Conectar
by Kaylee R. Jacobs, Caleb M. Ardizzone, Arkaprabha Banerjee, Evelyn Toh, Xiaoli Zhang, David E. Nelson
Chlamydia are obligate intracellular bacterial pathogens that infect a wide range of vertebrate hosts. Despite having highly conserved genomes, closely related Chlamydia species can exhibit distinct host and tissue tropisms. The host tropisms of the human pathogen Chlamydia trachomatis and the closely related mouse pathogen Chlamydia muridarum are influenced by their ability to evade host immune responses, particularly those mediated by interferon gamma. However, there is evidence that tissue tropism is driven by additional poorly understood host and Chlamydia factors. In this study, we used a forward genetic approach to investigate the mechanisms that mediate C. muridarum tissue tropism. We conducted a tropism screen using a randomly mutagenized C. muridarum library and murine cell lines representing different tissues. We identified a mutant isolate whose growth was restricted in murine rectal and oviduct epithelial cells in an interferon gamma-independent manner. This phenotype was mapped to a missense mutation in tc0237, a gene that mediates the affinity of C. muridarum for cultured human epithelial cells. Our analysis of growth dynamics showed that the tc0237 mutant exhibits a developmental delay in rectal epithelial cells. Together, these results suggest that TC0237 plays a role in C. muridarum tissue tropism.
Venous thromboembolism (VTE) occurs when a blood clot forms in a vein. It is comprised of deep vein thrombosis (DVT) and pulmonary embolism and can be potentially life-threatening. Patients undergoing surgery are at increased risk of developing VTE within hospital admission and 90 days after hospital discharge are collectively known as hospital-acquired thrombosis (HAT). Without the use of thromboprophylaxis, the untreated risk of VTE is reported to be as high as 40–60% in those undergoing major orthopaedic procedures and around 15–40% in the general surgical population.
HAT accounts for around 12 000 deaths per year in the UK. For patients undergoing surgery, there is good evidence for the use of thromboprophylaxis to prevent VTE.
Thromboprophylaxis is available in both pharmacological and mechanical forms. While there is a huge body of evidence demonstrating that pharmacological thromboprophylaxis significantly reduces VTE by 30–65%, the benefit of graduated compression stockings (GCS) has been called into question. The GRACE study (Graduated Compression stocking as an adjunct to Extended duration pharmacological thromboprophylaxis for venous thromboembolism prevention) aims to evaluate the adjuvant benefit of GCS in addition to extended duration pharmacological thromboprophylaxis (EDPTP) for elective surgical patients at highest risk of VTE.
GRACE is a pragmatic, multicentre randomised trial of adults undergoing surgery who are at high risk of VTE. Participants are randomised into a 1:1 ratio to either EDPTP and compression stockings (control arm) or EDPTP (intervention arm). Following randomisation, participants will undergo surgery and be followed up centrally at 7, 21–35 and 90 days after their procedure. All participants will be offered a bilateral full lower limb duplex scan at 21–35 days post procedure to capture any asymptomatic DVT.
The trial aims to randomise 8608 participants from around 50 National Health Service (NHS) and non-NHS sites in the UK over a 24-month period. The primary endpoint is any imaging-confirmed incidence of VTE within 90 days of surgery.
On 20 December 2023, GRACE received favourable ethical approval from the Wales Research Ethics Committee 3 Cardiff (23/WA/0350) and the Health Research Authority (IRAS 333539). The results of the study will be disseminated via peer-reviewed publications, presentation at national and international conferences and to study participants via electronic newsletter and social media channels.
by Kazuo Teramoto, Yuji Ueda, Ryosuke Murai, Kazumasa Ogasawara, Misako Nakayama, Hirohito Ishigaki, Yasushi Itoh
Reducing the number of immunosuppressive cells in blood is a potential strategy for activating anti-tumor immunity, which provides a promising approach to cancer treatment. In this study, we developed an adsorbent designed to selectively target and adsorb lymphocytes expressing latency-associated peptide (LAP), which is abundantly expressed on the surface of CD4+ regulatory T cells (Tregs) and CD14+ monocytes. We investigated whether diethylenetriamine-conjugated polysulfone adsorbent-based direct hemoperfusion (DHP) enhances anti-tumor immunity in a rat cancer model with KDH-V liver cells. Our findings revealed that DHP significantly reduced LAP+ Tregs in both peripheral blood and tumor tissues in treated mice. Consequently, cytotoxic T-lymphocytes increased in tumor-bearing rats. The anti-tumor effect was negated by the addition of cells detached from the absorbent, indicating that these cells play a crucial role in inhibiting the observed therapeutic effect. The results suggest that depleting LAP+ immunosuppressive cells in blood can enhance anti-tumor immunity and improve survival of patients.
by Kenji Sato, Eri Otaka, Kenichi Ozaki, Kenta Shiramoto, Rie Narukawa, Takeshi Kamiya, Masaki Kamiya, Daiki Shimotori, Chiaki Kamizato, Naoki Itoh, Hitoshi Kagaya, Izumi Kondo
BackgroundHome-based rehabilitation involves professional rehabilitation care and guidance offered by physical, occupational, and speech therapists to patients in their homes to help them recuperate in a familiar living environment. The effects on the patient’s motor function and activities of daily living (ADLs), and caregiver burden for community-dwelling patients are well-documented; however, little is known about the immediate benefits in patients discharged from the hospital. Therefore, we examined the effects of continuous home-based rehabilitation immediately after discharge to patients who received intensive rehabilitation during hospitalization.
MethodsWe retrospectively reviewed 150 patients [mean (standard deviation, SD) = 81 (9) years] discharged from the convalescent rehabilitation and community-based integrated care wards undergoing tailored home-based rehabilitation for 6 months (provided by physical or occupational therapists: 1–2 sessions of 40–60 min each per week). The outcome measures at baseline and after 3 and 6 months were compared.
ResultsThe participants included in this study had orthopedic (n = 76), cerebrovascular (n = 50), neuromuscular (n = 11), cardiovascular (n = 5), respiratory (n = 3), cancer (n = 3) and other diseases (n = 2). The mean (SD) time from discharge to the start of rehabilitation was 4 (4) days. One-way analysis of variance and post-hoc comparisons showed significant improvements at 3 months from baseline in grip strength (p = 0.002), 5-repetition sit-to-stand test (p Conclusions
Home-based rehabilitation improves motor function, ADLs, and instrumental ADLs even after intensive inpatient rehabilitation and decreases the burden of the caregiver in the long term. Hence, tailored home-based rehabilitation should be continuously implemented after the completion of intensive inpatient rehabilitation.
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