Rapamycin not dietary restriction improves resilience against pathogens: a meta-analysis.

Dietary restriction (DR) and rapamycin both increase lifespan across a number of taxa. Despite this positive effect on lifespan and other aspects of health, reductions in some physiological functions have been reported for DR, and rapamycin has been used as an immunosuppressant. Perhaps surprisingly, both interventions have been suggested to improve immune function and delay immunosenescence. The immune system is complex and consists of many components. Therefore, arguably, the most holistic measurement of immune function is survival from an acute pathogenic infection. We reanalysed published post-infection short-term survival data of mice (n = 1223 from 23 studies comprising 46 effect sizes involving DR (n = 17) and rapamycin treatment (n = 29) and analysed these results using meta-analysis. Rapamycin treatment significantly increased post infection survival rate (lnHR = - 0.72; CI = - 1.17, -0.28; p = 0.0015). In contrast, DR reduced post-infection survival (lnHR = 0.80; CI = 0.08, 1.52; p = 0.03). Importantly, the overall effect size of rapamycin treatment was significantly lower (p < 0.001) than the estimate from DR studies, suggesting opposite effects on immune function. Our results show that immunomodulation caused by rapamycin treatment is beneficial to the survival from acute infection. For DR, our results are based on a smaller number of studies, but do warrant caution as they indicate possible immune costs of DR. Our quantitative synthesis suggests that the geroprotective effects of rapamycin extend to the immune system and warrants further clinical trials of rapamycin to boost immunity in humans.

First report of Diplodia corticola causing dieback of white oak (Quercus alba) in Tennessee.

Diplodia corticola is a fungal pathogen causing oak dieback in Quercus (oak) spp. in parts of North America, northern Africa, and Europe (Ferreira et al., 2021; Smahi et al., 2017; Tsopelas et al., 2018). In August 2021, a single mature white oak (Q. alba) exhibiting wilt symptoms, vascular discoloration, and interveinal chlorosis was observed in Cove Lake State Park in Campbell County, Tennessee, U.S.A. Small sections of phloem tissues were cut from the margins of discolored vasculature of a single wilt symptomatic branch with a sterile scalpel and surface sterilized following Parra et al. (2020). Surface sterilized wood chips were plated onto potato dextrose agar amended with antibiotics (PDA++) following Gazis et al. (2018). Three days after plating, we recovered a single fungal isolate from wood chips that when grown in ½ PDA resembled D. corticola, having irregular margins and white aerial mycelia that progressively turned greyish-black 15 days after sub-culturing (Alves et al., 2004). Total genomic DNA was extracted from the isolate following Gazis et al. (2018). The internal transcribed spacer (ITS) was then amplified using the ITS1 and ITS4 primers and the subsequent PCR product was sequenced. Resulting reads were assembled into a consensus sequence and identity was assigned using BLAST on the NCBI nucleotide database. The assembled sequence (accession OM716006) had a 100% identity match with D. corticola type culture CBS 112549 (accession NR_111152). To complete Koch's postulates and identify potential host range, 5 red oaks (Q. rubra; 2-3 yrs old; caliper 14.7 ± 2 mm) and 5 white oaks (Q. alba; 2-3 yrs old; caliper 22.8 ± 2.3 mm) were inoculated with D. corticola (isolate DC_2.5). Trees were inoculated 15 cm above the soil line in a greenhouse with a 3 mm diameter plug of a 10-day old culture of D. corticola grown on PDA following Sitz et al. (2017). As a negative control, 5 red and 5 white oaks were inoculated with a 3 mm diameter plug of PDA. For each species, trees were sampled when seepage was observed from D. corticola inoculated sites (15 days post-inoculation for red and white oaks). At time of sampling, bark adjacent to inoculation sites on each tree was removed and cankers were photographed. Using a sterile scalpel, four wood chips were cut from canker margins and placed onto PDA++. For all trees, canker areas were measured using ImageJ software (Rasband, 2012). Recovered isolate identities were confirmed by extracting total genomic DNA as described above (Gazis et al. 2018) and PCR amplification of the ITS, large ribosomal subunit (LSU), and elongation factor 1-α (ef1-α) following (Ferreira et al., 2021). Diplodia corticola was reisolated from wood chips of D. corticola inoculated red (5/5 trees) and white (5/5 trees) oaks and ITS (accession OM716954), LSU (accession OM716955), and ef1-α (accession OM752198) sequences matched D. corticola type culture 112549 ITS (100% identity), LSU (99.76%-100% identity; accession KF766323), and ef1-α (98%-98.9% identity; accession XM_020275852). All D. corticola inoculated trees exhibited seepage from inoculation sites with streaking present in vasculature. Cankers were significantly larger in D. corticola inoculated red (2.34 ± 1.36 cm; P=0.042) and white (2.96 ± 0.52 cm; P=0.00029) oaks compared to agar inoculated trees. To the best of our knowledge, this is the first report of D. corticola causing decline of oaks in Tennessee.

Experiences of enhanced recovery after surgery in general gynaecology patients: An interpretative phenomenological analysis.

There is little qualitative research exploring non-cancer gynaecology patients' experiences of enhanced recovery after surgery (ERAS) protocols. Seven women participated in audio-recorded interviews, discussing their experiences of enhanced recovery after surgery for gynaecological surgery. Data were transcribed and analysed using interpretative phenomenological analysis. Three themes were identified: meeting informational needs, taking control of pain, and mobilising when feeling fragile. Control emerged as a key element throughout the themes and was supported by provision of factual information. While participants were generally satisfied with their experience, topics such as concerns about analgesic use, the informal role of staff in mobilisation, and the expressed desire for more experiential information for participants require further research.

"A peculiar time in my life": making sense of illness and recovery with gynaecological cancer.

PURPOSE: Worldwide there are nearly 1.1 million new cases of gynaecological cancer annually. In England, uterine, ovarian and cervical cancers comprize the third most common type of new cancer in women. Research with gynaecological cancer patients within 6 months of diagnosis is rare, as is data collection that is roughly contemporaneous with treatment. Our aim was to explore the experiences of women who were, at study entry, within 6 weeks of surgery or were undergoing chemotherapy or radiotherapy. METHODS: An interpretative phenomenological analysis (IPA) of data from 16 women in five focus groups was conducted in the UK, exploring women's experiences of being diagnosed with and treated for gynaecological cancer. RESULTS: Participants conceptualized their experiences temporally, from the shock of diagnosis, through their cancer treatment, to thinking about recovery. They tried to make sense of diagnosis, even with treatment being complete. In the context of the Self-Regulation Model, these women were struggling to interpret a changing and multi-faceted illness identity, and attempting to return to pre-illness levels of health. CONCLUSIONS: This study adds to this under-studied time period in cancer survivorship. The results suggest that survivors' goals may change from returning to pre-illness status to reformulating goals as survival time increases.

Phylogenetic relatedness of circulating HIV-1C variants in Mochudi, Botswana.

BACKGROUND: Determining patterns of HIV transmission is increasingly important for the most efficient use of modern prevention interventions. HIV phylogeny can provide a better understanding of the mechanisms underlying HIV transmission networks in communities. METHODS: To reconstruct the structure and dynamics of a local HIV/AIDS epidemic, the phylogenetic relatedness of HIV-1 subtype C env sequences obtained from 785 HIV-infected community residents in the northeastern sector of Mochudi, Botswana, during 2010-2013 was estimated. The genotyping coverage was estimated at 44%. Clusters were defined based on relatedness of HIV-1C env sequences and bootstrap support of splits. RESULTS: The overall proportion of clustered HIV-1C env sequences was 19.1% (95% CI 17.5% to 20.8%). The proportion of clustered sequences from Mochudi was significantly higher than the proportion of non-Mochudi sequences that clustered, 27.0% vs. 14.7% (p = 5.8E-12; Fisher exact test). The majority of clustered Mochudi sequences (90.1%; 95% CI 85.1% to 93.6%) were found in the Mochudi-unique clusters. None of the sequences from Mochudi clustered with any of the 1,244 non-Botswana HIV-1C sequences. At least 83 distinct HIV-1C variants, or chains of HIV transmission, in Mochudi were enumerated, and their sequence signatures were reconstructed. Seven of 20 genotyped seroconverters were found in 7 distinct clusters. CONCLUSIONS: The study provides essential characteristics of the HIV transmission network in a community in Botswana, suggests the importance of high sampling coverage, and highlights the need for broad HIV genotyping to determine the spread of community-unique and community-mixed viral variants circulating in local epidemics. The proposed methodology of cluster analysis enumerates circulating HIV variants and can work well for surveillance of HIV transmission networks. HIV genotyping at the community level can help to optimize and balance HIV prevention strategies in trials and combined intervention packages.