Negative Pressure Wound Therapy to Reduce Surgical Site Infections after CRS/HIPEC.

BACKGROUND: Surgical site infections (SSIs) are a common cause of morbidity after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal malignancy. Negative pressure wound therapy (NPWT) has been proposed as a method to reduce the rates of SSIs; however, there is paucity in the literature on the efficacy in this population. The goal of this study was to determine whether routine use of NPWT in patients undergoing CRS/HIPEC could reduce the risk of developing SSI. METHODS: We performed a retrospective before-after study to assess the rates of SSI with NPWT compared with a standard postoperative surgical dressing (SSD) in all patients undergoing CRS/HIPEC from November 2013 to December 2021 at a single tertiary care center. The primary outcome was rate of SSI. A multivariate logistic regression analysis was performed to evaluate for risk factors for SSI. RESULTS: A total of 178 patients were treated with CRS/HIPEC over the study period. Seventy patients had placement of SSD, and 108 patients had placement of NPWT. Rates of SSI were 11.4% (8/70) and 5.6% (6/108) in the two groups, respectively (p = 0.16). On multivariate analysis, patients treated with NPWT had a significantly lower risk of developing an SSI (OR 0.24 [0.06, 0.92], p = 0.037). Patients living >50 km from the hospital had significantly higher risk of developing SSI (OR 2.03 [1.09, 3.78], p = 0.026). CONCLUSIONS: These results suggest that routine use of NPWT can reduce the risk of developing an SSI in patients undergoing CRS/HIPEC for peritoneal malignancy.

Risk of lymph node metastasis in early gastric cancer for a Western population.

INTRODUCTION: Endoscopic resection (ER) of early gastric cancer (EGC) is increasingly used in Eastern countries due to their low rates of lymph node metastasis (LNM); however, there is a paucity of evidence in Western countries. We investigated LNM and its effect on overall survival (OS) in Western patients with EGC. METHODS: Patients diagnosed with T1 gastric cancer between 2000 and 2017 were retrospectively evaluated. Univariate Kaplan-Meier, multivariate logistic and Cox-regression models were used to assess the associations between clinical characteristics, LNM, and OS. RESULTS: Among 86 patients, median age was 68 years and 72% were male. Node positivity was 30%. Two percent of patients met the classical guidelines for ER and all were node-negative, while 16% met expanded criteria of which 14% were node-positive. T1b disease (odds ratio [OR] 41.2 [95% confidence interval [CI] 1.62-1048], p = 0.02) and lymphovascular/perineural invasion (OR 18.0 [95% CI 2.41-134], p = 0.01) were predictive of node positivity. The 5-year OS for node-negative and node-positive patients was 84% and 53% (p = 0.004), respectively. CONCLUSIONS: The risk of LNM in Western patients with EGC is higher; therefore, generalizability of the expanded criteria for ER should be interpreted with caution.

Intraoperative frozen section analysis of margin status as a quality indicator in gastric cancer surgery.

INTRODUCTION: Positive pathologic margins following gastric cancer (GC) resection carries a poor prognosis. We evaluated intraoperative frozen section (IFS) analysis of resection margins (RMs) as a quality indicator in GC surgery. METHODS: Patients referred to a provincial cancer agency with surgically resected non-metastatic GC between 2004 and 2012 were included. Associations between IFS analysis, other baseline characteristics, RMs, and overall survival (OS) were assessed using logistic regression, Kaplan-Meier analyses, and Cox proportional hazards modeling. RESULTS: Among 377 patients, median age was 67 years, 68% were male, and 16% had +RMs. Thirty-four percent of patients underwent IFS analysis, which protected against +RMs (odds ratio [OR]: 0.34, 95% confidence interval [CI]: 0.16-0.73, p = 0.006) and improved OS (hazards ratio [HR]: 0.72, 95% CI: 0.54-0.98, p = 0.037). OS following re-resection of IFS positive patients was similar to IFS negative patients (69 vs. 54 months, p = 0.317). Stage III disease (OR: 12.8, 95% CI: 3.00-55.0, p = 0.001) and gastroesophageal junction tumors (OR: 2.25, 95% CI: 1.05-4.78, p = 0.036) predicted +RMs. Stage III disease led to worse OS (HR: 2.89, 95% CI: 1.92-4.34, p < 0.001) while intestinal histology improved OS (HR: 0.67, 95% CI: 0.50-0.90, p = 0.007). CONCLUSIONS: IFS analysis reduce +RMs and improve OS and should be incorporated in curative intent GC surgery for patients with locally advanced GC.

Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) for peritoneal mesothelioma: Canadian practices and outcomes.

INTRODUCTION: Peritoneal mesothelioma (PM) is a rare malignancy originating from the peritoneal lining. Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) is the standard-of-care for patients with isolated PM. Due to a paucity of prospective data there are several different HIPEC protocols. The aims of this study are to describe the CRS and HIPEC protocols for PM and patient outcomes across Canada. METHODS: A multicenter retrospective study was performed on patients diagnosed and treated for PM with CRS and HIPEC in four major peritoneal disease centers in Canada between 2000 and 2021. Data on patient characteristics, treatment patterns, postoperative morbidity, recurrence, and survival were collected. RESULTS: A total of 72 patients were identified. Mean age was 52 years (17-75) and 37.5% were male. Epithelioid (70.1%) and multicystic (13%) mesothelioma were the most common subtypes. Twenty-one patients (30%) were treated with neoadjuvant chemotherapy. CRS and HIPEC was performed in 64 patients (91.4%). Of these, the mean PCI was 22 (2-39) and cisplatin+doxorubicin was the most common HIPEC regimen (n = 33, 51.6%). A semi-closed coliseum technique was used in 68.8% of HIPECs and the mean duration of surgery was 486 min (90-1052). Clavien-Dindo III or IV complications occurred in 12 patients (16.9%). With a median follow-up of 24 months (0.2-104.4), we found a 5-year overall survival of 61% and a 5-year recurrence-free survival of 35%. CONCLUSION: CRS and HIPEC is a safe and effective treatment modality for well-selected patients with PM, with some achieving prolonged survival.

Emergency surgical consultation for cancer patients: identifying the prognostic determinants of health.

BACKGROUND: Patients with malignancy often require urgent surgical consultation for treatment or palliation of disease. The objective of this study is to explore the prognostic determinants affecting care in acute cancer-related surgical presentations and the effect on patient outcomes. MAIN BODY: This is a retrospective review of patients referred to the acute general surgery (ACS) service at a tertiary hospital for management of cancer-related problem from July 2017 to September 2018. Patient demographics, course in hospital, and survival were recorded. Multivariant logistic regression and Kaplan-Meier estimates were performed. One hundred eighty-nine patients were identified (53% female) with a mean age of 65.9 years. Forty-two patients (22%) were newly diagnosed with cancer on presentation, and 94 (50%) patients had metastatic disease. Cancer staging was completed in 84% of patients, and 65% had multidisciplinary team (MDT) assessment during their hospital stay. Surgery was performed on 90 (48%) patients, of which 31.2% was with palliative intent. Overall mortality was 56% with 30- and 60-day mortality of 15% and 22%, respectively. The adjusted odds ratio (OR) for a 60-day mortality was high in patients presenting with new cancer diagnosis (OR 3.18, 95% CI 1.18-9.02, p=0.03), metastatic disease (OR 5.11, 95% CI 2.03-12.85, p=0.001), or systemic therapy on presentation (OR 3.46, 95% CI 1.30-9.22, p=0.013). CONCLUSION: Emergency surgical referral is common in patients with malignancy. Surgical decision making can be challenging due to the heterogeneity of this population and their associated comorbidities. Optimizing prognostic determinants such as goal-directed palliative care, MDT discussions, and bridging to systemic therapy can improve patient outcomes.

Continuous light (relative to a 12:12 photoperiod) has no effect on anxiety-like behaviour, boldness, and locomotion in coho salmon (Oncorhynchus kisutch) post-smolts in recirculating aquaculture systems at a salinity of either 2.5 or 10 ppt.

There is increased interest in rearing salmon in Recirculating Aquaculture Systems (RAS), where environmental conditions can be tightly controlled to optimize growth. Photoperiod and salinity are two important parameters that can be manipulated in RAS. A longer photoperiod permits more time for feeding, while intermediate salinities may reduce the energetic costs of ionoregulation, both of which may enhance growth. However, little is known about how rearing at different photoperiods and salinity affect behaviour, an understudied but important research topic for intensive fish rearing. To address this, we examined the behavioural effects of two salinities and two photoperiod regimes in coho salmon (Oncorhynchus kisutch) post-smolts reared continuously for 120 days in a RAS. Fish were reared on a photoperiod of either 12 h light:12 h dark (12:12), or 24 h light (24:0) at salinities of 2.5 and 10 ppt. To investigate behavioural differences associated with these treatments, we quantified: i) movement in an open-field test, ii) exploratory behaviour/boldness using a novel object approach test, and iii) anxiety-like behaviour with a light/dark test. The 24:0 groups displayed no differences in boldness/anxiety-like behaviour and locomotion relative to the 12:12 groups at their respective salinities. Taken together, fish reared under continuous light (24:0) show negligible behavioural alterations compared to fish reared under normal light dark conditions (12:12).

Lymph node mapping in gastric cancer: a pilot study in Western patients.

In East Asia, the role of lymph node (LN) mapping in assisting surgical lymphadenectomy, which is integral to the management of gastric cancer, has been explored. We sought to evaluate its safety and utility in Western patients. Thirteen patients with nonmetastatic gastric adenocarcinoma received endoscopic, peritumoural, submucosal indocyanine green fluorescence (ICG) injections before surgery, and ICG was assessed intraoperatively using a laparoscopic detection system. All patients underwent a laparoscopic subtotal gastrectomy, and 10 of them received D2 lymphadenectomies. ICG-mapped LNs fell outside the D1 distribution in all cases, outside the D1+ distribution in 54%, and within the D2 distribution in all cases. There were no ICG-related allergies, procedural complications, or perioperative deaths. We conclude that ICG LN mapping is safe and feasible in assisting LN dissections and localizing the primary tumour in Western patients. D2 dissections should be performed in patients with advanced gastric cancer, as LNs drained outside the D1/D1+ distributions in most cases.

Population-based assessment of sentinel lymph node biopsy in the management of cutaneous melanoma.

BACKGROUND: Sentinel lymph node biopsy (SLNB) for melanoma plays a central role in determining prognosis and guiding treatment and surveillance strategies. Despite widely published guidelines for SLNB, variation exists in its use. We aimed to determine the frequency of and predictive factors for SLNB in patients with clinically node-negative melanoma in British Columbia. METHODS: A retrospective review was performed of patients with clinically node-negative melanoma diagnosed between January 2015 and December 2017. Patients included had a Breslow depth greater than 0.75 mm or a Breslow depth less than or equal to 0.75 mm with ulceration, or a mitotic rate greater than or equal to 1/mm2. SLNB was considered to be indicated for clinical stages IB to IIC (American Joint Committee on Cancer's AJCC Cancer Staging Manual, seventh edition). RESULTS: A total of 759 patients were included. SLNB was performed in 54.8% (363/662) of patients when indicated. SLNB was more likely to be performed for tumours with a Breslow depth greater than 1.0 mm or a mitotic rate greater than or equal to 1/mm2. SLNB was less likely to be performed in patients older than 75 years and with a nonextremity tumour location. Compliance with SLNB guidelines decreased distant recurrence but did not significantly affect regional recurrence, nor did it have a significant impact on overall survival among patients aged 75 years and younger. CONCLUSION: SLNB is being underutilized in British Columbia. These results are concerning and highly relevant given the rapidly evolving field of adjuvant systemic therapy for high-risk patients and the increased proportion of patients who should be considered for SLNB on the basis of the eighth edition of the AJCC Cancer Staging Manual and current guidelines. Efforts should be made to increase the use of SLNB in appropriate patients.

Cost-Effectiveness Analysis of Cytoreductive Surgery and HIPEC Compared With Systemic Chemotherapy in Isolated Peritoneal Carcinomatosis From Metastatic Colorectal Cancer.

BACKGROUND: Cost-effectiveness evaluations of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal carcinomatosis (PC) from metastatic colorectal cancer (mCRC) in the United States are lacking. METHODS: The authors developed a Markov model to evaluate the cost-effectiveness of CRS/HIPEC compared with systemic chemotherapy for isolated PC from mCRC from a societal perspective in the United States. The systemic treatment regimens consisted of FOLFOX, FOLFIRI, bevacizumab, cetuximab, and pantitumumab. The model inputs including costs, probabilities, survival, progression, and utilities were taken from the literature. The cycle length for the model was 2 weeks, and the time horizon was 7 years. A discount rate of 3% was applied. The model was tested for internal and external validation, and robustness was established with univariate sensitivity and probabilistic sensitivity analyses (PSA). The primary outcomes were total costs, quality-adjusted life-years (QALYs), life-years (LYs), and incremental cost-effectiveness ratio (ICER). A willingness-to-pay (WTP) threshold of $100,000 per QALY was assumed. RESULTS: The ICER for treatment with CRS/HIPEC compared with systemic chemotherapy was $91,034 per QALY gained ($74,098 per LY gained). The univariate sensitivity analysis showed that the total costs for treatment with CRS/HIPEC had the largest effect on the calculated ICER. The CRS/HIPEC treatment was a cost-effective strategy during the majority of simulations in the PSA. The average ICER for 100,000 simulations in the PSA was $70,807 per QALY gained. The likelihood of CRS/HIPEC being a cost-effective strategy at the WTP threshold was 87%. CONCLUSIONS: The CRS/HIPEC procedure is a cost-effective treatment for isolated PC from mCRC in the United States.

Neurodevelopmental and Metabolomic Responses from Prenatal Coexposure to Perfluorooctanesulfonate (PFOS) and Methylmercury (MeHg) in Sprague-Dawley Rats.

Methylmercury (MeHg) and perfluorooctanesulfonate (PFOS) are major contaminants of human blood that are both common in dietary fish, thereby raising questions about their combined impact on human development. Here, pregnant Sprague-Dawley rats ingested a daily dose, from gestational day 1 through to weaning, of either 1 mg/kg bw PFOS (PFOS-only), 1 mg/kg MeHg (MeHg-only), a mixture of 0.1 mg/kg PFOS and 1 mg/kg MeHg (Low-Mix), or of 1 mg/kg of PFOS and 1 mg/kg MeHg (High-Mix). Newborns were monitored for physical milestones and reflexive developmental responses, and in juveniles the spontaneous activity, anxiety, memory, and cognition were assessed. Targeted metabolomics of 199 analytes was applied to sectioned brain regions of juvenile offspring. Newborns in the High-Mix group had decreased weight gain as well as delayed reflexes and innate behavioral responses compared to controls and individual chemical groups indicating a toxicological interaction on early development. In juveniles, cumulative mixture effects increased in a dose-dependent manner in tests of anxiety-like behavior. However, other developmental test results suggested antagonism, as PFOS-only and MeHg-only juveniles had increased hyperactivity and thigmotaxic behavior, respectively, but fewer effects in Low-Mix and High-Mix groups. Consistent with these behavioral observations, a pattern of antagonism was also observed in neurochemicals measured in rat cortex, as PFOS-only and MeHg-only juveniles had altered concentrations of metabolites (e.g., lipids, amino acids, and biogenic amines), while no changes were evident in the combined exposures. The cortical metabolites altered in PFOS-only and MeHg-only exposed groups are involved in inhibitory and excitatory neurotransmission. These proof-of-principle findings at relatively high doses indicate the potential for toxicological interaction between PFOS and MeHg, with developmental-stage specific effects. Future mixture studies at lower doses are warranted, and prospective human birth cohorts should consider possible confounding effects from PFOS and mercury exposure on neurodevelopment.

The impact of advanced age on short-term outcomes following gastric cancer resection: an ACS-NSQIP analysis.

BACKGROUND: Evidence on short-term outcomes for GC resection in elderly patients is limited by small samples from single-institutions. This study sought to examine the association between advanced age and short-term outcomes of gastrectomy for gastric cancer (GC). METHODS: Using ACS-NSQIP data, patients undergoing gastrectomy for GC (2007-2013) were identified. Primary outcome was 30-day major morbidity. Outcomes were compared across age categories (<65, 65-70, 71-75, 76-80, >80 years old). Univariable and multivariable regression was used to estimate the morbidity risk associated with age. RESULTS: Of 3637 patients, 60.6% were ≥65 years old. Major morbidity increased with age, from 16.3% (<65 years old) to 21.5% (76-80 years old), and 24.1% (>80 years old) (p < 0.001), driven by higher respiratory and infectious events. Perioperative 30-day mortality increased from 1.2% (<65years old) to 6.5% (>80 years old) (p < 0.0001). After adjustments, age was independently associated with morbidity for 76-80 years of age (RR 1.31, 95% CI, 1.08-1.60) and >80 years old (RR 1.49, 95% CI, 1.23-1.81). Predicted morbidity increased by 18.6% in those 75-80 years old and 27.5% in those >80 years old (compared to <65 years old) for total gastrectomy, and by 11.6% and 17.2% for subtotal gastrectomy, for worst case scenario. Morbidity increased by 5.1% in those 75-80 years old and 7.6% in those >80 years old for total gastrectomy, and by 3.1% and 4.7% for subtotal gastrectomy, for best case scenario. CONCLUSIONS: Advanced age, defined as more than 75 years, was independently associated with increased morbidity after GC resection. The magnitude of this impact is further modulated by clinical scenarios. Increased risk in elderly GC patient should be recognized and considered in indications for resection.

Results of Resection for Recurrent or Residual Retroperitoneal Sarcoma After Failed Primary Treatment.

BACKGROUND: Local recurrence after resection of retroperitoneal sarcoma (RPS) is a common and difficult problem. Gross residual disease after incomplete resection is a particular challenge. The authors reviewed their experience with patients referred for management of recurrent or residual RPS. METHODS: Patients seen at the authors' center from 1996 to 2013 who had undergone resection at an outside institution were identified from a prospective database. Kaplan-Meier survival curves were generated and compared by log-rank analysis. RESULTS: A total of 45 patients were referred with recurrent (n = 33) or residual (n = 12) disease. Before initial surgery elsewhere, cross-sectional imaging (computed tomograpy/magnetic resonance imaging) had been obtained for 30 patients (67 %) and percutaneous biopsy for 8 patients (18 %). At referral to the authors' center, 15 patients were deemed inappropriate for resection, with a subsequent median overall survival (OS) period of 15 months. At the authors' center, 30 patients (22 with recurrent and 8 with residual disease) were resected. The majority received preoperative radiation (77 %). The postoperative mortality rate was 0 % in the recurrent group and 25 % (2/8) in the residual group (p = 0.015). Among the 30 resected patients, the median and 5-year OS was 53 months (50 %), and the OS was better in the recurrent group (median, 77 months) than in the residual group (median, 41 months (p = 0.027). The median time to local re-recurrence was 49 months in the recurrent group and 35 months in the residual group (p = 0.730). CONCLUSIONS: Durable disease control and prolonged survival may be achieved for selected patients with recurrent RPS. In this study, resection after previous grossly incomplete resection was associated with high postoperative mortality and inferior OS. The benefit of extensive surgery for these patients may be limited.

Acid-base physiology, neurobiology and behaviour in relation to CO2-induced ocean acidification.

Experimental exposure to ocean and freshwater acidification affects the behaviour of multiple aquatic organisms in laboratory tests. One proposed cause involves an imbalance in plasma chloride and bicarbonate ion concentrations as a result of acid-base regulation, causing the reversal of ionic fluxes through GABAA receptors, which leads to altered neuronal function. This model is exclusively based on differential effects of the GABAA receptor antagonist gabazine on control animals and those exposed to elevated CO2 However, direct measurements of actual chloride and bicarbonate concentrations in neurons and their extracellular fluids and of GABAA receptor properties in aquatic organisms are largely lacking. Similarly, very little is known about potential compensatory mechanisms, and about alternative mechanisms that might lead to ocean acidification-induced behavioural changes. This article reviews the current knowledge on acid-base physiology, neurobiology, pharmacology and behaviour in relation to marine CO2-induced acidification, and identifies important topics for future research that will help us to understand the potential effects of predicted levels of aquatic acidification on organisms.

Dopamine D1 receptor activation leads to object recognition memory in a coral reef fish.

Object recognition memory is the ability to identify previously seen objects and is an adaptive mechanism that increases survival for many species throughout the animal kingdom. Previously believed to be possessed by only the highest order mammals, it is now becoming clear that fish are also capable of this type of memory formation. Similar to the mammalian hippocampus, the dorsolateral pallium regulates distinct memory processes and is modulated by neurotransmitters such as dopamine. Caribbean bicolour damselfish (Stegastes partitus) live in complex environments dominated by coral reef structures and thus likely possess many types of complex memory abilities including object recognition. This study used a novel object recognition test in which fish were first presented two identical objects, then after a retention interval of 10 min with no objects, the fish were presented with a novel object and one of the objects they had previously encountered in the first trial. We demonstrate that the dopamine D1-receptor agonist (SKF 38393) induces the formation of object recognition memories in these fish. Thus, our results suggest that dopamine-receptor mediated enhancement of spatial memory formation in fish represents an evolutionarily conserved mechanism in vertebrates.

Impact of Major Complications on Patients' Quality of Life After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

INTRODUCTION: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective treatment for selected patients with peritoneal surface malignancies (PSM). Although it can have significant morbidity, perioperative mortality is low. Little is known about whether major complications after CRS/HIPEC have a lasting impact on patients' quality of life (QOL). METHODS: We retrospectively reviewed data from a prospectively collected database on patients treated with CRS/HIPEC for PSM (2011-2014). Patients with CRS/HIPEC and 6-month QOL evaluation were included. Major perioperative complications (Clavien-Dindo grade 3/4) were the primary independent variable. QOL was evaluated using the validated EORTC QLQ-C30 score. The primary outcome was 6-month global health score. Secondary outcomes were individual functional and symptom domains. RESULTS: Forty-two patients were analyzed. Median age was 57.5; 64 % were female. Origin of PSM was appendix (55 %), colorectal (38 %), mesothelioma (5 %), and small bowel (2 %). Fourteen patients (33 %) had major (grade 3/4) complications. Median length of stay was 16 days; patients experiencing major complications had significantly increased length of stay (35.5 vs. 13 days, p < 0.01). Major complications included intra-abdominal abscess (9.5 %), bleeding (9.5 %), symptomatic pleural effusion (7.1 %), anastomotic leaks (7.1 %), and renal failure (2.4 %). The average global health score at 6 months was 68.1. The worst-rated symptom scores at 6 months were diarrhea (39.8) and fatigue (35.4). There were no significant differences in 6-month QOL scores between patients with and without major complications, globally or in specific domains. CONCLUSIONS: Although major complications are common after CRS/HIPEC, QOL at 6 months recovers and is similar to those without major complications.

Episodic-like memory in zebrafish.

Episodic-like memory tests often aid in determining an animal's ability to recall the what, where, and which (context) of an event. To date, this type of memory has been demonstrated in humans, wild chacma baboons, corvids (Scrub jays), humming birds, mice, rats, Yucatan minipigs, and cuttlefish. The potential for this type of memory in zebrafish remains unexplored even though they are quickly becoming an essential model organism for the study of a variety of human cognitive and mental disorders. Here we explore the episodic-like capabilities of zebrafish (Danio rerio) in a previously established mammalian memory paradigm. We demonstrate that when zebrafish were presented with a familiar object in a familiar context but a novel location within that context, they spend more time in the novel quadrant. Thus, zebrafish display episodic-like memory as they remember what object they saw, where they saw it (quadrant location), and on which occasion (yellow or blue walls) it was presented.

Modulation of distal calcium electrogenesis by neuropeptide Y1 receptors inhibits neocortical long-term depression.

In layer 5 neocortical pyramidal neurons, backpropagating action potentials (bAPs) firing at rates above a critical frequency (CF) induce supralinear Ca²âº influx and regenerative potentials in apical dendrites. Paired temporally with an EPSP, this Ca²âº influx can result in synaptic plasticity. We studied the actions of neuropeptide Y (NPY), an abundant neocortical neuropeptide, on Ca²âº influx in layer 5 pyramidal neurons of somatosensory neocortex in Sprague Dawley and Wistar rats, using a combination of somatic and dendritic intracellular recordings and simultaneous Ca²âº imaging. Ca²âº influx induced by trains of bAPs above a neuron's CF was inhibited by NPY, acting only at the distal dendrite, via Y1 receptors. NPY does not affect evoked synaptic glutamate release, paired synaptic facilitation, or synaptic rundown in longer trains. Extracellular Cs⁺ did not prevent NPY's postsynaptic effects, suggesting it does not act via either G-protein-activated inwardly rectifying K⁺ conductance (G(IRK)) or hyperpolarization-activated, cyclic nucleotide-gated channels. NPY application suppresses the induction of the long-term depression (LTD) normally caused by pairing 100 EPSPs with bursts of 2 bAPs evoked at a supracritical frequency. These findings suggest that distal dendritic Ca²âº influx is necessary for LTD induction, and selective inhibition of this distal dendritic Ca²âº influx by NPY can thus regulate synaptic plasticity in layer 5 pyramidal neurons.

CO2-induced ocean acidification increases anxiety in rockfish via alteration of GABAA receptor functioning.

The average surface pH of the ocean is dropping at a rapid rate due to the dissolution of anthropogenic CO2, raising concerns for marine life. Additionally, some coastal areas periodically experience upwelling of CO2-enriched water with reduced pH. Previous research has demonstrated ocean acidification (OA)-induced changes in behavioural and sensory systems including olfaction, which is due to altered function of neural gamma-aminobutyric acid type A (GABAA) receptors. Here, we used a camera-based tracking software system to examine whether OA-dependent changes in GABAA receptors affect anxiety in juvenile Californian rockfish (Sebastes diploproa). Anxiety was estimated using behavioural tests that measure light/dark preference (scototaxis) and proximity to an object. After one week in OA conditions projected for the next century in the California shore (1125 ± 100 µatm, pH 7.75), anxiety was significantly increased relative to controls (483 ± 40 µatm CO2, pH 8.1). The GABAA-receptor agonist muscimol, but not the antagonist gabazine, caused a significant increase in anxiety consistent with altered Cl(-) flux in OA-exposed fish. OA-exposed fish remained more anxious even after 7 days back in control seawater; however, they resumed their normal behaviour by day 12. These results show that OA could severely alter rockfish behaviour; however, this effect is reversible.

Identification of prognostic inflammatory factors in colorectal liver metastases.

BACKGROUND: The modified Glasgow Prognostic Score (mGPS) has been reported to be an important prognostic indicator in a number of tumor types, including colorectal cancer (CRC). The features of the inflammatory state thought to accompany elevated C-reactive protein (CRP), a key feature of mGPS, were characterized in patients with colorectal liver metastases. Additional inflammatory mediators that contribute to prognosis were explored. METHODS: In sera from 69 patients with colorectal liver metastases, a panel of 42 inflammatory mediators were quantified as a function of CRP levels, and as a function of disease-free survival. Multivariate statistical methods were used to determine association of each mediator with elevated CRP and truncated disease-free survival. RESULTS: Elevated CRP was confirmed to be a strong predictor of survival (HR 4.00, p = 0.001) and recurrence (HR 3.30, p = 0.002). The inflammatory state associated with elevated CRP was comprised of raised IL-1ß, IL-6, IL-12 and IL-15. In addition, elevated IL-8 and PDGF-AB/BB and decreased eotaxin and IP-10 were associated with worse disease-free and overall survival. CONCLUSIONS: Elevated CRP is associated with a proinflammatory state. The inflammatory state is an important prognostic indicator in CRC liver metastases. The individual contributions of tumor biology and the host to this inflammatory response will require further investigation.