A curvilinear association between therapists' use of discourse particles and therapist empathy in psychotherapy.

This study investigates the relationships between therapists' use of discourse particles and therapist empathy. Discourse particles, commonly found in non-English languages, are verbal elements that constitute metacommunication by encoding speakers' emotions and attitudes, which are typically expressed by nonverbal behaviors (e.g., intonation, tone, facial expression, nodding). We hypothesize an inverted U-shaped curvilinear relationship between therapists' use of discourse particles and therapist empathy, given the notion that an optimal level of therapists' emotion in psychotherapy can facilitate clients' inner experiencing and self-expression. Four psychotherapy sessions each from 39 therapist-client dyads were analyzed. After each session, therapist empathy was rated by trained observers using the Therapist Empathy Scale (TES) and by clients using the Barrett-Lennard Relationship Inventory (BLRI). Multilevel modeling shows that both the person-level negative quadratic term and positive linear term for therapists' usage of discourse particles are significant in predicting mean TES with large effect sizes. The same predictors do not yield significant results in predicting mean BLRI but they trend in similar directions of associations with medium effect sizes. Our results suggest the optimal usage of discourse particles by therapists is around 20.3% (out of all utterances). The nonsignificant results in BLRI may be attributed to the relatively small sample size of our data and the noncommunication orientation of the client-rated measure. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Operative Intervention Does Not Change Pain Perception in Patients With Diabetic Foot Ulcers.

Researchers investigated pain perception in patients with diabetic foot ulcers (DFUs) by analyzing pre- and postoperative physical function (PF), pain interference (PI), and depression domains of the Patient-Reported Outcome Measurement Information System (PROMIS). They hypothesized that 1) because of painful diabetic peripheral neuropathy (DPN), a majority of patients with DFUs would have high PROMIS PI scores unchanged by operative intervention, and 2) the initially assessed PI, PF, and depression levels would be correlated with final outcomes. Seventy-five percent of patients with DFUs reported pain, most likely because of painful DPN. Those who reported high PI and low PF were likely to report depression. PF, PI, and depression levels were unchanged after operative intervention or healing of DFUs.

Influenza A virus hemagglutinin mutations associated with use of neuraminidase inhibitors correlate with decreased inhibition by anti-influenza antibodies.

BACKGROUND: Vaccination and the use of neuraminidase inhibitors (NAIs) are currently the front lines of defense against seasonal influenza. The activity of influenza vaccines and antivirals drugs such as the NAIs can be affected by mutations in the influenza hemagglutinin (HA) protein. Numerous HA substitutions have been identified in nonclinical NAI resistance-selection experiments as well as in clinical specimens from NAI treatment or surveillance studies. These mutations are listed in the prescribing information (package inserts) for FDA-approved NAIs, including oseltamivir, zanamivir, and peramivir. METHODS: NAI treatment-emergent H1 HA mutations were mapped onto the H1N1 HA1 trimeric crystal structure and most of them localized to the HA antigenic sites predicted to be important for anti-influenza immunity. Recombinant A/California/04/09 (H1N1)-like viruses carrying HA V152I, G155E, S162 N, S183P, and D222G mutations were generated. We then evaluated the impact of these mutations on the immune reactivity and replication potential of the recombinant viruses in a human respiratory epithelial cell line, Calu- 3. RESULTS: We found that the G155E and D222G mutations significantly increased viral titers ~ 13-fold compared to the wild-type virus. The hemagglutination and microneutralization activity of goat and ferret antisera, monoclonal antibodies, and human serum samples raised against pandemic A(H1N1)pdm09 viruses was ~ 100-fold lower against mutants carrying G155E or D222G compared to the wild-type virus. CONCLUSIONS: Although the mechanism by which HA mutations emerge during NAI treatment is uncertain, some NAI treatment-emergent HA mutations correlate with decreased immunity to influenza virus.

Formality in psychotherapy: How are therapists' and clients' use of discourse particles related to therapist empathy?

Introduction: Previous studies explored the preferences for therapists' attire and office setting based on initial impressions as a reference for the formality in psychotherapy. This study examines the formality of psychotherapy by investigating therapists' and clients' use of discourse particles, the linguistic marker and quantifier of the formality in speech, in relation to therapist empathy in different stages of psychotherapy. Methods: Four psychotherapy sessions (representing early, mid, and late stages) each from 39 therapist-client dyads were analyzed. Trained observers rated therapist empathy in each session using the Therapist Empathy Scale. Results: Results of multilevel modeling show that synchrony in particle usage, hence synchrony in formality, between clients and therapists is not associated with therapist empathy. Therapists' use of particles (i.e., absolute formality of therapists) was also not associated with therapist empathy. In contrast, the relative formality of therapists plays significant roles: therapist empathy is generally observed when therapists are relatively more formal than the clients (i.e., lower relative usage of particles by the therapists when compared to the clients). However, for clients who speak formally with few particles, therapist casualness (i.e., higher relative usage of particles than the clients) at the beginning of therapy may be interpreted as therapist empathy as therapists help these clients ease into the therapeutic relationships. Discussion: Our results suggest that the examination of therapists' and clients' use of particles across different stages of treatment may illuminate dynamic interactional styles that facilitate or hinder the psychotherapy process.

Adaptation of influenza B virus by serial passage in human airway epithelial cells.

Influenza B viruses cause seasonal epidemics and are a considerable burden to public health. To understand their adaptation capability, we examined the genetic changes that occurred following 15 serial passages of two influenza B viruses, B/Brisbane/60/2008 and B/Victoria/504/2000, in human epithelial cells. Thirteen distinct amino acid mutations were found in the PB1, PA, hemagglutinin (HA), neuraminidase (NA), and M proteins after serial passage in the human lung epithelial cell line, Calu-3, and normal human bronchial epithelial (NHBE) cells. These changes were associated with significantly decreased viral replication levels. Our results demonstrate that adaptation of influenza B viruses for growth in human airway epithelial cells is partially conferred by selection of HA1, NA, and polymerase mutations that regulate receptor specificity, functional compatibility with the HA protein, and polymerase activity, respectively.

Effect of influenza H1N1 neuraminidase V116A and I117V mutations on NA activity and sensitivity to NA inhibitors.

Neuraminidase inhibitors (NAIs) play a key role in the management of influenza. Given the limited number of FDA-approved anti-influenza drugs, evaluation of potential drug-resistant variants is of high priority. Two NA mutations, V116A and I117V, are found in ∼0.6% of human, avian, and swine N1 isolates. Using the A/California/04/09-like (CA/04, H1N1) background, we examined the impact of V116A and I117V NA mutations on NAI susceptibility, substrate specificity, and replicative capacity in normal human bronchial (NHBE) cells and a human respiratory epithelial cell line (Calu-3). We compared the impact of V116A and I117V on the functional properties of NA and compared these mutations with that of previously reported NAI-resistant mutations, E119A, H275Y, and N295S. All NA mutations were genetically stable. None of the viruses carrying NA mutations grew to significantly lower titers than CA/04 in Calu-3 cells. In contrast, V116A, I117V, E119A, and N295S substitutions resulted in significantly lower viral titers (1.2 logs) than the parental CA/04 virus in NHBE cells. V116A conferred reduced sensitivity to oseltamivir and zanamivir (13.7-fold). When MUNANA, 3'SL, and 6'SL substrates were applied, we observed that V116A reduced binding ability for all substrates (13.9-fold) and I117V led to the significantly decreased affinity for MUNANA and 6'SL (4.2-fold). Neither mutation altered the catalytic efficiency (kcat/KM) in catalyzing 3'SL, but the efficiency in catalyzing MUNANA and 6'SL was significantly decreased: only ∼34.7% compared to the wild-type NA. The efficiencies of NAs with E119A, H275Y, and N295S mutations to catalyze all substrates were ∼19.4% of the CA/04 NA. Our study demonstrates the direct effect of drug-resistant mutations located inside or adjacent to the NA active site on NA substrate specificity.

The use of plant lectins to regulate H1N1 influenza A virus receptor binding activity.

We applied an in vitro selection approach using two different plant lectins that bind to α2,3- or α2,6-linked sialic acids to determine which genetic changes of the A/California/04/09 (H1N1) virus alter hemagglutinin (HA) receptor binding toward α2,3- or α2,6-linked glycans. Consecutive passages of the A/California/04/09 virus with or without lectins in human lung epithelial Calu-3 cells led to development of three HA1 amino acid substitutions, N129D, G155E, and S183P, and one mutation in the neuraminidase (NA), G201E. The S183P mutation significantly increased binding to several α2,6 SA-linked glycans, including YDS, 6'SL(N), and 6-Su-6'SLN, compared to the wild-type virus (↑3.6-fold, P < 0.05). Two other HA1 mutations, N129D and G155E, were sufficient to significantly increase binding to α2,6-linked glycans, 6'SLN and 6-Su-6'SLN, compared to S183P (↑4.1-fold, P < 0.05). These HA1 mutations also increased binding affinity for 3'SLN glycan compared to the wild-type virus as measured by Biacore surface plasmon resonance method. In addition, the HA1 N129D and HA1 G155E substitutions were identified as antigenic mutations. Furthermore, the G201E mutation in NA reduced the NA enzyme activity (↓2.3-fold). These findings demonstrate that the A/California/04/09 (H1N1) virus can acquire enhanced receptor affinity for both α2,3- and α2,6-linked sialic receptors under lectin-induced selective pressure. Such changes in binding affinity are conferred by selection of beneficial HA1 mutations that affect receptor specificity, antigenicity, and/or functional compatibility with the NA protein.