Low-intensity transcranial focused ultrasound suppresses pain by modulating pain-processing brain circuits.

ABSTRACT: There is an urgent and unmet clinical need to develop nonpharmacological interventions for chronic pain management because of the critical side effects of opioids. Low-intensity transcranial focused ultrasound (tFUS) is an emerging noninvasive neuromodulation technology with high spatial specificity and deep brain penetration. Here, we developed a tightly focused 128-element ultrasound transducer to specifically target small mouse brains using dynamic focus steering. We demonstrate that tFUS stimulation at pain-processing brain circuits can significantly alter pain-associated behaviors in mouse models in vivo. Our findings indicate that a single-session focused ultrasound stimulation to the primary somatosensory cortex (S1) significantly attenuates heat pain sensitivity in wild-type mice and modulates heat and mechanical hyperalgesia in a humanized mouse model of chronic pain in sickle cell disease. Results further revealed a sustained behavioral change associated with heat hypersensitivity by targeting deeper cortical structures (eg, insula) and multisession focused ultrasound stimulation to S1 and insula. Analyses of brain electrical rhythms through electroencephalography demonstrated a significant change in noxious heat hypersensitivity-related and chronic hyperalgesia-associated neural signals after focused ultrasound treatment. Validation of efficacy was carried out through control experiments, tuning ultrasound parameters, adjusting interexperiment intervals, and investigating effects on age, sex, and genotype in a head-fixed awake model. Importantly, tFUS was found to be safe, causing no adverse effects on motor function or the brain's neuropathology. In conclusion, the validated proof-of-principle experimental evidence demonstrates the translational potential of novel focused ultrasound neuromodulation for next-generation pain treatment without adverse effects.

Evolution of anti-SARS-CoV-2 spike protein titers after two-dose of COVID-19 vaccination among people living with HIV.

Background: A community COVID-19 outbreak caused by the B.1.1.7 SARS-CoV-2 variant occurred in Taiwan in May 2021. High-risk populations such as people living with HIV (PLWH) were recommended to receive two doses of COVID-19 vaccines. While SARS-CoV-2 vaccines have demonstrated promising results in general population, real-world information on the serological responses remains limited among PLWH. Methods: PLWH receiving the first dose of SARS-CoV-2 vaccine from 2020 to 2021 were enrolled. Determinations of anti-SARS-CoV-2 spike IgG titers were performed every one to three months, the third dose of the SARS-CoV-2 vaccine or confirmed SARS-CoV-2 infection. All serum samples were tested for anti-nucleocapsid antibody and those tested positive were excluded from analysis. Results: A total of 1189 PLWH were enrolled: 829 (69.7%) receiving two doses of the AZD1222 vaccine, 232 (19.5%) of the mRNA-1273 vaccine, and 128 (10.8%) of the BNT162b2 vaccine. At all time-points, PLWH receiving two doses of mRNA vaccines had consistently higher antibody levels than those receiving the AZD1222 vaccine (p <0.001 for all time-point comparisons). Factors associated with failure to achieve an anti-spike IgG titer >141 BAU/mL within 12 weeks, included type 2 diabetes mellitus (DM) (adjusted odds ratio [aOR], 2.24; 95% CI, 1.25-4), a CD4 T cell count <200 cells/mm3 upon receipt of the first dose of vaccination (aOR, 3.43; 95% CI, 1.31-9) and two homologous AZD1222 vaccinations (aOR, 16.85; 95%CI, 10.13-28). For those receiving two doses of mRNA vaccines, factors associated with failure to achieve an anti-spike IgG titer >899 BAU/mL within 12 weeks were a CD4 T cell count <200 cells/mm3 on first-dose vaccination (aOR, 3.95; 95% CI, 1.08-14.42) and dual BNT162b2 vaccination (aOR, 4.21; 95% CI, 2.57-6.89). Conclusions: Two doses of homologous mRNA vaccination achieved significantly higher serological responses than vaccination with AZD1222 among PLWH. Those with CD4 T cell counts <200 cells/mm3 and DM had consistently lower serological responses.

[Experience Providing Psychological Care to an HIV-Positive Patient With SARS-CoV-2 Infection].

Infectious diseases are often stigmatized and criminalized because of the way they are transmitted. An experience providing care to a 37-year-old patient with human immunodeficiency virus (HIV) infection who was admitted to a medical center's quarantine ward in July 2021 due to SARS-CoV-2 infection is described in this article. This patient lived with his mother, who was later diagnosed with COVID-19 as well. He was worried about his mother's health condition and, meanwhile, feared that information about his diseases and person would be exposed by the media. These stressors led to increased feelings of shame and anxiety and to situational low self-esteem. Several interventions were provided, including education regarding the importance of personal hygiene and of maintaining combination antiretroviral therapy (cART) to bolster immune system functions. During the isolation period, the nurses most regularly interacted with the patient directly. Thus, we worked to build the nurse-patient relationship by listening to the patient's worries, guaranteeing his privacy would not be compromised, and guiding him to express his emotions to reduce anxiety and enhance confidence. This experience demonstrated the importance of providing psychological care to COVID-19/HIV co-infected patients. We suggest that the government and media distribute correct and neutral information to destigmatize communicable diseases and to foster a friendlier healthcare environment.

Predation of Oysters Using an Autonomic Pharynx in the Oyster Leech Cryptostylochus sp. (Polycladida: Stylochidae).

Oyster farming has been threatened by marine flatworms for over 40 years, but few studies have been done to address this issue. Here, we examine the predatory behavior of the polyclad flatworm Cryptostylochus sp. from Penghu, Taiwan. Its predation process consists of three parts: the attack, invasion, and ingestion period. During the attack period, which begins 4 or more hours before the invasion, protruding pharynges form fragments that we call "autonomic pharynges". The autonomic pharynx is translucent white, membrane-like, and variable in length. Using time-lapse photography, we show that the pharynx moves around slowly and independently for roughly 10 hours before losing mobility. The autonomic pharynx moved toward the edge of the oyster shell and increases the frequency at which the oyster or clam opens and closes compared to the control group. The passageway demonstrates negative phototactic behavior in petri dishes. Linear regression showed a positive correlation between the number of autonomic pharynges and the clam mortality rate. Histological dissections showed that clam mantle tissue is externally digested by the autonomic pharynx. The fragments of multi-branched ruffled pharynx from polyclad flatworms slowly detach and play a critical role during the period of the attack on bivalves.

Capturing Pluripotency and Beyond.

During the development of a multicellular organism, the specification of different cell lineages originates in a small group of pluripotent cells, the epiblasts, formed in the preimplantation embryo. The pluripotent epiblast is protected from premature differentiation until exposure to inductive cues in strictly controlled spatially and temporally organized patterns guiding fetus formation. Epiblasts cultured in vitro are embryonic stem cells (ESCs), which recapitulate the self-renewal and lineage specification properties of their endogenous counterparts. The characteristics of totipotency, although less understood than pluripotency, are becoming clearer. Recent studies have shown that a minor ESC subpopulation exhibits expanded developmental potential beyond pluripotency, displaying a characteristic reminiscent of two-cell embryo blastomeres (2CLCs). In addition, reprogramming both mouse and human ESCs in defined media can produce expanded/extended pluripotent stem cells (EPSCs) similar to but different from 2CLCs. Further, the molecular roadmaps driving the transition of various potency states have been clarified. These recent key findings will allow us to understand eutherian mammalian development by comparing the underlying differences between potency network components during development. Using the mouse as a paradigm and recent progress in human PSCs, we review the epiblast's identity acquisition during embryogenesis and their ESC counterparts regarding their pluripotent fates and beyond.