Direct Comparative Studies Revealing the Contribution of TADF Activity of Organic Emitters Towards Efficient Electrochemiluminescence.

Electrochemiluminescence (ECL) featuring thermally activated delayed fluorescence (TADF) properties has attracted considerable interest, showcasing their potential for 100 % exciton harvesting, which marks a significant advancement in the realm of organic ECL. However, the challenge of elucidating the precise contribution of TADF to the enhanced ECL efficiency arises due to the lack of comparative studies of organic compounds with or without efficient TADF properties. In this study, we present four carbazole-benzonitrile molecules possessing similar chemical structures and comparable exchange energy (ΔEST). Despite their comparable properties, these compounds exhibited varying TADF efficiencies, warranting a closer examination of their underlying structural and electronic characteristics governing the optical properties. Consequently, intense ECL emission was only observed from 4CzBN with a remarkable TADF efficiency, underscoring the substantial difference in the ECL signal among molecules with comparable ΔEST and similar spectral properties but varying TADF activity.

The guide RNA sequence dictates the slicing kinetics and conformational dynamics of the Argonaute silencing complex.

The RNA-induced silencing complex (RISC), which powers RNA interference (RNAi), consists of a guide RNA and an Argonaute protein that slices target RNAs complementary to the guide. We find that for different guide-RNA sequences, slicing rates of perfectly complementary, bound targets can be surprisingly different (>250-fold range), and that faster slicing confers better knockdown in cells. Nucleotide sequence identities at guide-RNA positions 7, 10, and 17 underlie much of this variation in slicing rates. Analysis of one of these determinants implicates a structural distortion at guide nucleotides 6-7 in promoting slicing. Moreover, slicing directed by different guide sequences has an unanticipated, 600-fold range in 3'-mismatch tolerance, attributable to guides with weak (AU-rich) central pairing requiring extensive 3' complementarity (pairing beyond position 16) to more fully populate the slicing-competent conformation. Together, our analyses identify sequence determinants of RISC activity and provide biochemical and conformational rationale for their action.

A highly sensitive stem-loop RT-qPCR method to study siRNA intracellular pharmacokinetics and pharmacodynamics.

Small interfering RNA (siRNA) is a powerful tool for sequence-specific silencing of disease-related genes. In this study, we established and validated a stem-loop reverse transcription-quantitative polymerase chain reaction (RT-qPCR) method applicable for both chemically unmodified and modified siRNA, aiming to elucidate mechanistic intracellular pharmacokinetic and pharmacodynamic (PK/PD) properties of siRNA. We conducted a comprehensive evaluation of factors affecting intracellular siRNA quantification. Our study revealed that immobilization-based siRNA extraction introduced high variation, making it unsuitable for absolute quantification. Conversely, direct cell lysis followed by stem-loop RT-qPCR demonstrated excellent reproducibility, with a quantification range from 0.0002 to 20 femtomole (fmole) for unmodified siRNA and 0.02 to 20 fmole for modified siRNA. The design of a 6-bp overlapping RT primer facilitated the distinction of full-length antisense from its 3'-metabolites, and pre-annealing of antisense to RT primer enhanced sensitivity and reproducibility. Differences in siRNA loss during storage and sample processing were noted among microcentrifuge tubes from various manufacturers. Endogenous miR-16 served as a reference for normalizing cytoplasmic siRNA, while protein concentration post-immunoprecipitation lysis was used to normalize RNA-induced silencing complex (RISC)-loaded siRNA levels. This method successfully enabled a detailed characterization of the time profiles of cytoplasmic and RISC-loaded siRNA, advancing the in vitro-in vivo translation of siRNA therapeutics.

Therapeutic siRNA Loaded to RISC as Single and Double Strands Requires an Appropriate Quantitative Assay for RISC PK Assessment.

In recent years, therapeutic siRNA projects are booming in the biotech and pharmaceutical industries. As these drugs act by silencing the target gene expression, a critical step is the binding of antisense strands of siRNA to RNA-induced silencing complex (RISC) and then degrading their target mRNA. However, data that we recently obtained suggest that double-stranded siRNA can also load to RISC. This brings a new understanding of the mechanism of RISC loading which may have a potential impact on how quantification of RISC loaded siRNA should be performed. By combining RNA immune precipitation and probe-based hybridization LC-fluorescence approach, we have developed a novel assay that can accurately quantify the RISC-bound antisense strand, irrespective of which form (double-stranded or single-stranded) is loaded on RISC. In addition, this novel assay can discriminate between the 5'-phosphorylated antisense (5'p-AS) and the nonphosphorylated forms, therefore specifically quantifying the RISC bound 5'p-AS. In comparison, stem-loop qPCR assay does not provide discrimination and accurate quantification when the oligonucleotide analyte exists as a mixture of double and single-stranded forms. Taking together, RISC loading assay with probe-hybridization LC-fluorescence technique would be a more accurate and specific quantitative approach for RISC-associated pharmacokinetic assessment.

A theoretical investigation of benzothiadiazole derivatives for high efficiency OLEDs.

It is of great importance and worthy of efforts to give a clear structure-property relationship and microscopic mechanism of fluorescence emitters with high quantum yield. In this work, we perform a detailed computational investigation to give an explanation to the high efficiency of a fluorescence emitter XBTD-NPh based TADF sensitized fluorescence (TSF) OLEDs, and construct a symmetry structure DSBNA-BTD. Theoretical calculations show that XBTD-NPh is a long-time phosphorescent material at 77 K and TADF is attributed to the RISC of T1 to S1 state. For DSBNA-BTD, excitons arrived at T1 state comes to a large rate of nonradiatively path to the ground state, meaning it is may not be an efficient TADF molecule. For both molecules, the fast IC between T2 and T1 state results in that the hot exciton channel T1-Tn-S1 makes no contribution to the TADF.

Anatomic shoulder arthroplasty: the correlation between patient resilience, mental health, and outcome.

BACKGROUND: Recovery from anatomic shoulder arthroplasty may be enhanced in patients with good mental health and the resilience to participate in the prescribed postoperative rehabilitation program. To test this concept, we utilized validated and reliable scales in determining whether resilience and mental health are associated with the outcome of anatomic arthroplasty. METHODS: Three hundred ninety-nine patients (195 ream and run [RnR] and 204 anatomic total shoulder arthroplasty [aTSA]) were surveyed at a mean follow-up of 6.3 ± 3.3 years. Preoperative variables included age, sex, body mass index, history of prior shoulder surgery, diabetes, visual analog scale for pain, Simple Shoulder Test (SST) scores, and Veteran's RAND 12 Mental Component Score (VR-12 MCS). Outcomes collected included the SST, American Shoulder and Elbow Surgeons (ASES) score, revision rate, and patient satisfaction. Resilience was documented using the Connor-Davidson Resilience Scale 10 (CD-RISC 10) at latest follow-up. Univariable and multivariable regression analyses were used to identify factors significantly associated with follow-up postoperative SST, ASES, and satisfaction. RESULTS: In the univariable analysis, CD-RISC 10 was positively correlated with postoperative SST, ASES, and satisfaction after both RnR and aTSA. The mean CD-RISC 10 scores were higher in the RnR cohort (34.3 ± 4.8 vs. 32.5 ± 6.2 for aTSA, P < .001). Male sex and lower preoperative visual analog scale for pain were correlated with higher ASES after RnR; VR-12 MCS was positively correlated with all outcomes except SST after RnR. In the multivariable linear regression analysis, CD-RISC 10 was independently associated with postoperative SST, ASES and satisfaction scores in aTSA patients. In the RnR cohort, CD-RISC 10 was only correlated with satisfaction. VR-12 MCS was correlated with ASES and satisfaction after RnR. DISCUSSION: In this study of anatomic arthroplasties, increased resilience and better mental health were correlated with better outcomes. RnR patients had higher resilience than aTSA patients. Greater resilience was associated with better outcomes after aTSA. Better mental health was associated with superior outcomes after the ream and run procedure.

Exploring the Theoretical Foundations of Thermally Activated Delayed Fluorescence (TADF) Emission: A Comprehensive TD-DFT Study on Phenothiazine Systems.

This study conducts a thorough theoretical investigation of Thermally Activated Delayed Fluorescence (TADF) in phenothiazine-based systems, examining ten molecular configurations recognized experimentally as TADF-active. Employing Time-Dependent Density Functional Theory (TD-DFT), our analysis spans the investigation of singlet-triplet energy gaps (ΔEST), spin-orbit coupling, and excitation characteristics using Multiwfn. This approach not only validates the adherence to El Sayed's rule across these systems but also provides a detailed understanding of charge transfer dynamics, as visualized through heat maps. A significant aspect of our study is the exploration of different oxidation states of sulfur and site substitutions on phenothiazine. This systematic variation aims to identify additional TADF-active compounds, drawing parallels with properties characterizing other known TADF emitters. Our investigation into Reverse Intersystem Crossing (rISC) rates and the analysis of dihedral angles in relation to ΔEST values offer nuanced insights into the TADF behaviours of these molecules. By integrating rigorous computational analysis with practical implications, we provide a foundational understanding that enhances the design and optimization of phenothiazine-based materials for optoelectronic applications. This work not only advances our theoretical understanding of TADF in phenothiazine derivatives but also serves as a guide for experimentalists and industry professionals in the strategic design of new TADF materials.

Regulatory Pathways in Growth Plate Chondrocytes that Are Impacted by Matrix Vesicle microRNA Identified by Targeted RISC Pulldown and Sequencing of the Resulting Transcriptome.

During endochondral bone formation, growth plate chondrocytes are differentially regulated by various factors and hormones. As the cellular phenotype changes, the composition of the extracellular matrix is altered, including the production and composition of matrix vesicles (MV) and their cargo of microRNA. The regulatory functions of these MV microRNA in the growth plate are still largely unknown. To address this question, we undertook a targeted bioinformatics approach. A subset of five MV microRNA was selected for analysis based on their specific enrichment in these extracellular vesicles compared to the parent cells (miR-1-3p, miR-22-3p, miR-30c-5p, miR-122-5p, and miR-133a-3p). Synthetic biotinylated versions of the microRNA were produced using locked nucleic acid (LNA) and were transfected into rat growth plate chondrocytes. The resulting LNA to mRNA complexes were pulled down and sequenced, and the transcriptomic data were used to run pathway analysis pipelines. Bone and musculoskeletal pathways were discovered to be regulated by the specific microRNA, notably those associated with transforming growth factor beta (TGFß) and Wnt pathways, cell differentiation and proliferation, and regulation of vesicles and calcium transport. These results can help with understanding the maturation of the growth plate and the regulatory role of microRNA in MV.

Psychometric Properties of the Connor-Davidson Resilience Scale (CD-RISC) in Spanish Adolescents.

Few studies have examined the psychometric properties of the Connor-Davidson Resilience Scale (CD-RISC) in a large adolescent community sample, finding a significant disparity. This study explores the psychometric properties of the CD-RISC among Spanish adolescents by means of exploratory factor analysis (EFA), Rasch analysis, and measurement invariance (MI) across sex, as well as internal consistency and criterion validity. The sample was comprised of 463 adolescents (231 girls), aged 12 to 18 years, who completed the CD-RISC and other measures on emotional status and quality of life. The EFA suggested that the CD-RISC structure presented a unidimensional model. Consequently, shorter unidimensional CD-RISC models observed in the literature were explored. Thus, the Campbell-Sills and Stein CD-RISC-10 showed the soundest psychometric properties, providing an adequate item fit and supporting MI and non-differential item functioning across sex. Item difficulty levels were biased toward low levels of resilience. Some items showed malfunctioning in lower response categories. With regard to reliability, categorical omega was. 82. Strong associations with health-related quality of life, major depressive disorder symptoms, and emotional symptoms were observed. A weak association was found between resilience and the male sex. Campbell-Sills and Stein's CD-RISC-10 model emerges as the best to assess resilience among Spanish adolescents, as already reported in adults. Thus, independently of the developmental stage, the core of resilience may reside in the aspects of hardiness and persistence.

Preferential cleavage of upstream targets in concatenated miRNA/siRNA target sites support a 5'-3' scanning model for RISC target recognition.

RNA interference (RNAi) is becoming medicine for curing human diseases. Still, we lack a thorough understanding of some fundamental aspects of RNAi that affect its efficiency and accuracy. One such question is how RNA-induced silencing complex (RISC) can efficiently find its targets. To address this question, we developed a strategy that involves the expression of mRNAs containing concatenations of identical miRNA/siRNA target sites. These mRNAs were cleaved by co-expressed miRNAs in plant cells or by co-transfected siRNAs in mammalian cells. The mRNA cleavage events were then detected using the 5'RACE assay. Using this strategy, we found that RISCs preferentially cleave the upstream ones of concatenated target sites, consistent with a model that RISC scans mRNA in 5'→3' direction to approach its target sites. The stability of the cleaved mRNA fragments correlates with the complementarity between siRNA and its target sequence. When siRNA perfectly complements its target sequence, the cleaved mRNA fragment becomes stable and may be cleaved in a second round. Our findings have practical implications for designing siRNAs with increased efficiency and reduced off-target effects.

Psychometric Properties of the Connor-Davidson Resilience Scale (CD-RISC) in Spanish Adolescents

Few studies have examined the psychometric properties of the Connor-Davidson Resilience Scale (CD-RISC) in a large adolescent community sample, finding a significant disparity. This study explores the psychometric properties of the CD-RISC among Spanish adolescents by means of exploratory factor analysis (EFA), Rasch analysis, and measurement invariance (MI) across sex, as well as internal consistency and criterion validity. The sample was comprised of 463 adolescents (231 girls), aged 12 to 18 years, who completed the CD-RISC and other measures on emotional status and quality of life. The EFA suggested that the CD-RISC structure presented a unidimensional model. Consequently, shorter unidimensional CD-RISC models observed in the literature were explored. Thus, the Campbell-Sills and Stein CD–RISC–10 showed the soundest psychometric properties, providing an adequate item fit and supporting MI and non-differential item functioning across sex. Item difficulty levels were biased toward low levels of resilience. Some items showed malfunctioning in lower response categories. With regard to reliability, categorical omega was. 82. Strong associations with health-related quality of life, major depressive disorder symptoms, and emotional symptoms were observed. A weak association was found between resilience and the male sex. Campbell-Sills and Stein’s CD–RISC–10 model emerges as the best to assess resilience among Spanish adolescents, as already reported in adults. Thus, independently of the developmental stage, the core of resilience may reside in the aspects of hardiness and persistence. (AU)

GNSS Radio Frequency Interference Monitoring from LEO Satellites: An In-Laboratory Prototype.

The disruptive effect of radio frequency interference (RFI) on global navigation satellite system (GNSS) signals is well known, and in the last four decades, many have been investigated as countermeasures. Recently, low-Earth orbit (LEO) satellites have been looked at as a good opportunity for GNSS RFI monitoring, and the last five years have seen the proliferation of many commercial and academic initiatives. In this context, this paper proposes a new spaceborne system to detect, classify, and localize terrestrial GNSS RFI signals, particularly jamming and spoofing, for civil use. This paper presents the implementation of the RFI detection software module to be hosted on a nanosatellite. The whole development work is described, including the selection of both the target platform and the algorithms, the implementation, the detection performance evaluation, and the computational load analysis. Two are the implemented RFI detectors: the chi-square goodness-of-fit (GoF) algorithm for non-GNSS-like interference, e.g., chirp jamming, and the snapshot acquisition for GNSS-like interference, e.g., spoofing. Preliminary testing results in the presence of jamming and spoofing signals reveal promising detection capability in terms of sensitivity and highlight room to optimize the computational load, particularly for the snapshot-acquisition-based RFI detector.

The subgenomic flaviviral RNA suppresses RNA interference through competing with siRNAs for binding RISC components.

During the life cycle of mosquito-borne flaviviruses, substantial subgenomic flaviviral RNA (sfRNA) is produced via incomplete degradation of viral genomic RNA by host XRN1. Zika virus (ZIKV) sfRNA has been detected in mosquito and mammalian somatic cells. Human neural progenitor cells (hNPCs) in the developing brain are the major target cells of ZIKV, and antiviral RNA interference (RNAi) plays a critical role in hNPCs. However, whether ZIKV sfRNA was produced in ZIKV-infected hNPCs as well as its function remains not known. In this study, we demonstrate that abundant sfRNA was produced in ZIKV-infected hNPCs. RNA pulldown and mass spectrum assays showed ZIKV sfRNA interacted with host proteins RHA and PACT, both of which are RNA-induced silencing complex (RISC) components. Functionally, ZIKV sfRNA can antagonize RNAi by outcompeting small interfering RNAs (siRNAs) in binding to RHA and PACT. Furthermore, the 3' stem loop (3'SL) of sfRNA was responsible for RISC components binding and RNAi inhibition, and 3'SL can enhance the replication of a viral suppressor of RNAi (VSR)-deficient virus in a RHA- and PACT-dependent manner. More importantly, the ability of binding to RISC components is conversed among multiple flaviviral 3'SLs. Together, our results identified flavivirus 3'SL as a potent VSR in RNA format, highlighting the complexity in virus-host interaction during flavivirus infection.IMPORTANCEZika virus (ZIKV) infection mainly targets human neural progenitor cells (hNPCs) and induces cell death and dysregulated cell-cycle progression, leading to microcephaly and other central nervous system abnormalities. RNA interference (RNAi) plays critical roles during ZIKV infections in hNPCs, and ZIKV has evolved to encode specific viral proteins to antagonize RNAi. Herein, we first show that abundant sfRNA was produced in ZIKV-infected hNPCs in a similar pattern to that in other cells. Importantly, ZIKV sfRNA acts as a potent viral suppressor of RNAi (VSR) by competing with siRNAs for binding RISC components, RHA and PACT. The 3'SL of sfRNA is responsible for binding RISC components, which is a conserved feature among mosquito-borne flaviviruses. As most known VSRs are viral proteins, our findings highlight the importance of viral non-coding RNAs during the antagonism of host RNAi-based antiviral innate immunity.

When Argonaute takes out the ribonuclease sword.

Argonaute (AGO) proteins in all three domains of life form ribonucleoprotein or deoxyribonucleoprotein complexes by loading a guide RNA or DNA, respectively. Since all AGOs retain a PIWI domain that takes an RNase H fold, the ancestor was likely an endoribonuclease (i.e., a slicer). In animals, most miRNA-mediated gene silencing occurs slicer independently. However, the slicer activity of AGO is indispensable in specific events, such as development and differentiation, which are critical for vertebrates and thus cannot be replaced by the slicer-independent regulation. This review highlights the distinctions in catalytic activation mechanisms among slicing-competent AGOs, shedding light on the roles of two metal ions in target recognition and cleavage. The precision of the target specificity by the RNA-induced silencing complexes is reevaluated and redefined. The possible coevolutionary relationship between slicer-independent gene regulation and AGO-binding protein, GW182, is also explored. These discussions reveal that numerous captivating questions remain unanswered regarding the timing and manner in which AGOs employ their slicing activity.

A Programmable Crypto-Processor for National Institute of Standards and Technology Post-Quantum Cryptography Standardization Based on the RISC-V Architecture.

The advancement of quantum computing threatens the security of conventional public-key cryptosystems. Post-quantum cryptography (PQC) was introduced to ensure data confidentiality in communication channels, and various algorithms are being developed. The National Institute of Standards and Technology (NIST) has initiated PQC standardization, and the selected algorithms for standardization and round 4 candidates were announced in 2022. Due to the large memory footprint and highly repetitive operations, there have been numerous attempts to accelerate PQC on both hardware and software. This paper introduces the RISC-V instruction set extension for NIST PQC standard algorithms and round 4 candidates. The proposed programmable crypto-processor can support a wide range of PQC algorithms with the extended RISC-V instruction set and demonstrates significant reductions in code size, the number of executed instructions, and execution cycle counts of target operations in PQC algorithms of up to 79%, 92%, and 87%, respectively, compared to RV64IM with optimization level 3 (-O3) in the GNU toolchain.

Exploration of violet-to-blue thermally activated delayed fluorescence emitters based on "CH/N" and "H/CN" substitutions at diphenylsulphone acceptor. A DFT study.

The violet-to-blue thermally activated delayed fluorescence (TADF) emitters were created employing several substituents based on 5,5-dimethyl-5,10-dihydropyrido [2,3-b][1,8] naphthyridine-diphenylsulphone (DMDHPN-DPS) called 1a via "CH/N" and "H/CN" substitutions at the diphenylsulphone acceptor (DPS) moiety. The parent compound 1a was selected from our former work after extensive research employing "CH/N" substitution on Dimethyl-acridine (DMAC) donor moiety. There is a little overlap amid the highest occupied molecular orbitals (HOMOs) and lowest un-occupied molecular orbitals (LUMOs) due to the distribution of HOMOs and LUMOs primarily on the DMDHPN donor and the DPS acceptor moieties, respectively. It resulted in a narrower energy gap (∆E ST) between the lowest singlet (S1) and triplet (T1) excited state. In nearly all derivatives, the steric hindrance results in a larger torsional angle (85°-98°) between the plane of the DMDHPN and the DPS moieties. The predicted ΔE ST values of the compounds with "H/CN" substitution were lower than those of the comparable "CH/N" substituents, demonstrating the superiority of the reversible inter-system crossing (RISC) from the T1 → S1 state. All derivatives have emission wavelengths (λ em) in the range of 357-449 nm. The LUMO → HOMO transition energies in the S1 states are lowered by the presence of -CN groups or -N = atoms at the ortho or meta sites of a DPS acceptor unit, causing the λ em values to red-shift. Furthermore, the λ em showed a greater red-shift as there were more-CN groups or -N = atoms. Three of the derivatives named 1b, 1g, and 1h, emit violet (394 nm, 399 nm, and 398 nm, respectively), while two others, 1f and 1i, emit blue shade (449 nm each) with reasonable emission intensity peak demonstrating that these derivatives are effective violet-to-blue TADF nominees. The lower ΔE ST value for derivative 1i (0.01 eV) with λ em values of 449 nm make this molecule the finest choice for blue TADF emitter amongst all the studied derivatives. We believe our research might lead to the development of more proficient blue TADF-OLEDs in the future.

miR-7 is recruited to the high molecular weight RNA-induced silencing complex in CD8+ T cells upon activation and suppresses IL-2 signaling.

Increasing evidence suggests mammalian Argonaute (Ago) proteins partition into distinct complexes within cells, but there is still little biochemical or functional understanding of the miRNAs differentially associated with these complexes. In naïve T cells, Ago2 is found almost exclusively in low molecular weight (LMW) complexes which are associated with miRNAs but not their target mRNAs. Upon T-cell activation, a proportion of these Ago2 complexes move into a newly formed high molecular weight (HMW) RNA-induced silencing complex (RISC), which is characterized by the presence of the GW182 protein that mediates translational repression. Here, we demonstrate distinct partitioning of miRNAs and isomiRs in LMW versus HMW RISCs upon antigen-mediated activation of CD8+ T cells. We identify miR-7 as highly enriched in HMW RISC and demonstrate that miR-7 inhibition leads to increased production of IL-2 and up-regulation of the IL-2 receptor, the transferrin receptor, CD71 and the amino acid transporter, CD98. Our data support a model where recruitment of miR-7 to HMW RISC restrains IL-2 signaling and the metabolic processes regulated by IL-2.

Organoboron Complexes as Thermally Activated Delayed Fluorescence (TADF) Materials for Organic Light-Emitting Diodes (OLEDs): A Computational Study.

We report on organoboron complexes characterized by very small energy gaps (ΔEST) between their singlet and triplet states, which allow for highly efficient harvesting of triplet excitons into singlet states for working as thermally activated delayed fluorescence (TADF) devices. Energy gaps ranging between 0.01 and 0.06 eV with dihedral angles of ca. 90° were registered. The spin-orbit couplings between the lowest excited S1 and T1 states yielded reversed intersystem crossing rate constants (KRISC) of an average of 105 s-1. This setup accomplished radiative decay rates of ca. 106 s-1, indicating highly potent electroluminescent devices, and hence, being suitable for application as organic light-emitting diodes.

Associations of Perceived Stress and Psychological Resilience With Cognition and a Modifiable Dementia Risk Score in Middle-Aged Adults.

OBJECTIVES: Psychological stress has been proposed as a risk factor for cognitive impairment and dementia. However, it remains unclear how an individual's stress-coping ability (i.e., psychological resilience) is related to cognition. This cross-sectional study investigated whether perceived stress and psychological resilience were associated with cognition and a modifiable dementia risk score in a large community-based sample of cognitively normal adults. The moderating effect of psychological resilience was also examined. METHODS: Participants (mean age = 57 ± 7 years) enrolled in the web-based Healthy Brain Project completed the Perceived Stress Scale and the Connor-Davidson Resilience Scale. Domains of attention and working memory were assessed using the Cogstate Brief Battery (n = 1,709), and associative memory was assessed using the Cambridge Neuropsychological Test Automated Battery (n = 1,522). Dementia risk was estimated for 1,913 participants using a modified version of the Cardiovascular Risk Factors, Aging, and Incidence of Dementia dementia risk score, calculated using only readily modifiable dementia risk factors. RESULTS: In separate linear regression analyses adjusted for age, sex, education, and race, greater levels of perceived stress and lower levels of psychological resilience were associated with poorer performance across all cognitive domains, as well as a higher modifiable dementia risk score. Psychological resilience did not moderate the effect of perceived stress on cognition or the dementia risk score. DISCUSSION: Higher perceived stress and lower resilience were associated with poorer cognition and a greater burden of modifiable dementia risk factors. Intervention studies are required to determine if lowering stress and building resilience can mitigate cognitive deficits and reduce dementia risk.

A Study of the Clinical Profile and Respiratory Index of Severity in Children (RISC) Score in Infants Admitted With Acute Respiratory Infections at a Tertiary Care Hospital.

Background Pneumonia is a major infectious cause of mortality in young children worldwide. The Respiratory Index of Severity in Children (RISC) score was designed with the intent to provide an objective mean to quantify the severity of lower respiratory tract infection in young children based on their risk of mortality. Knowledge about the clinical profile of acute respiratory infections and the scoring system predicting the risk of mortality helps in modifying treatment strategies. This study was undertaken at a resource-limited, tertiary-care public hospital in southern India with the objectives of describing the clinical profile of infants admitted with acute respiratory infections and determining the association of the RISC score with mortality. Method This was a retrospective observational study conducted over six months. Case records of infants admitted with acute respiratory infections were reviewed. The socio-demographic and clinical details of each case were recorded. The RISC score was calculated using clinical parameters which included the history of refusal of feeds, oxygen saturation lower than 90%, chest in-drawing, wheezing, and low weight-for-age. The maximum score was six. Descriptive data was represented using mean, standard deviation, and percentage or proportion. The association between any two categorical variables was analyzed using the chi-square test. The differences between any two continuous variables were analyzed using the independent sample t-test. A p-value of < 0.05 was considered statistically significant. Results A total of 75 infants were admitted with a diagnosis of acute respiratory infection during the study period. Of these, 68 were included in the study. The mean age of infants was 6.69 ± 3.96 months; 58.8% were male, 41 (60%) were exclusively breastfed, and 51 (75%) were up-to-date immunized. Twenty (29.4%) infants had a history of exposure to indoor smoke. The majority (67.6%) had pneumonia. Nine (13.2%) were mechanically ventilated. The mean duration of hospital stay was 8.16 ± 5.45 days. Sixty-three (92.64%) infants recovered and there were five deaths. The presence of less than 90% oxygen saturation (p-value=0.004), a diagnosis of severe pneumonia (p-value <0.001), and the need for mechanical ventilation (p-value <0.001) were significantly associated with mortality. A statistically significant (p-value=0.001) association was observed between the RISC score and mortality. Conclusions Addressable factors like the absence of exclusive breastfeeding, partial-immunization status, exposure to indoor smoke, and malnutrition were observed in infants with acute respiratory infections, which reinforces the importance of protective and preventive strategies for the control of pneumonia. The RISC score was observed to be beneficial in predicting mortality in an infant with acute respiratory infection. Triaging and early identification of infants at risk of mortality using this score could be very helpful in initiating timely treatment to reduce mortality, especially in resource-limited settings.