Comparing fine needle biopsy techniques in solid pancreatic lesions: A prospective randomized study.

INTRODUCTION: Endoscopic ultrasound-guided fine-needle biopsies (EUS-FNB) are the best technique for sampling solid pancreatic lesions. However, the most appropriate biopsy technique has not been standardized using Fine Needle Biopsy (FNB) needles. The aim of this work was to identify the best biopsy technique to achieve the best tissue integrity and cause the least blood contamination. MATERIAL AND METHODS: Patients ≥18 years of age with solid pancreatic lesions who underwent EUS-FNB at our institution from January 2020 to May 2021 were consecutively selected. Three passes were performed with each of the threee techniques to obtain tissue: suction with 10 ml of vacuum, capillary, and wet. An independent pathologist evaluated the received tissue integrity and the degree of blood contamination of each sample according to scales. RESULTS: Seventy-five patients were recruited for our study. A superior tissue integrity was observed using the wet-suction technique in lesions located in the body and/or tail of the pancreas, and an average score of 4.40 (p = 0.027) was assigned for this technique. Regarding the contamination of the sample in the whole cohort, the simple-suction technique shown a higher contamination, 1.55 (p < 0.001). There was no statistically significant difference among the techniques when evaluating tissue integrity or contamination in lesions larger or smaller than 3 cm. CONCLUSION: When performing EUS-FNB for solid pancreatic lesions located in the head/uncinated process, the three methods provided similar diagnostic yields. The wet-suction technique had a higher score in tissue integrity when lesions were located in the body and/or tail of the pancreas.

Interim safety and immunogenicity results from an NDV-based COVID-19 vaccine phase I trial in Mexico.

There is still a need for safe, efficient, and low-cost coronavirus disease 2019 (COVID-19) vaccines that can stop transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we evaluated a vaccine candidate based on a live recombinant Newcastle disease virus (NDV) that expresses a stable version of the spike protein in infected cells as well as on the surface of the viral particle (AVX/COVID-12-HEXAPRO, also known as NDV-HXP-S). This vaccine candidate can be grown in embryonated eggs at a low cost, similar to influenza virus vaccines, and it can also be administered intranasally, potentially to induce mucosal immunity. We evaluated this vaccine candidate in prime-boost regimens via intramuscular, intranasal, or intranasal followed by intramuscular routes in an open-label non-randomized non-placebo-controlled phase I clinical trial in Mexico in 91 volunteers. The primary objective of the trial was to assess vaccine safety, and the secondary objective was to determine the immunogenicity of the different vaccine regimens. In the interim analysis reported here, the vaccine was found to be safe, and the higher doses tested were found to be immunogenic when given intramuscularly or intranasally followed by intramuscular administration, providing the basis for further clinical development of the vaccine candidate. The study is registered under ClinicalTrials.gov identifier NCT04871737.

Successful quality improvement project to increase hydroxyurea prescriptions for children with sickle cell anaemia.

Hydroxyurea (HU) is an effective but underused disease-modifying therapy for patients with sickle cell anaemia (SCA). EMBRACE SCD, a sickle cell disease treatment demonstration project, aimed to improve access to HU by increasing prescription (Rx) rates by at least 10% from baseline in children with SCA.The Model for Improvement was used as the quality improvement framework. HU Rx was assessed from clinical databases in three paediatric haematology centres. Children aged 9 months-18 years with SCA not on chronic transfusions were eligible for HU treatment. The health belief model was the conceptual framework to discuss with patients and promote HU acceptance. A visual aid showing erythrocytes under the effect of HU and the American Society of Hematology HU brochure were used as educational tools. At least 6 months after offering HU, a Barrier Assessment Questionnaire was given to assess reasons for HU acceptance and refusals. If HU was declined, the providers discussed with family again. We conducted chart audits to find missed opportunities to prescribe HU as one plan-do-study-act cycle.At initial measurement, 50.2% of 524 eligible patients had HU prescribed. During the testing and initial implementation phase, the mean performance after 10 data points was 53%. After 2 years, the mean performance was 59%, achieving an 11% increase in mean performance and a 29% increase from initial to the last measurement (64.8% HU Rx). During a 15-month period, 32.1% (N=168) of the eligible patients who were offered HU completed the barrier questionnaire with 19% (N=32) refusing HU, mostly based on not perceiving enough severity of their children's SCA or fearing side effects.Reviewing patient charts for missed opportunity of offering HU with feedback and evaluating the reasons of declining HU via a questionnaire were key components in increasing HU Rx in our population.

Safety and immunogenicity of a live recombinant Newcastle disease virus-based COVID-19 vaccine (Patria) administered via the intramuscular or intranasal route: Interim results of a non-randomized open label phase I trial in Mexico.

There is still a need for safe, efficient and low-cost coronavirus disease 2019 (COVID-19) vaccines that can stop transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we evaluated a vaccine candidate based on a live recombinant Newcastle disease virus (NDV) that expresses a stable version of the spike protein in infected cells as well as on the surface of the viral particle (AVX/COVID-12-HEXAPRO, also known as NDV-HXP-S). This vaccine candidate can be grown in embryonated eggs at low cost similar to influenza virus vaccines and it can also be administered intranasally, potentially to induce mucosal immunity. We evaluated this vaccine candidate in prime-boost regimens via intramuscular, intranasal, or intranasal followed by intramuscular routes in an open label non-randomized non-placebo-controlled phase I clinical trial in Mexico in 91 volunteers. The primary objective of the trial was to assess vaccine safety and the secondary objective was to determine the immunogenicity of the different vaccine regimens. In the interim analysis reported here, the vaccine was found to be safe and the higher doses tested were found to be immunogenic when given intramuscularly or intranasally followed by intramuscular administration, providing the basis for further clinical development of the vaccine candidate. The study is registered under ClinicalTrials.gov identifier NCT04871737. Funding was provided by Avimex and CONACYT.

Brief Report: Hispanic Patients' Trajectory of Cancer Symptom Burden, Depression, Anxiety, and Quality of Life.

Background: Anxiety and depression symptoms are known to increase cancer symptom burden, yet little is known about the longitudinal integrations of these among Hispanic/Latinx patients. The goal of this study was to explore the trajectory and longitudinal interactions among anxiety and depression, cancer symptom burden, and health-related quality of life in Hispanic/Latinx cancer patients undergoing chemotherapy. METHODS: Baseline behavioral assessments were performed before starting chemotherapy. Follow-up behavioral assessments were performed at 3, 6, and 9 months after starting chemotherapy. Descriptive statistics, chi-square tests, Fisher's exact tests, and Mann-Whitney tests explored associations among outcome variables. Adjusted multilevel mixed-effects linear regression models were also used to evaluate the association between HADS scores, follow-up visits, FACT-G scale, MDASI scale, and sociodemographic variables. RESULTS: Increased cancer symptom burden was significantly related to changes in anxiety symptoms' scores (adjusted ß^ = 0.11 [95% CI: 0.02, 0.19]. Increased quality of life was significantly associated with decreased depression and anxiety symptoms (adjusted ß^ = -0.33; 95% CI: -0.47, -0.18, and 0.38 adjusted ß^= -0.38; 95% CI: -0.55, -0.20, respectively). CONCLUSIONS: Findings highlight the need to conduct periodic mental health screenings among cancer patients initiating cancer treatment.

Safety and Immunogenicity of a Newcastle Disease Virus Vector-Based SARS-CoV-2 Vaccine Candidate, AVX/COVID-12-HEXAPRO (Patria), in Pigs.

Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were developed in record time and show excellent efficacy and effectiveness against coronavirus disease 2019 (COVID-19). However, currently approved vaccines cannot meet the global demand. In addition, none of the currently used vaccines is administered intranasally to potentially induce mucosal immunity. Here, we tested the safety and immunogenicity of a second-generation SARS-CoV-2 vaccine that includes a stabilized spike antigen and can be administered intranasally. The vaccine is based on a live Newcastle disease virus vector expressing a SARS-CoV-2 spike protein stabilized in a prefusion conformation with six beneficial proline substitutions (AVX/COVID-12-HEXAPRO; Patria). Immunogenicity testing in the pig model showed that both intranasal and intramuscular application of the vaccine as well as a combination of the two induced strong serum neutralizing antibody responses. Furthermore, substantial reactivity to B.1.1.7, B.1.351, and P.1 spike variants was detected. Finally, no adverse reactions were found in the experimental animals at any dose level or delivery route. These results indicate that the experimental vaccine AVX/COVID-12-HEXAPRO (Patria) is safe and highly immunogenic in the pig model. IMPORTANCE Several highly efficacious vaccines for SARS-CoV-2 have been developed and are used in the population. However, the current production capacity cannot meet the global demand. Therefore, additional vaccines-especially ones that can be produced locally and at low cost-are urgently needed. This work describes preclinical testing of a SARS-CoV-2 vaccine candidate which meets these criteria.

Microglia enable mature perineuronal nets disassembly upon anesthetic ketamine exposure or 60-Hz light entrainment in the healthy brain.

Perineuronal nets (PNNs), components of the extracellular matrix, preferentially coat parvalbumin-positive interneurons and constrain critical-period plasticity in the adult cerebral cortex. Current strategies to remove PNN are long-lasting, invasive, and trigger neuropsychiatric symptoms. Here, we apply repeated anesthetic ketamine as a method with minimal behavioral effect. We find that this paradigm strongly reduces PNN coating in the healthy adult brain and promotes juvenile-like plasticity. Microglia are critically involved in PNN loss because they engage with parvalbumin-positive neurons in their defined cortical layer. We identify external 60-Hz light-flickering entrainment to recapitulate microglia-mediated PNN removal. Importantly, 40-Hz frequency, which is known to remove amyloid plaques, does not induce PNN loss, suggesting microglia might functionally tune to distinct brain frequencies. Thus, our 60-Hz light-entrainment strategy provides an alternative form of PNN intervention in the healthy adult brain.

Dissociation of functional and structural plasticity of dendritic spines during NMDAR and mGluR-dependent long-term synaptic depression in wild-type and fragile X model mice.

Many neurodevelopmental disorders are characterized by impaired functional synaptic plasticity and abnormal dendritic spine morphology, but little is known about how these are related. Previous work in the Fmr1-/y mouse model of fragile X (FX) suggests that increased constitutive dendritic protein synthesis yields exaggerated mGluR5-dependent long-term synaptic depression (LTD) in area CA1 of the hippocampus, but an effect on spine structural plasticity remains to be determined. In the current study, we used simultaneous electrophysiology and time-lapse two photon imaging to examine how spines change their structure during LTD induced by activation of mGluRs or NMDA receptors (NMDARs), and how this plasticity is altered in Fmr1-/y mice. We were surprised to find that mGluR activation causes LTD and AMPA receptor internalization, but no spine shrinkage in either wildtype or Fmr1-/y mice. In contrast, NMDAR activation caused spine shrinkage as well as LTD in both genotypes. Spine shrinkage was initiated by non-ionotropic (metabotropic) signaling through NMDARs, and in wild-type mice this structural plasticity required activation of mTORC1 and new protein synthesis. In striking contrast, NMDA-induced spine plasticity in Fmr1-/y mice was no longer dependent on acute activation of mTORC1 or de novo protein synthesis. These findings reveal that the structural consequences of mGluR and metabotropic NMDAR activation differ, and that a brake on spine structural plasticity, normally provided by mTORC1 regulation of protein synthesis, is absent in FX. Increased constitutive protein synthesis in FX appears to modify functional and structural plasticity induced through different glutamate receptors.

Fibromatosis gástrica: un tumor raro en una localización infrecuente. Reporte de un caso.

La fibromatosis tipo desmoide es un tumor benigno de suma rareza con características localmente agresivas. Se desarrolla en especial en tejidos blandos por su origen en los músculos y las aponeurosis. El diagnóstico se establece por inmunohistoquímica con positividad para vimentina, B-catenina y en ocasiones para actina de músculo liso. El espectro clínico de presentación es amplio, y según este y la resecabilidad se ofrece el tratamiento. Presentamos el caso de una paciente con síntomas de obstrucción al vaciamiento gástrico secundaria a una lesión subepitelial en cuerpo con inmunohistoquímica concluyente para fibromatosis gástrica.Desmoid-type fibromatosis is an extremely rare benign tumor with locally aggressive features. It is predominantly developing in soft tissues due to its origin in muscles and aponeurosis. The diagnosis is established by immunohistochemistry with positivity for vimentin, B-catenin and sometimes for smooth muscle actin. The clinical spectrum of presentation is wide, based on this and resectability the treatment is offered. We present the case of a patient with symptoms of gastric outlet obstruction secondary to a subepithelial lesion in the gastric body with conclusive immunohistochemistry for gastric fibromatosis.

Código azul, histerotomía de reanimación en embarazo de término: reporte de un caso / Blue Code, resuscitative hysterotomy on a term pregnancy: a case report

Resumen: ANTECEDENTES: El paro cardiorrespiratorio durante el embarazo es un evento poco común, ocurre en 1 de cada 12,500 a 30,000 gestaciones, con una tasa de supervivencia de 17-59%. CASO CLÍNICO: Paciente de 23 años, con evolución normal del embarazo de 41.2 semanas; acudió a la consulta de Urgencias por actividad uterina irregular. Durante la conducción del trabajo de parto, y después de la analgesia espinal, tuvo un paro cardiorrespiratorio. Se le aplicaron las maniobras de reanimación básicas y monitoreo de la asistolia; a los 4 minutos se le practicaron: histerotomía de reanimación y retorno espontáneo de la circulación. La paciente requirió cuidados inmediatos, con seguimiento y tratamiento en terapia intensiva obstétrica durante 1 mes; fue dada de alta con mínimo daño de las funciones mentales, con restablecimiento íntegro de las mismas a los 3 meses de seguimiento. CONCLUSIONES: Debido a las implicaciones éticas y características de la enfermedad, no existe un modelo experimental para establecer las medidas durante la reanimación cardiopulmonar en el embarazo; por tanto, se implementan con base en la revisión de casos y estudios de la fisiología cardiovascular en esta etapa fisiológica de la vida. El apego y seguimiento de las recomendaciones establecidas se asocian con buen desenlace y pronóstico para la madre y su hijo, como sucedió en el caso aquí reportado.

Abstract: BACKGROUND: Cardiorespiratory arrest during pregnancy is a rare event that occurs in 1 in 12,500 to 30,000 pregnancies, with a survival rate of 17-59%. CLINICAL CASE: We report the case of a 23-year-old female patient, late-term pregnancy and labor. During labor conduction and after spinal analgesia, she presented cardiorespiratory arrest. After the start of basic resuscitation maneuvers, monitoring, and confirmed asystole, advanced maneuvers were started, culminating at 4 minutes with resuscitation hysterotomy and a subsequent spontaneous return of circulation. The patient required immediate post-arrest cares with follow-up and management in the intensive obstetric care unit for one month, after which the patient was discharged with minimal compromise of her superior mental functions; after 3 months of out clinic follow-up, the patient was healthy and her superior functions deemed to have been fully restored. CONCLUSIONS: Due to the ethical implications and characteristics of the pathology, there are no experimental models to establish measures during cardiopulmonary resuscitation in pregnancy, they are developed based on the review of clinical cases and the study of cardiovascular physiology during pregnancy. In this case report, we conclude that adhering to the established recommendations were associated with a good outcome and prognosis for both mother and child.

Correction: D-cycloserine improves synaptic transmission in an animal mode of Rett syndrome.

[This corrects the article DOI: 10.1371/journal.pone.0183026.].

Repeated mild traumatic brain injury produces neuroinflammation, anxiety-like behaviour and impaired spatial memory in mice.

PRIMARY OBJECTIVE: Repeated traumatic brain injuries (rmTBI) are frequently associated with debilitating neuropsychiatric conditions such as cognitive impairment, mood disorders, and post-traumatic stress disorder. We tested the hypothesis that repeated mild traumatic brain injury impairs spatial memory and enhances anxiety-like behaviour. RESEARCH DESIGN: We used a between groups design using single (smTBI) or repeated (rmTBI) controlled cranial closed skull impacts to mice, compared to a control group. METHODS AND PROCEDURES: We assessed the effects of smTBI and rmTBI using measures of motor performance (Rotarod Test [RT]), anxiety-like behaviour (Elevated Plus Maze [EPM] and Open Field [OF] tests), and spatial memory (Morris Water Maze [MWM]) within 12 days of the final injury. In separate groups of mice, astrocytosis and microglial activation were assessed 24 hours after the final injury using GFAP and IBA-1 immunohistochemistry. MAIN OUTCOMES AND RESULTS: RmTBI impaired spatial memory in the MWM and increased anxiety-like behaviour in the EPM and OFT. In addition, rmTBI elevated GFAP and IBA-1 immunohistochemistry throughout the mouse brain. RmTBI produced astrocytosis and microglial activation, and elicited impaired spatial memory and anxiety-like behaviour. CONCLUSIONS: rmTBI produces acute cognitive and anxiety-like disturbances associated with inflammatory changes in brain regions involved in spatial memory and anxiety.

Hematoma subcapsular hepático en síndrome de HELLP: reporte de dos casos / Hepatic subcapsular hematoma in HELLP syndrome. Report of 2 cases

Resumen OBJETIVO Reportar el tratamiento clínico-quirúrgico y en la unidad de cuidados intensivos obstétricos de dos pacientes con síndrome de HELLP y hematoma subcapsular hepático. CASO CLINICO A Paciente de 29 años en curso de las 36.1 semanas de embarazo, con ausencia de movimientos fetales, choque hipovolémico, desprendimiento prematuro de placenta normoinserta y óbito. Hemoperitoneo de 2000 mL y hematoma subcapsular del lóbulo hepático izquierdo. Se le colocó un empaquetamiento Miculicz durante 48 horas. Permaneció en la unidad de cuidados intensivos durante nueve días. Reporte de tomografía axial computada de hematoma subcapsular hepático. CASO CLINICO B Paciente de 15 años, con embarazo de 38.6 semanas, dolor epigástrico y lumbar, bradicardia fetal y síndrome de HELLP. Hemoperitoneo de 300 cc, feto de 2400 g, Apgar 1-5, desprendimiento de placenta del 100%, hematoma hepático subcapsular contenido por el ligamento triangular sin necesidad de empaquetamiento. Atención en la unidad de cuidados intensivos obstétricos durante tres días. Reporte de tomografía axial computada de hematoma hepático subcapsular. CONCLUSIÓN El síndrome de HELLP puede originar complicaciones hepáticas graves, como: rotura hepática o hematoma subcapsular roto o no roto. La mortalidad es de 18 a 86% en caso de rotura del hematoma. Las pacientes deben tratarse en hospitales de tercer nivel. La intervención temprana, la atención multidisciplinaria, el soporte hemodinámico y el seguimiento con estudios de imagen son decisivos para reducir su elevada morbilidad y mortalidad.

Abstract OBJECTIVE Report clinical-surgical management and in the Obstetric Intensive Care Unit of the HELLP Syndrome and hepatic subcapsular hematoma of two clinical cases. CLINICAL CASE A 29 years of age, 36.1 weeks of gestation, absence of fetal movements, hypovolemic shock, premature detachment of normoinserta placenta, stillbirth. Hemoperitoneum finding of 2000 mL and subcapsular hematoma of the left hepatic lobe; Miculicz packaging is placed for 48 hours. Management in the Obstetric Intensive Care Unit for 9 days. Computed Axial Tomography reports hepatic subcapsular hematoma. CLINICAL CASE B 15 years of age, 38.6 weeks of gestation, pain in the hypogastrium and lumbar region, fetal bradycardia and HELLP syndrome; hemoperitoneum finding of 300 cc, product of 2,400 gr, Apgar 1-5, placental abruption of 100%, hepatic subcapsular hematoma contained by triangular ligament without the need for packaging. Management in the Obstetric Intensive Care Unit for 3 days. Computed Axial Tomography reports hepatic subcapsular hematoma. CONCLUSION The HELLP syndrome can present serious hepatic complications such as ruptured hepatic or subcapsular hematoma. Mortality is 18 to 86% in case of hematoma rupture. They require management in highly complex centers. Early intervention, multidisciplinary management, hemodynamic support and follow-up with imaging studies are essential to reduce their high morbidity and mortality.

D-cycloserine improves synaptic transmission in an animal model of Rett syndrome.

Rett syndrome (RTT), a leading cause of intellectual disability in girls, is predominantly caused by mutations in the X-linked gene MECP2. Disruption of Mecp2 in mice recapitulates major features of RTT, including neurobehavioral abnormalities, which can be reversed by re-expression of normal Mecp2. Thus, there is reason to believe that RTT could be amenable to therapeutic intervention throughout the lifespan of patients after the onset of symptoms. A common feature underlying neuropsychiatric disorders, including RTT, is altered synaptic function in the brain. Here, we show that Mecp2tm1.1Jae/y mice display lower presynaptic function as assessed by paired pulse ratio, as well as decreased long term potentiation (LTP) at hippocampal Schaffer-collateral-CA1 synapses. Treatment of Mecp2tm1.1Jae/y mice with D-cycloserine (DCS), an FDA-approved analog of the amino acid D-alanine with antibiotic and glycinergic activity, corrected the presynaptic but not LTP deficit without affecting deficient hippocampal BDNF levels. DCS treatment did, however, partially restore lower BDNF levels in the brain stem and striatum. Thus, treatment with DCS may mitigate the severity of some of the neurobehavioral symptoms experienced by patients with Rett syndrome.

Cacna1c: Protecting young hippocampal neurons in the adult brain.

Neuropsychiatric disease is the leading cause of disability in the United States, and fourth worldwide.1,2 Not surprisingly, human genetic studies have revealed a common genetic predisposition for many forms of neuropsychiatric disease, potentially explaining why overlapping symptoms are commonly observed across multiple diagnostic categories. For example, the CACNA1C gene was recently identified in the largest human genome-wide association study to date as a risk loci held in common across 5 major forms of neuropsychiatric disease: bipolar disorder, schizophrenia, major depressive disorder (MDD), autism spectrum disorder and attention deficit-hyperactivity disorder.3 This gene encodes for the Cav1.2 subunit of the L-type voltage-gated calcium channel (LTCC), accounting for 85% of LTCCs in the brain, while the Cav1.3 subunit comprises the remainder.4 In neurons, LTCCs mediate calcium influx in response to membrane depolarization,5 thereby regulating neurotransmission and gene expression. Here, we describe our recent finding that Cav1.2 also controls survival of young hippocampal neurons in the adult brain, which has been linked to the etiology and treatment of neuropsychiatric disease. We also describe the effective restoration of young hippocampal neuron survival in adult Cav1.2 forebrain-specific conditional knockout mice using the neuroprotective compound P7C3-A20.

Loss of estrogen-related receptor alpha disrupts ventral-striatal synaptic function in female mice.

Eating disorders (EDs), including anorexia nervosa, bulimia nervosa and binge-ED, are mental illnesses characterized by high morbidity and mortality. While several studies have identified neural deficits in patients with EDs, the cellular and molecular basis of the underlying dysfunction has remained poorly understood. We previously identified a rare missense mutation in the transcription factor estrogen-related receptor alpha (ESRRA) associated with development of EDs. Because ventral-striatal signaling is related to the reward and motivation circuitry thought to underlie EDs, we performed functional and structural analysis of ventral-striatal synapses in Esrra-null mice. Esrra-null female, but not male, mice exhibit altered miniature excitatory postsynaptic currents on medium spiny neurons (MSNs) in the ventral striatum, including increased frequency, increased amplitude, and decreased paired pulse ratio. These electrophysiological measures are associated with structural and molecular changes in synapses of MSNs in the ventral striatum, including fewer pre-synaptic glutamatergic vesicles and enhanced GluR1 function. Neuronal Esrra is thus required for maintaining normal synaptic function in the ventral striatum, which may offer mechanistic insights into the behavioral deficits observed in Esrra-null mice.

The Neuropsychiatric Disease-Associated Gene cacna1c Mediates Survival of Young Hippocampal Neurons.

Genetic variations in CACNA1C, which encodes the Cav1.2 subunit of L-type calcium channels (LTCCs), are associated with multiple forms of neuropsychiatric disease that manifest high anxiety in patients. In parallel, mice harboring forebrain-specific conditional knockout of cacna1c (forebrain-Cav1.2 cKO) display unusually high anxiety-like behavior. LTCCs in general, including the Cav1.3 subunit, have been shown to mediate differentiation of neural precursor cells (NPCs). However, it has not previously been determined whether Cav1.2 affects postnatal hippocampal neurogenesis in vivo. Here, we show that forebrain-Cav1.2 cKO mice exhibit enhanced cell death of young hippocampal neurons, with no change in NPC proliferation, hippocampal size, dentate gyrus thickness, or corticosterone levels compared with wild-type littermates. These mice also exhibit deficits in brain levels of brain-derived neurotrophic factor (BDNF), and Cre recombinase-mediated knockdown of adult hippocampal Cav1.2 recapitulates the deficit in young hippocampal neurons survival. Treatment of forebrain-Cav1.2 cKO mice with the neuroprotective agent P7C3-A20 restored the net magnitude of postnatal hippocampal neurogenesis to wild-type levels without ameliorating their deficit in BDNF expression. The role of Cav1.2 in young hippocampal neurons survival may provide new approaches for understanding and treating neuropsychiatric disease associated with aberrations in CACNA1C. Visual Abstract.

The effects of weak versus strong relational judgments on response bias in Two-Alternative-Forced-Choice recognition: Is the test criterion-free?

It is widely believed that a Two-Alternative-Forced-Choice (2AFC) in an old/new recognition memory test is made by comparing the two items and choosing the item with the higher strength. For this reason, it is considered to be criterion-free by some researchers. We found evidence that subjects probabilistically compromised the comparison by choosing the left item when they recognized it as old. Using both normal test pairs (comprised of one new and one old item) and two types of null pairs (comprised of both-new or both-old items), we found that a left-biased choice was coupled with higher hit and false alarm rates and a shorter left than right-choice RT for the normal pairs, consistent with the hypothesis of a bias for making a choice on the basis of a left individual-item recognition. For the null pairs, RT was much longer for the both-new than for the both-old pairs, providing additional evidence for basing decision on an individual-item's absolute, rather than a relative, familiarity. Additionally, subjects gave higher confidence ratings to choices for the both-old than the normal and both-new pairs, again suggesting that their decision was based on absolute familiarity of the items. The results were found to be not due to a fast-response instruction. A comparative judgment experiment in which subjects chose the item higher or lower in an attribute magnitude did not show the response side bias and RT asymmetry. The presence of bias in the former, and the absence of it in the latter can be explained by a weak versus strong relational judgment in the former and the latter type of 2AFC, respectively. We discuss the implications these findings have for the use of the 2AFC as a method for testing recognition memory.