Postcraniotomy Headache: Etiologies and Treatments.

PURPOSE OF REVIEW Postcraniotomy headache (PCH) is a highly underappreciated and very common adverse event following craniotomy. RECENT FINDINGS Analgetic medication with opioids often interferes with neurologic evaluation in the acute phase of recovery and should be kept to a minimal, in general, in the treatment of chronic pain as well. We provide an update on the latest evidence for the management of acute and chronic PCH. Especially in the neurosurgical setting, enhanced recovery after surgery protocols need to include a special focus on pain control. Patients at risk of developing chronic pain must be identified and treated as early as possible

Laboratory selection of trypanosomatid pathogens for drug resistance

The selection of parasites for drug resistance in the laboratory is an approach frequently used to investigate the mode of drug action, estimate the risk of emergence of drug resistance, or develop molecular markers for drug resistance. Here, we focused on the How rather than the Why of laboratory selection, discussing different experimental set-ups based on research examples with Trypanosoma brucei, Trypanosoma cruzi, and Leishmania spp. The trypanosomatids are particularly well-suited to illustrate different strategies of selecting for drug resistance, since it was with African trypanosomes that Paul Ehrlich performed such an experiment for the first time, more than a century ago. While breakthroughs in reverse genetics and genome editing have greatly facilitated the identification and validation of candidate resistance mutations in the trypanosomatids, the forward selection of drug-resistant mutants still relies on standard in vivo models and in vitro culture systems. Critical questions are: is selection for drug resistance performed in vivo or in vitro? With the mammalian or with the insect stages of the parasites? Under steady pressure or by sudden shock? Is a mutagen used? While there is no bona fide best approach, we think that a methodical consideration of these questions provides a helpful framework for selection of parasites for drug resistance in the laboratory

Impact of Intraoperative Fluid Balance and Norepinephrine on Postoperative Acute Kidney Injury after Cystectomy and Urinary Diversion over Two Decades: A Retrospective Observational Cohort Study.

The use of norepinephrine and the restriction of intraoperative hydration have gained increasing acceptance over the last few decades. Recently, there have been concerns regarding the impact of this approach on renal function. The objective of this study was to examine the influence of norepinephrine, intraoperative fluid administration and their interaction on acute kidney injury (AKI) after cystectomy. In our cohort of 1488 consecutive patients scheduled for cystectomies and urinary diversions, the overall incidence of AKI was 21.6% (95%-CI: 19.6% to 23.8%) and increased by an average of 0.6% (95%-CI: 0.1% to 1.1%, p = 0.025) per year since 2000. The fluid and vasopressor regimes were characterized by an annual decrease in fluid balance (-0.24 mL·kg-1·h-1, 95%-CI: -0.26 to -0.22, p < 0.001) and an annual increase in the amount of norepinephrine of 0.002 µg·kg-1·min-1 (95%-CI: 0.0016 to 0.0024, p < 0.001). The interaction between the fluid balance and norepinephrine levels resulted in a U-shaped association with the risk of AKI; however, the magnitude and shape depended on the reference categories of confounders (age and BMI). We conclude that decreased intraoperative fluid balance combined with increased norepinephrine administration was associated with an increased risk of AKI. However, other potential drivers of the observed increase in AKI incidence need to be further investigated in the future

Plasma disappearance rate of albumin when infused as a 20% solution.

BACKGROUND The transcapillary leakage of albumin is increased by inflammation and major surgery, but whether exogenous albumin also disappears faster is unclear. METHODS An intravenous infusion of 3 mL/kg of 20% albumin was given over 30 min to 70 subjects consisting of 15 healthy volunteers, 15 post-burn patients, 15 patients who underwent surgery with minor bleeding, 10 who underwent surgery with major bleeding (mean, 1.1 L) and 15 postoperative patients. Blood Hb and plasma albumin were measured on 15 occasions over 5 h. The rate of albumin disappearance from the plasma was quantitated with population kinetic methodology and reported as the half-life (T1/2). RESULTS No differences were observed for T1/2 between volunteers, post-burn patients, patients who underwent surgery with minor bleeding and postoperative patients. The T1/2 averaged 16.2 h, which corresponds to 3.8% of the amount infused per h. Two groups showed plasma concentrations of C-reactive protein of approximately 60 mg/L and still had a similarly long T1/2 for albumin. By contrast, patients undergoing surgery associated with major hemorrhage had a shorter T1/2, corresponding to 15% of the infused albumin per h. In addition, our analyses show that the T1/2 differ greatly depending on whether the calculations consider plasma volume changes and blood losses. CONCLUSION The disappearance rate of the albumin in 20% preparations was low in volunteers, in patients with moderately severe inflammation, and in postoperative patients

Evolution of the telomere-associated protein POT1a in arabidopsis thaliana is characterized by positive selection to reinforce protein-protein interaction

© The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. Gene duplication is a major driving force in genome evolution. Here, we explore the nature and origin of the POT1 gene duplication in Arabidopsis thaliana. Protection of Telomeres (POT1) is a conserved multifunctional protein that modulates telomerase activity and its engagement with telomeres. Arabidopsis thaliana encodes two divergent POT1 paralogs termed AtPOT1a and AtPOT1b. AtPOT1a positively regulates telomerase activity, whereas AtPOT1b is proposed to negatively regulate telomerase and promote chromosome end protection. Phylogenetic analysis uncovered two independent POT1 duplication events in the plant kingdom, including one at the base of Brassicaceae. Tests for positive selection implemented in PAML revealed that the Brassicaceae POT1a lineage experienced positive selection postduplication and identified three amino acid residues with signatures of positive selection. A sensitive and quantitative genetic complementation assay was developed to assess POT1a function in A. thaliana. The assay showed that AtPOT1a is functionally distinct from single-copy POT1 genes in other plants. Moreover, for two of the sites with a strong signature of positive selection, substitutions that swap the amino acids in AtPOT1a for residues found in AtPOT1b dramatically compromised AtPOT1a function in vivo. In vitro-binding studies demonstrated that all three sites under positive selection specifically enhance the AtPOT1a interaction with CTC1, a core component of the highly conserved CST (CTC1/STN1/TEN1) telomere protein complex. Our results reveal a molecular mechanism for the role of these positively selected sites in AtPOT1a. The data also provide an important empirical example to refine theories of duplicate gene retention, as the outcome of positive selection here appears to be reinforcement of an ancestral function, rather than neofunctionalization. We propose that this outcome may not be unusual when the duplicated protein is a component of a multisubunit complex whose function is in part specified by other members

Evidence of neutral transcriptome evolution in plants

The transcriptome of an organism is its set of gene transcripts (mRNAs) at a defined spatial and temporal locus. Because gene expression is affected markedly by environmental and developmental perturbations, it is widely assumed that transcriptome divergence among taxa represents adaptive phenotypic selection. This assumption has been challenged by neutral theories which propose that stochastic processes drive transcriptome evolution. To test for evidence of neutral transcriptome evolution in plants, we quantified 18 494 gene transcripts in nonsenescent leaves of 14 taxa of Brassicaceae using robust cross-species transcriptomics which includes a two-step physical and in silicobased normalization procedure based on DNA similarity among taxa. Transcriptome divergence correlates positively with evolutionary distance between taxa and with variation in gene expression among samples. Results are similar for pseudogenes and chloroplast genes evolving at different rates. Remarkably, variation in transcript abundance among root-cell samples correlates positively with transcriptome divergence among root tissues and among taxa. Because neutral processes affect transcriptome evolution in plants, many differences in gene expression among or within taxa may be nonfunctional, reflecting ancestral plasticity and founder effects. Appropriate null models are required when comparing transcriptomes in space and time

Multimodal prehabilitation for major surgery in elderly patients to lower complications: protocol of a randomised, prospective, multicentre, multidisciplinary trial (PREHABIL Trial).

INTRODUCTION The global volume of surgery is growing and the population ageing, and economic pressure is rising. Major surgery is associated with relevant morbidity and mortality. Postoperative reduction in physiological and functional capacity is especially marked in the elderly, multimorbid patient with low fitness level, sarcopenia and malnutrition. Interventions aiming to optimise the patient prior to surgery (prehabilitation) may reduce postoperative complications and consequently reduce health costs. METHODS AND ANALYSIS This is a multicentre, multidisciplinary, prospective, 2-arm parallel-group, randomised, controlled trial with blinded outcome assessment. Primary outcome is the Comprehensive Complications Index at 30 days. Within 3 years, we aim to include 2×233 patients with a proven fitness deficit undergoing major surgery to be randomised using a computer-generated random numbers and a minimisation technique. The study intervention consists of a structured, multimodal, multidisciplinary prehabilitation programme over 2-4 weeks addressing deficits in physical fitness and nutrition, diabetes control, correction of anaemia and smoking cessation versus standard of care. ETHICS AND DISSEMINATION The PREHABIL trial has been approved by the responsible ethics committee (Kantonale Ethikkomission Bern, project ID 2020-01690). All participants provide written informed consent prior to participation. Participant recruitment began in February 2022 (10 and 8 patients analysed at time of submission), with anticipated completion in 2025. Publication of the results in peer-reviewed scientific journals are expected in late 2025. TRIAL REGISTRATION NUMBER NCT04461301

Reporting quality of randomized controlled trials in prehabilitation: a scoping review.

BACKGROUND Inadequate study reporting precludes interpretation of findings, pooling of results in meta-analyses, and delays knowledge translation. While prehabilitation interventions aim to enhance candidacy for surgery, to our knowledge, a review of the quality of reporting in prehabilitation has yet to be conducted. Our objective was to determine the extent to which randomized controlled trials (RCTs) of prehabilitation are reported according to methodological and intervention reporting checklists. METHODS Eligibility criteria: RCTs of unimodal or multimodal prehabilitation interventions. SOURCES OF EVIDENCE search was conducted in March 2022 using MEDLINE, Embase, PsychINFO, Web of Science, CINAHL, and Cochrane. CHARTING METHODS identified studies were compared to CONSORT, CERT & Modified CERT, TIDieR, PRESENT, and CONSORT-SPI. An agreement ratio (AR) was defined to evaluate if applicable guideline items were correctly reported. Data were analyzed as frequency (n, %) and mean with standard deviation (SD). RESULTS We identified 935 unique articles and included 70 trials published from 1994 to 2022. Most prehabilitation programs comprised exercise-only interventions (n = 40, 57%) and were applied before oncologic surgery (n = 32, 46%). The overall mean AR was 57% (SD: 20.9%). The specific mean ARs were as follows: CONSORT: 71% (SD: 16.3%); TIDieR: 62% (SD:17.7%); CERT: 54% (SD: 16.6%); Modified-CERT: 40% (SD:17.8%); PRESENT: 78% (SD: 8.9); and CONSORT-SPI: 47% (SD: 22.1). CONCLUSION Altogether, existing prehabilitation trials report approximately half of the checklist items recommended by methodological and intervention reporting guidelines. Reporting practices may improve with the development of a reporting checklist specific to prehabilitation interventions

Tandem quadruplication of HMA4 in the zinc (Zn) and cadmium (Cd) hyperaccumulator noccaea caerulescens

Zinc (Zn) and cadmium (Cd) hyperaccumulation may have evolved twice in the Brassicaceae, in Arabidopsis halleri and in the Noccaea genus. Tandem gene duplication and deregulated expression of the Zn transporter, HMA4, has previously been linked to Zn/Cd hyperaccumulation in A. halleri. Here, we tested the hypothesis that tandem duplication and deregulation of HMA4 expression also occurs in Noccaea. A Noccaea caerulescens genomic library was generated, containing 36,864 fosmid pCC1FOSTM clones with insert sizes ~20–40 kbp, and screened with a PCR-generated HMA4 genomic probe. Gene copy number within the genome was estimated through DNA fingerprinting and pooled fosmid pyrosequencing. Gene copy numbers within individual clones was determined by PCR analyses with novel locus specific primers. Entire fosmids were then sequenced individually and reads equivalent to 20-fold coverage were assembled to generate complete whole contigs. Four tandem HMA4 repeats were identified in a contiguous sequence of 101,480 bp based on sequence overlap identities. These were flanked by regions syntenous with up and downstream regions of AtHMA4 in Arabidopsis thaliana. Promoter-reporter b-glucuronidase (GUS) fusion analysis of a NcHMA4 in A. thaliana revealed deregulated expression in roots and shoots, analogous to AhHMA4 promoters, but distinct from AtHMA4 expression which localised to the root vascular tissue. This remarkable consistency in tandem duplication and deregulated expression of metal transport genes between N. caerulescens and A. halleri, which last shared a common ancestor >40 mya, provides intriguing evidence that parallel evolutionary pathways may underlie Zn/Cd hyperaccumulation in Brassicaceae