Global impacts of COVID-19 pandemic on sexual and reproductive health services: An international comparative study on primary care from the INTRePID Consortium.

OBJECTIVE: To understand how the COVID-19 pandemic has impacted sexual and reproductive health (SRH) visits. DESIGN: An ecological study comparing SRH services volume in different countries before and after the onset of the COVID-19 pandemic. SETTING: Seven countries from the INTernational ConsoRtium of Primary Care BIg Data Researchers (INTRePID) across four continents. POPULATION: Over 3.8 million SRH visits to primary care physicians in Australia, China, Canada, Norway, Singapore, Sweden and the USA. METHODS: Difference in average SRH monthly visits before and during the pandemic, with negative binomial regression modelling to compare predicted and observed number of visits during the pandemic for SRH visits. MAIN OUTCOME MEASURES: Monthly number of visits to primary care physicians from 2018 to 2021. RESULTS: During the pandemic, the average volume of monthly SRH visits increased in Canada (15.6%, 99% CI 8.1-23.0%) where virtual care was pronounced. China, Singapore, Sweden and the USA experienced a decline (-56.5%, 99% CI -74.5 to -38.5%; -22.7%, 99% CI -38.8 to -6.5%; -19.4%, 99% CI -28.3 to -10.6%; and -22.7%, 99% CI -38.8 to -6.5%, respectively); while Australia and Norway showed insignificant changes (6.5%, 99% CI -0.7 to -13.8% and 1.7%, 99% CI -6.4 to -9.8%). The countries that maintained (Australia, Norway) or surpassed (Canada) pre-pandemic visit rates had the greatest use of virtual care. CONCLUSIONS: In-person SRH visits to primary care decreased during the pandemic. Virtual care seemed to counterbalance that decline. Although cervical cancer screening appeared insensitive to virtual care, strategies such as incorporating self-collected samples for HPV testing may provide a solution in a future pandemic.

Enantio- and Diastereoselective Synthesis of Chiral Tetrasubstituted α-Amino Allenoates Bearing a Vicinal All-Carbon Quaternary Stereocenter with Dual-Copper-Catalysis.

The skeletons of chiral tetrasubstituted allenes bearing a vicinal all-carbon quaternary stereocenter are of importance but still challenging to synthesize. Herein, we report enantio- and diastereoselective γ-additions of 1-alkynyl ketimines with dual-copper-catalysis under mild conditions, affording chiral tetrasubstituted α-amino allenoates bearing a vicinal all-carbon quaternary stereocenter in high yields (up to 99 % yield) with excellent enantioselectivities (up to 99 % ee) and diastereoselectivities (up to >20 : 1 dr). Importantly, the stereodivergent synthesis of the products was realized by the asymmetric γ-addition reaction and the Grignard reagent promoted epimerization. Moreover, the dual-copper-catalyzed γ-addition reactions were smoothly applied to a gram-scale reaction and adopted to introduce chiral tetrasubstituted allenyl moieties into bioactive molecules. Mechanistic experiments and density functional theory (DFT) calculations demonstrated that the asymmetric γ-addition reactions were catalyzed by double chiral copper catalysts.

Targeting inflammatory monocytes by immune-modifying nanoparticles prevents acute kidney allograft rejection.

Inflammatory monocytes are a major component of the cellular infiltrate in acutely rejecting human kidney allografts. Since immune-modifying nanoparticles (IMPs) bind to circulating inflammatory monocytes via the specific scavenger receptor MARCO, causing diversion to the spleen and subsequent apoptosis, we investigated the therapeutic potential of negatively charged, 500-nm diameter polystyrene IMPs to prevent kidney allograft rejection. Kidney transplants were performed from BALB/c (H2d) to C57BL/6 (H2b) mice in two groups: controls (allo) and allo mice infused with IMPs. Groups were studied for 14 (acute rejection) or 100 (chronic rejection) days. Allo mice receiving IMPs exhibited superior survival and markedly less acute rejection, with better kidney function, less tubulitis, and diminished inflammatory cell density, cytokine and cytotoxic molecule expression in the allograft and lower titers of donor-specific IgG2c antibody in serum at day 14, as compared to allo mice. Cells isolated from kidneys from allo mice receiving IMPs showed reduced Ly6Chi monocytes, CD11b+ cells and NKT+ cells compared to allo mice. IMPs predominantly bound CD11b+ cells in the bloodstream and CD11b+ and CD11c-B220+ marginal zone B cells in the spleen. In the spleen, IMPs were found predominantly in red pulp, colocalized with MARCO and expression of cleaved caspase-3. At day 100, allo mice receiving IMPs exhibited reduced macrophage M1 responses but were not protected from chronic rejection. IMPs afforded significant protection from acute rejection, inhibiting both innate and adaptive alloimmunity. Thus, our current experimental findings, coupled with our earlier demonstration of IMP-induced protection in kidney ischemia-reperfusion injury, identify IMPs as a potential induction agent in kidney transplantation.

Copper-Catalyzed Regioselective [3+3] Annulations of Alkynyl Ketimines with α-Cyano Ketones: the Synthesis of Polysubstituted 4H-Pyran Derivatives with a CF3 -Containing Quaternary Center.

Regioselective [3+3] annulation of alkynyl ketimines with α-cyano ketones for the synthesis of polysubstituted 4H-pyran derivatives with a quaternary CF3 -containing center has been realized by using Cu(OAc)2 as the catalyst. The novel strategy tolerates a wide range of α-CF3 alkynyl ketimines and α-cyano ketones with both aryl and alkyl substitutents. A preliminary asymmetric synthesis of chiral product 3 has been attempted by using copper and chiral thiourea as the cocatalyst with excellent yields (86-99 %) and good enantioselectivities (71-78 % ee). Furthermore, product 3 aa could be obtained on a gram-scale reaction with 75 % yield and 99 % ee after recrystallization. Several products were also transformed readily. Control experiments indicate that the reaction involves a process with a base-catalyzed or chiral thiourea-catalyzed Mannich-type reaction followed by a highly regioselective copper-catalyzed ring-closing reaction on the alkynyl moiety in a 6-endo-dig fashion.

Further evidence that antipsychotic medication does not prevent long-term psychosis in higher-risk individuals.

OBJECTIVE: Although existing guidelines have discouraged use of antipsychotics for general clinical high-risk (CHR) individuals, it is unclear if antipsychotics can prevent psychosis in higher-risk population. We aimed to study the comparative real-world effectiveness of antipsychotic treatments for preventing psychosis in higher-risk CHR individuals. METHODS: A total of 300 CHR individuals were identified using the structured interview for prodromal syndromes (SIPS) and followed the participants for 3 years. In total, 228(76.0%) individuals completed baseline assessments using the NAPLS-2 risk calculator (NAPLS-2-RC), and 210(92.1%) completed the follow-up. The sample was further stratified according to risk level. "Higher-risk" was defined based on the NAPLS-2-RC risk score (≥ 20%) and SIPS positive symptom total scores (≥ 10). The main outcome was conversion to psychosis and poor functional outcomes, defined as a global assessment of function (GAF) score lower than 60 at follow-up. RESULTS: In higher-risk CHR individuals, we found no significant difference in the rate of conversion to psychosis or poor functional outcomes between the antipsychotic and no-antipsychotic groups. Low-risk individuals treated with antipsychotic drugs were more likely exhibit poor functional outcomes compared with the no-antipsychotics group(NAPLS-2-RC estimated risk: χ2 = 8.330, p = 0.004; Positive symptom severity: χ2 = 12.997, p < 0.001). No significant effective factors were identified for prevention of the conversion to psychosis; conversely, CHR individuals who were treated with high dose antipsychotics (olanzapine, aripiprazole) showed a significantly increased risk of poor functional outcomes. CONCLUSIONS: In CHR individuals, antipsychotic treatment should be provided with caution because of the risk of poor functional outcomes. Further, antipsychotic treatment does not appear to prevent onset of psychosis in real-world settings.

Targeted Nanoscale 3D Thermal Imaging of Tumor Cell Surface with Functionalized Quantum Dots.

Measuring the changes in tumor cell surface temperature can provide insights into cellular metabolism and pathological features, which is significant for targeted chemotherapy and hyperthermic therapy. However, conventional micro-nano scale methods are invasive and can only measure the temperature of cells across a single plane, which excludes specific organelles. In this study, fluorescence quantum dots (QDs) are functionalized with the membrane transport protein transferrin (Tf) as a thermo-sensor specific for tumor cell membrane. The covalent conjugation is optimized to maintain the relative fluorescence intensity of the Tf-QDs to >90%. In addition, the Tf-QDs undergo changes in the fluorescence spectra as a function of temperature, underscoring its thermo-sensor function. Double helix point spread function imaging optical path is designed to locate the probe at nanoscale, and 3D thermal imaging technology is proposed to measure the local temperature distribution and direction of heat flux on the tumor cell surface. This novel targeted nanoscale 3D thermometry method can be a highly promising tool for measuring the local and global temperature distribution across intracellular organelles.

Basic insights into Zika virus infection of neuroglial and brain endothelial cells.

Zika virus (ZIKV) has recently emerged as an important human pathogen due to the strong evidence that it causes disease of the central nervous system, particularly microcephaly and Guillain-Barré syndrome. The pathogenesis of disease, including mechanisms of neuroinvasion, may include both invasion via the blood-brain barrier and via peripheral (including cranial) nerves. Cellular responses to infection are also poorly understood. This study characterizes the in vitro infection of laboratory-adapted ZIKV African MR766 and two Asian strains of (1) brain endothelial cells (hCMEC/D3 cell line) and (2) olfactory ensheathing cells (OECs) (the neuroglia populating cranial nerve I and the olfactory bulb; both human and mouse OEC lines) in comparison to kidney epithelial cells (Vero cells, in which ZIKV infection is well characterized). Readouts included infection kinetics, intracellular virus localization, viral persistence and cytokine responses. Although not as high as in Vero cells, viral titres exceeded 104 plaque-forming units (p.f.u.) ml-1 in the endothelial/neuroglial cell types, except hOECs. Despite these substantial titres, a relatively small proportion of neuroglial cells were primarily infected. Immunolabelling of infected cells revealed localization of the ZIKV envelope and NS3 proteins in the cytoplasm; NS3 staining overlapped with that of dsRNA replication intermediate and the endoplasmic reticulum (ER). Infected OECs and endothelial cells produced high levels of pro-inflammatory chemokines. Nevertheless, ZIKV was also able to establish persistent infection in hOEC and hCMEC/D3 cells. Taken together, these results provide basic insights into ZIKV infection of endothelial and neuroglial cells and will form the basis for further study of ZIKV disease mechanisms.

Comparison of laboratory threshold criteria in drug-induced liver injury detection algorithms for use in pharmacovigilance.

PURPOSE: For the purpose of pharmacovigilance, we sought to determine the best performing laboratory threshold criteria to detect drug-induced liver injury (DILI) in the electronic medical records (EMR). METHODS: We compared three commonly used liver chemistry criteria from the DILI expert working group (DEWG), DILI network (DILIN), and Council for International Organizations of Medical Sciences (CIOMS), based on hospital EMR for years 2010 and 2011 (42 176 admissions), using independent medical record review. The performance characteristics were compared in terms of sensitivity, specificity, positive predictive value (PPV), negative predictive value, accuracy, F-measure, and area under the receiver operating characteristic curve (AUROC). RESULTS: DEWG had the highest PPV (5.5%, 95% CI: 4.1%-7.2%), specificity (97.0%, 95% CI: 96.8%-97.2%), accuracy (96.8%, 95% CI: 96.6%-97.0%) and F-measure (0.099). CIOMS had the highest sensitivity (74.0%, 95% CI: 64.3%-82.3%) and AUROC (85.2%, 95% CI: 80.8%-89.7%). Besides the laboratory criteria, including additional keywords in the classification algorithm improved the PPV and F-measure to a maximum of 29.0% (95% CI: 22.3%-36.5%) and 0.379, respectively. CONCLUSIONS: More stringent criteria (DEWG and DILIN) performed better in terms of PPV, specificity, accuracy and F-measure. CIOMS performed better in terms of sensitivity. An algorithm with high sensitivity is useful in pharmacovigilance for detecting rare events and to avoid missing cases. Requiring at least two abnormal liver chemistries during hospitalization and text-word searching in the discharge summaries decreased false positives without loss in sensitivity.

Zika virus encephalitis in immunocompetent mice is dominated by innate immune cells and does not require T or B cells.

BACKGROUND: Until the end of the twentieth century, Zika virus (ZIKV) was thought to cause a mostly mild, self-limiting disease in humans. However, as the geographic distribution of ZIKV has shifted, so too has its pathogenicity. Modern-day ZIKV infection is now known to cause encephalitis, acute disseminated encephalomyelitis, and Guillain-Barré syndrome in otherwise healthy adults. Nevertheless, the underlying pathogenetic mechanisms responsible for this shift in virulence remain unclear. METHODS: Here, we investigated the contribution of the innate versus the adaptive immune response using a new mouse model involving intracranial infection of adult immunocompetent mice with a moderately low dose of ZIKV MR766. To determine the contribution of type I interferons (IFN-Is) and adaptive immune cells, we also studied mice deficient for the IFN-I receptor 1 (Ifnar1-/-) and recombination-activating gene 1 (Rag1-/-). RESULTS: We show that intracranial infection with ZIKV resulted in lethal encephalitis. In wild-type mice, ZIKV remained restricted predominantly to the central nervous system (CNS) and infected neurons, whereas astrocytes and microglia were spared. Histological and molecular analysis revealed prominent activation of resident microglia and infiltrating monocytes that were accompanied by an expression of pro-inflammatory cytokines. The disease was independent of T and B cells. Importantly, unlike peripheral infection, IFN-Is modulated but did not protect from infection and lethal disease. Lack of IFN-I signaling resulted in spread of the virus, generalized inflammatory changes, and accelerated disease onset. CONCLUSIONS: Using intracranial infection of immunocompetent wild-type mice with ZIKV, we demonstrate that in contrast to the peripheral immune system, the CNS is susceptible to infection and responds to ZIKV by initiating an antiviral immune response. This response is dominated by resident microglia and infiltrating monocytes and macrophages but does not require T or B cells. Unlike in the periphery, IFN-Is in the CNS cannot prevent the establishment of infection. Our findings show that ZIKV encephalitis in mice is dependent on the innate immune response, and adaptive immune cells play at most a minor role in disease pathogenesis.

Nanoscale 3D temperature gradient measurement based on fluorescence spectral characteristics of the CdTe quantum dot probe.

The existing quantum dot temperature measurement techniques can only measure the planar temperature in the cell but fails in 3D temperature investigation. We present a novel method of measuring the 3D temperature field on nano scale, combining fluorescence spectral characteristics of the CdTe quantum dot probe with optical spatial positioning. Based on dual-helix point spread function, a 3D temperature optical measurement system with a resolution of 0.625 °C is established, providing a new perspective of 3D temperature measurement inside the cell. We thus offer an original research tool for further revealing the evolution process of secretions in cell metabolism.

Application and optimisation of the Comparison on Extreme Laboratory Tests (CERT) algorithm for detection of adverse drug reactions: Transferability across national boundaries.

PURPOSE: The Singapore regulatory agency for health products (Health Sciences Authority), in performing active surveillance of medicines and their potential harms, is open to new methods to achieve this goal. Laboratory tests are a potential source of data for this purpose. We have examined the performance of the Comparison on Extreme Laboratory Tests (CERT) algorithm, developed by Ajou University, Korea, as a potential tool for adverse drug reaction detection based on the electronic medical records of the Singapore health care system. METHODS: We implemented the original CERT algorithm, comparing extreme laboratory results pre- and post-drug exposure, and 5 variations thereof using 4.5 years of National University Hospital (NUH) electronic medical record data (31 869 588 laboratory tests, 6 699 591 drug dispensings from 272 328 hospitalizations). We investigated 6 drugs from the original CERT paper and an additional 47 drugs. We benchmarked results against a reference standard that we created from UpToDate 2015. RESULTS: The original CERT algorithm applied to all 53 drugs and 44 laboratory abnormalities yielded a positive predictive value (PPV) and sensitivity of 50.3% and 54.1%, respectively. By raising the minimum number of cases for each drug-laboratory abnormality pair from 2 to 400, the PPV and sensitivity increased to 53.9% and 67.2%, respectively. This post hoc variation, named CERT400, performed particularly well for drug-induced hepatic and renal toxicities. DISCUSSION: We have demonstrated that the CERT algorithm can be applied across national boundaries. One modification (CERT400) was able to identify adverse drug reaction signals from laboratory data with reasonable PPV and sensitivity, which indicates potential utility as a supplementary pharmacovigilance tool.

[Asthenozoospermia is not correlated with 3' UTR polymorphisms of the GRP78 gene].

OBJECTIVE: To investigate the correlation of the single nucleotide polymorphisms (SNPs) rs12009, rs1140763 and rs16927997 in the 3'-untranslated region (3'UTR) of the glucose-regulated protein 78 (GRP78) gene with the risk of male asthenozoospermia (AZS). METHODS: We included 400 AZS patients in the AZS group and another 400 fertile men as normal controls. Using the SNaPshot technique, we genotyped the rs12009, rs1140763 and rs16927997 polymorphisms in the 3'UTR of the GRP78 gene in all the male subjects and analyzed the association of the three SNPs with AZS. RESULTS: The percentage of progressively motile sperm was significantly lower in the AZS group than in the normal controls (ï¼»20.09 ± 8.18ï¼½ % vs ï¼»57.16 ± 13.45ï¼½ %, P <0.01). Three genotypes of CC, CT and TT and 2 alleles of C and T were found in rs12009 and rs1140763 of the GRP78 gene, and another three genotypes of GG, GA and AA and two alleles of G and A were observed in rs16927997. There were no statistically significant differences between the control and AZS groups in the frequencies of the C and T alleles in rs12009 (44.3% vs 47.3% and 55.7% vs 52.7%, P >0.05) or rs1140763 (50.0% vs 52.0% and 50.0% vs 48.0%, P >0.05) or those of the G and A alleles in rs16927997 (6.0% vs 4.4% and 94.0% vs 95.6%, P >0.05), nor in the genotypes and allele frequencies of the 3 polymorphisms (P >0.05). Furthermore, three haplotypes of C-C-A, T-C-G and T-T-A were observed in the male subjects but showed no evident correlation between the AZS and normal control groups. CONCLUSIONS: The polymorphisms in the 3'UTR of the GRP78 gene are not correlated with the risk of male asthenozoospermia.

Flexible and conductive MXene films and nanocomposites with high capacitance.

MXenes, a new family of 2D materials, combine hydrophilic surfaces with metallic conductivity. Delamination of MXene produces single-layer nanosheets with thickness of about a nanometer and lateral size of the order of micrometers. The high aspect ratio of delaminated MXene renders it promising nanofiller in multifunctional polymer nanocomposites. Herein, Ti3C2T(x) MXene was mixed with either a charged polydiallyldimethylammonium chloride (PDDA) or an electrically neutral polyvinyl alcohol (PVA) to produce Ti3C2T(x)/polymer composites. The as-fabricated composites are flexible and have electrical conductivities as high as 2.2 × 10(4) S/m in the case of the Ti3C2T(x)/PVA composite film and 2.4 × 10(5) S/m for pure Ti3C2T(x) films. The tensile strength of the Ti3C2T(x)/PVA composites was significantly enhanced compared with pure Ti3C2T(x) or PVA films. The intercalation and confinement of the polymer between the MXene flakes not only increased flexibility but also enhanced cationic intercalation, offering an impressive volumetric capacitance of ∼530 F/cm(3) for MXene/PVA-KOH composite film at 2 mV/s. To our knowledge, this study is a first, but crucial, step in exploring the potential of using MXenes in polymer-based multifunctional nanocomposites for a host of applications, such as structural components, energy storage devices, wearable electronics, electrochemical actuators, and radiofrequency shielding, to name a few.

Interaction of Heat Shock Protein Cpn10 with the Cyclin E/Cdk2 Substrate Nuclear Protein Ataxia-Telangiectasia (NPAT) Is Involved in Regulating Histone Transcription.

Precise modulation of histone gene transcription is critical for cell cycle progression. As a direct substrate of Cyclin E/CDK2, nuclear protein ataxia-telangiectasia (NPAT) is a crucial factor in regulating histone transcription and cell cycle progression. Here we identified that Cpn10/HSPE, a 10-kDa heat shock protein, is a novel interacting partner of NPAT. A pool of Cpn10 is colocalized with NPAT foci during G1 and S phases in nuclei. Gain- and loss-of-function experiments unraveled an essential role of Cpn10 in histone transcription. A conserved DLFD motif within Cpn10 was critical for targeting NPAT and modulating histone transcription. More importantly, knockdown of Cpn10 disrupted the focus formation of both NPAT and FADD-like interleukin-1ß-converting enzyme-associated huge protein without affecting Coilin-positive Cajal bodies. Finally, Cpn10 is important for S phase progression and cell proliferation. Taken together, our finding revealed a novel role of Cpn10 in the spatial regulation of NPAT signaling and disclosed a previously unappreciated link between the heat shock protein and histone transcription regulation.

Freeze-drying for sustainable synthesis of nitrogen doped porous carbon cryogel with enhanced supercapacitor and lithium ion storage performance.

A chitosan (CS) based nitrogen doped carbon cryogel with a high specific surface area (SSA) has been directly synthesized via a combined process of freeze-drying and high-temperature carbonization without adding any activation agents. The as-made carbon cryogel demonstrates an SSA up to 1025 m(2) g(-1) and a high nitrogen content of 5.98 wt%, while its counterpart derived from CS powder only shows an SSA of 26 m(2) g(-1). Freeze-drying is a determining factor for the formation of carbon cryogel with a high SSA, where the CS powder with a size of ca. 200 µm is transformed into the sheet-shaped cryogel with a thickness of 5-8 µm. The as-made carbon cryogel keeps the sheet-shaped structure and the abundant pores are formed in situ and decorated inside the sheets during carbonization. The carbon cryogel shows significantly enhanced performance as supercapacitor and lithium ion battery electrodes in terms of capacity and rate capability due to its quasi two-dimensional (2D) structure with reduced thickness. The proposed method may provide a simple approach to configure 2D biomass-derived advanced carbon materials for energy storage devices.

Magnetically recoverable Ni/C catalysts with hierarchical structure and high-stability for selective hydrogenation of nitroarenes.

Here we report that magnetic Ni/C catalysts with hierarchical structure can be fabricated from a mixture of nickel acetate, polyethylene glycol-200 and furfural by a one-step hydrothermal method, followed by calcination. It has been found that the calcination temperature is the key factor affecting the structure, morphology and the catalytic performance of the Ni/C catalysts. Of the as-made catalysts, the Ni/C sample calcined at 300 °C features small-size metallic Ni particles with high dispersion in the carbon matrix and a unique hierarchical structure, and has the highest rate of conversion of o-chloronitrobenzene with high selectivity to o-chloroanilines. The concerned Ni/C catalysts are magnetic due to the presence of metallic Ni particles, which makes their recovery easy after the reaction by an external magnetic field. The recovered Ni/C catalysts can be recycled at least ten times without obvious loss both in Ni loading and the catalytic performance. This kind of catalyst is also active for the selective hydrogenation of other nitroarenes to the corresponding anilines.

Synthesis of carbon/sulfur nanolaminates by electrochemical extraction of titanium from Ti2SC.

Herein we electrochemically and selectively extract Ti from the MAX phase Ti2SC to form carbon/sulfur (C/S) nanolaminates at room temperature. The products are composed of multi-layers of C/S flakes, with predominantly amorphous and some graphene-like structures. Covalent bonding between C and S is observed in the nanolaminates, which render the latter promising candidates as electrode materials for Li-S batteries. We also show that it is possible to extract Ti from other MAX phases, such as Ti3AlC2, Ti3SnC2, and Ti2GeC, suggesting that electrochemical etching can be a powerful method to selectively extract the "M" elements from the MAX phases, to produce "AX" layered structures, that cannot be made otherwise. The latter hold promise for a variety of applications, such as energy storage, catalysis, etc.

Age-appropriate adaptation of creativity tasks for infants aged 12-24 months.

Creativity is an important skill that relates to innovation, problem-solving and artistic achievement. However, relatively little is known about the early development of creative potential in very young children, in part due to a paucity of tasks suitable for use during infancy. Current measures of creativity in early childhood include the Unusual Box Test, Torrance's Thinking Creatively in Action and Movement (TCAM) task and the Toca Kitchen Monsters task. These tasks are designed for children aged above 12, 36 and 18 months respectively, but very few measures of creativity can be used for infants aged below 2. Accordingly, here we report age-appropriate adaptations of TCAM and Toca Kitchen Monsters tasks for infants as young as 12 to 24 months. Considerations taken into account include (1) infants' cognitive capacities (i.e., attention span, language comprehension skills, motor skills, and approach to play), and (2) practicality of the stimuli, including suitability for use amid the COVID-19 pandemic. The modified creativity battery for infants includes three tasks: Music Play, Object Play and Exploratory Play tasks. The task protocols elaborated in this paper are intended to facilitate studies on the early development of creativity in infants aged between 12 and 24 months. Primary highlights include:•Age-appropriate adaptation of creativity tasks for use with infants aged between 12 and 24 months.•Consideration of infants' cognitive capacities and stimulus practicality.•Innovative use of movement as expression of infants' creative behaviour.

Effect of the COVID-19 pandemic on mental health visits in primary care: an interrupted time series analysis from nine INTRePID countries.

Background: The COVID-19 pandemic impacted mental health disorders, affecting both individuals with pre-existing conditions and those with no prior history. However, there is limited evidence regarding the pandemic's impact on mental health visits to primary care physicians. The International Consortium of Primary Care Big Data Researchers (INTRePID) explored primary care visit trends related to mental health conditions in Argentina, Australia, Canada, China, Norway, Peru, Singapore, Sweden, and the USA. Methods: We conducted an interrupted time series analysis in nine countries to examine changes in rates of monthly mental health visits to primary care settings from January 1st, 2018, to December 31st, 2021. Sub-group analysis considered service type (in-person/virtual) and six categories of mental health conditions (anxiety/depression, bipolar/schizophrenia/other psychotic disorders, sleep disorders, dementia, ADHD/eating disorders, and substance use disorder). Findings: Mental health visit rates increased after the onset of the pandemic in most countries. In Argentina, Canada, China, Norway, Peru, and Singapore, this increase was immediate ranged from an incidence rate ratio of 1·118 [95% CI 1.053-1.187] to 2.240 [95% CI 2.057-2.439] when comparing the first month of pandemic with the pre-pandemic trend. Increases in the following months varied across countries. Anxiety/depression was the leading reason for mental health visits in most countries. Virtual visits were reported in Australia, Canada, Norway, Peru, Sweden, and the USA, accounting for up to 40% of the total mental health visits. Interpretation: Findings suggest an overall increase in mental health visits, driven largely by anxiety/depression. During the COVID-19 pandemic, many of the studied countries adopted virtual care in particular for mental health visits. Primary care plays a crucial role in addressing mental ill-health in times of crisis. Funding: Canadian Institutes of Health Research grant #173094 and the Rathlyn Foundation Primary Care EMR Research and Discovery Fund.

Changes in primary care visits for respiratory illness during the COVID-19 pandemic: a multinational study by the International Consortium of Primary Care Big Data Researchers (INTRePID).

Objectives: The majority of patients with respiratory illness are seen in primary care settings. Given COVID-19 is predominantly a respiratory illness, the INTernational ConsoRtium of Primary Care BIg Data Researchers (INTRePID), assessed the pandemic impact on primary care visits for respiratory illnesses. Design: Definitions for respiratory illness types were agreed on collectively. Monthly visit counts with diagnosis were shared centrally for analysis. Setting: Primary care settings in Argentina, Australia, Canada, China, Norway, Peru, Singapore, Sweden and the United States. Participants: Over 38 million patients seen in primary care settings in INTRePID countries before and during the pandemic, from January 1st, 2018, to December 31st, 2021. Main outcome measures: Relative change in the monthly mean number of visits before and after the onset of the pandemic for acute infectious respiratory disease visits including influenza, upper and lower respiratory tract infections and chronic respiratory disease visits including asthma, chronic obstructive pulmonary disease, respiratory allergies, and other respiratory diseases. Results: INTRePID countries reported a marked decrease in the average monthly visits for respiratory illness. Changes in visits varied from -10.9% [95% confidence interval (CI): -33.1 to +11.3%] in Norway to -79.9% (95% CI: -86.4% to -73.4%) in China for acute infectious respiratory disease visits and - 2.1% (95% CI: -12.1 to +7.8%) in Peru to -59.9% (95% CI: -68.6% to -51.3%) in China for chronic respiratory illness visits. While seasonal variation in allergic respiratory illness continued during the pandemic, there was essentially no spike in influenza illness during the first 2 years of the pandemic. Conclusion: The COVID-19 pandemic had a major impact on primary care visits for respiratory presentations. Primary care continued to provide services for respiratory illness, although there was a decrease in infectious illness during the COVID pandemic. Understanding the role of primary care may provide valuable information for COVID-19 recovery efforts and planning for future global emergencies.