3 mixture with atrazine; however, tolpyralate is commercially applied at a dose of 30 to 40 g ai ha−1with a minimum of 560 g ai ha−1of atrazine. Therefore, five field trials were conducted over 3 yr (2019 to 2021) to determine the ED of atrazine to complement 30 g ai ha−1of tolpyralate to achieve 80%, 90%, and 95% control of seven weed species 2, 4, and 8 wk after application (WAA). Tolpyralate was applied alone and in a mixture with atrazine doses ranging from 50 to 2,000 g ai ha−1. At 8 WAA, the ED of atrazine for 95% control of velvetleaf, common ragweed, common lambsquarters, and wild mustard was below the minimum label dose of atrazine on the commercial tolpyralate label, ranging from 430 to 520 g ai ha−1, which supports the use of the minimum label dose of atrazine. In contrast, redroot pigweed required 1,231 g ai ha−1of atrazine to complement tolpyralate for 95% control 8 WAA. At 8 WAA, barnyardgrass and a mixture of green foxtail and giant foxtail (Setariaspp.) were not controlled by 80%, 90%, or 95% with tolpyralate applied alone or co-applied with any dose of atrazine evaluated in this study. The results of this study conclude that tolpyralate + atrazine is highly efficacious on several weed species at atrazine doses of 40 to 130 g ai ha−1below the label dose of 560 g ai ha−1, but the use of the higher dose of tolpyralate or another herbicide may be required to improve control of redroot pigweed and grass weed species.

In this work, we introduce and investigate a new class k-U⁢S~s⁢(b,μ,γ,t){k-\widetilde{US}_{s}(b,\mu,\gamma,t)}of analytic functions in the open unit disk Uwith negative coefficients. The object of the present paper is to determine coefficient estimates, neighborhoods and partial sums for functions fbelonging to this class.

An efficient synthetic organic transformation was developed to access isoquinoline-substituted isobenzofurans by reaction of substituted 1,5-diynes with isoquinoline N-oxides. Moderate to excellent yields of isoquinoline-derived isobenzofurans were achieved by formation of a new C–C and two C–O bonds in the presence of copper catalyst in one pot. whereas quinoline-substituted isobenzofurans were obtained when the reaction was conducted using quinoline N-oxides and 1,5-diynes in the presence copper catalyst.

AbstractTolpyralate is commonly mixed with atrazine for improved control of common annual weed species in corn production systems in the United States and Canada. Weed control efficacy with this mixture is enhanced with the addition of methylated seed oil (MSO) Concentrate®; however, there is little information on the efficacy of tolpyralate + atrazine with other proprietary adjuvants. Therefore, four trials were conducted at field research sites in Ontario, Canada, to evaluate the efficacy of tolpyralate + atrazine when applied with six different commercially available adjuvants on four annual broadleaf and two annual grass weed species in corn. The adjuvants evaluated were MSO Concentrate®, Agral® 90, Assist® Oil Concentrate, Carrier®, LI 700®, and Merge®. A treatment of tolpyralate + atrazine applied with no adjuvant was also included in the study. For the control of velvetleaf and wild mustard, the adjuvants evaluated with tolpyralate + atrazine did not improve control. At 8 wk after application (WAA), the use of Agral® 90, Assist® Oil Concentrate, Carrier®, MSO Concentrate®, or Merge® with tolpyralate + atrazine provided similar or greater control of common ragweed than tolpyralate + atrazine applied with LI 700®. At 8 WAA, the adjuvants performed similarly with tolpyralate + atrazine for the control of common lambsquarters; however, LI 700® was the only adjuvant that did not improve control compared to tolpyralate + atrazine applied without an adjuvant. At 8 WAA, MSO Concentrate®, Carrier®, and Merge® improved control of barnyardgrass and foxtail species with tolpyralate + atrazine to a similar or greater level than Assist® Oil Concentrate, Agral® 90, and LI 700®. Overall, MSO Concentrate®, Carrier®, or Merge® should be added to tolpyralate + atrazine for control of the myriad of weed species interfering with corn production.

AbstractTolpyralate is a 4-hydroxyphenylpyruvate dioxygenase–inhibiting herbicide that is applied postemergence for control of annual broadleaf and grass weeds in corn. Current Canadian label recommendations for tolpyralate specify the addition of a methylated seed oil (MSO) adjuvant (MSO Concentrate®) for improved weed control. The efficacy of tolpyralate applied with other proprietary adjuvants has not been widely reported in the peer-reviewed literature. Therefore, four field trials were conducted in corn over 2020 and 2021 in Ontario, Canada, to evaluate MSO Concentrate®, Agral® 90 (nonionic surfactant), Assist® Oil Concentrate (blended surfactant), Carrier® (blended surfactant), LI 700® (nonionic surfactant), and Merge® (blended surfactant) as adjuvants with tolpyralate for the control of annual broadleaf and grass weeds. At 8 wk after application (WAA), tolpyralate applied with MSO Concentrate®, Agral® 90, Assist® Oil Concentrate, Carrier®, or Merge® controlled velvetleaf, wild mustard, barnyardgrass, and foxtail species similarly. These adjuvants also enhanced the efficacy of tolpyralate similarly for the control of common ragweed at 8 WAA with the exception that Agral® 90 was inferior to Merge®. At 8 WAA, tolpyralate controlled common lambsquarters the greatest when applied with MSO Concentrate®, Agral® 90, Carrier®, or Merge®; these adjuvants with the exception of Agral® 90 were superior to Assist® Oil Concentrate. At 8 WAA, tolpyralate applied with LI 700® controlled common ragweed, barnyardgrass, and foxtail species less than when tolpyralate was applied with the other adjuvants tested; control of these weed species with tolpyralate was not improved with LI 700® when compared to tolpyralate applied without an adjuvant. Overall, tolpyralate applied with either MSO Concentrate®, Carrier®, or Merge® controlled all annual broadleaf and grass weed species similarly or greater than tolpyralate applied without an adjuvant or tolpyralate with Agral® 90, Assist® Oil Concentrate, or LI 700® at 8 WAA.

Physical activity is defined as any bodily movement produced by skeletal muscles which causes energy consumption; moderate and constant physical activity is known to be beneficial and to slow the muscle loss process associated with aging. The aim of the present study was to test, in an in vitroexercise model, the biological effects of a new formulation composed of magnesium and potassium combined with vitamin D and curcumin created to support muscle activity and to prevent hypercontraction damage.

Gene therapy can be used to restore cell function in monogenic disorders or to endow cells with new capabilities, such as improved killing of cancer cells, expression of suicide genes for controlled elimination of cell populations, or protection against chemotherapy or viral infection. While gene therapies were originally most often used to treat monogenic diseases and to improve hematopoietic stem cell transplantation outcome, the advent of genetically modified immune cell therapies, such as chimeric antigen receptor modified T cells, has contributed to the increased numbers of patients treated with gene and cell therapies. The advancement of gene therapy with integrating retroviral vectors continues to depend upon world-wide efforts. As the topic of this special issue is “Spotlight on Germany,” the goal of this review is to provide an overview of contributions to this field made by German clinical and research institutions. Research groups in Germany made, and continue to make, important contributions to the development of gene therapy, including design of vectors and transduction protocols for improved cell modification, methods to assess gene therapy vector efficacy and safety (e.g., clonal imbalance, insertion sites), as well as in the design and conduction of clinical gene therapy trials.

Alzheimer’s disease (AD) is the most frequent cause of dementia in the elderly. Few cases are familial (FAD), due to autosomal dominant mutations in presenilin-1 (PS1), presenilin-2 (PS2) or amyloid precursor protein (APP). The three proteins are involved in the generation of amyloid-beta (Aβ) peptides, providing genetic support to the hypothesis of Aβ pathogenicity. However, clinical trials focused on the Aβ pathway failed in their attempt to modify disease progression, suggesting the existence of additional pathogenic mechanisms. Ca2+dysregulation is a feature of cerebral aging, with an increased frequency and anticipated age of onset in several forms of neurodegeneration, including AD. Interestingly, FAD-linked PS1 and PS2 mutants alter multiple key cellular pathways, including Ca2+signaling. By generating novel tools for measuring Ca2+in living cells, and combining different approaches, we showed that FAD-linked PS2 mutants significantly alter cell Ca2+signaling and brain network activity, as summarized below.