SAM68 regulates neuronal activity-dependent alternative splicing of neurexin-1.

The assembly of synapses and neuronal circuits relies on an array of molecular recognition events and their modification by neuronal activity. Neurexins are a highly polymorphic family of synaptic receptors diversified by extensive alternative splicing. Neurexin variants exhibit distinct isoform-specific biochemical interactions and synapse assembly functions, but the mechanisms governing splice isoform choice are not understood. We demonstrate that Nrxn1 alternative splicing is temporally and spatially controlled in the mouse brain. Neuronal activity triggers a shift in Nrxn1 splice isoform choice via calcium/calmodulin-dependent kinase IV signaling. Activity-dependent alternative splicing of Nrxn1 requires the KH-domain RNA-binding protein SAM68 that associates with RNA response elements in the Nrxn1 pre-mRNA. Our findings uncover SAM68 as a key regulator of dynamic control of Nrxn1 molecular diversity and activity-dependent alternative splicing in the central nervous system.

Fatal Invasive Mold Infections after Transplantation of Organs Recovered from Drowned Donors, United States, 2011-2021.

Drowned organ donors can be exposed to environmental molds through the aspiration of water; transplantation of exposed organs can cause invasive mold infections in recipients. We describe 4 rapidly fatal cases of potentially donor-derived invasive mold infections in the United States, highlighting the importance of maintaining clinical suspicion for these infections in transplant recipients.

Interpersonal conflict increases interpersonal neural synchronization in romantic couples.

Previous studies on dual-brain social interaction have shown different patterns of interpersonal neural synchronization (INS) between conflictual and supportive interactions, but the role of emotion in the dual-brain mechanisms of such interactions is not well understood. Furthermore, little is known about how the dual-brain mechanisms are affected by relationship type (e.g., romantic relationship vs. friendship) and interaction mode (e.g., verbal vs. nonverbal). To elaborate on these issues, this study used functional near-infrared spectroscopy to collect hemodynamic signals from romantic couples and cross-sex friends while they were discussing conflictual, neutral, or supportive topics. For the couples but not the friends, INS between the sensorimotor cortex of both participants was greater when discussing the conflictual topic than when discussing the supportive topic. INS was positively correlated with the arousal level but not the valence level of communication contents. INS was also positively correlated with interpersonal physiological synchronization based on galvanic skin response, a physiological measure of arousal. Furthermore, the differences in INS between the conflictual and supportive topics were closely associated with verbal rather than nonverbal behaviors. Together, these findings suggest that it is the arousal level induced by verbal interactions during interpersonal conflicts that increases romantic couples' INS.

Prevention Techniques Have Had Minimal Impact on the Population Rate of Prosthetic Joint Infection for Primary Total Hip and Knee Arthroplasty: A National Database Study.

BACKGROUND: Several studies over the years have offered modalities that may greatly decrease the rate of periprosthetic joint infection when implemented. As a result, one would expect a drastic decrease in infection rate among the implementing population with its widespread use. The purpose of this study was to assess whether there exists a decrease in infection rate over time, after accounting for available confounding variables, within a large national database. METHODS: A large national database from 2005 to 2019 was queried for primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). In total, 221,416 THAs and 354,049 TKAs were performed over the study period. Differences in 30-day infection rate were assessed with time and available preoperative risk factors using multinominal logistic regressions. RESULTS: Rate of infection overall trended downward for both THA and TKA. After accounting for confounding variables, odds of THA infection marginally decreased over time (odds ratio 0.968 [0.952-0.985], P < .0001), while the odds of a TKA infection marginally increased with time (odds ratio 1.037 [1.020-1.054], P < .0001). CONCLUSION: Individual peer-reviewed publications have presented infection control modalities demonstrating dramatic decreases in infection rate while analysis at a population level shows almost no changes in infection rate over a 15-year time period. This study supports continued investigation for influential modalities in preventing periprosthetic joint infection and care in patient selection for primary hip and knee arthroplasty.

Artificial Intelligence Autonomously Measures Cup Orientation, Corrects for Pelvis Orientation, and Identifies Retroversion From Antero-Posterior Pelvis Radiographs.

BACKGROUND: Measuring cup orientation is time consuming and inaccurate, but orientation influences the risk of impingement and dislocation following total hip arthroplasty (THA). This study designed an artificial intelligence (AI) program to autonomously determine cup orientation, correct for pelvis orientation, and identify cup retroversion from an antero-posterior pelvic radiographs. METHODS: There were 2,945 patients between 2012 and 2019 identified to have 504 computed tomographic (CT) scans of their THA. A 3-dimensional (3D) reconstruction was performed on all CTs, where cup orientation was measured relative to the anterior pelvic plane. Patients were randomly allocated to training (4,000 x-rays), validation (511 x-rays), and testing (690 x-rays) groups. Data augmentation was applied to the training set (n = 4,000,000) to increase model robustness. Statistical analyses were performed only on the test group in their accuracy with CT measurements. RESULTS: AI predictions averaged 0.22 ± 0.03 seconds to run on a given radiograph. Pearson correlation coefficient was 0.976 and 0.984 for AI measurements with CT, while hand measurements were 0.650 and 0.687 for anteversion and inclination, respectively. The AI measurements more closely represented CT scans when compared to hand measurements (P < .001). Measurements averaged 0.04 ± 2.21°, 0.14 ± 1.66°, -0.31 ± 8.35°, and 6.48° ± 7.43° from CT measurements for AI anteversion, AI inclination, hand anteversion, and hand inclination, respectively. AI predictions identified 17 radiographs as retroverted with 100.0% accuracy (total retroverted, n = 45). CONCLUSION: The AI algorithms may correct for pelvis orientation when measuring cup orientation on radiographs, outperform hand measurements, and may be implemented in a timely fashion. This is the first method to identify a retroverted cup from a single AP radiograph.

Spread of Sporothrix spp. through respiratory droplets from infected cats: A potential route of transmission.

Cases of cat-transmitted sporotrichosis in Brazil have increased in recent years. We collected respiratory secretions expelled while sneezing from 28 cats diagnosed with sporotrichosis. We identified the presence of Sporothrix spp. in respiratory droplets expelled in the sneeze of infected cats. The results raise concerns about a new transmission route for cat-transmitted sporotrichosis. Physicians who diagnose and treat human cases of sporotrichosis should be aware of this potential new transmission method to improve clinical suspicion. Approximately half of patients with granulomatous conjunctival sporotrichosis did not report experiencing traumatic injury from cats.

Cat-transmitted sporotrichosis is a zoonosis in geographic expansion from Brazil to other Latin American countries and is considered a public health problem. Data suggest that transmission can occur through the sneeze of an infected cat. The One Health approach is necessary to control the disease.

Factors Associated with Participation in Elementary School-Based SARS-CoV-2 Testing - Salt Lake County, Utah, December 2020-January 2021.

During December 3, 2020-January 31, 2021, CDC, in collaboration with the University of Utah Health and Economic Recovery Outreach Project,* Utah Department of Health (UDOH), Salt Lake County Health Department, and one Salt Lake county school district, offered free, in-school, real-time reverse transcription-polymerase chain reaction (RT-PCR) saliva testing as part of a transmission investigation of SARS-CoV-2, the virus that causes COVID-19, in elementary school settings. School contacts† of persons with laboratory-confirmed SARS-CoV-2 infection, including close contacts, were eligible to participate (1). Investigators approached parents or guardians of student contacts by telephone, and during January, using school phone lines to offer in-school specimen collection; the testing procedures were explained in the preferred language of the parent or guardian. Consent for participants was obtained via an electronic form sent by e-mail. Analyses examined participation (i.e., completing in-school specimen collection for SARS-CoV-2 testing) in relation to factors§ that were programmatically important or could influence likelihood of SARS-CoV-2 testing, including race, ethnicity, and SARS-CoV-2 incidence in the community (2). Crude prevalence ratios (PRs) were calculated using univariate log-binomial regression.¶ This activity was reviewed by CDC and was conducted consistent with federal law and CDC policy.*.

Low SARS-CoV-2 Transmission in Elementary Schools - Salt Lake County, Utah, December 3, 2020-January 31, 2021.

School closures affected more than 55 million students across the United States when implemented as a strategy to prevent the transmission of SARS-CoV-2, the virus that causes COVID-19 (1). Reopening schools requires balancing the risks for SARS-CoV-2 infection to students and staff members against the benefits of in-person learning (2). During December 3, 2020-January 31, 2021, CDC investigated SARS-CoV-2 transmission in 20 elementary schools (kindergarten through grade 6) that had reopened in Salt Lake County, Utah. The 7-day cumulative number of new COVID-19 cases in Salt Lake County during this time ranged from 290 to 670 cases per 100,000 persons.† Susceptible§ school contacts¶ (students and staff members exposed to SARS-CoV-2 in school) of 51 index patients** (40 students and 11 staff members) were offered SARS-CoV-2 reverse transcription-polymerase chain reaction (RT-PCR) testing. Among 1,041 susceptible school contacts, 735 (70.6%) were tested, and five of 12 cases identified were classified as school-associated; the secondary attack rate among tested susceptible school contacts was 0.7%. Mask use among students was high (86%), and the median distance between students' seats in classrooms was 3 ft. Despite high community incidence and an inability to maintain ≥6 ft of distance between students at all times, SARS-CoV-2 transmission was low in these elementary schools. The results from this investigation add to the increasing evidence that in-person learning can be achieved with minimal SARS-CoV-2 transmission risk when multiple measures to prevent transmission are implemented (3,4).

Discriminatory questions asked during residency programme interviews: perspective from both interviewers and applicants.

BACKGROUND: The National Resident Matching Program (NRMP) policy requires interview officials to refrain from asking illegal or coercive questions that may introduce discrimination; however, compliance is insufficient. METHOD: An Institutional Review Board-approved 12 question survey was distributed to 130 allopathic medical schools with 551 responses from 18 187 students applying in the 2015-2016 residency match. In addition, a 16-question survey was distributed through residency coordinators to residency programme interviewers with 481 responses from 21 of 22 residency specialities. RESULTS: Discriminatory topics were frequently discussed across all specialities. Surgical interviews were significantly more likely to discuss age (relative risk (RR) 2.0, p<0.01) and gender (RR 2.7, p<0.01) during formal interviews. More-competitive specialities more frequently discussed age (RR 1.9, p<0.01) and gender (RR 2.0, p<0.01) during the formal interview, and gender (RR 1.4, p<0.05) during informal interview events. 47.8% of interviewers discussed potentially coercive topics during the interview, 57.5% considered these topics when evaluating candidates and 72.6% had misunderstandings. Interviewers given both oral and written instruction showed the greatest effect change towards discussing coercive topics (p<0.01) and correctly identifying non-discriminatory and discriminatory topics (p<0.01). While age and gender both constitute discriminatory topics, each of these topics is included in the majority of written The Electronic Residency Application System applications (85.5% and 89.8%, respectively). CONCLUSIONS: In modern recruitment where differential attainment is of interest, the presence of such explicit discrimination is worrisome. Formal interview training might reduce discrimination, but more active overnight is needed and a zero-tolerance approach to overt discrimination should be the ambition.

The cortical surface area of the insula mediates the effect of DBH rs7040170 on novelty seeking.

Novelty seeking (NS) is a personality trait important for adaptive functioning, but an excessive level of NS has been linked to psychiatric disorders such as ADHD and substance abuse. Previous research has investigated separately the neural and genetic bases of the NS trait, but results were mixed and neural and genetic bases have yet to be examined within the same study. In this study, we examined the interrelationships among the dopamine beta-hydroxylase (DBH) gene, brain structure, and the NS trait in 359 healthy Han Chinese subjects. We focused on the DBH gene because it encodes a key enzyme for dopamine metabolism, NS is believed to be related to the dopaminergic system and has been reported associated with DBH variation. Results showed a significant positive association between the cortical surface area of the left insula and NS score. Furthermore, the DBH genetic polymorphism at the SNP rs7040170 was strongly associated with both the surface area of the left insula and NS score, with G carriers having a larger left insula surface area and a higher NS score than AA homozygotes. Subsequent path analysis suggested that the insula partially mediated the association between the DBH gene and the NS trait. Our data provided the first evidence for the involvement of the insula in the dopamine-NS relationship. Future studies of molecular mechanisms underlying the NS personality trait and related psychiatric disorders should consider the mediation effect of the neural structure.

Repeated measures study of weekly and daily cytomegalovirus shedding patterns in saliva and urine of healthy cytomegalovirus-seropositive children.

BACKGROUND: To better understand potential transmission risks from contact with the body fluids of children, we monitored the presence and amount of CMV shedding over time in healthy CMV-seropositive children. METHODS: Through screening we identified 36 children from the Atlanta, Georgia area who were CMV-seropositive, including 23 who were shedding CMV at the time of screening. Each child received 12 weekly in-home visits at which field workers collected saliva and urine. During the final two weeks, parents also collected saliva and urine daily. RESULTS: Prevalence of shedding was highly correlated with initial shedding status: children shedding at the screening visit had CMV DNA in 84% of follow-up saliva specimens (455/543) and 28% of follow-up urine specimens (151/539); those not shedding at the screening visit had CMV DNA in 16% of follow-up saliva specimens (47/303) and 5% of follow-up urine specimens (16/305). Among positive specimens we found median viral loads of 82,900 copies/mL in saliva and 34,730 copies/mL in urine (P=0.01), while the viral load for the 75th percentile was nearly 1.5 million copies/mL for saliva compared to 86,800 copies/mL for urine. Younger age was significantly associated with higher viral loads, especially for saliva (P<0.001). Shedding prevalence and viral loads were relatively stable over time. All children who were shedding at the screening visit were still shedding at least some days during weeks 11 and 12, and median and mean viral loads did not change substantially over time. CONCLUSIONS: Healthy CMV-seropositive children can shed CMV for months at high, relatively stable levels. These data suggest that behavioral prevention messages need to address transmission via both saliva and urine, but also need to be informed by the potentially higher risks posed by saliva and by exposures to younger children.

The cytokine macrophage migration inhibitory factor (MIF) acts as a neurotrophin in the developing inner ear of the zebrafish, Danio rerio.

Macrophage migration inhibitory factor (MIF) plays versatile roles in the immune system. MIF is also widely expressed during embryonic development, particularly in the nervous system, although its roles in neural development are only beginning to be understood. Evidence from frogs, mice and zebrafish suggests that MIF has a major role as a neurotrophin in the early development of sensory systems, including the auditory system. Here we show that the zebrafish mif pathway is required for both sensory hair cell (HC) and sensory neuronal cell survival in the ear, for HC differentiation, semicircular canal formation, statoacoustic ganglion (SAG) development, and lateral line HC differentiation. This is consistent with our findings that MIF is expressed in the developing mammalian and avian auditory systems and promotes mouse and chick SAG neurite outgrowth and neuronal survival, demonstrating key instructional roles for MIF in vertebrate otic development.

Dermal changes in superficial basal cell carcinoma, melanoma in situ and actinic keratosis and their implications.

BACKGROUND: Basal cell carcinoma (BCC) has a characteristic stroma, but less is known about the dermal characteristics associated with melanoma in situ (MIS) and actinic keratosis (AK). MATERIALS AND METHODS: Dermal changes were studied in 301 specimens of AK, BCC and MIS. Subsequently, blinded images of dermal changes from 90 randomly selected cases of those entities were used to assess the predictive value of the dermal changes. Agreement with the final diagnosis was calculated using kappa coefficient (κ). RESULTS: Fibromyxoid stroma was present in 82% of BCC cases; fibrous stroma was seen in 25% of BCC, 58% of MIS and 35.6% of AK specimens (p < 0.05). A lichenoid inflammatory infiltrate was frequently associated with AK and a perifollicular infiltrate with periadnexal fibrosis with MIS. Blinded evaluation of images of the dermal changes associated with the tumors yielded the correct diagnosis in (54.4, 41.1 and 27.8%; average 41.2%) by the three appraisers. Coefficient of agreement in blinded imaged evaluation with the actual diagnosis was higher in the BCC and MIS compared with AK (κ = 0.37, p = 0.0001; κ = 0.2, p = 0.0005 and κ = -0.06, p = 0.84, respectively). CONCLUSION: Dermal features may be helpful in predicting the correct diagnosis when tumor is not visible.

Public Health Research Priorities for Fungal Diseases: A Multidisciplinary Approach to Save Lives.

Fungal infections can cause severe disease and death and impose a substantial economic burden on healthcare systems. Public health research requires a multidisciplinary approach and is essential to help save lives and prevent disability from fungal diseases. In this manuscript, we outline the main public health research priorities for fungal diseases, including the measurement of the fungal disease burden and distribution and the need for improved diagnostics, therapeutics, and vaccines. Characterizing the public health, economic, health system, and individual burden caused by fungal diseases can provide critical insights to promote better prevention and treatment. The development and validation of fungal diagnostic tests that are rapid, accurate, and cost-effective can improve testing practices. Understanding best practices for antifungal prophylaxis can optimize prevention in at-risk populations, while research on antifungal resistance can improve patient outcomes. Investment in vaccines may eliminate certain fungal diseases or lower incidence and mortality. Public health research priorities and approaches may vary by fungal pathogen.

Handsome or Rugged? : A Speed-Dating Study of Ovulatory Shifts in Women's Preferences for Masculinity in Men.

We tested the good genes ovulatory shift hypothesis through speed-dating, an ecologically valid paradigm with real life consequences. Fifteen speed-dating sessions of 262 single Asian Americans were held. We analyzed 850 speed-dates involving 132 men and 100 normally ovulating women, finding ovulatory shifts in the desirability of men with more masculine facial measurements (smaller eye-mouth-eye angle, larger lower face to full face height ratio, and smaller facial width to lower face height ratio) in the predicted direction. However, there was no support for ovulatory shifts in preferences for men's self-reported height. In addition, the expected shifts were not found for women's second date offers to men. Therefore, with natural stimuli and in a competitive dating scenario, we partially replicated previously documented ovulatory shifts in women's preferences for men.

Healthcare Provider Testing Practices for Tinea and Familiarity with Antifungal-Drug-Resistant Tinea-United States, 2022.

Tinea, a dermatophyte fungal infection, is a common outpatient complaint that is easily misdiagnosed by visual inspection. Antifungal-drug-resistant tinea is an emerging global public health problem, with several cases reported in the United States. We analyzed data from a Spring 2022 web-based survey of healthcare provider attitudes and practices. Among 1500 healthcare providers, only 20.1% reported typically using diagnostic testing for tinea, and 19.5% reported clinical experience with drug-resistant tinea. Drug-resistant tinea may be more widespread than previously recognized. However, the low frequency of diagnostic testing indicates potential misunderstanding or misdiagnosis of drug-resistant tinea and missed opportunities to detect drug-resistant cases.

High Frequency of Self-Diagnosis and Self-Treatment in a Nationally Representative Survey about Superficial Fungal Infections in Adults-United States, 2022.

Data about the prevalence, diagnosis, treatment, and public knowledge of superficial fungal infections in the United States are scarce. These infections are a growing concern given the emergence of antifungal drug resistance. We analyzed data from a national survey of nearly 6000 U.S. adults. Overall, 114 (2.7%) participants reported having ringworm and 415 (10.0%) reported a fungal nail infection in the past 12 months; 61.4% of participants with any superficial fungal infection were self-diagnosed. Most patients (55.5%) used over-the-counter antifungals. The common nature of superficial fungal infections and the high rates of self-diagnosis and treatment indicate that community education about these infections should be considered a public health priority.