Evaluating Patterns of Injectate Spread After Rectus Sheath Block: A Cadaveric Dissection Study.

INTRODUCTION: This cadaveric dye study assesses the effect of volume and number of injections on the spread of solution after ultrasound-guided rectus sheath injections. In addition, this study evaluates the impact of the arcuate line on solution spread. MATERIALS AND METHODS: Ultrasound-guided rectus sheath injections were performed on seven cadavers on both sides of the abdomen, for a total of 14 injections. Three cadavers received one injection of 30 mL of a solution consisting of bupivacaine and methylene blue at the level of the umbilicus. Four cadavers received two injections of 15 mL of the same solution, one midway between the xiphoid process and umbilicus and one midway between the umbilicus and pubis. RESULTS: Six cadavers were successfully dissected and analyzed for a total of 12 injections, while one cadaver was excluded due to poor tissue quality that was inadequate for dissection and analysis. There was a significant spread of solution with all injections caudally to the pubis without limitation by the arcuate line. However, a single 30 mL injection showed inconsistent spread to the subcostal margin in four of six injections, including in a cadaver with an ostomy. A double injection of 15 mL showed consistent spread from xiphoid to pubis in five of six injections, except in a cadaver with a hernia. CONCLUSIONS: Injections deep to the rectus abdominis muscle, using the same technique as an ultrasound-guided rectus sheath block, achieve spread along a large and continuous fascial plane without limitation by the arcuate line and may provide coverage of the entire anterior abdomen. A large volume is necessary for complete coverage and spread is improved with multiple injections. We suggest that two injections with a total volume of at least 30 mL per side may be needed to achieve adequate coverage in the absence of preexisting abdominal abnormalities.

COVID-19 mRNA vaccination, reactogenicity, work-related absences and the impact on operating room staffing: A cross-sectional study.

BACKGROUND: The COVID-19 pandemic has caused disruption to healthcare delivery worldwide including in the delivery of surgical services. The introduction of mRNA COVID vaccines and the significant reactogenicity seen with vaccination has caused an unanticipated impact on the operating room workforce via unanticipated paid time off after employee vaccination. METHODS: A retrospective cross-sectional survey was made available to approximately 33,000 front-line healthcare workers, students and volunteers who were offered voluntary vaccination in a state-wide healthcare system during phase one of the state's vaccine roll-out. The primary study aim was to determine the frequency of unanticipated paid time off, and the secondary study aim was to identify any demographic determinants influencing the need for unanticipated time off work secondary to adverse effects. RESULTS: 4009 responses were received, a 12.15% response rate. When looking specifically at individuals who did not proactively schedule themselves for time off after vaccination, we determined that unanticipated paid administrative leave was required for 4.9% and 19.79% of individuals after the first and second doses of vaccine, respectively. The average lengths of absence were 1.66 days and 1.39 days for the first and second doses, respectively. There were no statistically significant differences found in the need for unanticipated leave when compared by vaccine manufacturer, gender, age, ethnicity, or job description. However, individuals with a bachelor's degree demonstrated a significantly higher unanticipated leave requirement than respondents who reported other educational backgrounds. CONCLUSIONS: The ability to staff operating rooms and other critical healthcare services may be negatively affected as a result of COVID-19 mRNA vaccination reactogenicity and subsequent unanticipated paid administrative leave. For future COVID-19 boosters or during other pandemics in which mRNA vaccination is recommended, employees should proactively schedule their vaccination(s) in conjunction with their work schedules to minimize the impact of reactogenicity and unanticipated time off on the operating room schedule and patient care.

COVID-19 mRNA Vaccination, ABO Blood Type and the Severity of Self-Reported Reactogenicity in a Large Healthcare System: A Brief Report of a Cross-Sectional Study.

Introduction It has been anecdotally observed that ABO blood type may have an impact on the severity of the side-effects experienced by those receiving mRNA vaccination for COVID-19.  Methods As part of a larger study, a retrospective cross-sectional survey was made available to approximately 33,000 front-line healthcare workers, students and volunteers who were offered voluntary vaccination in a state-wide healthcare system during phase one of the state's vaccine roll-out. A secondary endpoint of the survey was to determine if there was any relationship between vaccination reactogenicity and ABO blood type.  Results 4009 responses were received - a 12.15% response rate. 3700 respondents answered the blood type question, and of those, 2878 knew their blood type. By Kruskal-Wallis test, there was no statistically significant association between any blood type and any side effect for either of the COVID-19 mRNA vaccines.  Conclusions COVID-19 mRNA vaccination may cause significant reactogenicity. However, ABO blood type does not appear to be a predictor of vaccine reactogenicity.

Geriatric assessment in surgical oncology: a systematic review.

BACKGROUND: The comprehensive geriatric assessment (CGA) has developed as an important prognostic tool to risk stratify older adults and has recently been applied to the surgical field. In this systematic review, we examined the utility of CGA components as predictors of adverse outcomes among geriatric patients undergoing major oncologic surgery. MATERIALS AND METHODS: MEDLINE, Embase, and the Cochrane Library were searched for prospective studies examining the association of components of the CGA with specific outcomes among geriatric patients undergoing elective oncologic surgery. Outcome parameters included 30-d postoperative complications (POC), mortality, and discharge to a nonhome institution. RESULTS: The initial search identified 178 potentially relevant articles, with six studies meeting inclusion criteria. Deficiencies in instrumental activities of daily living, activities of daily living, fatigue, cognition, frailty, and cognitive impairment were associated with increased POC. No CGA predictors were identified for postoperative mortality whereas frailty, deficiencies in instrumental activities of daily living, and depression predicted discharge to a nonhome institution. CONCLUSIONS: Across a variety of surgical oncologic populations and cancer types, components of the CGA appear to be predictive of POC and discharge to a nonhome institution. These results argue for inclusion of focused geriatric assessments as part of routine preoperative care in the geriatric surgical oncology population.

Resident involvement and experience do not affect perioperative complications following robotic prostatectomy.

PURPOSE: Most urologic training programs use robotic prostatectomy (RP) as an introduction to teach residents appropriate robotic technique. However, concerns may exist regarding differences in RP outcomes with resident involvement. Our objective was therefore to evaluate whether resident involvement affects complications, operative time, or length of stay (LOS) following RP. METHODS: Using the National Surgical Quality Improvement Program database (2005-2011), we identified patients who underwent RP, stratified them by resident presence or absence during surgery, and compared hospital LOS, operative time, and postoperative complications using bivariable and multivariable analyses. A secondary analysis comparing outcomes of interest across postgraduate year (PGY) levels was also performed. RESULTS: A total of 5,087 patients who underwent RPs were identified, in which residents participated in 56%, during the study period. After controlling for potential confounders, resident present and absent groups were similar in 30-day mortality (0.0 vs. 0.2%, p = 0.08), serious morbidity (1.8 vs. 2.1%, p = 0.33), and overall morbidity (5.1 vs. 5.4%, p = 0.70). While resident involvement did not affect LOS, operative time was longer when residents were present (median 208 vs. 183 min, p < 0.001). Similar findings were noted when assessing individual PGY levels. CONCLUSIONS: Regardless of PGY level, resident involvement in RPs appears safe and does not appear to affect postoperative complications or LOS. While resident involvement in RPs does result in longer operative times, this is necessary for the learning process.

Extreme telomere length dimorphism in the Tasmanian devil and related marsupials suggests parental control of telomere length.

Telomeres, specialised structures that protect chromosome ends, play a critical role in preserving chromosome integrity. Telomere dynamics in the Tasmanian devil (Sarcophilus harrisii) are of particular interest in light of the emergence of devil facial tumour disease (DFTD), a transmissible malignancy that causes rapid mortality and threatens the species with extinction. We used fluorescent in situ hybridisation to investigate telomere length in DFTD cells, in healthy Tasmanian devils and in four closely related marsupial species. Here we report that animals in the Order Dasyuromorphia have chromosomes characterised by striking telomere length dimorphism between homologues. Findings in sex chromosomes suggest that telomere length dimorphism may be regulated by events in the parental germlines. Long telomeres on the Y chromosome imply that telomere lengthening occurs during spermatogenesis, whereas telomere diminution occurs during oogenesis. Although found in several somatic cell tissue types, telomere length dimorphism was not found in DFTD cancer cells, which are characterised by uniformly short telomeres. This is, to our knowledge, the first report of naturally occurring telomere length dimorphism in any species and suggests a novel strategy of telomere length control. Comparative studies in five distantly related marsupials and a monotreme indicate that telomere dimorphism evolved at least 50 million years ago.

Heat shock protein 70 inhibits hydrogen peroxide-induced nucleolar fragmentation via suppressing cleavage and down-regulation of nucleolin.

It has been reported that nucleolar fragmentation is a part of the overall apoptotic morphology, however, it is currently obscure whether and how nucleolar fragmentation can be induced by hydrogen peroxide (H(2)O(2)) and heat shock protein 70 (Hsp70) can prevent nucleolar fragmentation. To dissect these two questions, C(2)C(12) myogenic cells and immortalized mouse embryonic fibroblasts (MEFs) with heat shock transcriptional factor 1 (HSF1) null mutation were treated with heat shock response (HS) (42.5 ± 0.5°C for 1 h and recovery at 37°C for 24 h) and then were insulted with 0.5 mmol/L H(2)O(2). Morphological changes of nucleoli were observed under contrast microscope or electronic microscope. It was found that (1) stimulation with H(2)O(2)-induced nucleolar fragmentation by mediating cleavage and down-regulation of nucleolar protein, nucleolin in C(2)C(12) myocytes and MEFs; (2) HS suppressed nucleolar fragmentation by inducing the expression of Hsp70 in an HSF1-dependent manner as indicated by assays of transfection with Hsp70 antisense oligonucleotides (AS-ONs) or recombinant plasmids of full-length Hsp70 cDNA; (3) protection of Hsp70 against nucleolar fragmentation was related to its accumulation in nucleolus mediated by nuclear localization sequence and its inhibition against cleavage and down-regulation of nucleolin. These results suggested that H(2)O(2)-induced nucleolar fragmentation and HS or Hsp70 inhibit H(2)O(2)-induced nucleolar fragmentation through the translocation of Hsp70 into nucleolar and its protection against impairment of nucleolin.

Does the human X contain a third evolutionary block? Origin of genes on human Xp11 and Xq28.

Comparative gene mapping of human X-borne genes in marsupials defined an ancient conserved region and a recently added region of the eutherian X, and the separate evolutionary origins of these regions was confirmed by their locations on chicken chromosomes 4p and 1q, respectively. However, two groups of genes, from the pericentric region of the short arm of the human X (at Xp11) and a large group of genes from human Xq28, were thought to be part of a third evolutionary block, being located in a single region in fish, but mapping to chicken chromosomes other than 4p and 1q. We tested this hypothesis by comparative mapping of genes in these regions. Our gene mapping results show that human Xp11 genes are located on the marsupial X chromosome and platypus chromosome 6, indicating that the Xp11 region was part of original therian X chromosome. We investigated the evolutionary origin of genes from human Xp11 and Xq28, finding that chicken paralogs of human Xp11 and Xq28 genes had been misidentified as orthologs, and their true orthologs are represented in the chicken EST database, but not in the current chicken genome assembly. This completely undermines the evidence supporting a separate evolutionary origin for this region of the human X chromosome, and we conclude, instead, that it was part of the ancient autosome, which became the conserved region of the therian X chromosome 166 million years ago.

Bird-like sex chromosomes of platypus imply recent origin of mammal sex chromosomes.

In therian mammals (placentals and marsupials), sex is determined by an XX female: XY male system, in which a gene (SRY) on the Y affects male determination. There is no equivalent in other amniotes, although some taxa (notably birds and snakes) have differentiated sex chromosomes. Birds have a ZW female: ZZ male system with no homology with mammal sex chromosomes, in which dosage of a Z-borne gene (possibly DMRT1) affects male determination. As the most basal mammal group, the egg-laying monotremes are ideal for determining how the therian XY system evolved. The platypus has an extraordinary sex chromosome complex, in which five X and five Y chromosomes pair in a translocation chain of alternating X and Y chromosomes. We used physical mapping to identify genes on the pairing regions between adjacent X and Y chromosomes. Most significantly, comparative mapping shows that, contrary to earlier reports, there is no homology between the platypus and therian X chromosomes. Orthologs of genes in the conserved region of the human X (including SOX3, the gene from which SRY evolved) all map to platypus chromosome 6, which therefore represents the ancestral autosome from which the therian X and Y pair derived. Rather, the platypus X chromosomes have substantial homology with the bird Z chromosome (including DMRT1) and to segments syntenic with this region in the human genome. Thus, platypus sex chromosomes have strong homology with bird, but not to therian sex chromosomes, implying that the therian X and Y chromosomes (and the SRY gene) evolved from an autosomal pair after the divergence of monotremes only 166 million years ago. Therefore, the therian X and Y are more than 145 million years younger than previously thought.

Origin and evolution of candidate mental retardation genes on the human X chromosome (MRX).

BACKGROUND: The human X chromosome has a biased gene content. One group of genes that is over-represented on the human X are those expressed in the brain, explaining the large number of sex-linked mental retardation (MRX) syndromes. RESULTS: To determine if MRX genes were recruited to the X, or whether their brain-specific functions were acquired after relocation to the mammalian X chromosome, we examined the location and expression of their orthologues in marsupials, which diverged from human approximately 180 million years ago. We isolated and mapped nine tammar wallaby MRX homologues, finding that six were located on the tammar wallaby X (which represents the ancient conserved mammal X) and three on chromosome 5, representing the recently added region of the human X chromosome. The location of MRX genes within the same synteny groups in human and wallaby does not support the hypothesis that genes with an important function in the brain were recruited in multiple independent events from autosomes to the mammalian X chromosome. Most of the tammar wallaby MRX homologues were more widely expressed in tammar wallaby than in human. Only one, the tammar wallaby ARX homologue (located on tammar chromosome 5p), has a restricted expression pattern comparable to its pattern in human. The retention of the brain-specific expression of ARX over 180 million years suggests that this gene plays a fundamental role in mammalian brain development and function. CONCLUSION: Our results suggest all the genes in this study may have originally had more general functions that became more specialised and important in brain function during evolution of humans and other placental mammals.

Deletion of hexose-6-phosphate dehydrogenase activates the unfolded protein response pathway and induces skeletal myopathy.

Hexose-6-phosphate dehydrogenase (H6PD) is the initial component of a pentose phosphate pathway inside the endoplasmic reticulum (ER) that generates NADPH for ER enzymes. In liver H6PD is required for the 11-oxoreductase activity of 11beta-hydroxysteroid dehydrogenase type 1, which converts inactive 11-oxo-glucocorticoids to their active 11-hydroxyl counterparts; consequently, H6PD null mice are relatively insensitive to glucocorticoids, exhibiting fasting hypoglycemia, increased insulin sensitivity despite elevated circulating levels of corticosterone, and increased basal and insulin-stimulated glucose uptake in muscles normally enriched in type II (fast) fibers, which have increased glycogen content. Here, we show that H6PD null mice develop a severe skeletal myopathy characterized by switching of type II to type I (slow) fibers. Running wheel activity and electrically stimulated force generation in isolated skeletal muscle are both markedly reduced. Affected muscles have normal sarcomeric structure at the electron microscopy level but contain large intrafibrillar membranous vacuoles and abnormal triads indicative of defects in structure and function of the sarcoplasmic reticulum (SR). SR proteins involved in calcium metabolism, including the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA), calreticulin, and calsequestrin, show dysregulated expression. Microarray analysis and real-time PCR demonstrate overexpression of genes encoding proteins in the unfolded protein response pathway. We propose that the absence of H6PD induces a progressive myopathy by altering the SR redox state, thereby impairing protein folding and activating the unfolded protein response pathway. These studies thus define a novel metabolic pathway that links ER stress to skeletal muscle integrity and function.

Development of an ultra-performance liquid chromatography-mass spectrometry method for the detection of lipophilic marine toxins.

A rapid method for the detection of marine toxins was developed using an ultra-performance liquid chromatography (UPLC) system coupled to a latest generation mass spectrometry (MS) system. The analysis of 21 lipophilic marine toxins was achieved on an Acquity C18 column using a water-acetonitrile gradient with a cycle time of 6.6 min, reducing analysis time by more than a factor two compared to HPLC while maintaining peak resolution. Linear ranges, limits of detection and limits of quantification were established for okadaic acid (OA), pectenotoxin-2, azaspiracid-1 (AZA1), yessotoxin, gymnodimine and 13-desmethylspirolide C. The method was found to be accurate when using a triplicate methanolic extraction. Matrix effects were assessed by standard addition of OA and AZA1 in extracts of raw and heat-treated flesh of mussels and oysters. For the analysis of AZA1, the UPLC-MS method was always prone to signal suppression, while for OA analysis signal suppression was observed in extracts of raw shellfish flesh and signal enhancement in extracts of heat-treated flesh. Matrix effects occurring in the method presented are diminished compared to previous studies.

Characterizing the chromosomes of the platypus (Ornithorhynchus anatinus).

Like the unique platypus itself, the platypus genome is extraordinary because of its complex sex chromosome system, and is controversial because of difficulties in identification of small autosomes and sex chromosomes. A 6-fold shotgun sequence of the platypus genome is now available and is being assembled with the help of physical mapping. It is therefore essential to characterize the chromosomes and resolve the ambiguities and inconsistencies in identifying autosomes and sex chromosomes. We have used chromosome paints and DAPI banding to identify and classify pairs of autosomes and sex chromosomes. We have established an agreed nomenclature and identified anchor BAC clones for each chromosome that will ensure unambiguous gene localizations.