The association between dietary fiber intake and gastric cancer: a pooled analysis of 11 case-control studies.

PURPOSE: Gastric cancer (GC) is among the leading causes of cancer mortality worldwide. The objective of this study was to investigate the association between dietary fiber intake and GC. METHODS: We pooled data from 11 population or hospital-based case-control studies included in the Stomach Cancer Pooling (StoP) Project, for a total of 4865 histologically confirmed cases and 10,626 controls. Intake of dietary fibers and other dietary factors was collected using food frequency questionnaires. We calculated the odds ratios (OR) and 95% confidence intervals (CI) of the association between dietary fiber intake and GC by using a multivariable logistic regression model adjusted for study site, sex, age, caloric intake, smoking, fruit and vegetable intake, and socioeconomic status. We conducted stratified analyses by these factors, as well as GC anatomical site and histological type. RESULTS: The OR of GC for an increase of one quartile of fiber intake was 0.91 (95% CI: 0.85, 0.97), that for the highest compared to the lowest quartile of dietary fiber intake was 0.72 (95% CI: 0.59, 0.88). Results were similar irrespective of anatomical site and histological type. CONCLUSION: Our analysis supports the hypothesis that dietary fiber intake may exert a protective effect on GC.

Altered lipid homeostasis is associated with cerebellar neurodegeneration in SNX14 deficiency.

Dysregulated lipid homeostasis is emerging as a potential cause of neurodegenerative disorders. However, evidence of errors in lipid homeostasis as a pathogenic mechanism of neurodegeneration remains limited. Here, we show that cerebellar neurodegeneration caused by Sorting Nexin 14 (SNX14) deficiency is associated with lipid homeostasis defects. Recent studies indicate that SNX14 is an interorganelle lipid transfer protein that regulates lipid transport, lipid droplet (LD) biogenesis, and fatty acid desaturation, suggesting that human SNX14 deficiency belongs to an expanding class of cerebellar neurodegenerative disorders caused by altered cellular lipid homeostasis. To test this hypothesis, we generated a mouse model that recapitulates human SNX14 deficiency at a genetic and phenotypic level. We demonstrate that cerebellar Purkinje cells (PCs) are selectively vulnerable to SNX14 deficiency while forebrain regions preserve their neuronal content. Ultrastructure and lipidomic studies reveal widespread lipid storage and metabolism defects in SNX14-deficient mice. However, predegenerating SNX14-deficient cerebella show a unique accumulation of acylcarnitines and depletion of triglycerides. Furthermore, defects in LD content and telolysosome enlargement in predegenerating PCs suggest lipotoxicity as a pathogenic mechanism of SNX14 deficiency. Our work shows a selective cerebellar vulnerability to altered lipid homeostasis and provides a mouse model for future therapeutic studies.

Disparities in SARS-CoV-2 Infection by Race, Ethnicity, Language, and Social Vulnerability: Evidence from a Citywide Seroprevalence Study in Massachusetts, USA.

OBJECTIVES: Uncovering and addressing disparities in infectious disease outbreaks require a rapid, methodical understanding of local epidemiology. We conducted a seroprevalence study of SARS-CoV-2 infection in Holyoke, Massachusetts, a majority Hispanic city with high levels of socio-economic disadvantage to estimate seroprevalence and identify disparities in SARS-CoV-2 infection. METHODS: We invited 2000 randomly sampled households between 11/5/2020 and 12/31/2020 to complete questionnaires and provide dried blood spots for SARS-CoV-2 antibody testing. We calculated seroprevalence based on the presence of IgG antibodies using a weighted Bayesian procedure that incorporated uncertainty in antibody test sensitivity and specificity and accounted for household clustering. RESULTS: Two hundred eighty households including 472 individuals were enrolled. Three hundred twenty-eight individuals underwent antibody testing. Citywide seroprevalence of SARS-CoV-2 IgG was 13.1% (95% CI 6.9-22.3) compared to 9.8% of the population infected based on publicly reported cases. Seroprevalence was 16.1% (95% CI 6.2-31.8) among Hispanic individuals compared to 9.4% (95% CI 4.6-16.4) among non-Hispanic white individuals. Seroprevalence was higher among Spanish-speaking households (21.9%; 95% CI 8.3-43.9) compared to English-speaking households (10.2%; 95% CI 5.2-18.0) and among individuals in high social vulnerability index (SVI) areas based on the CDC SVI (14.4%; 95% CI 7.1-25.5) compared to low SVI areas (8.2%; 95% CI 3.1-16.9). CONCLUSIONS: The SARS-CoV-2 IgG seroprevalence in a city with high levels of social vulnerability was 13.1% during the pre-vaccination period of the COVID-19 pandemic. Hispanic individuals and individuals in communities characterized by high SVI were at the highest risk of infection. Public health interventions should be designed to ensure that individuals in high social vulnerability communities have access to the tools to combat COVID-19.

Salud bucal y factores de riesgo en campesinos de la comunidad rural La Picadora, Yaguajay, Sancti Spíritus

Fundamento: El panorama económico y epidemiológico ha repercutido en la salud bucal de las comunidades rurales. Objetivo: Describir el estado de salud bucal, así como identificar factores de riesgo en 16 campesinos de la comunidad rural La Picadora. Metodología: En 2022 se realizó un estudio transversal descriptivo en 16 campesinos de la comunidad rural La Picadora, Yaguajay, Sancti Spíritus. Se hicieron entrevistas y examen bucal. Se calcularon indicadores epidemiológicos estomatológicos en el SPSS 16 y se resumieron los factores de riesgo mediante estadística descriptiva. Resultados: El índice de COP-D fue de 10.7 con predominio de dientes perdidos, el índice gingival fue de 1.4 y el de placa bacteriana de 1.0. Fue frecuente el desgaste de incipiente a moderado en menores de 60 años y de moderado a severo en mayores de 60 años. El 75 % de la muestra presentó oclusión normal o maloclusión mínima y el 94 % necesitó rehabilitación protésica. El 81.2 % consumió bebidas alcohólicas en los últimos 30 días, el 62.5 % ha fumado o fuma actualmente, el 87.5 % refirió el cepillado diario menor de 3 veces y el 43.8 % no asistió al estomatólogo en los últimos 10 años. Conclusiones: Se identificó la necesidad de atención estomatológica, así como la urgencia de acciones de prevención y promoción en esta comunidad.

Background: The economic and epidemiological panorama has impacted on oral health in rural communities. Objective: To describe the oral health status, as well as to identify risk factors in 16 farmers from the La Picadora rural community. Methodology: In 2022, a descriptive cross-sectional study was conducted in 16 farmers in the La Picadora rural community, Yaguajay, Sancti Spíritus. Interviews and oral examination were performed. Stomatological epidemiological indicators in SPSS 16 were calculated and risk factors were summarized using descriptive statistics. Results: The COP-D index was 10.7 with a predominance of missing teeth, The COP-D index was 10.7 with a predominance of missing teeth, the gingival index was 1.4 and the bacterial plaque index was 1.0. Incipient to moderate wear was frequent in people under 60 years of age and moderate to severe in over 60 years of age. 75% of the sample presented normal occlusion or minimal malocclusion and 94% required prosthetic rehabilitation. 81.2% consumed alcoholic beverages in the last 30 days, 62.5% have smoked or currently smokes, 87.5% referred the daily brushing less than 3 times a day and 43.8% did not attend a stomatologist in the last 10 years. Conclusions: The need for stomatological attention, was identified, as well as the urgency for prevention and promotion actions in this community.

Gut microbiome perturbation, antibiotic resistance, and Escherichia coli strain dynamics associated with international travel: a metagenomic analysis.

BACKGROUND: Culture-based studies have shown that acquisition of extended-spectrum ß-lactamase-producing Enterobacterales is common during international travel; however, little is known about the role of the gut microbiome before and during travel, nor about acquisition of other antimicrobial-resistant organisms. We aimed to identify (1) whether the gut microbiome provided colonisation resistance against antimicrobial-resistant organism acquisition, (2) the effect of travel and travel behaviours on the gut microbiome, and (3) the scale and global heterogeneity of antimicrobial-resistant organism acquisition. METHODS: In this metagenomic analysis, participants were recruited at three US travel clinics (Boston, MA; New York, NY; and Salt Lake City, UT) before international travel. Participants had to travel internationally between Dec 8, 2017, and April 30, 2019, and have DNA extractions for stool samples both before and after travel for inclusion. Participants were excluded if they had at least one low coverage sample (<1 million read pairs). Stool samples were collected at home before and after travel, sent to a clinical microbiology laboratory to be screened for three target antimicrobial-resistant organisms (extended-spectrum ß-lactamase-producing Enterobacterales, carbapenem-resistant Enterobacterales, and mcr-mediated colistin-resistant Enterobacterales), and underwent DNA extraction and shotgun metagenomic sequencing. We profiled metagenomes for taxonomic composition, antibiotic-resistant gene content, and characterised the Escherichia coli population at the strain level. We analysed pre-travel samples to identify the gut microbiome risk factors associated with acquisition of the three targeted antimicrobial resistant organisms. Pre-travel and post-travel samples were compared to identify microbiome and resistome perturbation and E coli strain acquisition associated with travel. FINDINGS: A total of 368 individuals travelled between the required dates, and 296 had DNA extractions available for both before and after travel. 29 travellers were excluded as they had at least one low coverage sample, leaving a final group of 267 participants. We observed a perturbation of the gut microbiota, characterised by a significant depletion of microbial diversity and enrichment of the Enterobacteriaceae family. Metagenomic strain tracking confirmed that 67% of travellers acquired new strains of E coli during travel that were phylogenetically distinct from their pre-travel strains. We observed widespread enrichment of antibiotic-resistant genes in the gut, with a median 15% (95% CI 10-20, p<1 × 10-10) increase in burden (reads per kilobase per million reads). This increase included antibiotic-resistant genes previously classified as threats to public health, which were 56% (95% CI 36-91, p=2 × 10-11) higher in abundance after travel than before. Fluoroquinolone antibiotic-resistant genes were aquired by 97 (54%) of 181 travellers with no detected pre-travel carriage. Although we found that visiting friends or relatives, travel to south Asia, and eating uncooked vegetables were risk factors for acquisition of the three targeted antimicrobial resistant organisms, we did not observe an association between the pre-travel microbiome structure and travel-related antimicrobial-resistant organism acquisition. INTERPRETATION: This work highlights a scale of E coli and antimicrobial-resistant organism acquisition by US travellers not apparent from previous culture-based studies, and suggests that strategies to control antimicrobial-resistant organisms addressing international traveller behaviour, rather than modulating the gut microbiome, could be worthwhile. FUNDING: US Centers for Disease Control and Prevention and National Institute of Allergy and Infectious Diseases.

Age-period-cohort analysis of lung cancer mortality inequalities in Southern Spain: missed opportunities for implementing equitable tobacco control policies.

BACKGROUND: Lung cancer mortality in European countries shows different epidemiological patterns according to sex and socioeconomic variables. Some countries show decreasing rates in both sexes, while others show a delayed profile, with increasing mortality in women, inconsistently influenced by socioeconomic status. Our aim was to evaluate the effect of age, period and birth cohort on lung cancer mortality inequalities in men and women in Andalusia, the southernmost region in Spain. METHODS: We used the Longitudinal Database of the Andalusian Population, which collects demographic and mortality data from the 2001 census cohort of more than 7.35 million Andalusians, followed up between 2002 and 2016. Mortality rates were calculated for men and women by educational level, and small-area deprivation. Poisson models were used to assess trends in socioeconomic inequalities in men and women. Finally, age-period-cohort (APC) models were used separately for each educational level and gender. RESULTS: There were 39,408 lung cancer deaths in men and 5,511 in women, yielding crude mortality rates of 78.1 and 11.4 × 105 person-years, respectively. In men higher mortality was found in less educated groups and inequalities increased during the study period: i.e. the rate ratio for primary studies compared to university studies increased from 1.30 (CI95:1.18-1.44) to 1.57 (CI95:1.43-1.73). For women, educational inequalities in favour of the less educated tended to decrease moderately. In APC analysis, a decreasing period effect in men and an increasing one in women were observed. Cohort effect differed significantly by educational level. In men, the lower the educational level, the earlier the peak effect was reached, with a 25-year difference between the least-educated and college-educated. Conversely, college-educated women reached the peak effect with a 12-year earlier cohort than the least-educated women. The decline of mortality followed the same pattern both in men and women, with the best-educated groups experiencing declining rates with earlier birth cohorts. CONCLUSIONS: Our study reveals that APC analysis by education helps to uncover changes in trends occurring in different socioeconomic and gender groups, which, combined with data on smoking prevalence, provide important clues for action. Despite its limitations, this approach to the study of lung cancer inequalities allows for the assessment of gaps in historical and current tobacco policies and the identification of population groups that need to be prioritised for public health interventions.

Consumption of aspartame and other artificial sweeteners and risk of cancer in the Spanish multicase-control study (MCC-Spain).

Use of artificial sweeteners (AS) such as aspartame, cyclamate, saccharin and sucralose is widespread. We evaluated the association of use of aspartame and other AS with cancer. In total 1881 colorectal, 1510 breast, 972 prostate and 351 stomach cancer and 109 chronic lymphocytic leukaemia (CLL) cases and 3629 population controls from the Spanish Multicase-Control (MCC-Spain) study were recruited (2008-2013). The consumption of AS, from table-top sweeteners and artificially sweetened beverages, was assessed through a self-administered and validated food frequency questionnaire (FFQ). Sex-specific quartiles among controls were determined to compare moderate consumers (

PI3K Targeting in Non-solid Cancer.

Despite the therapeutic progress, relapse remains a major problem in the treatment of acute lymphoblastic leukemia (ALL). Most leukemia cells that survive chemotherapy are found in the bone marrow (BM), thus resistance to chemotherapy and other treatments may be partially attributed to pro-survival signaling to leukemic cells mediated by leukemia cell-microenvironment interactions. Adhesion of leukemia cells to BM stromal cells may lead to cell adhesion-mediated drug resistance (CAM-DR) mediating intracellular signaling changes that support survival of leukemia cells. In ALL and chronic lymphocytic leukemia (CLL), adhesion-mediated activation of the PI3K/AKT signaling pathway has been shown to be critical in CAM-DR. PI3K targeting inhibitors have been approved for CLL and have been evaluated preclinically in ALL. However, PI3K inhibition has yet to be approved for clinical use in ALL. Here, we review the role of PI3K signaling for normal hematopoietic and leukemia cells and summarize preclinical inhibitors of PI3K in ALL.

Lipomics: A Potential Carrier for the Intravenous Delivery of Lipophilic and Hydrophilic Drugs.

In the present work, we propose the development of a novel carrier that does not need organic solvents for its preparation and with the potential for the intravenous delivery of lipophilic and hydrophilic drugs. Named lipomics, this is a mixed colloid of micelles incorporated within a liposome. This system was designed through ternary diagrams and characterized by physicochemical techniques to determine the particle size, zeta potential, shape, morphology, and stability properties. The lipomics were subjected to electron microscopy (SEM, TEM, and STEM) to evaluate their physical size and morphology. Finally, pharmacokinetic studies were performed by radiolabeling the lipomics with Technetium-99m chelated with BMEDA to evaluate the in vivo biodistribution through techniques of molecular imaging (microSPECT/CT) in rats. Radiolabeling efficiency was used to compare the encapsulation efficiency of the hydrophilic and lipophilic molecules in lipomics and liposomes. According to the results, lipomics are potentially carriers of lipophilic and hydrophilic drugs.

A wearable textile-based pneumatic energy harvesting system for assistive robotics.

Wearable assistive, rehabilitative, and augmentative devices currently require bulky power supplies, often making these tools more of a burden than an asset. This work introduces a soft, low-profile, textile-based pneumatic energy harvesting system that extracts power directly from the foot strike of a user during walking. Energy is harvested with a textile pump integrated into the insole of the user's shoe and stored in a wearable textile bladder to operate pneumatic actuators on demand, with system performance optimized based on a mechano-fluidic model. The system recovered a maximum average power of nearly 3 W with over 20% conversion efficiency-outperforming electromagnetic, piezoelectric, and triboelectric alternatives-and was used to power a wearable arm-lift device that assists shoulder motion and a supernumerary robotic arm, demonstrating its capability as a lightweight, low-cost, and comfortable solution to support adults with upper body functional limitations in activities of daily living.

Logic-enabled textiles.

Textiles hold great promise as a soft yet durable material for building comfortable robotic wearables and assistive devices at low cost. Nevertheless, the development of smart wearables composed entirely of textiles has been hindered by the lack of a viable sheet-based logic architecture that can be implemented using conventional fabric materials and textile manufacturing processes. Here, we develop a fully textile platform for embedding pneumatic digital logic in wearable devices. Our logic-enabled textiles support combinational and sequential logic functions, onboard memory storage, user interaction, and direct interfacing with pneumatic actuators. In addition, they are designed to be lightweight, easily integrable into regular clothing, made using scalable fabrication techniques, and durable enough to withstand everyday use. We demonstrate a textile computer capable of input-driven digital logic for controlling untethered wearable robots that assist users with functional limitations. Our logic platform will facilitate the emergence of future wearables powered by embedded fluidic logic that fully leverage the innate advantages of their textile construction.

A buckling-sheet ring oscillator for electronics-free, multimodal locomotion.

Locomotion of soft robots typically relies on control of multiple inflatable actuators by electronic computers and hard valves. Soft pneumatic oscillators can reduce the demand on controllers by generating complex movements required for locomotion from a single, constant input pressure, but either have been constrained to low rates of flow of air or have required complex fabrication processes. Here, we describe a pneumatic oscillator fabricated from flexible, but inextensible, sheets that provides high rates of airflow for practical locomotion by combining three instabilities: out-of-plane buckling of the sheets, kinking of tubing attached to the sheets, and a system-level instability resulting from connection of an odd number of pneumatic inverters made from these sheets in a loop. This device, which we call a "buckling-sheet ring oscillator" (BRO), directly generates movement from its own interaction with its surroundings and consists only of readily available materials assembled in a simple process-specifically, stacking acetate sheets, nylon film, and double-sided tape, and attaching an elastomeric tube. A device incorporating a BRO is capable of both translational and rotational motion over varied terrain (even without a tether) and can climb upward against gravity and downward against the buoyant force encountered under water.

Primary staging in patients with intermediate- and high-risk prostate cancer: Multiparametric MRI and 68Ga-PSMA-PET/MRI - What is the value of quantitative data from multiparametric MRI alone or in conjunction with clinical information?

PURPOSE: Comparing mpMRI and 68Ga-PSMA-PET/MRI in primary staging of PCa and investigating the value of quantitative mpMRI-measurements for prediction of extracapsular extension and N-metastases. METHODS: Patients with PCa undergoing 68Ga-PSMA-PET/MRI and mpMRI during January 2016 to February 2019 were retrospectively included. Two readers each on 68Ga-PSMA-PET/MRI or mpMRI rated extraprostatic extension (≥T3) and regional lymph-node-metastasis (N1) on a Likert-scale. A fifth reader measured tumor volume, maximum diameter, and capsular contact length on mpMRI. Probability of lymph-node-metastasis was additionally calculated using the 2018 Briganti model. Interobserver-agreement was assessed by squared Cohen's kappa, and diagnostic accuracy was determined using radical prostatectomy (n = 35/49) as reference standard. RESULTS: 49 patients (median age 66 years [IQR: 61-72 years]) were evaluated. Interobserver-agreement for mpMRI and 68Ga-PSMA-PET/MRI was: ≥T3: κ = 0.58/0.47; N1: κ = 0.55/0.92. Diagnostic accuracy for mpMRI vs 68Ga-PSMA-PET/MRI readers for ≥ T3 was AUC: 0.72, 0.62 vs 0.71, 0.72 (p > 0.38) and for N1 was AUC: 0.39, 0.55 vs 0.72, 0.78 (p < 0.01). Quantitative parameters delivered diagnostic accuracies of: AUC: 0.70-0.72 for ≥ T3. The 2018 Briganti model achieved an AUC of 0.89 for N1. CONCLUSIONS: Interreader-agreement regarding ≥ T3 was similar for mpMRI and 68Ga-PSMA-PET/MRI while for N1 it was higher for 68Ga-PSMA-PET/MRI. Diagnostic accuracy was comparable for ≥ T3 while for N1 it was higher in 68Ga-PSMA-PET/MRI and the 2018 Briganti model. Combining clinical data and quantitative data from mpMRI in the 2018 Briganti model yielded the highest AUC for prediction of lymph node metastasis and may aid in selecting patients who will benefit from 68Ga-PSMA-PET/MRI for primary staging.

Evaluation of Traumatic Spinal Cord Injury in a Rat Model Using 99mTc-GA-5 as a Potential In Vivo Tracer.

Spinal cord injury (SCI) refers to the damage suffered in the spinal cord by any trauma or pathology. The purpose of this work was to determine whether 99mTc-GA-5, a radiotracer targeting Glial Fibrillary Acidic Protein (GFAP), can reveal in vivo the reactivation of astrocytes in a murine model with SCI. A method for the 99mTc radiolabeling of the mouse anti-GFAP monoclonal antibody GA-5 was implemented. Radiochemical characterization was performed, and radioimmunohistochemistry assays were used to evaluate the integrity of 99mTc-GA-5. MicroSPECT/CT was used for in vivo imaging to trace SCI in the rats. No alterations in the GA-5's recognition/specificity ability were observed after the radiolabeling. The GA-5's radiolabeling procedure implemented in this work offers a practical method to allow the in vivo following of this monoclonal antibody to evaluate its biodistribution and specificity for GFAP receptors using SPECT/CT molecular imaging.

Seroprevalence of Severe Acute Respiratory Syndrome Coronavirus 2 IgG in Juba, South Sudan, 20201.

Relatively few coronavirus disease cases and deaths have been reported from sub-Saharan Africa, although the extent of its spread remains unclear. During August 10-September 11, 2020, we recruited 2,214 participants for a representative household-based cross-sectional serosurvey in Juba, South Sudan. We found 22.3% of participants had severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor binding domain IgG titers above prepandemic levels. After accounting for waning antibody levels, age, and sex, we estimated that 38.3% (95% credible interval 31.8%-46.5%) of the population had been infected with SARS-CoV-2. At this rate, for each PCR-confirmed SARS-CoV-2 infection reported by the Ministry of Health, 103 (95% credible interval 86-126) infections would have been unreported, meaning SARS-CoV-2 has likely spread extensively within Juba. We also found differences in background reactivity in Juba compared with Boston, Massachusetts, USA, where the immunoassay was validated. Our findings underscore the need to validate serologic tests in sub-Saharan Africa populations.

Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Juba, South Sudan: a population-based study.

BACKGROUND: Relatively few COVID-19 cases and deaths have been reported through much of sub-Saharan Africa, including South Sudan, although the extent of SARS-CoV-2 spread remains unclear due to weak surveillance systems and few population-representative serosurveys. METHODS: We conducted a representative household-based cross-sectional serosurvey in Juba, South Sudan. We quantified IgG antibody responses to SARS-CoV-2 spike protein receptor-binding domain and estimated seroprevalence using a Bayesian regression model accounting for test performance. RESULTS: We recruited 2,214 participants from August 10 to September 11, 2020 and 22.3% had anti-SARS-CoV-2 IgG titers above levels in pre-pandemic samples. After accounting for waning antibody levels, age, and sex, we estimated that 38.5% (32.1 - 46.8) of the population had been infected with SARS-CoV-2. For each RT-PCR confirmed COVID-19 case, 104 (87-126) infections were unreported. Background antibody reactivity was higher in pre-pandemic samples from Juba compared to Boston, where the serological test was validated. The estimated proportion of the population infected ranged from 30.1% to 60.6% depending on assumptions about test performance and prevalence of clinically severe infections. CONCLUSIONS: SARS-CoV-2 has spread extensively within Juba. Validation of serological tests in sub-Saharan African populations is critical to improve our ability to use serosurveillance to understand and mitigate transmission.

Effect of Savings on a Gas-Like Model Economy with Credit and Debt.

In kinetic exchange models, agents make transactions based on well-established microscopic rules that give rise to macroscopic variables in analogy to statistical physics. These models have been applied to study processes such as income and wealth distribution, economic inequality sources, economic growth, etc., recovering well-known concepts in the economic literature. In this work, we apply ensemble formalism to a geometric agents model to study the effect of saving propensity in a system with money, credit, and debt. We calculate the partition function to obtain the total money of the system, with which we give an interpretation of the economic temperature in terms of the different payment methods available to the agents. We observe an interplay between the fraction of money that agents can save and their maximum debt. The system's entropy increases as a function of the saved proportion, and increases even more when there is debt.

Viral manipulation of functionally distinct interneurons in mice, non-human primates and humans.

Recent success in identifying gene-regulatory elements in the context of recombinant adeno-associated virus vectors has enabled cell-type-restricted gene expression. However, within the cerebral cortex these tools are largely limited to broad classes of neurons. To overcome this limitation, we developed a strategy that led to the identification of multiple new enhancers to target functionally distinct neuronal subtypes. By investigating the regulatory landscape of the disease gene Scn1a, we discovered enhancers selective for parvalbumin (PV) and vasoactive intestinal peptide-expressing interneurons. Demonstrating the functional utility of these elements, we show that the PV-specific enhancer allowed for the selective targeting and manipulation of these neurons across vertebrate species, including humans. Finally, we demonstrate that our selection method is generalizable and characterizes additional PV-specific enhancers with exquisite specificity within distinct brain regions. Altogether, these viral tools can be used for cell-type-specific circuit manipulation and hold considerable promise for use in therapeutic interventions.