Proper preservation of stool samples to minimize microbial community shifts and inactivate infectious agents is important for self-collected specimens requiring shipment to laboratories when cold ...chain transport is not feasible. In this study, we evaluated the performance of six preservation solutions (Norgen, OMNI, RNAlater, CURNA, HEMA, and Shield) for these aspects. Following storage of human stool samples with these preservatives at room temperature for 7 days, three hypervariable regions of the bacterial 16S rRNA gene (V1-V2, V3-V4, and V4) were amplicon sequenced. We found that samples collected in two preservatives, Norgen and OMNI, showed the least shift in community composition relative to -80°C standards compared with other storage conditions, and both efficiently inhibited the growth of aerobic and anaerobic bacteria. RNAlater did not prevent bacterial activity and exhibited relatively larger community shift. Although the effect of preservation solution was small compared to intersubject variation, notable changes in microbiota composition were observed, which could create biases in downstream data analysis. When community profiles inferred from different 16S rRNA gene hypervariable regions were compared, we found differential sensitivity of primer sets in identifying overall microbial community and certain bacterial taxa. For example, reads generated by the V4 primer pair showed a higher alpha diversity of the gut microbial community. The degenerate 27f-YM primer failed to detect the majority of
. Our data indicate that choice of preservation solution and 16S rRNA gene primer pair are critical determinants affecting gut microbiota profiling.
Large-scale human microbiota studies require specimens collected from multiple sites and/or time points to maximize detection of the small effects in microbe-host interactions. However, batch biases caused by experimental protocols, such as sample collection, massively parallel sequencing, and bioinformatics analyses, remain critical and should be minimized. This work evaluated the effects of preservation solutions and bacterial 16S rRNA gene primer pairs in revealing human gut microbiota composition. Since notable changes in detecting bacterial composition and abundance were observed among choice of preservatives and primer pairs, a consistent methodology is essential in minimizing their effects to facilitate comparisons between data sets.
PICO question
In cats with feline infectious peritonitis (FIP), does treatment with the nucleoside analogue GS-441524 or the protease inhibitor GC376, compared to supportive measures alone, lead to ...longer survival times?
Clinical bottom line
Category of research question
Treatment
The number and type of study designs reviewed
Five studies, including four uncontrolled interventional studies and one case-series were critically reviewed
Strength of evidence
Moderate
Outcomes reported
The reviewed studies collectively provide moderate evidence in support of the application of GS-441524 or GC376 to extend the survival time of cats suffering from feline infectious peritonitis
Conclusion
While these antiviral drugs are considered the most likely options for FIP treatment, more robust evidence should be obtained through well-designed randomised controlled trials to verify the observed positive effects in treating various forms of the disease and the potential long-term side effects. However, the ethical dilemmas of conducting double blinded placebo-controlled trials, which by necessity include untreated cats with an invariably fatal disease are recognised
How to apply this evidence in practice
The application of evidence into practice should take into account multiple factors, not limited to: individual clinical expertise, patient’s circumstances and owners’ values, country, location or clinic where you work, the individual case in front of you, the availability of therapies and resources.
Knowledge Summaries are a resource to help reinforce or inform decision making. They do not override the responsibility or judgement of the practitioner to do what is best for the animal in their care.
Background
Gynaecological cancers account for 15% of newly diagnosed cancer cases in women worldwide. In recent years, increasing evidence demonstrates that traditional approaches in perioperative ...care practice may be unnecessary or even harmful. The enhanced recovery after surgery (ERAS) programme has therefore been gradually introduced to replace traditional approaches in perioperative care. There is an emerging body of evidence outside of gynaecological cancer which has identified that perioperative ERAS programmes decrease length of postoperative hospital stay and reduce medical expenditure without increasing complication rates, mortality, and readmission rates. However, evidence‐based decisions on perioperative care practice for major surgery in gynaecological cancer are limited. This is an updated version of the original Cochrane Review published in Issue 3, 2015.
Objectives
To evaluate the beneficial and harmful effects of perioperative enhanced recovery after surgery (ERAS) programmes in gynaecological cancer care on length of postoperative hospital stay, postoperative complications, mortality, readmission, bowel functions, quality of life, participant satisfaction, and economic outcomes.
Search methods
We searched the following electronic databases for the literature published from inception until October 2020: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PubMed, AMED (Allied and Complementary Medicine), CINAHL (Cumulative Index to Nursing and Allied Health Literature), Scopus, and four Chinese databases including the China Biomedical Literature Database (CBM), WanFang Data, China National Knowledge Infrastructure (CNKI), and Weipu Database. We also searched four trial registration platforms and grey literature databases for ongoing and unpublished trials, and handsearched the reference lists of included trials and accessible reviews for relevant references.
Selection criteria
We included randomised controlled trials (RCTs) that compared ERAS programmes for perioperative care in women with gynaecological cancer to traditional care strategies.
Data collection and analysis
Two review authors independently screened studies for inclusion, extracted the data and assessed methodological quality for each included study using the Cochrane risk of bias tool 2 (RoB 2) for RCTs. Using Review Manager 5.4, we pooled the data and calculated the measures of treatment effect with the mean difference (MD), standardised mean difference (SMD), and risk ratio (RR) with a 95% confidence interval (CI) to reflect the summary estimates and uncertainty.
Main results
We included seven RCTs with 747 participants. All studies compared ERAS programmes with traditional care strategies for women with gynaecological cancer. We had substantial concerns regarding the methodological quality of the included studies since the included RCTs had moderate to high risk of bias in domains including randomisation process, deviations from intended interventions, and measurement of outcomes.
ERAS programmes may reduce length of postoperative hospital stay (MD ‐1.71 days, 95% CI ‐2.59 to ‐0.84; I2 = 86%; 6 studies, 638 participants; low‐certainty evidence). ERAS programmes may result in no difference in overall complication rates (RR 0.71, 95% CI 0.48 to 1.05; I2 = 42%; 5 studies, 537 participants; low‐certainty evidence). The certainty of evidence was very low regarding the effect of ERAS programmes on all‐cause mortality within 30 days of discharge (RR 0.98, 95% CI 0.14 to 6.68; 1 study, 99 participants). ERAS programmes may reduce readmission rates within 30 days of operation (RR 0.45, 95% CI 0.22 to 0.90; I2 = 0%; 3 studies, 385 participants; low‐certainty evidence). ERAS programmes may reduce the time to first flatus (MD ‐0.82 days, 95% CI ‐1.00 to ‐0.63; I2 = 35%; 4 studies, 432 participants; low‐certainty evidence) and the time to first defaecation (MD ‐0.96 days, 95% CI ‐1.47 to ‐0.44; I2 = 0%; 2 studies, 228 participants; low‐certainty evidence). The studies did not report the effects of ERAS programmes on quality of life. The evidence on the effects of ERAS programmes on participant satisfaction was very uncertain due to the limited number of studies. The adoption of ERAS strategies may not increase medical expenditure, though the evidence was of very low certainty (SMD ‐0.22, 95% CI ‐0.68 to 0.25; I2 = 54%; 2 studies, 167 participants).
Authors' conclusions
Low‐certainty evidence suggests that ERAS programmes may shorten length of postoperative hospital stay, reduce readmissions, and facilitate postoperative bowel function recovery without compromising participant safety. Further well‐conducted studies are required in order to validate the certainty of these findings.
Allopurinol was investigated in 3 x 6 cm congested island skin flaps in rats. Eight hours of venous occlusion produced total flap necrosis. Pretreatment with systemic allopurinol, an inhibitor of ...xanthine oxidase, enhanced the survival rate of hyperemic skin flaps. Xanthine oxidase activities were demonstrated in skin, and these enzyme activities were noted to increase in skin flaps during ischemia and reperfusion. Much of this increase in enzyme activity was prevented by allopurinol treatment. The xanthine oxidase system appears to be one of the sources of the superoxide radical, which may be involved in ischemic and reperfusion injury in skin.
Dear Editor, The goat has long been an important domesticated animal. Gene modification of goats to improve their production traits, ability to resist disease, and ability to produce valuable and ...high-quality proteins has been widely applied in the fields of agriculture and biopharming.
PSR J1119−6127 is a radio pulsar that behaved with magnetar-like bursts, and we performed a comprehensive investigation of this pulsar using the archival high-energy observations obtained after its ...outburst in 2016 July. After the 2016 outburst, specific regions on the neutron star (NS) surface were heated up to >0.3 and >1 keV from ∼0.2 keV. A hard nonthermal spectral component with a photon index <0.5 related to the magnetospheric emission can be resolved from the NuSTAR spectra above 10 keV. We find that the thermal emitting regions did not cool down and gradually shrank by about 20%-35% 4 months after the outburst. Hard X-ray pulsations were detected with NuSTAR immediately after the outburst at a 5 confidence level and with a background-subtracted pulsed fraction of 40% 10%. However, the signal became undetectable after a few days. Using Fermi data, we found that the gamma-ray emission in 0.5-300 GeV was suppressed along with the disappearance of the radio pulsations. This is likely caused by a reconfiguration of the magnetic field. We also discovered that the timing noise evolved dramatically, and the spin-down rate significantly increased after the 2016 glitch. We proposed that postoutburst temporal and spectral behaviors from radio to gamma-ray bands were caused by changes of the magnetosphere structure, pair plasma injection, and the shrinking emission sites on the NS.
Background Left ventricular (LV) involvement is frequently observed in arrhythmogenic cardiomyopathy (ACM). We investigated the association of LV myocardial assessment using cardiac magnetic ...resonance (CMR) with clinical outcomes including heart failure (HF)-related events in ACM. Methods and Results We retrospectively analyzed 60 patients with ACM between 2005 and 2020 according to the 2010 Task Force Criteria and assessed HF-related events (HF hospitalization, heart transplantation, and cardiac death) and ventricular tachycardia events. We analyzed CMR findings including late gadolinium enhancement (LGE) in all subjects and obtained mapping values (native T1, extracellular volume, and T2) on 30 (50%) patients out of them. Among the study population (mean age 49 years, 77% male), 41 (68%) patients had LV LGE. During a median follow-up of 34 months, there were 13 (22%) HF-related events, and 20 (30%) ventricular tachycardia events. Kaplan-Meier survival analysis revealed that HF-related events occurred only in patients with LV LGE (+) (versus LV LGE (-), log-rank
=0.006), and the events were not significantly different regarding right ventricular LGE (log-rank
>0.999). When categorized by median value for each mapping parameter, HF-related events occurred more in patients with higher native T1 (versus lower native T1, log-rank
=0.002), and higher T2 (versus lower T2, log-rank
=0.002), higher extracellular volume (versus lower extracellular volume, log-rank
=0.002). However, regarding ventricular tachycardia events, there were no significant differences according to these CMR markers. Conclusions LV myocardial assessment using CMR with LGE imaging and native T1, T2, and extracellular volume markers were significantly associated with HF-related event risk in patients with ACM.
Summary Background Pretreatment with topical imiquimod, a synthetic agonist of toll-like receptor 7, significantly improved the immunogenicity of influenza vaccination in elderly people. We aimed to ...clarify its effect in a younger age group. Methods In this double-blind, randomised controlled trial, we enrolled healthy volunteers aged 18–30 years in early 2014 to receive the 2013–14 northern-hemisphere winter trivalent influenza vaccine at the Queen Mary Hospital, (Hong Kong, China). Eligible participants were randomly assigned (1:1:1:1) to one of the four vaccination groups: the study group, topical imiquimod-cream followed by intradermal trivalent influenza vaccine (INF-Q-ID), or one of three control groups, topical aqueous-cream control followed by intradermal trivalent influenza vaccine (INF-C-ID), topical aqueous-cream control followed by intramuscular trivalent influenza vaccine (INF-C-IM), and topical imiquimod-cream followed by intradermal normal-saline injection (SAL-Q-ID). Randomisation was by computer-generated lists in blocks of four. The type of topical treatment was masked from volunteers and investigators, although not from the study nurse. Serum haemagglutination-inhibition and microneutralisation-antibody titres were assayed. The primary outcome was seroconversion at day 7 after treatment for three vaccine strains of influenza (A/California/07/2009 H1N1-like virus A/California/H1N1, A/Victoria/361/2011 H3N2-like virus A/Victoria/H3N2, and B/Massachusetts/2/2012-like virus B/Yamagata lineage) and four non-vaccine strains (A/HK/485197/14 H3N2 Switzerland-like lineage, prototype A/WSN/1933 H1N1, A/HK/408027/09 prepandemic seasonal H1N1, and B/HK/418078/11 Victoria lineage). Analysis was done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov , number NCT02103023. Findings We enrolled 160 healthy volunteers between March 1 and May 31, 2014, and 40 participants were randomly assigned to each study group. For the A/California/H1N1 strain, seroconversion at day 7 occurred in 39 participants (98%) in the INF-Q-ID group, 25 (63%) in the INF-C-ID group, 18 (45%) in the INF-C-IM group, and none in the SAL-Q-ID group; for the A/Victoria/H3N2, this was 30 (75%) in the INF-Q-ID group, four (10%) in the INF-C-ID group, four (10%) in the INF-C-IM group, and none in the SAL-Q-ID group; and for the B/Massachusetts (Yamagata lineage) strain, this was 36 (90%) in the INF-Q-ID group, 27 (68%) in the INF-C-ID group, 17 (43%) in the INF-C-IM group, and one (3%) in the SAL-Q-ID group (p<0·0001 for all three vaccine strains). Adverse reactions were infrequent and self-limited and did not differ between the four groups. Furthermore, the seroconversion rate against the four non-vaccine strains was better in the INF-Q-ID group than in the control groups on days 7 and 21 (p<0·0001). The most common adverse events were grade 1 redness (five participants in the INF-Q-ID group, three in INF-C-ID, one in INF-C-IM, and one in SAL-Q-ID) and grade 1 swelling (seven participants in INF-Q-ID group, five in INF-C-ID, three in INF-C-IM, and two in SAL-Q-ID. Interpretation Topical application of imiquimod before intradermal trivalent influenza vaccine significantly improved immunogenicity against the vaccine influenza strains in young healthy individuals and increased immunogenicity against the non-vaccine strains, especially the antigenically drifted H3N2 strain of 2015, which was not included in the 2013–14 recommended vaccine. Further studies should be done to establish the efficacy and safety of this approach for other injectable vaccines to augment the onset and range of protection. Funding The Shaw Foundation Hong Kong, Health and Medical Research Fund (Hong Kong, China), The Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Disease for the HKSAR (Department of Health, Hong Kong, China), The Providence Foundation, Respiratory Viral Research Foundation.
Cooperation is a social behavior crucial for the survival of many species, including humans. Several experimental paradigms have been established to study cooperative behavior and related neural ...activity in different animal species. Although mice exhibit limited cooperative capacity in some behavioral paradigms, it is still interesting to explore their cooperative behavior and the underlying neural mechanisms. Here, we developed a new paradigm for training and testing cooperative behavior in mice based on coordinated lever-pressing and analyzed social interactions between the animals during cooperation. We observed extensive social contact and waiting behavior in cooperating animals, with the number of such events positively correlated with the success of cooperation. Using c-Fos immunostaining and a high-speed volumetric imaging with synchronized on-the-fly scan and readout (VISoR) system, we further mapped whole-brain neuronal activity trace following cooperation. Significantly higher levels of c-Fos expression were observed in cortical areas including the frontal pole, motor cortex, anterior cingulate area, and prelimbic area. These observations highlight social interaction and coordination in cooperative behavior and provide clues for further study of the underlying neural circuitry mechanisms.
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