A care coordination program to support patients with hepatitis B virus at Kaiser Permanente Mid-Atlantic States.

BACKGROUND: Eliminating hepatitis B virus (HBV) is a significant worldwide challenge requiring innovative approaches for vaccination, screening, disease management, and the prevention of related conditions. Programs that support patients in accessing needed clinical services can help optimize access to preventive services and treatment resources for hepatitis B. METHODS: Here, we outline a coordinator-supported program (HBV Pathway) that connects patients infected with HBV to laboratory testing, imaging, and specialty care for treatment initiation and/or liver cancer surveillance (screening of high-risk patients for liver cancer). This study describes the HBV Pathway steps and reports sociodemographic factors of patients by initiation and completion. RESULTS: Results showed a 72.5% completion rate (defined as completing all Pathway steps including the final specialty visit) among patients who initiated the Pathway. Differences in completion were observed by age, race, ethnicity, and service area, with higher rates for younger ages, Asian race, non-Hispanic ethnicity, and lower rates for patients within one service area. Of those who completed the specialty visit, 59.5% were referred for hepatocellular carcinoma surveillance. CONCLUSIONS: The HBV Pathway offers dual benefits- care coordination support for patients to promote Pathway completion and a standardized testing and referral program to reduce physician burden. This program provides an easy and reliable process for patients and physicians to obtain updated clinical information and initiate treatment and/or liver cancer screening if needed.

Reduction of left ventricular diastolic pressure as a key regulator of infarct coronary flow under mechanical left ventricular support.

Restoring ischaemic myocardial tissue perfusion is crucial for minimizing infarct size. Acute mechanical left ventricular (LV) support has been suggested to improve infarct tissue perfusion. However, its regulatory mechanism remains unclear. We investigated the physiological mechanisms in six Yorkshire pigs, which were subjected to 90-min balloon occlusion of the left anterior descending artery. During the acute reperfusion phase, LV support using an Impella heart pump was initiated. LV pressure, coronary flow and pressure of the infarct artery were simultaneously recorded to evaluate the impact of LV support on coronary physiology. Coronary wave intensity was calculated to understand the forces regulating coronary flow. Significant increases in coronary flow velocity and its area under the curve were found after mechanical LV support. Among the coronary flow-regulating factors, coronary pressure was increased mainly during the late diastolic phase with less pulsatility. Meanwhile, LV pressure was reduced throughout diastole resulting in significant and consistent elevation of coronary driving pressure. Interestingly, the duration of diastole was prolonged with LV support. In the wave intensity analysis, the duration between backward suction and pushing waves was extended, indicating that earlier myocardial relaxation and delayed contraction contributed to the extension of diastole. In conclusion, mechanical LV support increases infarct coronary flow by extending diastole and augmenting coronary driving pressure. These changes were mainly driven by reduced LV diastolic pressure, indicating that the key regulator of coronary flow under mechanical LV support is downstream of the coronary artery, rather than upstream. Our study highlights the importance of LV diastolic pressure in infarct coronary flow regulation. KEY POINTS: Restoring ischaemic myocardial tissue perfusion is crucial for minimizing infarct size. Although mechanical left ventricular (LV) support has been suggested to improve infarct coronary flow, its specific mechanism remains to be clarified. LV support reduced LV pressure, and elevated coronary pressure during the late diastolic phase, resulting in high coronary driving pressure. This study demonstrated for the first time that mechanical LV support extends diastolic phase, leading to increased infarct coronary flow. Future studies should evaluate the correlation between improved infarct coronary flow and resulting infarct size.

Multicationic Tetrahedra Networks: Alkaline-Earth-Centered Polyhedra and Non-Condensed AlN6-Octahedra in the Imidonitridophosphates AE2AlP8N15(NH) (AE=Ca, Sr, Ba).

A series of isostructural imidonitridophosphates AE2AlP8N15(NH) (AE=Ca, Sr, Ba) was synthesized at high-pressure/high-temperature conditions (1400 °C and 5-9 GPa) from alkaline-earth metal nitrides or azides Ca3N2/Sr(N3)2/Ba(N3)2 and the binary nitrides AlN and P3N5. NH4F served as a hydrogen source and mineralizing agent. The crystal structures were determined by single-crystal X-ray diffraction and feature a three-dimensional network of vertex-sharing PN4-tetrahedra forming diverse-sized rings that are occupied by aluminum and alkaline earth ions. These structures represent another example of nitridophosphate-based networks that simultaneously incorporate AlN6-octahedra and alkaline-earth-centered polyhedra, with aluminum not participating in the tetrahedra network. They differ from previously reported ones by incorporating non-condensed octahedra instead of strongly condensed octahedra units and contribute to the diversity of multicationic nitridophosphate network structures. The results are supported by atomic resolution EDX mapping, solid-state NMR and FTIR measurements. Eu2+-doped samples show strong luminescence with narrow emissions in the range of green to blue under UV excitation, marking another instance of Eu2+-luminescence within imidonitridophosphates.

Bactericidal/permeability-increasing protein instructs dendritic cells to elicit Th22 cell response.

Neutrophil-derived bactericidal/permeability-increasing protein (BPI) is known for its bactericidal activity against gram-negative bacteria and neutralization of lipopolysaccharide. Here, we define BPI as a potent activator of murine dendritic cells (DCs). As shown in GM-CSF-cultured, bone-marrow-derived cells (BMDCs), BPI induces a distinct stimulation profile including IL-2, IL-6, and tumor necrosis factor expression. Conventional DCs also respond to BPI, while M-CSF-cultivated or peritoneal lavage macrophages do not. Subsequent to BPI stimulation of BMDCs, CD4+ T cells predominantly secrete IL-22 and, when naive, preferentially differentiate into T helper 22 (Th22) cells. Congruent with the tissue-protective properties of IL-22 and along with impaired IL-22 induction, disease severity is significantly increased during dextran sodium sulfate-induced colitis in BPI-deficient mice. Importantly, physiological diversification of intestinal microbiota fosters BPI-dependent IL-22 induction in CD4+ T cells derived from mesenteric lymph nodes. In conclusion, BPI is a potent activator of DCs and consecutive Th22 cell differentiation with substantial relevance in intestinal homeostasis.

Effects of midazolam on high-frequency oscillations in amygdala and hippocampus of epilepsy patients.

High-frequency oscillations (HFOs) are associated with normal brain function, but are also increasingly recognized as potential biomarkers of epileptogenic tissue. Considering the important role of interneuron activity in physiological HFO generation, we studied their modulation by midazolam (MDZ), an agonist of γ-aminobutyric acid type A (GABAA)-benzodiazepine receptors. Here, we analyzed 80 intracranial electrode contacts in amygdala and hippocampus of 13 patients with drug-refractory focal epilepsy who had received MDZ for seizure termination during presurgical monitoring. Ripples (80-250 Hz) and fast ripples (FRs; 250-400 Hz) were compared before and after seizures with MDZ application, and according to their origin either within or outside the individual seizure onset zone (SOZ). We found that MDZ distinctly suppressed all HFOs (ripples and FRs), whereas the reduction of ripples was significantly less pronounced inside the SOZ compared to non-SOZ contacts. The rate of FRs inside the SOZ was less affected, especially in hippocampal contacts. In a few cases, even a marked increase of FRs following MDZ administration was seen. Our results demonstrate, for the first time, a significant HFO modulation in amygdala and hippocampus by MDZ, thus giving insights into the malfunction of GABA-mediated inhibition within epileptogenic areas and its role in HFO generation.

Feasibility Study for Monitoring an Ultrasonic System Using Structurally Integrated Piezoceramics.

This paper presents a new approach to monitoring ultrasonic systems using structurally integrated piezoceramics. These are integrated into the sonotrode at different points and with different orientations. The procedure for integrating the piezoceramics into the sonotrode and their performance is experimentally investigated. We examine whether the measured signal can be used to determine the optimal operating frequency of the ultrasonic system, if integrating several piezoceramics enables discernment of the current vibration shape, and if the piezoceramics can withstand the high strains caused by the vibrations in a frequency range of approximately 20-25 kHz. The signals from the piezoceramic sensors are compared to the real-time displacement at different points of the sonotrode using a 3D laser scanning vibrometer. To evaluate the performance of the sensors, different kinds of excitation of the ultrasonic system are chosen.

In vitro neurotoxicity of particles from diesel and biodiesel fueled engines following direct and simulated inhalation exposure.

Combustion-derived particulate matter (PM) is a major source of air pollution. Efforts to reduce diesel engine emission include the application of biodiesel. However, while urban PM exposure has been linked to adverse brain effects, little is known about the direct effects of PM from regular fossil diesel (PMDEP) and biodiesel (PMBIO) on neuronal function. Furthermore, it is unknown to what extent the PM-induced effects in the lung (e.g., inflammation) affect the brain. This in vitro study investigates direct and indirect toxicity of PMDEP and PMBIO on the lung and brain and compared it with effects of clean carbon particles (CP). PM were generated using a common rail diesel engine. CP was sampled from a spark generator. First, effects of 48 h exposure to PM and CP (1.2-3.9 µg/cm2) were assessed in an in vitro lung model (air-liquid interface co-culture of Calu-3 and THP1 cells) by measuring cell viability, cytotoxicity, barrier function, inflammation, and oxidative and cell stress. None of the exposures caused clear adverse effects and only minor changes in gene expression were observed. Next, the basal medium was collected for subsequent simulated inhalation exposure of rat primary cortical cells. Neuronal activity, recorded using microelectrode arrays (MEA), was increased after acute (0.5 h) simulated inhalation exposure. In contrast, direct exposure to PMDEP and PMBIO (1-100 µg/mL; 1.2-119 µg/cm2) reduced neuronal activity after 24 h with lowest observed effect levels of respectively 10 µg/mL and 30 µg/mL, indicating higher neurotoxic potency of PMDEP, whereas neuronal activity remained unaffected following CP exposure. These findings indicate that combustion-derived PM potently inhibit neuronal function following direct exposure, while the lung serves as a protective barrier. Furthermore, PMDEP exhibit a higher direct neurotoxic potency than PMBIO, and the data suggest that the neurotoxic effects is caused by adsorbed chemicals rather than the pure carbon core.

Psychological impact of medical evacuation for ICU saturation in Covid-19-related ARDS patients.

PURPOSE: Psychological impact of Medical Evacuation (MEDEVAC) in Covid-19 patients is undetermined. The objectives were to evaluate: Post-traumatic Stress Disorder (PTSD) in MEDEVAC patients hospitalized in ICU for Covid-19-related acute respiratory distress syndrome (ARDS) compared to control group; anxiety, depression rates and outcomes in patients and PTSD in relatives. MATERIAL AND METHODS: This is a retrospective multicentric 1/1 paired cohort performed in 10 ICUs in the West of France. Evaluation was performed 18 months after discharge. Patients and closest relatives performed IES-R (Impact and Event Scale-Revised) and/or HADS (Hospital Anxiety and Depression Scale) scales. RESULTS: Twenty-six patients were included in each group. Patients were 64 ± 11 years old, with 83% male. We report 12 vs 20% of PTSD in control vs MEDEVAC groups (p = 0.7). Anxiety disorder affected 43.5 vs 28.0% (p = 0.26) and depression 12.5 vs 14.3% (p > 0.99) in control vs MEDEVAC groups. PTSD affects 33.3 vs 42.1% of closest relatives (p = 0.55). Ways of communication were adapted: video calls were more frequent in MEDEVAC patients (8.7 vs 60.9%, p < 0.01) whereas physical visits concerned more control group (45.8 vs 13.0%, p = 0.01). CONCLUSIONS: PTSD rate were similar between groups. Adaptive ways of communication, restricted visits and global uncertainties could explain the absence of differences.

Acute Exercise Increases GDF15 and Unfolded Protein Response/Integrated Stress Response in Muscle in Type 2 diabetes.

CONTEXT: Regular exercise is a key prevention strategy for obesity and type 2 diabetes (T2D). Exerkines secreted in response to exercise or recovery may contribute to improved systemic metabolism. Conversely, an impaired exerkine response to exercise and recovery may contribute to cardiometabolic diseases. OBJECTIVE: We investigated if the exercise-induced regulation of the exerkine, growth/differentiation factor 15 (GDF15) and its putative upstream regulators of the unfolded protein response (UPR)/integrated stress response (ISR) is impaired in skeletal muscle in patients with T2D compared with weight-matched glucose-tolerant men. METHODS: Thirteen male patients with T2D and 14 age- and weight-matched overweight/obese glucose-tolerant men exercised at 70% of VO2max for 1-h. Blood and skeletal muscle biopsies were sampled before, immediately after, and 3-h into recovery. Serum and muscle transcript levels of GDF15 and key markers of UPR/ISR were determined. Additionally, protein/phosphorylation levels of key regulators in UPR/ISR were investigated. RESULTS: Acute exercise increased muscle gene expression and serum GDF15 levels in both groups. In recovery, muscle expression of GDF15 decreased toward baseline, whereas serum GDF15 remained elevated. In both groups, acute exercise increased the expression of UPR/ISR markers, including ATF4, CHOP, EIF2K3 (encoding PERK) and PPP1R15A (encoding GADD34), of which only CHOP remained elevated 3-h into recovery. Downstream molecules of the UPR/ISR including XBP1-U, XBP1-S, and EDEM1 were increased with exercise and 3-h into recovery in both groups. The phosphorylation levels of eIF2α-Ser51, a common marker of UPR and ISR, increased immediately after exercise in controls, but decreased 3-h into recovery in both groups. CONCLUSION: In conclusion, exercise-induced regulation of GDF15 and key markers of UPR/ISR are not compromised in patients with type 2 diabetes compared with weight-matched controls.

Ultraviolet interlayer excitons in bilayer WSe2.

Interlayer excitons in van der Waals heterostructures are fascinating for applications like exciton condensation, excitonic devices and moiré-induced quantum emitters. The study of these charge-transfer states has almost exclusively focused on band edges, limiting the spectral region to the near-infrared regime. Here we explore the above-gap analogues of interlayer excitons in bilayer WSe2 and identify both neutral and charged species emitting in the ultraviolet. Even though the transitions occur far above the band edge, the states remain metastable, exhibiting linewidths as narrow as 1.8 meV. These interlayer high-lying excitations have switchable dipole orientations and hence show prominent Stark splitting. The positive and negative interlayer high-lying trions exhibit significant binding energies of 20-30 meV, allowing for a broad tunability of transitions via electric fields and electrostatic doping. The Stark splitting of these trions serves as a highly accurate, built-in sensor for measuring interlayer electric field strengths, which are exceedingly difficult to quantify otherwise. Such excitonic complexes are further sensitive to the interlayer twist angle and offer opportunities to explore emergent moiré physics under electrical control. Our findings more than double the accessible energy range for applications based on interlayer excitons.

Differential impact of preventive cognitive therapy while tapering antidepressants versus maintenance antidepressant treatment on affect fluctuations and individual affect networks and impact on relapse: a secondary analysis of a randomised controlled trial.

Background: There is an urgent need to better understand and prevent relapse in major depressive disorder (MDD). We explored the differential impact of various MDD relapse prevention strategies (pharmacological and/or psychological) on affect fluctuations and individual affect networks in a randomised setting, and their predictive value for relapse. Methods: We did a secondary analysis using experience sampling methodology (ESM) data from individuals with remitted recurrent depression that was collected alongside a randomised controlled trial that ran in the Netherlands, comparing: (I) tapering antidepressants while receiving preventive cognitive therapy (PCT), (II) combining antidepressants with PCT, or (III) continuing antidepressants without PCT, for the prevention of depressive relapse, as well as ESM data from 11 healthy controls. Participants had multiple past depressive episodes, but were remitted for at least 8 weeks and on antidepressants for at least six months. Exclusion criteria were: current (hypo)mania, current alcohol or drug abuse, anxiety disorder that required treatment, psychological treatment more than twice per month, a diagnosis of organic brain damage, or a history of bipolar disorder or psychosis. Fluctuations (within-person variance, root mean square of successive differences, autocorrelation) in negative and positive affect were calculated. Changes in individual affect networks during treatment were modelled using time-varying vector autoregression, both with and without applying regularisation. We explored whether affect fluctuations or changes in affect networks over time differed between treatment conditions or relapse outcomes, and predicted relapse during 2-year follow-up. This ESM study was registered at ISRCTN registry, ISRCTN15472145. Findings: Between Jan 1, 2014, and Jan 31, 2015, 72 study participants were recruited, 42 of whom were included in the analyses. We found no indication that affect fluctuations differed between treatment groups, nor that they predicted relapse. We observed large individual differences in affect network structure across participants (irrespective of treatment or relapse status) and in healthy controls. We found no indication of group-level differences in how much networks changed over time, nor that changes in networks over time predicted time to relapse (regularised models: hazard ratios [HR] 1063, 95% CI <0.0001->10 000, p = 0.65; non-regularised models: HR 2.54, 95% CI 0.23-28.7, p = 0.45) or occurrence of relapse (regularised models: odds ratios [OR] 22.84, 95% CI <0.0001->10 000, p = 0.90; non-regularised models: OR 7.57, 95% CI 0.07-3709.54, p = 0.44) during complete follow-up. Interpretation: Our findings should be interpreted with caution, given the exploratory nature of this study and wide confidence intervals. While group-level differences in affect dynamics cannot be ruled out due to low statistical power, visual inspection of individual affect networks also revealed no meaningful patterns in relation to MDD relapse. More studies are needed to assess whether affect dynamics as informed by ESM may predict relapse or guide personalisation of MDD relapse prevention in daily practice. Funding: The Netherlands Organisation for Health Research and Development, Dutch Research Council, University of Amsterdam.

The Etiology of Parkinson's Disease: New Perspectives from Gene-Environment Interactions.

Parkinson's disease is now the most rapidly growing neurodegenerative disease worldwide. It is therefore critical to identify which factors, and to what extent, contribute to the multifactorial etiology of Parkinson's disease. Here, we address two interesting elements from the perspective of genetics, namely (a) the estimated age of several genetic risk factors related to Parkinson's disease; and (b) the relative contribution of genetics to the etiology of Parkinson's disease, as derived from twin studies. Based on these two perspectives, we argue that most genetic risk factors are by themselves insufficient to explain the majority of Parkinson's disease, and that environmental factors are required for these genetic factors to become pathophysiologically relevant.

Why are different estimates of the effective reproductive number so different? A case study on COVID-19 in Germany.

The effective reproductive number Rt has taken a central role in the scientific, political, and public discussion during the COVID-19 pandemic, with numerous real-time estimates of this quantity routinely published. Disagreement between estimates can be substantial and may lead to confusion among decision-makers and the general public. In this work, we compare different estimates of the national-level effective reproductive number of COVID-19 in Germany in 2020 and 2021. We consider the agreement between estimates from the same method but published at different time points (within-method agreement) as well as retrospective agreement across eight different approaches (between-method agreement). Concerning the former, estimates from some methods are very stable over time and hardly subject to revisions, while others display considerable fluctuations. To evaluate between-method agreement, we reproduce the estimates generated by different groups using a variety of statistical approaches, standardizing analytical choices to assess how they contribute to the observed disagreement. These analytical choices include the data source, data pre-processing, assumed generation time distribution, statistical tuning parameters, and various delay distributions. We find that in practice, these auxiliary choices in the estimation of Rt may affect results at least as strongly as the selection of the statistical approach. They should thus be communicated transparently along with the estimates.

Genomic analysis of Chlamydia psittaci from a multistate zoonotic outbreak in two chicken processing plants.

Four Chlamydia psittaci isolates were recovered from clinical specimens from ill workers during a multistate outbreak at two chicken processing plants. Whole genome sequencing analyses revealed high similarity to C. psittaci genotype D. The isolates differed from each other by only two single nucleotide polymorphisms, indicating a common source.

Understanding suicidality in Pacific adolescents in New Zealand using network analysis.

INTRODUCTION: Pacific adolescents in New Zealand (NZ) are three to four times more likely than NZ European adolescents to report suicide attempts and have higher rates of suicidal plans. Suicidal thoughts, plans, and attempts, termed suicidality in this study, result from a complex dynamic interplay of factors, which emerging methodologies like network analysis aim to capture. METHODS: This study used cross-sectional network analysis to model the relationships between suicidality, self-harm, and individual depression symptoms, whilst conditioning on a multi-dimensional set of variables relevant to suicidality. A series of network models were fitted to data from a community sample of New Zealand-born Pacific adolescents (n = 550; 51% male; Mean age (SD) = 17 (0.35)). RESULTS: Self-harm and the depression symptom measuring pessimism had the strongest associations with suicidality, followed by symptoms related to having a negative self-image about looks and sadness. Nonsymptom risk factors for self-harm and suicidality differed markedly. CONCLUSIONS: Depression symptoms varied widely in terms of their contribution to suicidality, highlighting the valuable information gained from analysing depression at the symptom-item level. Reducing the sources of pessimism and building self-esteem presented as potential targets for alleviating suicidality amongst Pacific adolescents in New Zealand. Suicide prevention strategies need to include risk factors for self-harm.

Optimal objective measurement of physical function and its predictive capacity for mortality among community-dwelling older women.

AIM: Objective measurements of physcial function, including gait speed, handgrip strength, and the chair stand test, have been shown to have predictive capacity for negative health-related outcomes. The aim of this study was to examine campariatively which of these common assessments may be optimal in terms of their predictive capacity for mortality. METHODS: A total of 9834 community-dwelling older women aged 65-89 years from the Study of Osteoporotic Fractures (SOF) were followed for 20 years. Gait speed, handgrip strength, and the chair stand test were measured every 2-4 years on up to 9 visits. All deaths were adjudicated. RESULTS: All three measurements of physical function were significantly associated with overall, cardiovascular disease and other mortality. Gait speed had the greatest magnitude of hazard ratios (HRs) for all outcomes of interest. A one-unit standard deviation increase in gait speed was associated with a 33% (HR = 0.67, 95% confidence interval [95% CI]: 0.64-0.70) lower risk for overall mortality, a 31% (HR = 0.69, 95% CI: 0.64-0.73) lower risk for cardiovascular disease mortality, a 15% (HR = 0.85, 95% CI: 0.78-0.92) lower risk for cancer mortality and a 42% (HR = 0.58, 95% CI: 0.55-0.62) lower risk for other mortality. Further examination of gait speed identified two cut-points (0.9 and 0.7 m/s) that were strongly indicative of increased mortality risk. CONCLUSION: Our large prospective study indicates that gait speed possesses a better prediction of mortality among older women compared with handgrip strength or the chair stand test. Using cut-points of 0.9 and 0.7 m/s can help identify older women at higher mortality risk, who may benefit from physical function improvement interventions. Geriatr Gerontol Int 2023; 23: 715-721.

AMPKγ3 Controls Muscle Glucose Uptake in Recovery From Exercise to Recapture Energy Stores.

Exercise increases muscle glucose uptake independently of insulin signaling and represents a cornerstone for the prevention of metabolic disorders. Pharmacological activation of the exercise-responsive AMPK in skeletal muscle has been proven successful as a therapeutic approach to treat metabolic disorders by improving glucose homeostasis through the regulation of muscle glucose uptake. However, conflicting observations cloud the proposed role of AMPK as a necessary regulator of muscle glucose uptake during exercise. We show that glucose uptake increases in human skeletal muscle in the absence of AMPK activation during exercise and that exercise-stimulated AMPKγ3 activity strongly correlates to muscle glucose uptake in the postexercise period. In AMPKγ3-deficient mice, muscle glucose uptake is normally regulated during exercise and contractions but impaired in the recovery period from these stimuli. Impaired glucose uptake in recovery from exercise and contractions is associated with a lower glucose extraction, which can be explained by a diminished permeability to glucose and abundance of GLUT4 at the muscle plasma membrane. As a result, AMPKγ3 deficiency impairs muscle glycogen resynthesis following exercise. These results identify a physiological function of the AMPKγ3 complex in human and rodent skeletal muscle that regulates glucose uptake in recovery from exercise to recapture muscle energy stores. ARTICLE HIGHLIGHTS: Exercise-induced activation of AMPK in skeletal muscle has been proposed to regulate muscle glucose uptake in recovery from exercise. This study investigated whether the muscle-specific AMPKγ3-associated heterotrimeric complex was involved in regulating muscle glucose metabolism in recovery from exercise. The findings support that exercise-induced activation of the AMPKγ3 complex in human and mouse skeletal muscle enhances glucose uptake in recovery from exercise via increased translocation of GLUT4 to the plasma membrane. This work uncovers the physiological role of the AMPKγ3 complex in regulating muscle glucose uptake that favors replenishment of the muscle cellular energy stores.

Hippocampal output profoundly impacts the interpretation of tactile input patterns in SI cortical neurons.

Due to continuous state variations in neocortical circuits, individual somatosensory cortex (SI) neurons in vivo display a variety of intracellular responses to the exact same spatiotemporal tactile input pattern. To manipulate the internal cortical state, we here used brief electrical stimulation of the output region of the hippocampus, which preceded the delivery of specific tactile afferent input patterns to digit 2 of the anesthetized rat. We find that hippocampal output had a diversified, remarkably strong impact on the intracellular response types displayed by each neuron in the primary SI to each given tactile input pattern. Qualitatively, this impact was comparable to that previously described for cortical output, which was surprising given the widely assumed specific roles of the hippocampus, such as in cortical memory formation. The findings show that hippocampal output can profoundly impact the state-dependent interpretation of tactile inputs and hence influence perception, potentially with affective and semantic components.